Wills Eye Institute 5-minute ophthalmology consult 9781451186031, 1451186037, 9781608316656, 1608316653

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Wills Eye Institute

5-Minute Ophthalmology Consult

EDITORIAL BOARD Jacqueline R. Carrasco, MD Assistant Professor, Oculoplastic Surgery Wills Eye Institute Philadelphia, Pennsylvania Oculoplastics

Ralph C. Eagle, Jr., MD Director, Department of Pathology Wills Eye Hospital The Noel T. and Sara L. Simmonds Professor of Ophthalmic Pathology Wills Eye Institute Professor of Ophthalmology and Pathology Jefferson Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Consultant in Ocular Pathology

Professor Ophthalmology and Pediatrics Thomas Jefferson University Hospital Philadelphia, Pennsylvania Pediatrics

Robert B. Penne, MD Assistant Clinical Professor Ophthalmology Jefferson Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Oculoplastics

Peter J. Savino, MD Clinical Professor of Ophthalmology Shiley Eye Center University of California, San Diego La Jolla, California Neuro-Ophthalmology

Sunir J. Garg, MD, FACS

Robert C. SergoH, MD

Associate Professor of Ophthalmology The Retina Service of Wills Eye Institute Thomas Jefferson University Philadelphia, Pennsylvania Retina/Vitreous/Uvea

Chief Neuro-Ophthalmology Service Wills Eye Institute Professor of Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Neuro-Ophthalmology

Colleen Halfpenny, MD Member, Cornea Service Clinical Instructor, Cornea Wills Eye Institute Assistant Professor, Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Anterior SegmenVCornea

L. Jay Katz, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania Glaucoma

Alex V. Levin, MD, MHSc, FRCSC Professor Ophthalmology and Pediatrics Jefferson Medical College Chief, Pediatric Ophthalmology and Ocular Genetics Wills Eye Institute

Chirag P. Shah, MD, MPH Vitreoretinal Surgeon Ophthalmic Consultants of Boston Associate Professor Harvard Medical School and Tufts New England Medical Center Boston, Massachusetts Systemic Ophthalmology

Carol L. Shields, MD Co-Director Oncology Service Wills Eye Institute Philadelphia, Pennsylvania Oncology

Marc J. Spirn, MD Retina Service Wills Eye Institute Philadelphia, Pennsylvania Retina/Vitreous

Wi lis Eye Institute

5-Minute Ophthalmology Consult Senior Edltora:

Joseph I. Maguire, MD Attending Surgeon Retina Service The Wills Eye Institute Associate Professor of Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania Ann P. Mun:hison, MD, MPH Attending Surgeon Oculoplastic and Orbital Surgery Service Co-Director Wills Eye Emergency Room The Wills Eye Institute Assistant Professor of Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania Edward A. Jaeger, MD Professor of Ophthalmology Jefferson Medical College Thomas Jefferson University Attending Surgeon The Wills Eye Hospital Philadelphia, Pennsylvania

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Library of Congress Cataloging·in·Public:atian Data

Maguire, Joseph I. Wills Eye Institute 5-minute ophthalmology consult I senior editors, Joseph I. Maguire, Ann P. Murchison, Edward A Jaeger. p. ; em. - (5-minute consult series) Wills Eye Institute five-minute ophthalmology consult 5-minute ophthalmology consult Includes bibliographical references and index. ISBN 13: 978-1-60831-665-6 (alk. paper) ISBN 10: 1·60831-665-3 (alk. paper) I. Murchison, Ann P. II. Jaeger, Edward A Ill. Title. IV. Title: Wills Eye Institute five-minute ophthalmology consult. V. Title: 5-minute ophthalmology consult VI. Series: 5-minute consult. [DNLM: 1. Eye Diseases-Handbooks. 2. Eye Abnormalities-Handbooks. WW 39]617.7-dc23

2011036417

Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of the information in a particular situation remains the professional responsibility of the practitioner. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA} clearance for limited use in restricted research settings. It is the responsibility of the health care providers to ascertain the FDA status of each drug or device planned for use in their clinical practice. To purchase additional copies of this book, call our customer service department at (800} 638-3030 or fax orders to (30 1) 223-2320. International customers should call (30 1) 223-2300. Visit Lippincott Williams & Wilkins on the Internet: at LWW.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6 pm, EST. 10 9 8 7 6 5 4 3 2 1

To the Wills Eye family, whose physicians, graduates, and staff define excellence in patient care

CONTRIBUTORS

Fatima K. Ahmad, MD Resident Physician, 2009-201 2 Wills Eye Institute Department of Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania

Anthony J. Aldave, MD Resident Physician, 1997-2000 Wills Eye Institute Philadelphia, Pennsylvania Associate Professor of Ophthalmology Director, Cornea Service, Cornea and Refractive Surgery Fellowship The Jules Stein Eye Institute Los Angeles, California

AmroAii,MD Instructor Ophthalmology Casey Eye Institute-Oregon Health & Science University Portland, Oregon

David R. P. Almeida Department of Ophthalmology Queen's University Hotel Dieu Hospital Kingston, Ontario, Canada

Rizwan Alvi, MBBS, MD Research Assistant Pediatric Ophthalmology and Ocular Genetics Wills Eye Institute Philadelphia, Pennsylvania

Nicholas G. Anderson, MD Fellow, Retina and Vitreous Surgery, 2003-2005 Wills Eye Institute Philadelphia, Pennsylvania Associate Clinical Professor Department of Surgery University of Tennessee Medical Center Southeastern Retina Associates Knoxville, Tennessee

David B. Auerbach, DO Volunteer Faculty of the University of Central Florida, College of Medicine Medical Education University of Central Florida College of Medicine Active Staff Ophthalmology Orlando Regional Medical Center Orlando, Florida Brandon D. Ayres, MD Instructor Ophthalmology Jefferson Medical College Assistant Surgeon Cornea Service Wills Eye Institute Associate Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania Avnl Badami, BS Medical Student Jefferson Medical College Philadelphia, Pennsylvania RobertS. Bailey, Jr., MD Clinical Associate Professor Ophthalmology Jefferson Medical College Director Cataract and Primary Eye Care Services Wills Eye Institute Chief, Division of Ophthalmology Surgery, Division of Ophthalmology Chestnut Hill Hospital Philadelphia, Pennsylvania Steven T. Bailey, MD Assistant Professor and Attending Physician Department of Ophthalmology Casey Eye Institute-Oregon Health and Science University Portland, Oregon PaulS. Baker, MD Retina Service Wills Eye Institute Jefferson Medical College Philadelphia, Pennsylvania

Brad Ballard, MD Resident in Ophthalmology Madigan Army Medical Center Tacoma, Washington Alok S. Bansal, MD Fellow, Vitreoretinal Surgery, 201 0-2012 Retina Service Wills Eye Institute Philadelphia, Pennsylvania Behln I. Barahlml, MD Resident, 2008-2011 Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Oculoplastics Fellow Ophthalmology University of Minnesota Minneapolis, Minnesota Michael J. Bartiss, OD, MD, FAAO, FAAP,FACS Fellow Pediatric Ophthalmology and Strabismus, 1991-1992 Wills Eye Institute Philadelphia, Pennsylvania Medical Director Pediatric Ophthalmology Services Departments of Surgery and Pediatrics First Health of the Carolinas Pinehurst, North Carolina Darrell E. Baskin, MD Vitreoretinal Fellow Retina Service Wills Eye Institute Philadelphia, Pennsylvania Caroline R. Baumal, MD Former Fellow Vitreoretinal Dieseases and Surgery and Intraocular Tumors Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor of Ophthalmology Tufts University School of Medicine Boston, Massachusetts Gitanjali B. Baveja, MD Comprehensive Ophthalmology Ashburn, Virginia

vii

viii • • • Contributors Stephanie A. Baxter, MD Fellow, 2003-2004 Cornea/External Disease Wills Eye Institute Philadelphia, Pennsylvania Assistant Clinical Professor Queens University Hospital Kingston, Ontario, Canada

Edward H. Bedrossian, Jr., MD, FACS Attending Surgeon, Ophthalmic Plastic and Reconstructive Surgery Department Wills Eye Institute Assistant Clinical Professor of Ophthalmology Jefferson Medical School Director, Ophthalmic Plastic and Reconstructive Surgery Associate Clinical Professor of Ophthalmology Temple University School of Medicine Philadelphia, Pennsylvania Chief of Ophthalmology Delaware County Memorial Hospital Drexel Hill, Pennsylvania Robert D. Behar, MD Attending Surgeon Cataract and Primary Eye Care Service Wills Eye Institute Jefferson Medical College Philadephia, Pennsylvania Raed Behbehani, MD, FRCSC Consultant Ophthalmologist Neuro-Ophthalmology/Orbit Service AI-Bahar Ophthalmology Center Kuwait City, Kuwait Irina Belinsky, MD Resident in Ophthalmology New York University New York, New York Michael J. Belliveau, MD Resident Queen's University Department of Ophthalmology London, Ontario, Canada Robert L Bergren, MD Resident, 1988-1991 and Retina Fellow, 1991-1993 Wills Eye Institute Philadelphia, Pennsylvania Clinical Instructor Department of Ophthalmology University of Pittsburgh Medical Center Pittsburgh, Pennsylvania

ChrisS. Bergstrom, MD, OD Assistant Professor Ophthalmology Emory University Atlanta, Georgia

Stephen Best, MD Fellow, 1991-1992 Neuro-ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Clinical Senior Lecturer Eye Department University of Auckland Ophthalmologist Eye Department Greenlane Clinical Centre Auckland, New Zealand

Carlos Bianciotto., MD Fellow Ophthalmology Jefferson Medical College Ocular Oncology Wills Eye Institute Philadelphia, Pennsylvania

Jurij R. Bilyk, MD Associate Professor Ophthalmology Wills Eye Institute and Jefferson University Hospital Attending Surgeon Oculoplastic and Orbital Surgery Service Wills Eye Institute Philadelphia, Pennsylvania

Gil Binenbaum, MD Division of Ophthalmology Children's Hospital of Philadelphia Philadelphia, Pennsylvania

Mark H. Blecher, MD Assistant Clinical Professor Ophthalmology Jefferson Medical College Attending Surgeon Co-Director, Cataract and Primary Eye Care Wills Eye Institute Philadelphia, Pennsylvania

Jeffrey P. Blice, MD Retina Fellow, 1995-1997 Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Surgery Uniformed Services Health Sciences University Staff Ophthalmologist Ophthalmology Walter Reed National Military Medical Center Bethesda Bethesda, Maryland Benjamin H. Bloom, MD Cataract and Primary Eye Care Service Wills Eye Institute Philadelphia, Pennsylvania Louis C. Blumenfeld, MD Fellow, 1995 Neuro-ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Volunteer Faculty College of Medicine University of Central Florida Department of Ophthalmology Arnold Palmer Hospital of Children Orlando, Florida J. Luigi Borrillo, MD Ophthalmologist San Mateo, California Christopher J. Brady, MD Resident Department of Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Gary Brown, MD, MBA Ophthalmologist Glenside, Pennsylvania Vatinee Y. Bunya, MD Assistant Professor, Cornea & External Disease Ophthalmology Scheie Eye Institute, University of Pennsylvania Philadelphia, Pennsylvania William A. Cantore, MD Associate Professor Ophthalmology and Neurology Penn State College of Medicine Hershey, Pennsylvania

Contributors Jacqueline R. Carrasco, MD Assistant Professor, Oculoplastic Surgery Wills Eye Institute Philadelphia, Pennsylvania Christopher B. Chambers, MD Assistant Professor of Ophthalmology Northwestern University Northwestern Memorial Hospital/ Children's Memorial Hospital Chicago, Illinois Eric Chen, MD Retina Consultants of Houston The Methodist Hospital Houston, Texas Hall F. Chew, MD, FRCSC Clinical Fellow, 2007-2008 Cornea, External Disease, &Refractive Surgery Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Department of Ophthalmology & Vision Sciences University of Toronto Staff Physician Department of Ophthalmology Sunnybrook Health Sciences Centre Toronto, Ontario, Canada Lan Chen, MD, PhD Clinical Associate Professor Medicine University of Pennsylvania Attending Physician Medicine Penn Presbyterian Medical Center Philadelphia, Pennsylvania Allen Chiang, MD Vitreoretinal Fellow, 2009-2011 Retina Service Wills Eye Institute Philadelphia, Pennsylvania Hyung Cho, MD Retina Fellow Ophthalmology Tufts/New England Eye Center Boston, Massachusetts Colleen Christian, MD Ocular Oncology Service Wills Eye Institute Thomas Jefferson University Philadelphia, Pennsylvania

Christine W. Chung, MD Resident, 1996-1999 Fellow, Corneal & External Disease, 1999-2000 Wills Eye Institute Philadelphia, Pennsylvania Jennifer E. Cohn, MD, MPH Assistant Professor Infectious Diseases University of Pennsylvania School of Medicine Philadelphia, Pennsylvania Brian P. Connolly, MD Retina Service Wills Eye Institute Philadelphia, Pennsylvania Mary Ellen P. Cullom, MD Department of Surgery Riverside Regional Medical Center Newport News, Virginia Melissa B. Daluvoy, MD Cornea External Disease Fellow, 2009-2010 Wills Eye Institute Philadelphia, Pennsylvania Ophthalmologist Veterans Affairs Hospital Washington, DC Helen V. Danesh·Meyer, FRANZCO Associate Clinical Professor Sir William and Lady Stevenson Associate Professor of Ophthalmology Department of Ophthalmology University of Auckland Auckland, New Zealand John B. Davies, MD Ophthalmologist St Paul, Minnesota Matthew R. Debiec, MD Resident in Ophthalmology Madigan Army Medical Center Tacoma, Washington Emily A. DeCarlo, MD Tri-County Eye Physicians Southampton, Pennsylvania Char DeCroos Associate Faculty Member Wills Eye Institute Philadelphia, Pennsylvania

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ix

Michael A. DellaVecchia, MD, PhD, FACS Cataract and Primary Eye Care Service Wills Eye Institute Co-Director, Wills Eye Emergency Department at Jefferson Hospital Assistant Professor of Ophthalmology Jefferson Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Kristin DiDomenico, MD Resident Wills Eye Institute Philadelphia, Pennsylvania Harminder S. Dua, MD, FRCOphth, PhD Henry and Corrine Bower Research Scholar, 199D-1991 Fellow, Cornea 1992-1993 Wills Eye Institute Philadelphia, Pennsylvania Chair and Professor of Ophthalmology Ophthalmology and Visual Sciences University of Nottingham Consultant Ophthalmologist Queens Medical Centre, University Hospital Nottingham, England Ryan P. Edmonds, OD Low Vision/Contact Lens Service Wills Eye Institute Philadelphia, Pennsylvania Scott A. Edmonds, OD Adjunct Instructor Public Health Salus University Elkins Park, Pennsylvania Co-Director Low Vision/Contact Lens Service Wills Eye Institute Philadelphia, Pennsylvania Specified Health Professional Lankenau Hospital Wynnewood, Pennsylvania

Susan E. Edmonds, OD Low Vision/Contact Lens Service Wills Eye Institute Philadelphia, Pennsylvania Specified Health Professional, Ophthalmology Lankenau Hospital Wynnewood, Pennsylvania

x •••

Contributors

Justis P. Ehlers, MD Chief Resident, 2007-2008 and Resident, 2005-2008 Wills Eye Institute Philadelphia, Pennsylvania Staff Physician, Vitreoretinal Service Cole Eye Institute Cleveland Clinic Foundation Cleveland, Ohio J. Mark Engel, MD Assistant Clinical Professor Pediatric Ophthalmology University of Medicine and Dentistry of New Jersey Newark, New Jersey AnH1ony W. Farah, MD Resident Wills Eye Institute Philadelphia, Pennsylvania Christopher M. Fecarotta, MD Resident Wills Eye Institute Philadelphia, Pennsylvania Brad H. Feldman, MD Attending Surgeon Cornea and Cataract & Primary Eye Care Wills Eye Institute Instructor Department of Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Mark M. Fernandez, MD Duke Eye Center North Carolina MitchellS. Fineman, MD Retina Service Wills Eye Institute Assistant Professor of Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Thomas A. Finley, MD Fellow, Retinal Consultants of Alabama Retina/Vitreous Surgery Homewood, Alabama David Fintak., MD Division of Emergency Medicine Washington University in St. Louis School of Medicine St. Louis, Missouri

Robert Fintelmann, MD Former Resident in Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Cornea Fellow Proctor Institute University of California-San Francisco San Francisco, California

Sunir J. Garg, MD, FACS Associate Professor of Ophthalmology The Retina Service of Wills Eye Institute Thomas Jefferson University Fellow, 2004 The Retina Service Wills Eye Institute Philadelphia, Pennsylvania

Brian J. R. Forbes, MD, PhD Assistant Professor of Ophthalmology The University of Pennsylvania Assistant Professor of Ophthalmology Pediatric Ophthalmology The Children's Hospital of Philadelphia Philadelphia, Pennsylvania

Adam T. Gerstenblith, MD Resident, 2008-2011 Vitreoretinal Surgery Fellow Wills Eye Institute Thomas Jefferson University Hospital Philadelphia, Pennsylvania

Alan R. Forman, MD Wills Eye Institute Faculty Member Assistant Professor of Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Rod Foroozan, MD Resident, 1998-2001 Fellow, 2001-2002 Neuro-Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor of Ophthalmology Baylor College of Medicine Houston, Texas Nicole R. Fram, MD Co-Chief Resident, 2007 Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania Clinical Instructor Department of Ophthalmology University of California Los Angeles Associate Staff Ophthalmology Cedars Sinai Medical Center Los Angeles, California Kathryn Burleigh Freidl, MD Fellow, Glaucoma Service, Wills Eye Institute, 2010-2011 Philadelphia, Pennsylvania Fellowship-trained Glaucoma Specialist Florida Eye Specialists Jacksonville, Florida Scott J. Fudemberg, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania

Neelofar Ghaznawi, MD Fellow, 2009-2010 Comea and External Disease Wills Eye Institute Philadelphia, Pennsylvania Clinical Instructor Department of Ophthalmology New York University Attending Department of Ophthalmology New York University Medical Center New York, New York Ahmara V. Gibbons, BA Thomas Jefferson University Philadelphia, Pennsylvania Katherine G. Gold, MD Resident Class of 20 10 Ophthalmology Wills Eye Institute, Thomas Jefferson University Philadelphia, Pennsylvania Fellow-Ophthalmic Plastic Surgery Ophthalmology New York University School of Medicine Assistant Clinical Professor Ophthalmology New York University Medical Center New York, New York Scott M. Goldstein, MD Adjunct Clinical Assistant Professor Department of Ophthalmology Jefferson Medical College Oculoplastic Attending Assistant Professor, Oculoplastic Surgery Wills Eye Institute Philadelphia, Pennsylvania

Matthew Gorski, MD Resident Ophthalmology SUNY Downstate Medical Center Brooklyn, New York

Contributors Robert J. Goulet, Ill, MD Glaucoma Fellow, 2010-2011 Wills Eye Institute Philadelphia, Pennsylvania Robert J. Granadler, MD Fellow, Neuro-Ophthalmology,

1988-1989 Wills Eye Institute Philadelphia, Pennsylvania William Beaumont Eye Institute Royal Oak, Michigan

Florin Grigorian, MD Pediatric Ophthalmology Children's Mercy Hospital Kansas City, Missouri Paula Grigorian, MD Pediatric Ophthalmology Children's Mercy Hospital Kansas City, Missouri Deepak P. Grover, DO Fellow, 2009-2010 Neuro-Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Ophthalmologist on Staff Lehigh Valley Hospital Allentown, Pennsylvania Ophthalmologist on Staff St. Luke's Hospital Bethlehem, Pennsylvania Lili Grunwald, MD Medical Retina Private Practice Philadelphia, Pennsylvania Kamml Gunton, MD Assistant Professor Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Shelly R. Gupta, MD Fellow, 2010-2011 Glaucoma Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Ophthalmology The Ohio State University Columbus, Ohio Carlos Gustavo, MD Oncology Service Wills Eye Institute Philadelphia, Pennsylvania

Colleen Halfpenny, MD Resident, 2002-2005 Fellow, Corneal & External Disease, 2005-2006 Member, Cornea Service Clinical Instructor, Cornea Wills Eye Institute Assistant Professor, Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Kristin M. Hammersmith, MD Wilmer Eye Institute Johns Hopkins Hospital Baltimore, Maryland Sadeer B. Hannush, MD Assistant Professor Ophthalmology Jefferson Medical College Attending Surgeon Cornea Service Wills Eye Institute Philadelphia, Pennsylvania Dorothy H. Hendricks, MD Clinical Instructor Ophthalmology Jefferson University Hospital Philadelphia, Pennsylvania Clinical Instructor Pediatric Ophthalmology AI DuPont Hospital for Children Wilmington, Delaware Lawrence Y. Ho, MD Staff Physician Ophthalmology Holy Spirit Hospital/Pinnacle Hospital Mechanicsburg/Harrisburg, Pennsylvania Susan Hoch, MD Clinical Associate Professor of Medicine Department of Rheumatology University of Pennsylvania Philadelphia, Pennsylvania Elizabeth M. Hofmeister, MD Assistant Professor Department of Surgery Uniformed Services University of the Health Sciences Bethesda, Maryland Refractive Surgery Advisor for Navy Ophthalmology Head, Navy Refractive Surgery Center San Diego Naval Medical Center San Diego San Diego, California

•••

xi

DouglasS. Holsclaw, MD Assistant Clinical Professor Department of Ophthalmology Francis I. Proctor Foundation University of California, San Francisco San Francisco, California Eliza Hoskins, MD Resident, 2005-2008 Wills Eye Institute Philadelphia, Pennsylvania Cornea Fellow University of California, San Francisco San Francisco, California Jason Hsu, MD Clinical Instructor Ophthalmology Thomas Jefferson University Assistant Surgeon Retina Service Wills Eye Institute Philadelphia, Pennsylvania Denise Hug, MD Assistant Professor Ophthalmology University of Missouri-Kansas City School of Medicine Pediatric Ophthalmologist Surgery, Section of Ophthalmology Children's Mercy Hospital and Clinic Kansas City, Missouri Saunders L Hupp, MD Fellow, 1984-1985 Neuro-Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Clinical Professor Neurology University of South Alabama Attending Surgery Providence Hospital Mobile, Alabama ParullchhpuJanl, MD Former Clinical Research Fellow in Glaucoma Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Government Medical College and Hospital Chandigarh, India

xi i

•••

Contributors

Edsel lng, MO, FRCS Associate Professor Ophthalmology and Vision Sciences University of Toronto Attending Staff Ophthalmology Toronto East General Hospital Toronto, Ontario, Canada Suzanne K Jadico, MD Chief Resident, 2009-2010 and Resident, 2007-2010 Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Associate Ophthalmologist Department of Surgery University Medical Center of Princeton Princeton, New Jersey Edward A. Jaeger, MD Professor of Ophthalmology Jefferson Medical College Attending Surgeon Comprehensive Ophthalmology Service/Medical Education Wills Eye Institute Active Staff Member Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania Annie Jensen Department of Environmental Health Institute of Public Health University of Copenhagen Copenhagen, Denmark Jing Jin, MD, PhD Clinical Assistant Professor Ophthalmology and Pediatrics Thomas Jefferson University Pediatric Ophthalmology Wills Eye Hospital Philadelphia, Pennsylvania Pediatric Ophthalmologist Surgery Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware Brandon B. Johnson, MD Resident Ophthalmology Wills Eye Institute Thomas Jefferson University Hospital Philadelphia, Pennsylvania

Paul B. Johnson, MD Attending Ophthalmologist Emergency Department Wills Eye Institute Associate Oculoplastic Surgeon Ophthalmology Soli Eye Associates Philadelphia, Pennsylvania RickS. Kaiser, MD Associate Professor Ophthalmology Jefferson Medical College Associate Surgeon Retina Service Wills Eye Institute Philadelphia, Pennsylvania Steven J. Kanoff, MD Clinical Instructor Wills Eye Institute Philadelphia, Pennsylvania Tulay Kansu, MD Professor Neurology Hacettepe University School of Medicine Professor Neurology, Neuro-ophthalmology Unit Hacettepe University Hospitals Ankara, Turkey L. Jay Katz, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania Matthew D. Kay, MD Fellow, 1991-1992 Neuro-Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Assistant Clinical Professor Ophthalmology Florida International University College of Medicine Miami, Florida Bhairavi V. Kharod, MD Clinical Associate Cornea and Refractive Surgery Service Duke University Eye Center Durham, North Carolina

Monica R. Khitri, MD Department of Ophthalmology Scheie Eye Institute, University of Pennsylvania Attending Physician Department of Surgery Philadelphia VA Medical Center Philadelphia, Pennsylvania Hyunjin J. Kim, MD Clinical Fellow, 2010-2011 Ocular Oncology Wills Eye Institute Clinical Instructor Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania Terry Kim, MD Department of Ophthalmology New York University Medical Center New York, New York Robert A- King, MD Fellow, 1985-1986 Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Children's Eye Physicians Wheat Ridge, Colorado Harold P. Koller, MD, FAAP, FACS Professor of Ophthalmology Jefferson Medical College Attending Surgeon Pediatric Ophthalmology Attending Surgeon Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Susan M. Ksiazek, MD Neuro-Ophthalmology Fellow,

1987-1988 Department of Ophthalmology, Section of Neuro-Ophthalmology Wills Eye Hospital Philadelphia, Pennsylvania Associate Professor Department of Surgery, Section of Ophthalmology and Visual Science University of Chicago Residency Program Director Department of Surgery, Section of Ophthalmology and Visual Science University of Chicago Hospitals Chicago, Illinois

Contributors Kenneth C. Kubis, MD Captain Medical Corps, United States Navy Fellow, 1998-1999 Neuro-Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor, Uniformed Services University Department of Ophthalmology Naval Medical Center Chairman Department of Ophthalmology Naval Medical Center San Diego Director, Neuro-Ophthalmology San Diego, California Peter R. Laibson, MD Director Emeritus Cornea Service Wills Eye Institute Professor of Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania David R. Lally, MD Resident Physician Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Sara Lally, MD Oncology Service Wills Eye Institute Philadelphia, Pennsylvania Andrew Lam, MD Resident, 2003-2006, and Retina Fellow,

2006-2008 Wills Eye Institute Philadelphia, Pennsylvania New England Retina Consultants Attending Surgeon Department of Surgery Baystate Medical Center Springfield, Massachusetts

Katherine A. Lane, MD Resident, 2004-2007 Wills Eye Institute Philadelphia, Pennsylvania Attending Surgeon Fletcher Allen Hospital Center Burlington, Vermont Judith B. Lavrich, MD Department of Pediatric Ophthalmology Wills Eye Institute Jefferson Medical College Philadelphia, Pennsylvania

•••

Esther Lee, MD Preliminary Residency in Internal Medicine Drexei/Hahnemann University Philadelphia, Pennsylvania

Wayne R. Lo, MD Staff Physician Department of Ophthalmology Northwest Permanente Portland, Oregon

Sharon S. Lehman, MD Clinical Professor Ophthalmology and Pediatrics Jefferson Medical College Assistant Surgeon Pediatric Ophthalmology Jefferson Medical College/Wills Eye Institute Philadelphia, Pennsylvania Chief Pediatric Ophthalmology Nemours Children's Clinic/AI Dupont Hospital for Children Wilmington, Delaware

Nikolas London, MD California Pacific Medical Center San Francisco, California

Alex V. Levin, MD, MHSc, FRCSC Professor Ophthalmology and Pediatrics Jefferson Medical College Chief, 2008-Current Pediatric Ophthalmology and Ocular Genetics Wills Eye Institute Professor Ophthalmology and Pediatrics Thomas Jefferson University Hospital Philadelphia, Pennsylvania Brett Levinson, MD Corneal, External Disease, and Refractive Surgery Fellow, 2006-2007 Wills Eye Institute Philadelphia, Pennsylvania Director of Anterior Segment Surgery and Contact Lenses Select Eye Care Active Staff Department of Ophthalmology Sinai Hospital of Baltimore Baltimore, Maryland Mimi Liu,MD Resident, Graduated 2003 Retina Fellow, Graduated 2005 Wills Eye Institute Philadelphia, Pennsylvania Attending Surgeon Ophthalmology Porter Adventist Hospital Denver, Colorado

xiii

Caesar Luo. MD

Ophthalmologist Royal Oak, Michigan

Assumpta Madu, MD Department of Ophthalmology Glaucoma Service Montefiore Medical Center Albert Einstein College of Medicine Bronx, New York Joseph I. Maguire, MD Attending Surgeon Retina Service The Wills Eye Institute Associate Professor of Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania Naresh Mandava, MD Professor and Chair Department of Ophthalmology University of Colorado-Denver Anschutz Medical Campus Aurora, Colorado Donelson Manley, MD Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Anand V. Mantravadi, MD Glaucoma Service Wills Eye Institute Instructor in Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Stephanie J. Marloneaux, MD Former Wills Eye Resident and Cornea Fellow Hospital Authority of Chesapeake Regional Medical Center Chesapeake Regional Medical Center Chesapeake, Virginia Assistant Professor Department of Ophthalmology Eastern Virginia Medical School Norfolk, Virginia

xiv • • • Contributors Bruce J. Markovitz, MD Clinical Instructor Cataract and Primary Eye Care Service Wills Eye Institute Philadelphia, Pennsylvania Ophthalmology Program Director Surgery Cooper University Hospital Camden, New Jersey

AmmarMiri School of Clinical Sciences Division of Ophthalmology and Visual Sciences University of Nottingham, United Kingdom Department of Surgery College of Medicine The University of Basrah Basrah, Republic of Iraq

Arman Mashayekhi, MD Assistant Professor Ophthalmology Thomas Jefferson University Staff Physician Oncology Service Wills Eye Institute Philadelphia, Pennsylvania

Dan P. Montzka, MD Retina Fellow, 1994-1995 Wills Eye Institute Philadelphia, Pennsylvania Gulf Coast Retina Port Richey, Florida

John 0. Mason Ill, MD Retina Consultants Birmingham, Alabama

Edward Moss, MD Resident in Ophthalmology Queen's University Hospital Kingston, Ontario, Canada

Amanda Matthews, MD Resident Physician Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Marion Maus, MD, MPH Former Residency Director Oculoplastics Thomas Jefferson University/Wills Eye Institute Philadelphia, Pennsylvania DrPH Candidate School of Public Health University of California, Berkeley Berkeley, California

J. Arch McNamara, MD* Assistant Professor Department of Ophthalmology Jefferson Medical College Attending Surgeon Retina Service Wills Eye Institute Philadelphia, Pennsylvania

Eugene Milder Fellow, Retina Service, 2009-2011 Wills Eye Institute Philadelphia, Pennsylvania Vitreoretinal Surgeon Ophthalmology Dewitt Army Community Hospital Fort Belvoir, Virginia

•Deceased

Mark L. Moster, MD Fellow, 1983-1984 Attending Surgeon Neu ro-Ophthalmology Wills Eye Institute Professor Neurology and Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Marlene R. Moster, MD Professor of Ophthalmology Jefferson Medical College Attending Surgeon Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Ann P. Murchison, MD, MPH Attending Surgeon Oculoplastic and Orbital Surgery Service Co-Director Wills Eye Emergency Room The Wills Eye Institute Assistant Professor of Ophthalmology Thomas Jefferson University Philadelphia, Pennsylvania Jonathan S. Myers, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania

Parveen K. Nagra, MD Assistant Professor Department of Ophthalmology Jefferson Medical College Cornea Service Wills Eye Institute Philadelphia, Pennsylvania Sarkis M. Nazarian, MD, FAAN, FNANOS Associate Professor Departments of Neurology & Ophthalmology University of Arkansas for Medical Sciences Chief Neurology Service Central Arkansas Veterans Hospital Little Rock, Arkansas Leonard B. Nelson, MD, MBA Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Mark L. Nelson, MD Retina Fellow, 2001-2003 Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor of Surgery Uniformed Services University of the Health Sciences Bethesda, Maryland Attending Surgeon Allenmore Hospital Tacoma, Washington Melissa D. NeuweH, MD Resident, 2007-2010 Wills Eye Institute Philadelphia, Pennsylvania Retinal Fellow Williams Beaumont Hospital Royal Oak, Michigan Erin M. Ney, MD, FACP Clinical Assistant Professor Jefferson Medical College Assistant Program Director Internal Medicine Residency Thomas Jefferson University Hospital Philadelphia, Pennsylvania Joshua J. Ney, MD Resident Ophthalmology Scheie Eye Institute Philadelphia, Pennsylvania

Contributors Rachel M. Niknam, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania Thaddeus S. Nowinski, MD Clinical Associate Professor Ophthalmology Jefferson Medical College Attending Surgeon Oculoplastic Service Wills Eye Institute Philadelphia, Pennsylvania Mary O'Hara, MD Professor Ophthalmology, Pediatrics University of California, Davis Chief, Pediatric Ophthalmology & Strabismus UC Davis Health System Eye Center Sacramento, California Linda H. Ohsie, MD Resident, 2007-2010 Fellow (Neuro-ophthalmology),

2010-2011 Wills Eye Institute Philadelphia, Pennsylvania Wisda Eye Center Vineland, New Jersey Comprehensive Ophthalmology Staff Physician Surgery South Jersey Healthcare Elmer Hospital Elmer, New Jersey

Scott E. Olitsky, MD Professor of Ophthalmology University of Missouri-Kansas City School of Medicine Chief of Ophthalmology Children's Mercy Hospitals and Clinics Kansas City, Missouri Scott C. N. Oliver, MD Assistant Professor Ophthalmology University of Colorado School of Medicine Faculty Physician Ophthalmology Children's Hospital Colorado Partner Ophthalmology University of Colorado Hospital Aurora, Colorado Jeffrey L Olson, MD Retina/Vitreous Surgery University of Colorado Hospital Aurora, Colorado

Sriranjani P. Padmanabhan, MD Resident in Ophthalmology Scheie Eye Institute University of Pennsylvania Philadelphia, Pennsylvania Vasudha A. Panday, MD Associate Professor Department of Ophthalmology San Antonio Uniformed Services Health Education Consortium San Antonio, Texas Former Resident Department of Ophthalmology Thomas Jefferson Medical College Philadelphia, Pennsylvania Chief, Cornea/External Disease and Refractive Surgery Department of Ophthalmology Wilford Hall Medical Center Lackland Air Force Base, Texas Kristina Yi-Hwa Pao, MD Resident, July '2009-present Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Britt J. Parvus, DO Clinical Fellow, 2008-2010 Ocular Oncology Wills Eye Institute Philadelphia, Pennsylvania Affiliate Faculty Ophthalmology Philadelphia College of Osteopathic Medicine Affiliate Staff Ophthalmology Riddle Memorial Hospital Media, Pennsylvania Apurva K. Patel, MD Retina Fellow New York Eye and Ear Infirmary New York, New York Chirag P. Patel, MD, MPH Resident, '2005-'2008 Retinal Fellow, '2008-'201 0 Wills Eye Institute Philadelphia, Pennsylvania Jayrag A. Patel, MD Wills Eye Institute Philadelphia, Pennsylvania Robert B. Penna, MD Assistant Clinical Professor Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania

• ••

Jared D. Peterson, MD Resident Ophthalmology Wills Eye Institute Thomas Jefferson University Hospital Philadelphia, Pennsylvania Arun Prasad, MD Former Clinical Fellow, 2007-2008 Glaucoma Department Wills Eye Institute Philadelphia, Pennsylvania Glaucoma Specialist Eye Care Center of Napa Valley Napa, California Michael J. Pro, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania Anam Quershl, MD Resident Crozer-Chester Hospital Chester, Pennsylvania Irving M. Raber, MD Clinical Assistant Professor Ophthalmology Jefferson Medical College Attending Surgeon Cornea Service Wills Eye Institute Associate Staff Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania Michael P. Rabinowitz, MD Resident Physician, 2008-20 11 The Wills Eye Institute Clinical Instructor Department of Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania Rajesh K. Rajpal, MD Fellow, 1991-1992 Corneal Service Wills Eye Institute Philadelphia, Pennsylvania Associate Clinical Professor Georgetown University Hospital Washington, DC Cornea/External Disease/Refractive Surgery Mclean, Virginia Kamalesh Janaksinh Ramaiya, MD Vitreoretinal Surgeon Eye Associates of New Mexico Albuquerque, New Mexico

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•••

Contributors

Aparna Ramasubramanian, MD Former Fellow, Oncology Service, 2008-2009 Wills Eye Institute Philadelphia, Pennsylvania Resident in Ophthalmology Indiana University Indianapolis, Indiana

Melvin Roat, MD, FACS Clinical Associate Professor Ophthalmology Jefferson Medical College Assistant Surgeon Cornea Wills Eye Institute Philadelphia, Pennsylvania

P. Kumar Rao, MD Associate Professor Ophthalmology and Visual Sciences Washington University St. Louis, Missouri

Kathleen Romero, BS, MS, MD Resident in Ophthalmology University of California San Diego San Diego, California

Christopher J. Rapuano, MD Professor Ophthalmology Jefferson Medical College Director, Cornea Service Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Mahta Rasouli, MD Retinal Fellow University of Alberta Edmonton, Alberta, Canada M. Reza Razeghinejad, MD Research Glaucoma Fellow, 2009-2010 Glaucoma Wills Eye Institute Philadelphia, Pennsylvania Associate Professor Ophthalmology Shiraz University of Medical Sciences Director of Glaucoma Service Ophthalmology Khalili Hospital Shiraz, Iran Swathi C. Reddy, MD, MPH Resident Ophthalmology Montefiore Medical Center Bronx, New York Carl D. Regillo, MD, FACS Professor of Ophthalmology Ophthalmology Jefferson Medical College Attending Surgeon Retina Service Wills Eye Institute Philadelphia, Pennsylvania David S. Rhee, MD Retinal Fellow, 2007-2009 Wills Eye Institute Philadelphia, Pennsylvania

Brett J. Rosenblatt, MD Kellogg Eye Center Department of Ophthalmology and Visual Science University of Michigan Ann Arbor, Michigan Julie M. Rosenthal, MD Resident, 2007-2010 Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Fellow, Vitreoretinal Surgery Casey Eye Institute Oregon Health and Science University Portland, Oregon Christine G. Saad, MD Cornea Fellow, 2006-2007 Cornea and External Disease/Cornea Service Wills Eye Institute Philadelphia, Pennsylvania Ophthalmologist Department of Surgery Lehigh Valley Hospital Allentown, Pennsylvania Dalia G. Said Division of Ophthalmology and Visual Sciences University of Nottingham Nottingham, United Kingdom Arvind Saini, MD, MBA Cornea Fellow, 2004-2010 Wills Eye Hospital Philadelphia, Pennsylvania Milwaukee Eye Care Associate Milwaukee, Wisconsin

Jonathan H. Salvin, MD Clinical Assistant Professor Departments of Ophthalmology & Pediatrics Jefferson Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Division of Ophthalmology Nemours/AI duPont Hospital for Children Wilmington, Delaware Rob Sambursky, MD Former Resident, 2001-2004 Cornea Fellow, 2004-2005 The Wills Eye Institute Philadelphia, Pennsylvania Lov Sarin, MD Wills Eye Institute Philadelphia, Pennsylvania Andrea K. Sawchyn, MD Clinical Glaucoma Fellow, 2009-2010 Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Ophthalmology The Ohio State University Columbus, Ohio Emil Anthony T. Say, MD Research Fellow, 2009-2010 Ocular Oncology Wills Eye Institute Philadelphia, Pennsylvania Retina Fellow, 2010-2012 Department of Ophthalmology University of North Carolina Chapel Hill, North Carolina Anita P. Schadlu, MD Wills Eye Hospital Philadelphia, Pennsylvania Ramin Schadlu, MD Scheie Eye Institute University of Pennsylvania Abington, Pennsylvania Joseph W. Schmitz, MD Resident Ophthalmology Naval Medical Center San Diego San Diego, California Bruce Schnall, MD Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania

Contributors Herman D. Schubert, MD Professor of Clinical Ophthalmology and Pathology Columbia University Attending Ophthalmology New York Presbyterian Hospital New York, New York Geoffrey P. Schwartz, MD Glaucoma Service Wills Eye Institute Jefferson Medical College Philadelphia, Pennsylvania Kelly D. Schweitzer, MD Department of Ophthalmology Queen's University Hospital Kingston, Ontario, Canada Margaret E. M. Scott, DO General Medical Officer Ophthalmology Naval Medical Center San Diego San Diego, California Vikram J. Setlur, MD Resident Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Chirag P. Shah, MD, MPH Vitreoretinal Surgery Fellow, 2008-2010, Co-Chief Resident, 2007-2008, and Resident, 2005-2008 Wills Eye Institute Philadelphia, Pennsylvania Vitreoretinal Surgeon Ophthalmic Consultants of Boston Associate Professor Harvard Medical School and Tufts New England Medical Center Boston, Massachusetts Gaurav K. Shah, MD Retinal Consultants of Arizona Phoenix, Arizona Rajiv Shah, MD Department of Ophthalmology St Vincent's Hospital Sydney, Australia Raza M. Shah, MD Resident Ophthalmology Drexel Eye Physicians Philadelphia, Pennsylvania

Sumit P. Shah, MD Tufts Medical Center Department of Ophthalmology Boston, Massachusetts Tiffany Shiau, MHS Medical Student Jefferson Medical College Philadelphia, Pennsylvania Carol L. Shields, MD Co-Director Oncology Service Wills Eye Institute Philadelphia, Pennsylvania Jerry A. Shields, MD Co-Director Oncology Service Wills Eye Institute Professor of Ophthalmology Jefferson Medical College Philadelphia, Pennsylvania Gary Shienbaum, MD Resident, 2008 Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Vitreoretinal Fellow Ophthalmology Bascom Palmer Eye Institute Miami, Florida

•• •

xvii

Bradley T. Smith, MD Ophthalmology Resident, 2003-2006 Wills Eye Institute Philadelphia, Pennsylvania Clinical Instructor Department of Ophthalmology & Visual Sciences Washington University School of Medicine Vitreoretinal Specialist The Retina Institute St Louis, Missouri Rachel K. Sobel, MD Former Resident, 2007-2010 Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Fellow Department of Oculoplastics University of Iowa Iowa City, Iowa RizSomani Department of Ophthalmology Royal Alexandra Hospital University of Alberta Alberta, Edmonton, Canada George L. Spaeth, MD Professor Ophthalmology Jefferson Medical College Resident, 1963 Attending Surgeon Glaucoma Director, Research Center Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania

Olga A. Shif, MD Resident, Internal Medicine Pennsylvania Hospital Philadelphia, Pennsylvania

Justin M. Spaulding, OMS Ill Medical Student Rocky Vista University College of Osteopathic Medicine Parker, Colorado

Magdalena F. Shuler, MD, PhD Retina Fellow, 2000-2002 Retina Service Wills Eye Hospital Philadelphia, Pennsylvania Vitreoretinal Surgeon Department of Surgery Gulf Coast Medical Center Panama City, Florida

Benjamin D. Spirn, MD Attending Ophthalmology Riverview Medical Center Red Bank, New Jersey Marc J. Splrn, MD Retina Service Wills Eye Institute Philadelphia, Pennsylvania

Arunan Slvallngam, MD Wills Eye Institute Philadelphia, Pennsylvania

Erin D. Stahl, MD Assistant Professor of Ophthalmology University of Missouri School of Medicine Kansas City, Missouri

:xviii

•••

Contributors

Eliza S. Stroh, MS Ocular Genetics Counselor Pediatric Ophthalmology and Ocular Genetics Wills Eye Institute Philadelphia, Pennsylvania Tak Vee Tania Tai, MD Fellow, 2010-2011 Glaucoma Wills Eye Institute Philadelphia, Pennsylvania Department of Ophthalmology New York Eye and Ear Infirmary New York, New York MatthewS. Tennant, BA, MD, FRCSC Retina Fellow, 2003 Wills Eye Hospital Philadelphia, Pennsylvania Associate Clinical Professor Ophthalmology University of Alberta Associate Clinical Professor Ophthalmology Royal Alexandra Hospital Edmonton, Alberta, Canada Alex B. Theventhiran, BSE, MS, MD Resident Department of Ophthalmology Temple University Temple University Hospital Philadelphia, Pennsylvania Michael D. Tibbetts, MD Harvard Medical School Boston, Massachusetts Patrick Tiedeken, MD Glaucoma Service Wills Eye Institute Philadelphia, Pennsylvania

Elyse Trastman-Caruso, MD Glaucoma Fellow, 2008-2009 Glaucoma Service Wills Eye Institute Attending/Clinical Instructor Glaucoma/Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Tara A. Uhler, MD Assistant Professor Director of Resident Education Ophthalmology Jefferson Medical College Medical Staff Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania

Rudolph S. Wagner, MD Fellow, 1982-1983 Pediatric Ophthalmology and Adult Motility Wilfs Eye Hospital Philadelphia, Pennsylvania Clinical Professor Department of Ophthalmology UMDNJ-New Jersey Medical School Director of Pediatric Ophthalmology Institute of Ophthalmology & Visual Science University Hospital Newark, New Jersey Eileen X. Wang, MD Resident in Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania

Scott Uretsky, MD

Neu ro-Ophthalmology Section Neurological Surgery PC Lake Success, New York

James F. Vander, MD Wills Eye Institute Philadelphia, Pennsylvania G. Atma Vemulakonda, MD Assistant Professor Vitreoretinal Disease and Surgery Department of Ophthalmology University of Washington Attending Physician Vitreoretinal Disease and Surgery Department of Ophthalmology University of Washington Medical Center and Harborview Medical Center Seattle, Washington

Richard Tlppennan, MD Attending Surgeon Cataract and Primary Eye Care Wills Eye Institute Philadelphia, Pennsylvania

Frederick B. Vivino, MD, FACR Associate Professor of Clinical Medicine University of Pennsylvania School of Medicine Chief of Rheumatology Penn Presbyterian Medical Center Director, Penn Sjogren's Syndrome Center Philadelphia, Pennsylvania

Ethan H. littler, MD Intern Medicine University of Utah Salt Lake City, Utah Subintern Glaucoma Wills Eye Institute Philadelphia, Pennsylvania

Avni Vyas. MD Resident, 2006-2009 Co-Chief Resident, 2008-2009 Wills Eye Institute Philadelphia, Pennsylvania Clinical Instructor Ophthalmology University of Pittsburgh Pittsburgh, Pennsylvania

Daniel Warder, MD Resident in Ophthalmology Queen's University Hospital Kingston, Ontario, Canada Barry Wassennan, MD Clinical Instructor Pediatric Ophthalmology Wills Eye Institute Philadelphia, Pennsylvania Daniel T. Weaver, MD Fellow, 1991-1992 Wilfs Eye Institute Philadelphia, Pennsylvania Pediatric Ophthalmology Billings, Montana Hong Wei, MD Research Felfow, 2009-2010 Glaucoma Research Center Wilfs Eye Institute Philadelphia, Pennsylvania Lecturer Ophthalmology Department Sichuan University Physician Ophthalmology Department West China Hospital Chengdu, Sichuan, P.R. China Christian Wertenbaker, MD Associate Clinical Professor Ophthalmology and Neurology Albert Einstein College of Medicine Director, Neuro-Ophthalmology Service Montefiore Medical Center Bronx, New York

Contributors James H. Whelan, MD, FRCSC Fellow, 1998-2000 Retina/Vitreous Surgery Wills Eye Institute Philadelphia, Pennsylvania Comprehensive Ophthalmology St. John's, Newfoundland, Canada Susan Whlb'ner, MD Resident, Ophthalmology Naval Medical Center San Diego San Diego, California Douglas M. Wisner, MD Co-Chief Resident Ophthalmology Wills Eye Institute Co-Chief Resident Ophthalmology Thomas Jefferson University Hospital Philadelphia, Pennsylvania AndreJ. Witkin, MD Vitreoretinal Surgery Fellow Wills Eye Hospital Thomas Jefferson University Philadelphia, Pennsylvania

Jeremy D. Wolfe, MD, MS Vitreoretinal Surgery Fellow, 2008-2010 Wills Eye Institute Philadelphia, Pennsylvania Assistant Professor Oakland University William Beaumont School of Medicine Attending Surgeon Associated Retinal Consultants Royal Oak, Michigan

Vladimir Yakopson, MD, MAJ, Medical Corps, US Army Fellow, Oculoplastic and Orbital Surgery, 2009-2011 Oculoplastic and Orbital Surgery Service Wills Eye Institute Philadelphia, Pennsylvania Chief, Ophthalmology Service Department of Surgery Carl R. Darnall Army Medical Center Fort Hood, Texas

• • • xix

Jacky Y. T. Yeung Practicing Ophthalmologist Peterborough, Ontario, Canada William 0. Young, MD Adjunct Assistant Professor Family Medicine University of North Carolina School of Medicine Chapel Hill, North Carolina Surgery Greensboro, North Carolina Omaya H. Youssef Wills Eye Institute Thomas Jefferson University Philadelphia, Pennsylvania

FOREWORD ive minutes worth of advice from a colleague who knows as much about the topic as anyone in the world? What could be better? The Wills Eye Institute 5-Minute Consult in Ophthalmology provides just that type of targeted, focused advice; a quick curbside consult with an expert from Wills regarding a patient there in your office. Wills Eye has been in the business of providing exactly this sort of help to physicians worldwide since we opened the doors of our first hospital through a gift to the City of Philadelphia from James Wills, a Quaker merchant and grocer, who died in 1825 leaving his money to build a hospital to care for the "indigent blind." As a result, in 1839, the first ophthalmology residency was inaugurated at Wills, the beginning of a long and storied history of training physicians in our field. Our Wills history and experience with patient care and education translates into "right to the bottom line" eli nical decision-making and

F

advice. Drs. Maguire, Murchison, and Jaeger have organized this superb volume to provide just this type of very practical support: the maximum help within a minimum of time. This volume will be a well-thumbed, front-of-the-bookshelf addition for the busy practitioner who is absorbed with following Osier's great dictum for prioritizing the crush of clinical care, "The best preparation for tomorrow is to do today's work superbly well." This superb tome will help in that time-honored and noble taskl

JuUA A. H.w.ER, MD Ophthalmologist-in-Chief Wills Eye Institute Professor and Chair at Ophthalmology Jefferson Medical Collage at Thomas Jefferson University Philadelphia, Pennsylvania

xx:i

PREFACE

To see a World in a Grain of Sand And a Heaven in a Wild Flower Hold Infinity in the palm of your hand And Eternity in an hour William Blake

We have a privileged position, as ophthalmologists, of specializing in an anatomic structure so constructed that even Darwin considered it an exemption from evolution. Its visceral importance is measured by a position in romantic poetry equal only to the human heart As both the portal to our souls and our window onto the world, it holds a unique spot not only in the practice of medicine but in our psyches; there is no greater primal fear than loss of vision. We tell our residents and fellows that if it happens in the body, it can happen in the eye and its adnexae. That is a developmental fact What other organ has features of neuroectoderm, mesoderm, and epidermis? This is vast territory, and to orient ourselves we must necessarily start with large concepts and move to the small.

In an increasingly real-time world, with its explosion of medical and scientific information related to patient care and research, it is a constant struggle to keep abreast of new data and innovations in one's own specialty yet alone compensate for the breakneck pace of change in others. One can become easily adrift and lost in this data equivalent of the metaphorical "forest for the trees." It is therefore helpful to have a starting point, a chassis to which additional facts and information can be melded over time and as needed. We feel that the Wills Eye Institute 5-Minute Ophthalmology Consult format, with more than 300 topics and 45 algorithms, fills this void admirably. The eye's optical construct is ideally suited for photography and the multitude of accompanying photographs will be an additional rapid and invaluable resource. We hope that this inaugural edition will serve as a primer and valuable resource that informs, validates, and even comforts the ophthalmologist, internist, general practitioner, resident, intern, and emergency room physician in the hustling pace of daily practice and the isolation of the nights loneliest hours.

ANN

JOSEPH I. MAGUIRE, MD P. MURCHISON, M01 MPH EDwARD

A. JAEGER, MD

xxiii

ACKNOWLEDGMENTS

We extend our thanks to the associate editors and contributing authors who made this first edition of the Wills Eye Institute 5-Minute Ophthalmology Consult possible.

:xx:iv

CONTENTS

Contributors

vii

Photorefractive Surgery Complications (Late)

31

Foreword

xxi

Pigmented Conjunctival Lesion(s)

32

Preface

xxiii

Proptosis

33

Acknowledgments

xxiv

ptosis

34

Recurrent Corneal Erosion Syndrome

35

Retinal Detachment

36

Retinal Hemorrhage

37

Retinal Neovascularization

38

Secondary Angle-Closure Glaucoma

39

Stromal Corneal Dystrophies

40

Subluxated or Dislocated Lens

41

Tearing

42

Toxic Retinopathies

43

Transient Visual Loss

44

Vasculitis

45

I. Algorithms Acute Conjunctivitis Acute Primary Angle Closure Glaucoma

2

Blepharitis

3

Bull's Eye Maculopathy

4

Cataract: Age-Related

5

Choroidal Folds

6

Choroidal Tumors

7

Conjunctival Lesions

8

Conjunctival Tumors

9

Corneal Edema

10

Cotton Wool Spots

11

Crystalline Retinopathy

12

Dry Eye

13

Enophthalmos

14

Esotropia

15

Eyelash Loss

16

Eyelid Swelling

17

High lOP in Children

18

11. Topics Abducens/Cranial Nerve VI Palsy Sixth (VI) Nerve Palsy

46

Achromatopsia

48

Acne Rosacea

50

Acute Anterior Uveitis

52

Acute Primary Angle-Closure Glaucoma

54

Acute Retinal Necrosis/Necrotizing Herpetic Retinitis

56

Idiopathic Orbital Inflammatory Syndrome, Atypical

18A

Adie Tonic Pupil

Idiopathic Orbital Inflammatory Syndrome, Typical

58

188

60

lridocorneal Endothelial Syndrome

19

Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Iris Tumors

20

Age-Related (Senile) Retinoschisis

62

Keratoconus

21

Aicardi Syndrome

64

Albinism

66

LASIK Postoperative Complications-Complaints of Blurred Vision

22

Allergic Conjunctivitis

68

Lens Related Glaucoma

23

Alpert Syndrome

Leukocoria

70

24

Amaurosis Fugax

Low Vision Management

72

25

Amblyopia

Malignant Glaucoma

74

26

AMD-Dry

Neonatal Conjunctivitis

76

27

Night Blindness

28

AMPPE (Acute Multifocal Placoid Pigment Epitheliopathy)

78

Ocular Hypertension

29

Angioid Streaks

80

Photorefractive Keratotomy Complications (Early)

30

Anisocoria in Children

82

XXV

:xxvi

•••

Contents

Anisometropia Anophthalmia Anterior Basement Membrane Dystrophy Arcus Senilis Ataxia-Telangiectasia (Louis-Bar Syndrome, AT Syndrome, Boder-Sedgwick Syndrome) Axenfeld-Rieger Syndrome Band Keratopathy Bartonella Neuroretinitis Beh6.5rng/kg/day • Chloroquine: >3mg/kg/day • Basad on ideal body weight • Central VA loss • DFE: Early RPE changes, later "Bull's Eye" changes • Humphrey visual field (HVF): 1 0-2 red stimulus; paracentral scotoma • Retinopathy may progress despite cassation of medication

Cataract: Age-Related CATARACT

I

Cataract: Age related

~

I

I

I

I

Cortical

Nuclear

Posterior subcapsular

I

I

I

Develops as spoke-like opacities in the anterior peripheral cortex

• Yellowing of the lens nucleus • Increase in refractive index

Plaque-like formation in the posterior portion of the lens, usually in the visual axis

I

I

I

• Initial vision good • Symptomatic glare • Often difficult to predict vision and symptoms based on lens appearance

• Decreased distance vision • Refractive shift toward myopia

• Affects reading early, glare

• Also found with chronic steroid use, radiation, inflammation

Edward A. Jaeger

5

Choroidal Folds CHOROIDAL FOLDS

Key Ophthalmic Exam:

Key History: • Visual symptoms (metamorphopsia, pain, photophobia} • Prior ocular surgery, trauma? • History of rheumatologlc disease?

• • • • •

Male > Female Typically normal VA Usually hyperopic Bilateral, asymmebic Associated with idiopathic weal effusion

Ancllary Tests to consider.

• VIsual acuity and refraction • Intraocular pressure • Fundus exam w/ special attention to: • Disc edema? • Associated serous retinal detachment? • Mass lesion? •Inflammation? • Orbital exam (proptosis, rnoalty}

1. Postoperative a. Cataract extraction b. Glaucoma filtration surgery c. Vitrectomy 2. Trauma 3. Cyclodialysis cleft

1. Posterior scleritis 2. Vogt-Koyanagi-

1. Retrobulbar mass 2. Choroidal mass

Harada disease 3. ldiopalhic orbital inflammation

a. Melanoma b. Metastasis 3. Thyroid eye diseasa 4. Scleral buckle 5. Retrobulbar anesthesia

Alok S. Bansal, Joseph I. Maguire

6

• Fluorescein angiogram • ~can ultrasonography • Orbital CT/MRI

1. Pseudopapilledema a. Optic disc drusen b. Alagillea syndrome 2. Papilledema

Choroidal Tumors CHOROIDAL TUMORS Common symptoms: blurred vision, floaters, flashes, rarely pain

Congenital hypertrophy of retinal pigmented epithelium

(RPE)

Fine needle aspiration biopsy

Carol Shields

7

Conjunctival Lesions CONJUNCTIVAL LESIONS Common causes: pterygium, pingueculum, nevus, melanoma, prmary acquired melanosis, racial melanosis, squamous cell carcinoma (SCC), sebaceous CA, lymphoma/benign reactive ly!Tllhoid hyperplasia (BRLH)

r

Yes

I Pigment

~

No I

Yes

I

I

I

I

I Melanoma ~

No Pr1mary acquired melanosis (PAM)

I

I

I

~

Bilateral

~s

RacWJ melanosis

I

No

~I

Cysts

Corneal component

Yes

~

No

~I

PAM

SCC/Cervical intraepithelial neoplasia (CIN) sebaceous CA pterygium

~

Sara Lally

8

I

Salmon color

No

Yes

Papilloma ameloblastoma news CINISCC SebCA

Lymphoma/ BRLH amyloid

I

~s

Nevus

No

Yes

No

I

Feeder vessel nodule

Yes

Vascular (intrinsic or feeders)

Corneal component

~ No

r

I

~

White/ gelatinous

I Pinguaculum SebCA

~

1

Conjunctival Tumors CONJUNCTIVAL TUMORS Conjunctival Tumors (associated systemic conditions)

Bilateral: HBID, ring dermoid synd,

herniated fat

CollYllon causes: congenital, fair complexion, aging, UV exposure, tobacco use, immunosuppr9SSion

Presence of

cysts: nevus, lymphangioma

Pigmented

Lymphangioma {Turner's synd; Nonne Milroy Miege)

Metastasis (skin melanoma)

CIN HBID MM PAM

Complex choristoma (organoid nevussynd)

Cavernous hemangioma {Srurge Weber)

~

conjunctival intraepithelial neoplasia hereditary benign intraepithelial dyskeratosis in Haliwa Indians ~multiple myeloma ~ primary acquired melanosis sec ~ squamos cell carcinoma Synd ~ syndrome ~

Hyunjin J. Kim

9

Corneal Edema

CORNEAL EDEMA No

No Early postoperative edema

Pseudophakic or aphakic bullous keratopathy

Inflammatory glaucoma (Iritis, HSV, VZV, toxo, CMV) Neovascular glaucoma Angle-closure glaucoma

Michael J. Pro

10

Cotton Wool Spots COTTON WOOL SPOTS • Sm.~ II, whitish, fluffy, sll1htly ele1111bld lesions that appear to float within the Inner retina (•soft Exudates•) • Ulcely due to Interruption of axoplasmlc from focal Ischemia associated with occlusion of pre -capillary arterioles • A systemic e1111luatlon Is always warrantl!!d with thl!! finding of an Isolated cotton wool spot

I I

I

lachemlc

I

~

I

• Dlabl!!tes Mellitus • Hypertension • Ocular lschl!!mic Syndrome • Retina I Vascular Occlusion •Anemia • Radiation

I

Embolic

~

• Carotid Emboli • Cardiac Emboli (following cardiac surgery) • Deep Venous Emboli • Fore11n Bodies (IVDA) •Air Emboli • Flit Emboli (lone bone fractures) • Pllncreatttis (White Blood Cell Emboli)

I

I Immunologic

I

I

• Systemic Lupus Erythematosus • Dermatomyositis • Polyarteritis Nodosa •Scleroderma •Behcet's • Giant Cell Arteritis •Cryollobulinemia •Hemolytic Uremla/Thombotlc Thrombocytopenic Purpurll • Chronic Ren..l Failure

l~lty oyndrome

CCRst111o

llettnal deb!chm...,t

~

Hlstnry of"''" or facial RT

RBre causes

MAs

~

~

Secondary Angle-Closure Glaucoma SECONDARY ANGLE-CLOSURE GLAUCOMA I

l

1-ts!ory of rec.nt ocular surgery

I

Owar aonogrsphy

~

Unlateral

No hlslory of ocular surgery

~

~

Blataral

I Sift-lamp exam I Choroidal affusion or hemonhage

~~00 ~

rneds, c:ycloplegics,

8l8roid8

I

I

Cyclopleglcs and antlglaucoma

meda axcept xalatan

I ~effusion II or hemorrhage

I

Controlled lOP

effusion

Hypermatura cat, lens subiiiXadoo

Uncontrolled lOP

I

I

Cootinua cyclopleglcs andFAJ

Nd: Yag laser anterior hyaloldotomy

I

drU!ageol

Cyciopleglcs and anllglaucoma rneds, 11188r lridoplasty

I

II

~

Cydoplagics, lllllrolds,

Retinal dtllachrnent surgery

I

I~~Mid I u~~~ed

8

Topiramata use

No choroidal effusion or hemorrhage

Antiglaucoma

~

I

I vitrec:tomy Anterior

Phacomorphic glaucoma

I

~

I PI, antiglaucoma mads

I axl::on

~

Normal or mase or abnormal pigmentation in anlerior segment

I Iris NV I I NVG I

Iris atrophic

hole, iris nevus, corneal edama, bridgi ng broad

baaed PAS lntravltn~al

~

Ocular 80110 and ant segmentUBM Iris and ciliary body tumor or cyst, poet segment IUmors,serous retinal detachment

antiVEGF, PRP and

antigllu:oma mads Trab + MMC, shunt, or cyciodestructive prooeduras

ICE syndrome

ITn~at

Ilks a case with POAG

Manage appropriately

M. Reza Razeghinejad

39

Stromal Corneal Dystrophies STROMAL CORNEAL DYSTROPHIES Stromal corneal dystrophies

Gray/white opacities with cloudly intervening spaces

Colleen Halfpenny

40

Subluxated or Dislocated Lens SUBLUXATED or DISLOCATED Lens Subluxated or dislocated lens/ Intraocular lens

I Ocular diaordera 1) Retinitis pigmentosa 2) Retinopathy of prematurity 3) Aniricia 4) Congenital glaucoma 5) Iris coloboma 6) PHPV 7) Rieger's syndrome 8) Megalocornea 9) Simple ectopia Iantis (usually AD) 10) Ectopia Iantis e1 pupillae

I

Crystalline lens (ectopia lentis)

~

Systemic clsordera 1) Marfan's syndrome 2) Homocy&tin~ia 3) Weii-Marchesani syndrome

4) Ehlel'a-Danlos syndrome 5) Syphilis 6) Hypertyainemia 7) SuHHe OXidase deficiency 8) Sturge-Weber syndrome 9) Refsum's syndrome 10) Crouzon's clsease 11) Scleroderma

I

Intraocular lens (pseudophakia)

~

Trauma

Early

L...

1) Ocular trauma, usually blunt 2) Previous ocular sugery, usually vltnlo-retinal

1) latrogerk (inadequate cap&Uiar support or z.ooolar dehiscence) 2) Zonulopathy (z.ooolar insufficiency secondary to pseudoexfoliatiOn syndrome, RP, ROP, uwltis, previou81rauma)

1) Cepsule contractiOn (phimo&i& with z.ooolysis secondary to XFS, previous vltreo~alsurgery,trau~

uveitis, RP, ROP) 2) Scleral sut~n hydrolysis (usually greater than saven years following scleralsutured IOL)

Robert Behar

41

Tearing TEARING

I Dye disappearance

I

I I

Abnormal

Normal, check Schirmer's

I

Abnormal (diY eye) DIY eye treatment

I

I

I ~ II

Probe and irrigate ~ canaliculus

Lacrimal drain open, no treatment needed Examine for hypersecretion, lkl malposHlon, keratitis, etc.

Obstrucrted, recommend lacrimal surgery P~X~ctoplasty,

canallculoplasty, &tenting, OCR, or CDCR depending on location and extent of obstruction

Minimal change on DDT, check Schirmer's

I I

I

I

Abnormal (diY eye)

Schirmer normal or Increased

I

~

Probe and Irrigate canaliculus

I

I

Obstructed outflow

I

I

~

I

Also perform P & I to rule out lacrimal stenosis as secondal)' cause of tearing Duct open, functional obstruction Examine for lkllaxity, tear pumpfal ure

Canalicular, consider canalcular surge!)' orCDCR

Obstructed, needs lacrimal surQSIY to address area of stenosisfobstructlon (e.g., punctoplasty, OCR, etc.)

Consider horizontal tightening of ld or temporal)' &tenting of drain for functional obstructions

Scott Goldstein

42

[Increased tear film or overflow

Probe and Irrigate canaliculus

Treat dl)' eye

I

Nasolacrimal duct obstructed, consider OCR

Toxic Retinopathies TOXIC RETINOPATHIES Crystalline retinopathy

Uveitis

I

o o

CME

Rif.Jbutin Cidofovir

I

o o o

Vasculilr damage

Retina and RPE disruption

Prostasland in analoss Nicotinic acid Epinephrine

Aminoglycosides Intraocular injection may result in macular infarct ion

o

Tamoxifen o Typically >30 ms/day o Decreased VA and color vision o Perifovea~ crystalline intra retina I de posits t-/-CME o ERG: Decreased aand bwaves

I

I

Talc o Small, intravascular crystals seen in chronic IV d riJ8 abuser o Can lead to retinal exchemla, vascular occlusion, NV, and/orVH

others o canthaxanthine o Antiretrovirals o Methoxyflurane

I

Th loridazine Typically > 1200 rr181day o Decreased VA, nyctalopia, and dyschromatopsia o Pigment de posltio n In the pe rip hera I retina, cornea, lens, eyelids o ERG: decreased a- and b-waves o

Oral contraceptives o May result in thromboembolic vascular occlusion

Interferon Vascular closure associated with immune complex deposition o Findings may resemble NPDR o

I

Chlorpromazine o Typically 1200 to 2400 rr181day for 12 or more months o Pigment deposition in the retina, cornea, lens, eyelids and optic. nerve pallor

Chloroquine or Hydroxychloroquine Chloroquine: Typically >3.5 mslk«fd"f or 300 g cumulative o Hyd roxychloroq uine: Typically >6.5 rns/kt/day or 700gtotal o RPE mottlin& may progress to bulls-eye o ERG: enhanced a-wave, decreased b-wave o VF: central scoto rna to red test object o

I

other causes: • Antiretrovirals o Carmustine (Cisplatin and BCNU) o Cisplatin o Clofazimine o Corticosteroids o Deferoxamine o Potasium Iodate o Quinine sulfate

Nikolas London

43

Transient Visual Loss TRANSIENT VISUAL LOSS (TVL)

Ocular disease Comeal abnormalities Angle closure Glaucoma

Hyphema

Large vessel a1herosderotlc disease

Cardloembolic

Vasculitis

Large vessel a1herosderotic disease

Hypercoaguable states

Retinal vasospasm Central retinal vein occlusion Papilledema optic nerve drusen

Mary Ellen P. Collum

44

Cardloerrbolic

Vertebrobasilar dissection

VasculiUs VASCULITIS Ramal vascuilis

Necrotizing re11nls

Aneurysmal dllltatlon of ONHand retinal arterioles

cws

lntraretinal infiltrates Major criteria: • Oral apthous ulcers • Genital ulcera • Skin lesions • Ocular dieeese Minor crtterla • Arthritis •GIIeaions • Occlusive vascular lesions • Migratory thrombophlebitis • CNS Involvement • Pulmonary artery aneurysm • lnterstitallung changes

I Beh~rs I Frosted branch angiitis 4/11 ACR criteria: • Malar rash • Di&coid ra&h • Photosensitivity • Oral ulcers • Arthritis • Serositis • Renal disorder • Leukopenia/lymphopenia • Hemolytic anemia or thrombocylopen • Neurologic disorder • Positive anti·DNA, antl-8mllh antibody, or antiphosholipid antibodies • Elevated ANA

1

Clinical findings (unexplained fever, abdominal pain, renal failure, hypertension, arthralgia, muscle tenderness or weakne&1>, subcutaneous nodules, skin ulcers, pain in the abdomen or extremities, or rapidly developing hypertension) Biopsy (necrotizing arteritis) Arteriography (aneurysms in medium-sized arteries)

Abnormal CXR/chest CT Elev111ed ACE (60-90%) Elevated lysozyme CBCD Oeukopenia, eosinophilia In 24%) 24-hour urine (hypercalcurla In 4%) Biopsy with nonea&eeting granuldmas Positive gallum scan

Peripheral ava&eular retina Midperipheral: • Microaneurysm& • Dilatation of capillary channels • Tortuosity of neighboring vessels • Chorloretlnal scars

ll..l

Chronic, unexplained respiratory symptoms and signs (Including otitis media in adult&) Elevated ESA and CAP, decreased serum albumin and total protein, anemiua, thrombocytosis, mild eosinophilia, elevated serum creatinine Urinalysis with dysmorphlc RBCs and ABC cast&, proteinuria may be dalected Positive o-ANCA

"l

+HIVELISA and western blot

Inferior retinal snowbankingl snowballs Vrtreous cells

I ELs ~ M ACA criteria •Asthma • Eosinophilia • Paranasal sinusili& • Pulmonary lnftltrates • Histologic evidence of va&eulitis with extravascular eosinophils • Mononeuritis multiplex or polyneuropathy

PosHive serum cryoglobulins Abnormal urinalysis Elevated BUNter Elevated tranamlnases PosHive AF (lypee I and II) Abnormal CXR

Elevated CAP levels and ESA Abnormal urinalysis Positive p-ANCA Positive biopsy

ICh"ll

Cryoglobulnemia

Nikolas London

45

ABDUCENS/CRANIAL NERVE VI PALSY SIXTH (VI] NERVE PALSY William A. Cantore

~ BASICS DESCRIPTION • The abducens (VI) nerve (CN VI) innervates the ipsilateral lateral rectus (LR) muscle, abducting the eye. CN VI palsy is the most common isolated cranial nerve palsy. Patients present with binocular horizontal diplopia and esotropia. Children may not complain of diplopia. • In adu Its aged over 50 years. CN VI palsies are most often due to microvascular ischemic peripheral nerve injury. In children, CN VI palsies are particularly alarming because of the frequent association with brain tumors. • The CN VI nucleus is located in the dorsal lower pons. The nuclear complex contains motor neurons to the ipsilateral lateral rectus (LR) muscle and intemeurons that project, by the medial longitudinal fasciculus (MLF), to the medial rectus (M R) subnucleus of the contralateral CN Ill nuclear complex. Therefore, a nuclear lesion will produce an ipsilateral gaze palsy and not a CN VI palsy. The fascicles exit at the pontomedullary junction and the nerve runs along the clivus and travels over the petrous apex of the temporal bone, where it is tethered at the petroclinoid ligament in Dorelia's canal. The nerve courses within the cavernous sinus lateral to the internal carotid artery and enters the orbit through the superior orbital fissure.

EPIDEMIOLOGY • CN VI palsy can occur in all ages; etiology varies depending on age group • No racial or sex predilection

lnddence • 11 per 100,000 • Peak incidence in seventh decade

RISK FACTORS • Diabetes - Only independent risk factor linked to ischemic palsies • Hypertension • Hyperlipidemia • Obesity • Trauma • Alcohol abuse - Wernicke-Korsakoff syndrome is the best known neurologic complication ofthiamine (vitamin 81) deficiency.

46

PATHOPHYSIOLOGY

Pediatric Considerations

• Nucleus: -A CN VI palsy does not occur with nuclear lesions. • Fascicle in pons: - Demyelinating - Infarction -Neoplasm • Nerve root in cerebellopontine angle: - Neoplasm (acoustic neuroma) • Subarachnoid space: -Aneurysm - Meningitis - Inflammation -Infection -Neoplasm • Petrous ridge: - Recurrent otitis media - Nasopharyngeal carcinoma - Chondrosarcoma • Cavernous sinus: - Cavernous sinus fistula, thrombosis -Neoplasm - Internal carotid artery aneurysm, dissection • Orbital apex: - Optic neuropathy • Orbit: -Neoplasm - Inflammation -Infection

• Congenital - Isolated congenital absence of abduction extremely rare o Transient CN VI palsy may occur due to birth trauma. - Miibius syndrome o Facial diplegia associated with horizontal gaze abnormalities o Etiologies include maldevelopment and intrauterine insults. -Duane's retraction syndrome o Unilateral or bilateral abduction deficits. variable adduction abnormalities, palpebral fissure narrowing and globe retraction on attempted adduction o Congenital absence of 6N neurons with aberrant innervation of LR by branches of CN Ill • Most common causes of CN VI palsies in children are tumors (45%), trauma, increased intracranial pressure (IC P). -May be post-viral when isolated

ETIOLOGY • Ischemic -Diabetes - Hypertension o questionable independent risk factor • Compressive • Inflammatory • Traumatic - Unilateral or bilateral • Intracranial hypertension - Unilateral or bilateral • Intracranial hypotension - Post dural puncture, CSF lealc • Multiple sclerosis

COMMONLY ASSOCIATED CONDITIONS • Nucleus: - Conjugate horizontal gaze palsy • Fascicle in pons: - Ipsilateral CN V palsy - Ipsilateral CN VII palsy -Ipsilateral Horner's syndrome -Contralateral hemiparesis (Raymond's syndrome) • Nerve root in cerebellopontine angle: - Ipsilateral deafness or tinnitus • Petrous ridge: -Severe facial and eye pain (Gradenigo's syndrome) - Occasionally facial paralysis • Cavernous sinus: - CN Ill, IV, or V palsy - Ipsilateral Horner's syndrome • Orbital apex: - Optic neuropathy • Orbit: -Proptosis -Chemosis -Lid swelling

ABDUCENS/CRANIAL NERVE VI PALSY SIXTll (YI) NERVE PALSY

~ DIAGNOSIS HISTORY • Abrupt onset vmen microvascular Ischemic • Purely horizorrtaI diplopia -BinooJiar - Worse at distance - Worse in direction of action of the paretic LR • Inquire about headache, pain, hearing loss, trauma, symptOms of giant cell arteritis (GCA) PHYSICAL EXAM • Patients may present with a head turn. • Ipsilateral abduction defidt • lncomltant esotropia.. WD13e In dlrectlon of weak LR • ExophthalmometJ'Y and orbit examination • Forced duction test • Assess orbicularis oculi strength to look for myasthenia glliVis (MG) ALERT • Criticalto evaluate fu ndion of other aanial nerves • Look for papilledema

Diagnostic Pi'oalduras!Othflr • LP - Meningeal signs present - Elevated ICP signs present DIFFERENTIAL DIAGNOSIS • MG • Thyroid ophthalmopathy • Medial orbital wall or floor fracture • Duane's retraction syndrome - Patients not diplopic • Spasm of near reflex

.

TREATMENT

Most Importantly, Identify and treat unde~ylng condition If present

MEDICATION

FlrstUne • Aspirin - No sdentlflc data demonstrates red uctlon In risk of Ischemic CN VI palsy

Initial lab tests • HbAtc • ESR, CRP (for GCA) • Anti-ACh Rantibodies (for MG)

ADDmONAL TliEATMENT Gflftfll'ill MNSUIWS • Monocular ocd usion - Sector occlusion of eyeglass lens with translucent tape may be preferred - Altemate patch in children, not necessary in adults • Fresnel prisms

Imaging

Issues for Reftmel

DIAGNOSTIC TESTS & INTERPRETATION

Lab

lnitialappi'Oitdl • lnsufflclent CNVI palsy evidence to support MRl of all patients with 6NP • Nonisolalt'd - Brainstem signs oMRI - MeningeaI signs o MRI, LP - OrbitaI signs oCTorMRI - Elevated ICPsigns o MRI, MRV, LP • Isolated -Age 50 years with microvascular ~sk factors managed by close observation should have MRI if no improvement in 3 months. • CN VI palsy that worsens after 2 weeks or becomes assodated with a new neurologic finding should have MRI.

PROGNOSIS • Ischemic CN61eslons usually resolve within 3-4 months. - Angle of ocular deviation on presentation may predict recovery (2). -In vasculopathic CNVI palsies, 86% completely resolve (3) • Children with Isolated CN VI palsies usually rerowr within 4 months • Spontaneous improvement of traumatic CN VI palsies in 30-SO% - Complete reCOYI!ry < 25%

REFERENCES 1. Chi SL. Bhatti MT. The diagnostic dilemma of neuro-imaging in acute isolated sixth nerve palsy.

Curr Opn Ophtha/mo/2009;20(6):423-429. 2. Park. UC, Kim SJ, Hwang JM, et al. Clinical features and natural history of acquired third, fourth, and sixth aanial nerve palsy. Eye (Land) 200B;22(S}:

69H96. 3. Sanders SIC, Kawasaki A. Purvln VA. Long-term prognosis In patients with vasculopathlc sixth nerve palsy. Am 1 Ophlha/mo/2002;134(1):81~4.

ADDITIONAL READING • Brazis PW. Isolated palsies of cranial nerves Ill, IV. and VI. Semin Neuro/. Feb 2009;29(1 ):14-28.

.

CODES

ICD9 378.54 Sixth or abducens nerve palsy

CLINICAL PEARLS • Not all abduction dl!!icits are CN VI palsies. • Because of its location within the substance of cavemous sinus (free from the dural lateral waiO, typically first aanial nerve involved by a process there • When assodatecl with an Ipsilateral Homer's syndrome and no other neurological finding, careful investigation of the cavemous sinus is mandatory. • Bilateral CN VI palsies is not dUI! ID ischemia. • GCA may present as a CNVI palsy. • Look for papilledema In eYery CN VI palsy.

l'atient Monitoring In a patient aged >50 years with vasculopathic risk. factors in Vftlarn microvascular ischemic CN VI palsy is diagnosed, reeva Iuation in 2 weeks

47

I

ACHROMATOPSIA Eliza S. Stroh

Alex V. Levin

~ BASICS DESCRIPTION • Reduced or absent color discrimination with photophobia, reduced visual acuity, nystagmus, eccentric fixation, and small central scotoma all due to defective cone development • May be divided into partial (incomplete) versus complete phenotypes EPIDEMIOLOGY lnddence 1 per 30,000 individuals (1 )[C]

RISK FACTORS • Consanguineous parents • Family history Geneffa • Autosomal recessive inheritance • AC HM 1, gene unknown, chromosome, 14 • AC HM2, alpha subunit cone cG MPgated cation channel (CNGA3), 2q11 • AC HM3 (Pingelap variant), beta subunit cone cG MP gated cation channel (CNGB3). 8q21-22 • AC HM4 cone alpha subunit transducin (GNAT2), 1p13 GENERAL PREVENTION Genetic counseling PATHOPHYSIOLOGY Reduced or absent protein expression in cone photoreceptors leads to inhibition of the normal phototransduction cascade and dysfunctional cone development (2)]8] ETIOLOGY Mutated gene inherited from each parent COMMONLY ASSOCIATED CONDITIONS • None • Phenotypic heterogeneity includes cone dystrophy and cone-rod dystrophy

48

~ DIAGNOSIS HISTORY • Family history -Typically presents in infancy as fine nystagmus with photophobia - Stationary low vi sua I acuity with poor color discrimination -Children often referred to as "night owls" due to preference for night time activity and dim illumination PHYSICAL EXAM • Full ocular examination - Nystagmus is fine, high frequency, often milder with age -Assess visual function; best-corrected is typically 20/200 range - Hyperopia may be present - Photophobia on examination - Minimal if any foveal hypoplasia or subtle pigmentary changes. most often normal appearance - Fail color vision testing DIAGNOSTIC TESTS & INTERPRETATION

Lab Molecular genetic testing available

Imaging If nystagmus or presentation atypical, consider neuroimaging to rule out intracranial process

Diagnostic Procedures/Other • Color vision tests show impaired color discrimination along protan, deutan, and tritan axes. • Full-field ERG shows absent or severely diminished photopic response and typically normal scotopic response. • Visual field testing may reveal small central scotoma. • If able, OCT usually normal or shows macular thinning • If able, multifocal ERG usually isoelectric • Intravenous Huorescein angiography and fundus autofluorescence normal

Pathological Findings • Reduced cone number • Residual cones often abnormal in structure

DIFFERENTIAL DIAGNOSIS • Incomplete achromatopsia is associated with partial cone function, resulting in some color discrimination, better visual acuity than in complete achromatopsia, and absence of photophobia. - Blue-cone monochromatism (X-Iinked achromatopsia) has similar findings to achromatopsia and can be differentiated by Berson plates or by S-cone function on ERG (4)[C]. -Cone monochromatism, in which the L-or M-cones are functional. - Cone dystrophy is typically associated with normal cone function at birth, with gradual deterioration and progression. - Cone-rod dystrophy includes progressive rod dysfunction. - Other causes of photophobia and nystagmus - Fovealfmacular hypoplasia (see chapter) - Cerebral achromatopsia is associated with febrile illness or trauma.

ACIIROMAlDPSIA

.

TREATMENT

MEDICATION None

ADDITIONAL TREATMENT General Measures

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Children should have an ophthalmic evaluation every 6-12 months to monitor refraction and function PATIENT EDUCA110N

• Dark or Corning filter sunglasses or red-tinted contact lenses (often nat tolerated for abnormal appearance) red uc:e photophobia. - Low vision aIds - Children may benefit from an lndMduallzed Education Plan.

• Gene11c cou nsellng • hnp:l/www.dailystrength.org/c/Achromatopsia/ supporlijroup o http://www.lowvision.orglachromatopsia.and. color.blindnes.htm • http://Www.achromat.orgf

Issues for Referral

PROGNOSIS

• Genetic counseling - Low vision evaluation and support as indicated

o

Addition•/ Then~pies Correction of refractive error

COMPLEMENTARY & ALTERNATIVE THERAPIES None proven or indicated

Visual aruity is usually stable over time on later decades when slow degeneration may O«Ur with natural age related loss of photareceptors. - Nystagmus and photophobia may Improve slightly with age.

COMPUCATlONS o

Lowvision - Photophobia

SURGERY/OTHER PROCEDURES None

REFERENCES 1. Rojas 0/, Maria L.S, Santos JL., et al. A frameshift insertion in tl1e cone cyclic nucleatide gated calion channel causes carnple1e achromatopsia In a consanguineous family from a rural isola!!. Eur J Hum Genet 2002;1 [):638-42. 2. Wissinger B, Gamer D, Jagle H, et al. CNGA3 mutalions in hereditary cone photoreceptor disorders. Am 1 Hum Genet 2001;69:722-37.

3. Varsanyi 8, Wissinger B, Koh I S, et al. (lin ical and genetic features of Hunga~an achromatopsia patients. Mol Vis 2005;11 :996-1 001. 4. Moskowitz A. Hansen RM, Akula JD, et al. Rod and rod-driven function in achromiltopsia and blue cone monochromatism./nvest OphthalmoJ Vis Sd

2009;50(2):95D-i.

ADDITIONAL READING • http:ff'Mwl.ncbl.nlm.n lh .govfbookshelflbr.fcgl?book =gene&part=achm.

. .CODES ICD9 368.54 Al:hromatopsia

CLINICAL PEARLS • Consider ach romatopsla diagnosis In children with photophobia and nystagmus. • Color vision may appear rernarltably good if patients learn object assodalions or shades; forma I tesli ng is indicated. • Consider genetic testing and counseling.

49

I

ACNE ROSACEA Swathi Reddy

~ BASICS DESCRIPTION Acne rosacea is a chronic acneiform disorder affecting the nose, chin, forehead, or eyelids. EPIDEMIOLOGY Prevalence Affects approximately 1 in 20 Americans.

RISK FACTORS • Age (usually occurs between the ages of 3D-60 years) • Equal sex distribution • Suggestion that there is increased prevalence in fair-skinned persons of European or Celtic descent, although not well-substantiated • Dark pigmentation in black populations may mask presentation. Geneffa No gene identified as causing rosacea, but tends to run in families. GENERAL PREVENTION Rosacea cannot be prevented, although several factors may trigger flare-ups including sun, wind, hot, cold, exercise, stress, and certain foods. PATHOPHYSIOLOGY Anomalous vascular response.

ETIOLOGY • Poorly understood, although infectious, climactic, neurologic, and immunologic factors have been implicated. • Vasodilation may cause extravasation of plasma. which can induce an inflammatory response. • Demodex folliculorum has also been implicated, but this is largely circumstantial.

50

~ DIAGNOSIS HISTORY • Family history • Symptoms including flushing, persistent erythema, papules, pustules, burning or stinging of the skin, and dryness PHYSICAL EXAM • Skin involvement (nose. cheeks, chin, central forehead, neck, and chest) - Diffuse erythema -Telangiectasias -Papules -Pustules - Hypertrophy of sebaceous glands - Rhinophyma (thickening and purplish discoloration of nose skin) • Ophthalmologic - Blepharoconjunctivitis o Inspissation of meibomian glands o Telangiectasias of lid margin o Recurrent hordeolum and chalazion o Conjunctival hyperemia and congestion o Follicular reaction o Papillary hypertrophy • Corneal (usually involves inferior cornea) - Punctuate epithelial keratitis - Corneal vascularization - Corneal infiltration - Corneal ulceration - Corneal perforation • Reports of involvement of episclera, sclera. and iritis, although not widely reported

DIAGNOSTIC TESTS & INTERPRETATION Lab No lab testing required

Diagnostic Procedures/Other Diagnosis is clinical

Pathological Findings • Vascular dilatation of small vessels • Perivascular infiltration of histiocytes. plasma cells. and lymphocytes • Infiltration of conjunctiva and cornea by lymphocytes. epithelioid cells, giant, and plasma cells • loss of superficial dermal connective tissues -Edema - Collagen disruption -Elastosis • Rhinophyma shows increase in sebaceous glands and connective tissue • Skin biopsies show deposition of complement and immunoglobulin at dermal-i!pidermal junction

DIFFERENTIAL DIAGNOSIS Acne vulgaris lupus erythematosus Dermatitis Erysipelas Seborrheic dermatitis Carcinoid syndrome Tuberculosis Syphilis

• • • • • • • •

ACIE ROSACEA .

TREATMENT

MEDICATION FirstUne o Oral tetracycline (250 mg every 6 hours for 3-4 weeks, with tapering) o Doxycydlne or ml nocycllne (SD-1 00 mg every 12 hours) S«011d Une o Ora1erythromycin • Oral isotretinoin o Ampicillin • Metronidazole • Topical metronidazole (0.75% gel twice daily) o Azelaic Add • Sodium sulface1amlde lotion • Intensive lid hygiene o Bacteriostatic ointment at bedtimE! • Topical corticosteroids (short-term) • Electrocautery for telangiectasias

Pediatric Considerations

COMPLEMENTARY & ALTERNATIVE THERAPIES • Topical niacinamide o Bvitamins • Elimination and challenge diet SURGERY/OTHER PROCEDURES • Conjunctival flaps. tectonic lamellar keratoplasty. pene1rating keratoplasty o Laser, 1mense pulse light, photodynam lc therapy • Electrosurgery, surgical steel resculpturing. denmabrasion, or carbon dioxide laser treatment for rhinophyma

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Ophthalmology • Dermatology l'ltient Monitoring Close ophthalmologic monltorlng for comeal thlnn lng, ulceration, infiltration, or perforation o

• Tetracycline not for use In children 70%: - Carotid endarterectomy is indicated (3)[A].

•

ONGOING CARE

PROGNOSIS • Annual inddence of stroke in patients with amaurosis Is 2% (3). • 95% of endarterectomy patients are free of ipsilateral stroke for 8 years (1 ). COMPUCATIONS The rate of stroke and death assodated witll carotid endarterectomy is 6.5% (4).

REFERENCES 1. Bersteln EF, Dilley RB. Late results following carotid endarterectomy for amaurosis fugax. 1 VaseSurg 1987;6:333-340. 2. Brown RD, Petty GW, O'Fallon WM, et al. lnddence of trc~nsient ischemic attack in Rodlester. Minn~. 1985-1989.Srrcke

1998;29:2109-2113. 3. Ferguson GG. The North American SymptOmatic Carotid Endarterectomy Trial: Surgical results in 141 5 patients. Stroke 1999;3 0: t 751-1 758. 4. Poole CJM, Ross Russell RW. Mortality and stoke after amaurosis fugax. 1 Neural Neurasurg Psychiatry 1985;48:902-905.

ADDITIONAL READING • Benavente 0, Eliasziw M, Streifler JY, et al. Prognosis after transient monocular blindness assodated wltll carotid-artery stenosis. NEnfl 1 Med 2001;345: 1084-1 090. • The Amaurosis Fugax Study Group. Current management of amaurosis fugax. Stroke 1990;

23(2):201-208.

.

CODES

ICD9 362.34 Transient retinal artl!ria I occlusion

73

I

AMBLYOPIA Kammi B.

Gunton

~ BASICS DESCRIPTION • Decreased best-corrected visual acuity not solely attributable to organic pathology affecting one or both eyes: - Reduction in vision occurs during the first decade of life and is reversible with treatment during this critical window of visual development.

ETIOLOGY Strabismus, 38% (2) Anisometropia, 37% (2) Combined strabismus and anisometropia, 24% (2) Organic pathology uncorrected in critical window of visual development • Congenital media opacities create most dense form of amblyopia. • • • •

COMMONLY ASSOCIATED CONDITIONS Anisometropia Strabismus High refractive error Asymmetric or unilateral media opacities or other forms of visual pathway interruption

EPIDEMIOLOGY Incidence It is the leading cause of monocular visual loss in young and middle-aged Americans. Prevalence • Affects 2-4% of North American population • Projected lifetime risk of visual loss in patients with amblyopia is 1.2%

• • • •

RISK FACTORS • Anisometropia, odds ratio of 29 (1) -if - > 1.50 diopter (D) hyperopic spherical equivalent - >+ 1.00 D cylinder - >-f:i.OO Dmyopia • Strabismus • High refractive error in both eyes: - >+5.00 - >-10.00 D - >3.5 D cylinder • Organic pathology uncorrected in critical window in the first decade Geneffa • Follows the pattern of inheritance for the risk factors • May be familial predisposition for amblyopia but no specific inheritance pattern

• Presence of anisometropia, strabismus. combined anisometropia and strabismus, or organic pathology that reduces vision in one eye: -Above condition must be present during window of visual development. - Subnormal vision unexplained on the basis of physical abnormalities in the eye and in the setting of the condition known to result in amblyopia.

GENERAL PREVENTION • Visual screening of all children during the vulnerable age period allows for detection and treatment. - Pediatrician or family physician well child visits - School nurses PATHOPHYSIOLOGY • Unequal visual competition between eyes leads to the following: -Within the lateral geniculate nucleus, cells from the amblyopic eye atrophy -Within the primary visual cortex, cells lose ability to respond to stimuli of one or both eyes.

~ DIAGNOSIS HISTORY

PHYSICAL EXAM • At least 2 line difference in visual acuity between eyes • Crowding phenomenon results in reduction in vision when tested by multiple optotypes or crowding bars around isolated line of optotypes. -Grating acuity better than expected in strabismic amblyopia - low contrast visual acuity better than expected in strabismic amblyopia • Testing with single optotypes may show better vision than testing with lines of ootypes. • Strong fixation preference in preverbal children • Evaluation for strabismus • Cycloplegic refraction • Complete dilated ocular exam to rule out the presence of organic causes of visual loss DIAGNOSTIC TESTS & INTERPRETATION

Lab None

Imaging • Usually none indicated unless ruling out the presence of organic central nervous system cause for subnormal vision. • OCT may be useful in detecting subtle organic retinal or optic nerve causes of subnormal vision.

Diagnostic Procedures/Other • Contrast sensitivity testing may be useful. • Electrodiagnostic testing, especially multifocal electroretinography, may be useful to detect underlying organic retinal disease. • Visual evoked potentials may be useful in detecting asymmetry or organic deficits. • In severe amblyopia, asymmetry in the 30-lead visual evoked potential may be seen (test rarely needed).

Pathological Findings Decrease in the cell size of the parvocellular layer

of lateral geniculate nucleus laminae from amblyopic eye

DIFFERENTIAL DIAGNOSIS • Incorrect refractive correction • Organic pathology responsible for visual loss • Failure to comply with patching/penalization results in uncorrected visual deficit.

rJ

MEDICATION First Line None indicated

Second Line l-Dopa supplementation during amblyopia treatment under investigation. Improvement of additional 2 lines with l-Dopa supplementation following standard treatment (6). Improvement in the spatial extent of visual cortex activation with stimulation of amblyopic eye with l-Dopa demonstrated on MRI (7). Proper dosage is critical due to frequent side effects of nausea and emesis.

ADDITIONAL TREATMENT General Measures • Treatment of etiology of amblyopia • Refractive correction • Correction of strabismus • Correction of organic pathology if possible, e.g. cataract extraction, ptosis repair, corneal transplant • Amblyopia treatment may still be needed after organic deficit corrected. • Occlusion of nonamblyopic eye • Comparing all-day patching to fewer hours of patching revealed faster improvement in visual acuity with greater number of hours of daily patching, but by 6 months, the differences in improvement were not statistically significant (5). • Atropine penalization to nonamblyopic eye with spectacle correction as applicable: Requires ability to blur better eye to a visual acuity less than the amblyopic eye. Works best for hyperopic eye. • Improvement in visual acuity 3.6 lines with atropine compared to 3.7 lines with patching at 6 months in children younger than 7 with moderate amblyopia (8)

74

TREATMENT

AMBLYOPIA Issues for RefetTal • Refer for surgical correction of organic causes (e.g., cataract) • May require collaboration with primary care physician regarding behavioral issues secondary to pillch!ng and patching compUance Issues

Additional Thel'aple.s • There is no additional benefit of adding near activities du~ng amblyopia treatment (9). • Altl!rnatives to adhesive patch indude spectade-mounted occluder, opaque contact lens. or Bangerter foils. • Compliance with pillching may require adhesion supplements (e.g., benzoin, Tegademn, tape) or amn immobiliza1ion.

COMPLEMENTARY • ALTERNATIVE THERAPIES • None • No studies prove efficacy of vision therapy.

SURGERY/OTHER PROCEDURES Laser refractive correction under lnvest!gadon In severe anisometropia in noncompliant children.

IN-PATIENT CONSIDERATIONS Admission Criteria In-patient admission has rarely been used to facilitate occlusion therapy in recaldtrant children.

$

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Patient Monitoring • FoUow up to ensure compUance and prevent occlusion amblyopia. • Chec~ vision of both eyes during each visit -With full-lime patching. follow-up inll!rval is I week for every year of age to a maximum of 4weel:s. -With part-time patching, wider inll!rvals are acceptable but not > 2-3 months. Younger children require shorter intervals. - Consider treatment end point of fuU correction achieved with the normalization of vision or lack of Improvement following 3 successive Intervals of compliant treatment. • Recommend taper of ocdusion fo!!owing maximal Improvement In visual acuity (treatment end point).

PATIENT EDUCATION • Importance of compliance with treatment • Anticipatory guidanee regarding antidpated behavioral resistance to patching and strall!gies for successful patching (e.g., positive reinforcement, behavioral modtftcadon) • www.pgda.org

PROGNOSIS • 82% of padents maintain lnaeased acuity of within 10 letters after cessation of treatment (1 0). • Patching 2 h daily with spectacle correction improves visual acuity 2.2 lines compared to 1.3 lines with spectade correction alone In children 3-7 years of age (4). • Improvement in vision of >2 lines is shown with spectade correction alone with follow-up In 77% patients (3). • Improvement in vision continues on average 30 weeks before stablllzadon (3). • Improvement correlates with less anisometropia and better baseline visual acuity (3). • 46% of patients achieve 20125 or better with patChing or atropine (11). • Either 20130 in amblyopic eye or 3 log-Mar lines of improvement in visual acuity is shown by 6 months with patching or atropl ne In > 74%. • Moderall! amblyopia (vision better than 2011 DO) has better prognosis. • Treatment p~or to 7 years of age has better prognosis.

COMPLICATIONS • Oc.clusion or penalization therapy can uncommonly cause visual loss (usually reversible) in the iniiially normal eye. Treat by decreasing or discontinuing treatment May require switching treatment to other

eye. • Patches can cause periocular allergic skin rashes. Consider switching brands. • Patches can cause periocular skin abrasions. Treat with micropore tape under patch or ll!mporary discontinuation. • Atropine may cause systemit side effects. • PsychosodaI repercussions of patthing or anisometropia from atropine

REFERENCES I. Huynh SC, Wang x:-1, lp J, et al. Prevalence and associations of anisometropic and anisoasligmatism in a population based sample of 6 year old children. Br1 Of/lthalmo/ 2006;90: 597~01.

2. Pediatric Eye Disease Investigator Group. The clinical proflle of moderate amblyopia In children younger than 7 years. Arch Ophtha/mo/ 2002; 120:281-287. 3. Pediatric Eye Disease Investigator Group. Treatment of anisometropic amblyopia In children with refractive correction. Ophthalmology 2006; 1t 3:895-903. 4. Pediatric Eye Disease Investigator Group. A rcmdom ized trial to evaIuate two hours of daily patching for amblyopia in children. Ophthalmology 2006;113:904-912.

5. Pediatric Eye Disease Investigator Group. A compa~son of il'lroplne and patching treatments for moderate amblyopia by patient age. cause of amblyopia, depth of amblyopia and other faclllrs. Ophthalmology 2003; 11 0:163 2-163 7. 6. Dadeya S, Vats P, Malik KPS. Levodopa/camidopa in the treatment of amblyopia. 1 Pediatr Ophthalmo/ Strabismus 2009;46:87--90. 7. Yang C, Yang M, Huang J, et al. Functional MRI of amblyopia before and after levodopa. Neurosd Lett 2003;339:4~2. 8. Pedlill~c Eye Disease lnvesdgil'lor Group. TwD-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia In children. Arch Ophthalmo/2005; 123:149-157. 9. Pediatric Eye Disease Investigator Group. A randomized trial of near versus distance activities while patching for amblyopia in children aged 3 to 7 years. Ophthalmology 2008; 11 5:2071-2078. 10. Pediatric Eye Disease Investigator Group. Slllbility of visual acuity Improvement following discontinuation of amblyopia treatment in children 7 to 12 years old. Arch Ophtha/mo/ 2007;12S:65HS9. 11. Pediil'lric Eye Disease Investigator Group. A randomized trial of atropine versus patching for treatment of moderate amblyopia: Follow-up at 10 years of age.Ard! Ophthalmo/ 2008;126: 1039--1044.

.

CODES

ICD9 • 36a.00 Amblyopia, unspecified • 36a.01 Strabismic amblyopia • 36a.03 Refractive amblyopia

CLINICAL PEARLS • Screening to dell!ct amblyopia early is of paramount importance. • Compliance with occlusive treatment is more important than the type of occlusion utilized. • Appropriate refractive correction is vital to all treil'lments. • Treatment of underlying organit etiologies is essential.

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I

AMD-DRY Brad Ballard Mark L. Nelson

~ BASICS DESCRIPTION • Dry age-related macular degeneration (AM D) is a leading cause of severe vision loss in elderly populations of European descent. Dry AMD causes approximately half of permanent vision loss in older Caucasian patients in the US. • Retinal findings include drusen, pigmentary changes, and geographic atrophy. • AMD is a degenerative condition which affects the outer retina. as well as the retinal pigment epithelium (RPE). Bruch's membrane, and the choriocapillaris.

Geriatric Considerations This is a disease that predominantly affects patients over the age of 65 years. While non-neovascular AMD is less likely to cause severe vision loss than neovascular macular degeneration, it is still a significant cause of legal blindness in patients over 65 years old.

EPIDEMIOLOGY Incidence • The 5-year incidence of large drusen or pigmentary changes average 8.7% (ranging from 3.2% in people less than 60 years. and 18.3% in people in their 70s). • Population studies showed the 5·year incidence of advanced AMD to be 1.1% with 0% in ages less than 60 years, and 5.4% in those older than 80 years. • Progression of disease from drusen and pigmentary changes to advanced AM Dincluding neovascular AMD increases with age.

Prevalence Over 8 million people in the US have early AMD of whom 1 million will develop advanced AMD in the next 5 years.

RISKFAOORS • • • • •

Age is the most important risk factor Family history Caucasian ancestry Smoking is an important modifiable risk factor Studies have been inconsistent about the role of body-mass-index. cardiovascular disease, hypertension, HDL, and total cholesterol. • Very light pigmentation and blue irides may increase risk.

Genetics • Population studies with twins and family members have shown a familial component • Complement Factor H(CFH), complement factor B, HTRA1 on chr. 1Oq26 all predispose to AMD with CFH being most important.

GENERAL PREVENTION • AREDS (Age-Related Eye Disease Study) showed antioxidant vitamin supplementation can decrease progression of moderate to severe AMD. -Patients with a higher intake of dark. green leafy vegetables and omega·3 fatty acids have a lower risk of developing AM D. - Smoking cessation is critical.

PATHOPHYSIOLOGY • Degenerative changes involving outer portions of the retina, RPE, and Bruch's membrane, and less severely, the choriocapillaris • The earliest signs may be basal deposits in the RPE and between the RPE and Bruch's membrane. • Drusen develop because of these deposits and changes in the RPE. • Hard drusen are PAS-positive nodules between the RPE and Bruch's membrane. • Soft drusen are eosinophilic deposits adjacent to Bruch's membrane. • Whether photoreceptor atrophy occurs primarily or secondarily to changes in Bruch's membrane and the RPE, is not known. • Recent evidence cites A2E, a component of lipofuscin, as a possible pathologic linlc leading to RPE apoptosis

ETIOLOGY The nexus of a high photic and oxygen environment in highly metabolic tissue, creates a milieu rife for free radical formation and oxidative damage. Pathologic changes and deposits in Bruch's membrane and the RPE lead to structural changes that lead to AM D. Despite the prevalence of AMD, the etiology is not well understood.

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~ DIAGNOSIS HISTORY • Many times patients are asymptomatic and are diagnosed on a routine eye examination. • Symptoms suggest more advanced disease and include metamorphopsia and gradual impairment of vision over months to years. • AM Dis bilateral but may be asymmetric. • Sudden visual changes or metamorphopsia in patients with dry AMD may signify progression to exudative AMD.

PHYSICAL EXAM • Signs of AMD include drusen, RPE changes, incipient and geographic atrophy, and, in cases of exudative AM D, fluid, hard exudates, hemorrhage, and choroidal neovascular membrane (CNV). • Drusen are classified as small ( 124 ,.,.m) or as hard (discrete well demarcated), soft (poorly demarcated), and confluent (contiguous boundaries). • The RPE shows geographic or non-geographic atrophy and focal hyperpigmentation. • Geographic atrophy is described as well demarcated areas of RPE loss. Non-geographic atrophy is less well defined and has a more mottled appearance. Focal hyperpigmentation occurs at the outer retina. • Early AMD is defined as multiple small or intermediate drusen with no evidence of advanced AMD. • Intermediate AMD is defined as extensive intermediate drusen or 1 large drusen. • Advanced AM Dis defined as presence of geographic atrophy or signs of wet AMD.

DIAGNOSTIC TESTS & INTERPRETATION Imaging Initial approach • Optical coherence tomography (OCD. color photographs, and fluorescein angiography (FA) can be used to document and follow progression of AMD. • FA can show both hyper- and hypofluorescent areas. Hyperfluorescent lesions include RPE atrophy, RPE tears. CNV. pigment epithelial detachments (PED). and subretinal fibrosis. Hypofluorescent lesions are seen with hemorrhage, lipid deposits, and focal hyperpigmentation. Hemorrhage, fluid, and CNV are hallmarks of exudative (wet) AM D.

AMD-DRY • FA can be! used when aaJII! visual changes DCCllr to assess for possible progression to exudative AMD. • OCT can show CNV. edema, subretlnal fluid, PED, and drusen as well as delineate areas of RPE atrophy. • Fundus auiDfluorescence phoiDgraphy shows areas of RPE loss and surrounding damaged RPE. It is an evoMng me1hod of Imaging patients whh dry AMD. Folluw-up I; spetial consideration5 • Risk of progression to wet AM Dcan be calculated using the AREDS simplified severity score. The score is calOJ lated for each eye - Large Drusen - 1 point - Pigment abnormalities - 1 point - Bilall!ral intermediate drusen- 1 paint - Adva need AMD in one e>fe - 2 points • 0 factors - 1.5%, 1 factor - 3%, 2 factors - 12%, 3 factors- 25%, 4 factors- SO% DIFFERENnAL DIAGNOSIS

Central serous dJorioretinopathy, pattern dystrophy of the RPE, Best's disease, idiopathic juxtafaveal telangiectasia, and central areolar dystrophy

•

TREATMENT

ADDmONAL TREATMENT

Generalllleesui9S • Laser photocoagu latlon - Laser photocoagulation has no role in nor.exudative AMD. A controlled trial showed that it reduces drusen, but there was no reduction in risk for di!VI!Ioprnl!f1t of advanCI!d AMD. Laser photocoagulation appears ID inaease risk of CNV. • Amsler grid - Patients should be given a copy of an Amsler grid and should dJeck the vision in one eye at a time on a regular basis ID detect any subtle disiDrticns or blurriness. They should seek ophthalmologic care If changes develop. Issues for Refwnll Patierrts with drusen, RPE changes. and/or geographic atrophy should have routine dilated examinations.

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ONGOING CARE

Pat!errts should use their Amsler grid frequently and return for routine care based on AREDS risk. Development of distortion or central blur should lead ID prompt evaluation. DIET

RmLine

• Patients are encouraged to eat a healthy diet low In saturated fats. as reducing cardiovascular risk factors may help reduce progression of AMD. - Foods high in omega 3 fatty acids. as well as da~ green leafy vegetables may reduce the ris~ of AMD.

ALERT

• Use of beta carotene is not recommended in smokers or Iung cancer survivors as it may increase risk. of lung cancer. • AREDS showed that patients w1th Intermediate or advanced AMD benefited from vitamin supplementation. There is no data ID support a benefidal effect of vitamins in those with no or earlyAMD. • Reductions In modtflable risk factors are encouraged, espedally smoking cessation. Reducing BMI and controlling cholesterol and cardiovascular ris~ factars may help reduce the progression of AM D. Second Une Lutein, zeaxanthin, and long dJain unsaturated fatty acids are rurrently being investigated in the AREDS 2 study.

• Coleman HR. Chan CC, Fenis FL3rd, e1 a!. Age-related macular degeneration. Lancet 2008;372 (9652):1835-1845. • Mitchell P, Wang JJ, Foran S, Smith W. Five-year inddence of age-related maculopathy lesions: The Blue Mountains Eye Study. Ophthalmology 2002;109:1 092-1097. • Donaldson MJ, et. al. Treatment of nonexudative (dry) age-related macular degeneration. Curr O(in OphthaJmoJ 2006;17(3): 267-274. • Age-Related Eye Disease Study Research Group. AREDS report 8. Ardl 0/ilthalmol 2001;119:1417-1436. • Ferris FL. Davis MD, Clemons TE, et al. Age-Related Eye Disease Study (ARE OS) Research Group. A simplified si!VI!rity scale for age-tl!lated marular degeneration: AREDS Report No. 18. ArdJ OphthaJmoJ 2005;123(11):1570-1574.

FOLLOW-UP RECOMMENDATIONS

MEDICATION

The AREDS study showed vitamins can slow progression of disease. The AREDS formulation Is dally administration of 500 mg Vitamin C, 400 IU VItamin E.. 15 mg beta carotene, 80 mg zinc oxide, and 2 mg cupric oxide (to pll!lll!nt zinc induced anemia).

ADDI110NAL READING

PROGNOSIS

• Many patients with early AMD will maintain visual acuity for many years. • Some patil!rrts will progress as they get older ID more advanced forms of AM Das part of the natural history of the disease. • The AREDS sl mpllfled severity smre can be used ID calculate risk of progression to advanced AM D.

.

CODES

ICD9

• 362.51 Nonexudative senile marular degeneration of retina • 362.57 Drusen (degenerative) of retina • 362.89 Other retinal disorders

CLINICAL PEARLS • AMD is the most common cause of legal blindness in elderly Caucasian indMduals. It affects nearly 8 million people In the US. • ltls a degenerative condition lnvoMng the RPE. Bruch's membrane. and the outer retina. • It is diagnosed by dinicaI examination showing drusen, pigmentary changes. and exudative markers in the retina·Bruch's membrane-dloriocapillaris complex. • Amsler grid testing, vitamin supplementation, modification of diet, and reduction in smoking are the only therapies ID date ID show consistent benefrt. • There is much research in the area of laser, mlcronutrlents. neuromphlc factors. stem cells, modHiable environmental factors, genetics. and other modalities to help pll!lll!nt progression of AMD.

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I

AMPPE [ACUTE MULTIFOCAL PlACOID PIGMENT EPITHELIOPATHY] Marc J. Spirn

~ BASICS DESCRIPTION • Acquired multifocal inflammatory disorder affecting the retinal pigment epithelium (RPE) and choroid • Frequently bilateral yellowish-white plaques, often in various stages of resolution EPIDEMIOLOGY Incidence Unknown but rare RISK FACTORS Genetics HLA-87 and HLA-DR2 have been reported with increased frequency

PATHOPHYSIOLOGY Believed to result from choroidal vascular obstruction ETIOLOGY Etiology is un k.nown but a viral prodrome occurs in one-third of patients

COMMONLY ASSOCIATED CONDITIONS • Uveitis • Retinal vasculitis • Episcleritis • Erythema nodosum • Cerebral vasculitis

~ DIAGNOSIS HISTORY • Painless vision loss • Viral prodrome occurs in one-third of patients PHYSICAL EXAM • Funduscopic examination reveals yellowish-white placoid lesions in the macula - lesions are typically multiple, bilateral, and in various stages of resolution (resolution is denoted by RPE hyperplasia) - lesions reside at the level of the RPE and choroid

DIAGNOSTIC TESTS & INTERPRETATION Imaging Fluorescein angiogram shows early hypofluorescence with late hyperfluorescence.

DIFFERENTIAL DIAGNOSIS • Serpiginous choroiditis • Relentless/Ampiginous chorioretinitis • Ocular toxoplasmosis • Sarcoidosis • Ocular lymphoma • Harada disease

.

TREATMENT

MEDICATION • lesions typically resolve without medical treatment • If lesions affect the fovea and vision is poor, it is reasonable (but unproven) to consider a short course of oral steroids ADDITIONAL TREATMENT Issues for Refe"al • Suspected AMPPE should be referred to a retinal specialist to aid in diagnosis and care • Mental status changes should prompt an immediate referral to a neurologist to rule out cerebral vasculitis

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AIIPPE (IEUTE MII.TIFDCAI. PIACOII PIGMENT EI'ITIIELIOPATHY) •

ONGOING CARE

FOU.OW-UP RECOMMENDA110NS • Sporrtaneous resolution is the rule. • Recurrence is possible but is mre. When multiple reanrences occur, a different diagnosis should be considered. Patient Monitoring Cerebral YaSOJiitis is a rare associated finding. Merrtal status changes should prompt an immediate refl!rral to a neurologist PROGNOSIS Spontaneous recovery within 3-4 weeks is the norm. In rare instances. RPE changes in the macula can cause chronic vision lass.

ADDITIONAL READING • Gass JDM. Acute posterior multifocal placoid pigment epitheliopathy. Aich Ophthalmo/ 1966;80:177-185. • Heath JD. Acute poste~or multlfooll placold pigment eplthellopathy. lnr Ophrhalmol Clln 1995;35(2):93-1 OS. • O'Halloran HS. Berger JR. Lee WB. et al. Acute multifucal placoid pigment epithel iopathy and central nervous system involvement: Nine new cases and a review of the literature. Ophrhalmology 2001 ;1 08(5):861~.

~ CODES

~

ICD9 363.15 Disseminated retinitis and retinochoroiditis, pigment eplthellopathy

CLINICAL PEARLS • AMPPE is a self-limited inflammatory disease of the RPE and choroid • Rarely AM PP Emay be associated with life-threatening complications such as cerebral vasculitis • Patients often recover sign lftca nt visual acuity unless there are signif~eant RPE changes in the fovea

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I

ANGIOID STREAKS Mark L. Nelson Matthew R. Debiec

~ BASICS DESCRIPTION Irregular crack-like dehiscences in Bruch's membrane that can be associated with multiple systemic conditions. Significant sequelae include subretinal hemormage, choroidal rupture, and possible choroidal neovascularization (CNV).

EPIDEMIOLOGY lnddence

GENERAL PREVENTION • There are no treatments known to prevent angioid streaks in patients who may be at risk; some reports indicated increased complications following prophylactic laser therapy. • Patients are susceptible to choroidal rupture following mild trauma and should be educated to wear protective eyewear.

PATHOPHYSIOLOGY

• Incidence of angioid streaks is based on the underlying condition. Pseudoxanthoma elasticum (PXE), the most common underlying condition, has an incidence of 1 in 160,000. -Typically develops between the second and fifth decade of life.

• The crack-like dehiscences are produced by alterations in Bruch's membrane, making it more prone to cracks. Full thickness breaks may allow CNV membranes to form. • Subretinal hemorrhages can develop regardless of the presence of a CNV. Subretinal hemorrhage can follow traumatic breaks in Bruch's membrane and can disseminate toward the macula.

Prevalence

ETIOLOGY

Variable based on the underlying condition. Approximately one-third to half of cases have been reported to occur in patients with PXE. Of patients with PXE, more than 80% tend to have angioid streaks. Approximately 15% of patients with Paget's disease of bone and anywhere from 1-20% of patients with sickle-cell disease develop angioid streaks.

RISK FACTORS • The most common diseases related to angioid streaks are pseudoxanthoma elasticum, Paget's disease of bone, sickle-cell anemia, and Ehlers-Danlos. • Other diseases include: -Acquired hemochromatosis -Acromegaly - Diabetes mellitus -Acquired hemolytic anemia - Hereditary spherocytosis -Myopia - Neurofibromatosis - Sturge-Weber syndrome - Hyperphosphatemia - Senile elastosis -Tuberous sclerosis - Some patients have no identifiable systemic disease that can be attributed to angioid streaks and are considered to develop them idiopathically.

Geneffa • Varies based on the underlying condition causing angioid streaks. - Pseudoxanthoma elasticum, the most common associated condition, is due to an autosomal recessive or dominant mutation in the ABCC6 transporter gene.

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Underlying genetic predisposition of the aforementioned conditions combined with possible unknown environmental or acquired risk factors lead to angioid streaks.

COMMONLY ASSOCIATED CONDITIONS See risk factors above.

~ DIAGNOSIS HISTORY Angioid streaks are typically asymptomatic although they can present with metamorphopsia and decreased vision.

PHYSICAL EXAM • Diagnosis is typically based on the characteristic funduscopic appearance, although imaging such as FA or ICG aid in diagnosis. • Angioid streaks appear on exam as narrow jagged lines, deep to the retina, that radiate out from areas of peripapillary pigment alterations. • The streaks are almost always bilateral and usually occur in the posterior pole. Width ranges from so-soo ttm. The color of the streaks varies and may range from dark red to brown. • Eyes of patients with PXE may demonstrate peau d'orange, which is diffused mottling of the retinal pigmented epithelium (RPE) typically found temporal to the macula. These patients may also develop yellowish spots described as salmon spots at the level of the RPE.

• A choroidal neovascular membrane may develop at sites of angioid streaks and full thickness breaks in Bruch's membrane. • Over two-thirds of patients with angioid streaks develop CNV at some point; however, this rate varies greatly depending on the clinical condition. While patients with PXE have the relative highest probability of macular CNV, patients with sickle-cell anemia tend to have a substantially lower rate of CNV.

DIAGNOSTIC TESTS & INTERPRETATION Lab • laboratory work-up tends to center around evaluating for systemic conditions in those patients that do not have a predisposing diagnosis. • A focused medical work up may include: Skin biopsy, x-ray imaging, hemoglobin electrophoresis, genetic testing, or blood work.

Imaging Initial approach • Fluorescein angiography (FA) is not necessary for diagnosis. but is extremely helpful in establishing the diagnosis in early streaks adjacent to the optic disc and in evaluating the development of CNV. -Angioid streaks will appear hyperfluorescent (window defect) in the early phase of FA. - CNV shows early hyperfluorescenc.e and late staining. • lndocyanine Green (ICG) angiography may be employed when both funduscopy and FA are equivocal, for example, in cases of extensive hemorrhages or severe RPE lesions. ICG angiography may show hypeliluorescent lines with pinpoints over their length. Follow-up a special considerations Patients with angioid streaks may require on-going follow up with FA to assess for development of CNV.

Pathological Findings • Characteristic findings include irregular crack-like dehisc.ences in Bruch's membrane with atrophic degeneration of the overlying RPE.

AIGIIIID SIIIEAKS • Ey!!.s with angioid streaks haW! shown I!XIensivl! caldflcatlon and ttllckenlng of Bruch's membrane Ylittl PXE and Paget's disease of bone, although ttlls is not always found in other associated conditions. Bruch's membrane in Sickle hemoglobinopathies has demonstlllted iron deposition in addition to caldfication. • The elastic IamIna In the mlddle of Bruch's membrane is often affected with disintegration and fraying of the elastic fibers.

DIFFERENTlAL DIAGNOSIS • Age-related macular degeneration • Patholog lc myopia • Hlstoplasmosls • Toxoplasmosis • Retinal vaswlitis • ChoroidaI rupture

.

TREATMENT

MEDICATION FltstLine • More recently, off-label use of anti-vasrular endothelial growth factor therapy such as pegaptan lb, ranlblzumab, and bevaclzu mab has been used to treat CNV. -Short-term studies have shown favorable results. - One study examining results of bevacizumab up ID 24 months after initiation of therapy found recurrence of CNV In up to one-ttllrd of patients and new CNV lesions In 20% of patients. • Risk of intravitreal injections in these eyes is not fully known. ADDITlONAL TREATMENT

General Measures • Laser photocoagulation to CNV lesions In patients Ylith anglold streaks has modest results. Argon or Krypton laser phatotoi!guIation is typically considered in eyes with extrafDVI!aI or juxll!loveal CNV. Findings typically show modenatevisualloss in eyes treated with laser photocoagulation and greater ltlan SO% rate of persistence and/or recurrence. However, eyes with angioid streaks that are untreated and allowed to naturally progress haW! a very high rate of poor visual outmm e, often with visual acuities of 20/200 or WO!lie. - Proph)iactlc therapy of angioid streaks may actually Induce more rapid progression to development of CNV.

• Pho!Dclynamic therapy (PDT} with verteporfin may be considered for eyes with subfoveal CNV. 1hIs therapy has been attempted In some small retrospective and prospective studies atthough benefit is limited to a short period and it is often associated with recurrence or subsequent chorioretinal atrophy. SeveraI studies show contradictory results and many consider It as a method to slow, but not prevent ltle natural course of CNV in angioid streaks.

SURGERY/OTHER PROCEDURES Macular translocation and submacular surgery has been previously attempted in rare cases of angioid streaks with variable success.

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ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Patients with angioid streaks should have exam lnatlons at least every 6 months ID assess for the development of CNV given its relatively high inddfnce. This follow-up may includf FA to assess for CNV. • Development ofsym ptoms should prompt increased frequency of evaluation to at least every 3 months. - Patients that have recently been treated with laser andlor anti-VEGFtherapy should be evaluated regularly. • Patients can be instructed in the use of Amsler grid testing for home men ltorlng. PATIENT EDUCAnON Patierrts should be educated about the importance of protective eyewear as the chance of choroidal rupture or subretinal hemormage is high with even minor trauma. PROGNOSIS Visual prognosis of eyes with angioid streaks is poo~ although this varies based on the underlying diagnosis. time of onset of symptoms, and response ID various types of therapy. It appears that in the nalllral history of untreated eyes, most end up wlltl visual acu fly of 20/200 or worse. At present, therapy ~ directed toward slowing the rate of visual loss and CNV progression.

ADDI110NAL READING • Clarkson J, Altman R. Angioid sb'ea ks. Surv Ophtha/moJ 1982; 26(5): 235-246. • Sawa M, Gomi F, Tsujikawa M, et al. Long-term results of intravitreal bevadzumab injection for choroidaI neovascularization secondary to angioid streaks. Am J Ophtha/moi200g; 148{4): 584-590. • Lim J, Bressler N, MaBh M, et al. Laser treatment of choroidaI neovascularization in patients with angioid streaks. Am J Ophthalmo/1993; 116: 4t 4-423. • Georgalas I, Papaconstantinou D, Koutsandrea C, et al. Angioid streaks, clinical course. complications. and current ttlerapeutlc management. Ther C/ln Risk Manag 2009; 5(1): 81-39. • Gurwocd A. Mastrangelo D. Understanding angioid strea Its. JAm OptometricAssoc 1997; 68(5): 309-324.

t f ; coDES ICD9 363.43 Angioid streaks of choroid

CLINICAL PEARLS • Angioid streaks may be a sign of an unde~ylng disease such as pseudoxanthoma elasticum, Ehlers-Danlos syndrome, sickle-cell hemoglobinopathy, or Paget's disease of bone. It may also be idiopathic. • Angioid streaks rna Ice the eye susceptible to severe subretinal hemorrhages from even minor blunt trauma, so patients should wear eye protection at all time. • Choroidal neovascularization may develop in the areas of angioid streaks; patients need to self-fllonltor their vision and have regular fundus exams.

COMPUCA110NS Patlerrts with angioid streaks and Pseudoxanthoma Elastlcum are at lnaeased ~sk. for cardiovascular disease and spontaneous gastrointestinal bleeding.

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I

ANISOCORIA IN CHILDREN William 0. Young

~ BASICS DESCRIPTION Round pupi Is that differ in size by 0.5 mm or more EPIDEMIOLOGY

Prevalence • 15--30% (physiologic) • Other causes rare

RISK FACTORS • Physiologic: None • Trauma Oncluding intraocular or brain surgery) • Iritis • Meningitis • Topical contact with mydriatic or miotic (drop, ointment or plant) • Paraspinal neuroblastoma • Birth trauma • Family history of anterior segment dysgenesis

Genetics • Physiologic not genetic: -Anterior segment dysgenesis may be due to a genetic disorder.

GENERAL PREVENTION • Physiologic: None • Genetic counseling for anterior segment dysgeneses • Avoidance of contact with mydriatics and miotics • Careful follow-up screening for patients at risk for iritis (e.g., juvenile idiopathic arthritis) to detect inflammation early PATHOPHYSIOLOGY • Maldevelopment or dysfunction of the pupillary dilator or sphincter muscle or • Mechanical impairment of the pupil (e.g., posterior synechia) or • Idiopathic (physiologic)

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ETIOLOGY • Physiologididiopathic (most common) • Congenital Horner syndrome: - Birth trauma including brachial plexus injury - Neoplasm rare • Acquired Horner syndrome ALERT Can represent metastatic neuroblastoma: • Congenital third cranial nerve palsy • Acquired third cranial nerve palsy: -Trauma (most common) -surgical or nonsurgical - Meningitis -Tumor -Aneurysm: o Unlikely under age 14 • Traumatic mydriasis (sphincter tears) • Posterior synechiae due to iritis • Adie's tonic pupil: - Much less common in children than in young women - Usually idiopathic • Pharmacologic mydriasis: - Usually cycloplegic (pharmaceutical or environmental) • Congenital miosis • Aniridia and other anterior segment dysgenesis COMMONLY ASSOCIATED CONDITIONS • None in physiologic anisocoria • Neoplasm in 23% of pediatric Horner syndrome (1) ALERT Note especially neuroblastoma metastatic to cervical sympathetic chain, which can be life threatening and requires urgent workup. • Other neoplasms causing Horner syndrome in children include benign paraspinal neuroblastoma, rhabdomyosarcoma (2), Ewing sarcoma, and juvenile xanthogranuloma (1). • Abnormalities of extraocular muscle function and strabismus in third cranial palsy

~ DIAGNOSIS HISTORY • Trauma: - Nonocular: o Birth trauma o Surgical (neck or chest) or other postnatal trauma - Ocular blunt trauma - Intraocular surgery • Age of onset: - Review old photos • Duration • Ptosis: -Homer syndrome (1-2 mm or less) -Third cranial nerve palsy • Anhidrosis/hypohidrosis: - Seen in some but not all cases of Homer syndrome • Contralateral facial flushing and ipsilateral hypohidrosis (Harlequin sign): - Seen in some but not all cases of Homer syndrome in infants • longstanding iris heterochromia in congenital Homer and some anterior segment dysgenesis PHYSICAL EXAM • Acuity • Normal in physiologic anisocoria • May be decreased due to amblyopia in third nerve palsy and Adie's • Accommodative amplitudesldynamic retinoscopy: - May be decreased in third cranial nerve palsy and Adie's tonic pupil) • Pupils: -Anisocoria greater in darkness (smaller pupil is abnormal): o Physiologic anisocoria o Horner syndrome o Mechanical restriction -Anisocoria greater in light (larger pupil is abnormal): o Third cranial nerve palsy o Adie's pupil o Traumatic mydriasis o Pharmacologic mydriasis -Dilation lag of smaller pupil: o Horner syndrome -light-near dissociation: o Adie's tonic pupil - Segmental constriction: o Adie's tonic pupil - Relative difference in pupil size preserved in dim and bright illumination: Physiologic anisocoria - Iris heterochromia (lighter iris ipsilateral to smaller pupil): o Congenital Horner syndrome

ANISOCORIA IN CHILDREN • Eyelids: - 1-2 mm (but not more) of upper eyelid ptosis In Horner syndrome, ipsilateral to the smaller pupil -More profound ptosis in third nerve palsy, ipsilateral to the Iarger pupil - "Inverse ptDSis • (slight elevadon of the lower lid of the eye with the small pupil) with Homer syndrome) • Motility: - Normal with all causes of anisocoria except third nerve palsy -Limitation of elevation, depression, and adduction In third nerve palsy: o The palsied eye is typically ·down and out" (exotropic and hypotropic) • Palpate abdomen and supraclavicular region looking for neuroblastoma or other neoplasm

DIAGNOSnC TESTS & INTERPRETATION

U.b • If suspect Hornet with no dear evidence of birth injury: Spot urine for wn illylmandelic add (VMA) and homDYanllllc acid (HVA) • Note: Urine testing may not be as sensitive as imaging (1)[C) in diagnosing neuroblastoma lmagirlfl • MRI (with and without gadolinium) of the brain, neck, chest. and upper abdomen if suspect Homer syndrome unless clear evidence of birth trauma (1)[C]: -Some recent evidence (3)[C) questions the need for extensive evaluation of patients with Homer syndrome. • MRl of brain with MRA if suspect third craniaI palsy and no clear etiology Diagnostic l'raCIIilduru!Other • Review old photographs to help determine whether anisocoria is cnngenital or acquired • Pharmacologic testing for Homer syndrome: - Cocaine 5% drops dilate the normal pupil but not the Horner pupiI. - Apraclonidine 0.5% produces reversal of anisocoria in 30-60 min in Homer syndrome. o Effect easier to see in bright than in dim light

(4)[C) - Hydroxyamphetamlne 1% dilates preganglionic but not postganglionic Horner pupil. • Pharmacologic testing for Adie's tonic pupil: Pilocarpine D. 125% constricts Adie's pupil but not a normal pupiI or a pharmacologically dilated pupil.

REFERENCES .

TREATMENT

MEDICAnON • For Adle's tonic pupil: Pilocarpine 0.125% b.i.d.-ij.i.d. can be used for cosmesis and to aid accommodation. • For posterior synechiae due to I~tis: Pharmacologic mydriasis (such as atropine 1% drops) to break the synedliae, in addition to topical steroid treatment (with systemic medication as indicated) for the iritis. • Anisoco(lil due to other causes is not treated; instead, an underlying cal!Se is identified and treatable.

ADDITIONAL TREATMENT

GeneraiAieasures • Amblyopia (most llla!ly with third neNe palsy and Adie's) is treated with refractive correction if needed, and patching or atropine penalization. • Cosmetic contact lens is used if con cems about appearance In older children. Issues for Refem~l • Patients discovered to have evidence of a neoplasm should be referred without delay to approp~ate spedalists (oncology, neurosurgery). • Patients below 12 months of age with Adie's tonic pupil should be referred to pediatric neurology to rule out familial dysautonomia.

•

ONGOING CARE

1. Mahoney NR, Liu GT, Menacker SJ, et al. ~'~!!~iatric Horner syndrome: Etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophrha/mo/ 2006;142(4}:651 ~59.

2. Jeffery AR, Ellis FJ, Repka MX, et al. Pediatric Horner syndrome. JAAPOS 1998; 2(3):159-167. 3. Smith SJ, Diehl N,l.eavitt JA, et al. Incidence of pediatric Horner syndrome and neuroblastoma threat. Ard! Ophlha/mo/ 201 0;128(3):324-329. 4. Chen PL. Hsiao CH. Chen JT. et al. Efficacy of apraclonidine 0. 5% in the diagnosis of Horner syndrome in pediatric patients under low or high Illumlnatlon. Am 1 Ophrha/mo/2006;142(3): 469-474.

ADDITIONAL READING • Kardon RH, Thompson HS. Congenital and acquired anisocoria in children. In: Cibis GW, Tongue AC, Stass-lsern MI., eds. De 74% (6)

COMPUCATlONS • Occlusion amblyopia can occur in the treated eye. • High degrees of refractive errot espedally if anisometropic; if corrected by spectacles may have adverse psychosodal consequences that male!! wearing glasses a challenge.

REFERENCES 1. Donahue S. The relationship between anisometropia, patient age, and the development of amblyopia. Trans Am Ophtha/mol Soc 200 5; 103:313-336. 2. Choi MY, Lfe KM, Hwang JM, et al. Comparison between anisometropic and strabismic amblyopia using fu nctlonal magnetic resonance Imaglng. Br J Ophtha/mol 2001 ;85:1052-10 56. 3. Pediatric Eye Disease Investigator Group. Treatment of anisometropic amblyopia in children with refractive mrrection. O{ilthalmol 2006; 113: 89s-903.

4. Pediatric E}'l! Disease Investigator Group. A comparison of atropine and patchl ng treatments for moderate am blyopla by patient age, cause of amblyopia, depth of amblyopia and other factors. Ophthalmol2003;t 10:1632-1637. 5. Pediatric Eye Disease Investigator Group. A randomized trial to evaluate two hoors of daily patch lng for ambt,oopla In children. Ophtha/mo/ 2006;113:904-914. 6. Pediatric Eye Disease Investigator Group. A randomized trial of atropine ver:5US patching lor treatment of moderate amblyopia: Follow-tip at 10 years of age.Atdl OphtfuJimd 2008;126:

1039-1044.

.

CODES

ICD9 • 367. 1 Myopia • 367.31 An isometropia • 368.00 Amblyopia, unspecified

CLINICAL PEARLS • Detection of significant anisometropia at earlier age can prevent amblyopia. • Spectacle correction alone has signilicarrt impact on visuaI recovery. • Amblyopia treatment is effective. • Ongoing follow-up to measure vision and changes in refractive erTor is essential.

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ANOPHTHALMIA Jing Jin

~ BASICS DESCRIPTION • Absence of globe. Must be distinguished from severe microphthalmia in which globe remnants may only be detectable by ultrasound, neuroimaging, or tissue biopsy (e.g., exenteration or autopsy). • With or without systemic disease EPIDEMIOLOGY 10--19 per 100,000 newborns (1) (2)[C]

RISK FACTORS • Chromosomal aberrations, syndromes, and congenital disorders • Intrauterine factors: - Prenatal exposure to teratogenic factors including radiation, alcohol, thalidomide, retinoic acid (l)[C], hydantoin, and lysergic add diethylamide (LSD) Genetics There is no !mown gene defect specific for true anophthalmia. GENERAL PREVENTION • Prenatal ultrasound (4)[C] • Avoidance of in utero exposures to infection or teratogen PATHOPHYSIOLOGY Complete failure in the development of the primary optic vesicle during embryogenesis ETIOLOGY • Genetic • Prenatal exposure to infection or teratogen • Idiopathic

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COMMONLY ASSOCIATED CONDITIONS • No consistent systemic associations • Midline craniofacial anomalies • Developmental delay (often severe) with chromosomal aberration or other systemic syndrom ic findings • Craniofacial disproportion with enophthalmic appearance and small palpebral fiSsures and lids

~ DIAGNOSIS HISTORY • Family history of congenital ocular disease • Known exposure to infection or teratogen in utero • Other known associated anomalies or developmental delay

PHYSICAL EXAM • The condition may affect one or both eyes. -Reduced orbital volume with enophthalmic appearance - Eyelids may appear normal, small, or partially fused. Lashes, tarsal glands and lacrimal gland and drainage system are usually present. • Systemic examination for other anomalies, especially brain anomalies • Complete eye examination of both parents looking for coloboma- if present suggests that the child has severe microphthalmia rather than true anophthalmia

DIAGNOSTIC TESTS & INTERPRETATION Lab

Initial lab tests • None if no extraocular findings • Karyotype/microarray if other congenital anomalies are present • Molecular genetic testing for mutations in syndromes reportedly associated with anophthalmia Follow-up ll special considerations • Must follow orbital and periorbital growth • Follow for developmental delay

Imaging Initial approach MRl and CT show the absence of ocular tissue, optic nerve, and extraocular muscles. Follow-up ll special considerations Serial CT scan may assist in evaluating bony growth.

Pathological Findings Absence of ocular tissue in orbit

DIFFERENTIAL DIAGNOSIS Severe microphthalmia Cystic eye Acquired anophthalmia following trauma or surgery Phthisis (e.g., following infection or trauma) Cydopia/synophthalmia

• • • • •

AIIDPHniAI.MIA

.

TREATMENT

MEDICATION None ADDITIONAL TREATMENT General Measures • Safety glasses to protect the good eye in unilatelill cases • Sclelill shell to enmurage periorbital tissue growth Issues for Rmtral • Genetic mnsultation • SpedaI education and referral to services for ti1e blind SURGERY/OTHER PROCEDURES Placement of serial en larglng orbital expanders, dermal fat glilfdng, or Intraorbital balloons In severe cases(5)[C]

$

ONGOING CARE

FOLLOW-UP RECOM MENDA'nONS Regular evaluation by an orularist Follow orbital and periorular tissue growth especially in first 5 years of life, PaRent Monitoring • School performance and development • Patient concerns about appealilnce

PATIENT EDUCATION • Genetic cou nsellng • Blindness lntervendons • International Children's AnophthaImia and Microphti1almia Network (http:J.WWW. anophthalmia.org) PROGNOSIS Depends on associated systemic anomalies

REFERENCES 1. Dolk H, Busby A. Armstrong BG, et al. Geographical variation in anophti1almia and microphthalmia in England, 1988-1994. BrMed1 1998;317:905--909. 2. Yoan PW. Rasmussen SA, Lynberg MC, et al. The National Birth Defects Prevention Study. Public Health Rep 2001 ;116(Suppl1):32-40. 3. Lamer EJ, Chen DT, Hoar RM, et al. Retinoic add ern bryopathy. N Efl!i 1 Med 198S; 313:837-841 . 4. Wang HS, Parker S, Tait J, Pringle KC. Antenatal diagnosis of anophthaImia by three-dimensional ultrasound: Anovel appllcadon of the reverse face view. Ultrasound Obsret Gynetol 2008;32: 103-105. S. Schittkowski MP, Guti1off RF. Injectable self inflating hydrogel pellet expanders for ti1e treatment of orbital volume defidency in cangen itaI mlcrophthalmas: Preliminary results w1ti1 a new therapeutic approach. Br1 Ophtha/mo/ 2006; 90(9):1173-1177.

ADDITIONAL READING • http://www.ncbi.nlm.nih.gov.proxy1.1ib.tju.edu: 2048/bookshelflbr.fcgi?book=gene&part= anophti1almia·ov • Stoll C, Alembik Y, Dott B, Roti1 MP. Congenital eye malformations in 212,479 conserutive births. Ann Genet 1997;.W(2):122-128. • fl)'l1s JP, Legius E, Moerman P, et al. Apparently new • anophthalmia·plus• syndrome in sibs. Am J Med Genet 1995:58:113-114. • West B, Hove KE, Slavotinek AM. Two novel STRA6 mutadons In a patient w1th anophthalmia and dlaphragmadc eventradon. Am 1 Med Genet A 2009;149A(3):539-542.

.

CODES

ICD9 743.00 Clinical anophthalmos. unspedfll!d

CLINICAL PEARLS • Check the patient for possible associated system lc flndlngs. • Examine parents for coloboma. • Consider genetic mnsuIt • Prosti1esis fitting to ensure orbital and periocular tissue gt"'W1h

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ANTERIOR BASEMENT MEMBRANE DYSTROPHY Sadeer B. Hannush

~ BASICS DESCRIPTION Corneal anterior basement membrane dystrophy (ABMD) is the most common corneal dystrophy. It is also known as map-dot-fingerprint, mare's tail, and Cogan's microcystic dystrophy ALERT Corneal ABM Dis most commonly associated with two clinie 2 mm, fluid, symptoms. orange pigment, margln near disc, ultrasound hollow, halo absent, drusen absent Any small lesion with these features should be evaluated for melanoma by an experienced consultant

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CHOROIDAL NEOVASCUlARIZAnON J. Arch McNamara

~ BASICS DESCRIPTION • Choroidal neovascularization (CNV) is the development of new blood vessels from tile choroid layer through a dehiscence or disturbance in Bruch's membrane into the subretinal space. • Choroidal neovascularization is often accompanied by fibroblasts. The resulting fibrovascular complex is unstable and can frequently leak serous fluid, hemorrhage, and result in a disciform scar. • Multiple disorders that affect the retinal pigment epithelium (RPE)-Bruch's membrane-choriocapillaris complex can cause choroidal neovascularization. - Over 40 disease processes are associated with choroidal neovascularization with age-related macular degeneration (AM D), angioid streaks, pathologic myopia, ocular histoplasmosis syndrome, and blunt trauma being the commonest. EPIDEMIOLOGY Incidence • Varies by underlying diagnosis - Choroidal neovascularization associated with age-related macular degeneration is the leading cause of permanent visual loss in people over 65 years of age in developed countries. a Advanced AMD affects 25-30 million people worldwide and 1.75 million in the US.

Prevalence • Varies by underlying diagnosis - In AM D. the prevalence of choroidal neovascularization is primarily influenced by advancing age.

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RISK FACTORS • Varies by underlying diagnosis - In AM D. advancing age is an obvious risk factor. Other factors include strong family history of AM o, race (more common in whites and Hispanics than blacks), cigarette smoking, hypertension, hyperlipidemia, abdominal obesity, reduced physical activity, and high dietary fat intake.

Genetics • Varies by underlying diagnosis -AM D-and its most severe complication, choroidal neovascularization-- is recognized as resulting from a convergence of multiple risk factors. Family history is a consistent risk factor. Twin studies support a genetic basis for the disease with both early and late-onset findings (CNV) being approximately twice as high in monozygotic as dizygotic twins. a Genome-wide linkage analyses have identified a number of chromosomal loci lin ked to AMD.

GENERAL PREVENTION • Avoid modifiable risk factors • Nutritional supplementation has been shown to reduce the risk of progression of AM D to its more severe "wet" form in which tllere is development of CN\1. -The Age-related Eye Disease Study (AREDS) recommended the following: 500 mg vitamin C, 400 IU vitamin E, 15 mg betaus membrane graft (buccal}lamn lotlc membrane graft If t!if Is quiet and on patient is on systemic immunosuppression • Enlnlpion: Only perform when eye is quiet and patient is on systemic immunosuppression • Comeal transplantation/Permanent Keratoprosthesls: For successful comeaI transplantation, disease should be quiet and the patient should be on systemic therapy. Further, patient must have adequate tear production with functioning stem cells for re-epilhelialization. Permanent kl!ratoprosthesls may be considered In patients with adequate tear production and stem cell deficiency. ALERT Any surgical procedure may trigger aa.tte exacerbation of disease. Therefore, all procedures (eyelid, conjunctival, catalllct, or comeaO should be performed while patient is quiet and on systemic Immunosuppression.

(f) ONGOING CARE FOLLOW-UP RECOMMENDATIONS

Patient Monitoring • Monitor with regular exams and anterior segment photographs for progression • Serial bacte~al conjunctival cultures to evaluate overpopulation/colonization with bacteria that may lead to microbia I keratitis PROGNOSIS Depends on stage of disease at presentation. High d lnlcal suspicion, early dlag nosIs, and appropriate therapy can reduce morbidity.

REFERENCES 1. Holsdaw DS. Owlar clcatrtdal pernphlgold./nr Ophthalmo/ Clin 199a;38:89-1 06. [A] 2. Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmo/ Soc 1986;84:527-1i63. [AI 3. Zaltas MM, Ahmed AR, Foster CS. Assodation of HLA-DR4 with ocular dcatrlclal phemphlgold. Curr E~ Res 1989;8:134. [A] 4. Mondino BJ, Brown Sl. Ocular dcatricial pemphigoid. O{iltha/mo/agy 1981;88:95-100. [AI 5. Power WJ, Neves RA, Rodriguez A, Dutl JE, Foster CS. lnaeaslng the diagnostic y1eld of conjunctiva I biopsy In patients with suspected ocular dcatrlclal pemphigoid. O{ilthalmo/agy 199S; 102(8): 1158-63. [AI

ADDITlONAL READING • Roat Ml, Sossi G, LaCY, et aL Hyperproliferation of conjunctival fibrobroblasts from patients with clcalr1dal pemphigoid. Arch Ophthalmo/ 1989;1 07: 1064-1 067. [A] • Saw VPJ, Dart JKG, Rauz S, et al. Immunosuppressive therapy for ocular mucous membrane pemphigoid strategies and outcomes. Ophthalmology 200i;1t 5(2):253-261. [A] • Sam I N, L.etko E, Androudl S, Daoud Y, Foster CS, Ahmed AR.Intravenous immunoglobulin therapy in patients with ocular cicatricial pemphigoid: A long-term follow-up. Ophthalmology 2004; 111: BBD-1382. [A]

Q S11 Also 12 mm for full term infants) -Hand held slit-lamp examination may reveal cloudy corneas or Haab's striae (breaks in Descemet's membrane, usually horizontal) - Cycloplegic streak retinoscopy may be useful in detecting progressive myopia or rapid loss of hyperopia -Tonometry should be obtained at anesthesia induction with the Tonopen or Perkins tonometer. Normal infant lOP is 10--15 mm Hg; lOP in congenital glaucoma typically 25-35 mm Hg -Gonioscopy may reveal an anterior iris insertion and indistinct trabecular meshwork. - Ophthalmoscopy will reveal optic nerve cupping, which is usually concentric with healthy surrounding disc tissue until late stages (sloping, notching, and hemorrhage are uncommon). May be reversible. • In the office, assess the following: -Visual acuity - Pupils (assess for afferent pupillary defect) ALERT Beware of falsely high (hypercarbia, speculum, pressure from anesthetic mask, 2-5 minutes after intubation, ketamine) or falsely low (corneal epithelial edema, halothane, hypocarbia) lOP DIAGNOSTIC TESTS & INTERPRETATION Imaging • Optic disc photos • Consider hand held optical coherence tomography

(ocn

Diagnostic Procedures/Other • Visual field (once the child is old enough to complete this test reliably; the age will vary depending on the child)

Pathological Findings • Haab's striae: Breaks in Descemet's membrane • Variable amounts of goniodysgenesis including collagenous tissue in the trabecular meshwork or juxtacanalicular tissue, mucopolysaccharides in the juxtacanalicular tissue, +1- absence of Schlemm's canal (3)]C] • Optic cupping with posterior bowing of the lamina cribosa.

DIFFERENTIAL DIAGNOSIS • Differential of tearing: - Nasolacrimal duct obstruction - Conjunctivitis - Corneal epithelial defect -Uveitis -Trichiasis or foreign body - Blepharitis • Differential of Haab's striae: - Birth trauma (forceps injury) - Covert or overt trauma -Syphilis - Descemet folds • Differential of corneal clouding: - Congenital hereditary endothelial or stromal corneal dystrophy -Keratitis - Metabolic disorders -Infection - Peters anomaly - Sclerocornea • Differential of enlarged cornea: - X-linked recessive megalocornea - Phakomatoses • Differential of buphthalmos: - Exorbitism -High myopia • Differential of optic neiVe cupping: - Physiologic cupping - Optic nerve pit - Optic nerve coloboma

CONGENITAL AND INFANnLE GLAUCOMA

.

TREATMENT

MEDICATION

FirstUne o

o o

o

Medic.ations can be used as a temporizing measure ID lower the intraocular pressure and clear the cornea p~or to proceeding with angle surgery and may also be used as adjunctive treatment following su rgic.al management. Topical beta-blotla!rs (e.g., timolol 0.25%, levobunolol 0.25%, betaxolol) Topic.al carbooic anhydrase inhibi!Drs (e.g., dorzolamide, brinzolamide) Prostaglandin analogues (e.g., latanoprost, travoprost, and bimatoprost)

ALERT Use of alpharagonists (e.g., iopidine, brimonidine) in children < 1 year of age is not recommended due to potential central neMlus system depression.

SecondUne o

OraI carbonic anhydrase inhibi!Drs (e.g., acetazolamide 15-30 mg/kg per day, divided into 3-4 doses)

ADDITIONAL 111EATMENT

General MHsutes o o o

Spectacles for refractive error Treat am bylopia and strabismus Tinted (or transition) lenses may help with photophobia

ALERT Amblyopia Is the most common cause of visual loss in rongenitallinfantile glaucoma. Correction of refractive error (especially astigmatism and anisometropia) Is attlcalln preventing the development of amblyopia. Frequent cycloplegic refraction (q H months) is often necessary with rapid lOP changes. Issues for Refwraf o Consider a genetics consultation for counseling. molea.ilar testing, and identification of systemic syndromes. • Consider a low vision referral if indicated.

SURGERY/OTHER PROCEDURES • Procedures of choice: - Goniotomy is the mainstay of initial surgical treatment. Approximately 80% of children are cured with goniotomy. - Trabeculotomy +1- trabeculectomy Is an alternative in the setting of a doudy cornea and is preferred as the iniliaI choice by some surgeons. • If angle surgery falls: (4)[B) -Tube shunt - Trabeculectomy+l-Mitornycin-C (lifelong risks must be considered) - Transderal or endoscopic cyclophotocoagulation in advanced c.ases that have failed medical and surgicaI treatment.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS o All patients require lifelong follow up. • Patients should be monitored closely during the first 4-6 weeks pos!Dperatiwely to moniiDr for corneal dearing, reversa I of optic nerve cupping, and lOP reduction. • During the first few years of life, office visits and exams under anesthesia should be completed every 3-4 months depending on dlsease severity. • Remember awake examinations ID screen for amblyopia. PATlENT MONITORING • Repeat examination under anesthesia every 3 months for the first year of life periodic.ally including measurements and imaging to assess disease control. o Regular reexamination during early childhood induding measurements and imaging should be completed to assess disease (ontrol. • Visual fields should be repeated at least annually once reliable tests can be obtai ned. PATlENT EDUCATION • The Pediatric Glaucoma and Cataract Family Assodation www.pgda.org o American Association for Pediatric Ophthalmology and Strabismus www.aapos.org PROGNOSIS • The prognosis Is variable dependlng on age at presentation and timing of surgery. The prognosis for congen itaI glaucoma is worse than the infantile presentation. • Patients who undergo angle surgery between 2-12 months of age tend ID achieve better lOP control than those who undergo surgery before or after this age range. o Intraocular pressure control can be achieved in approximately 80'!1. of cases, induding those on medications. • 40% of affected patients may maintain a visual awity of 20/40 or better (5)[C] COMPLICATIONS • Glaucomatous visual field loss • Deaeased visual acuity o Blindness o Anisometropia o Astigmatism • Myopia • Amblyopia • Cataract • Corneal scarring • Phthisis bulbi • Intractable pain

REFERENCES 1. Aponte EP, Diehl N, Mohney BG. Incidence and clinical characteristics of child hood glaucoma: A population based study. Arch Ophtha/mo/ 201 0;128:478-482. 2. Naroole-Nejad M, Ch ltsazlan F, KhoramIan Tusl B, et al. Genotyping results of lr.~nian PCG families suggests one or more PCG lod other than GCL3A, GCL3B, and GLC3C exist. Mol VIs 2009;15: 2155-2161. 3. Hollander DA, Sarfarazi M, Soilow I, et al. Genotype and p~enotype correlations in congenital glaucoma: CYP1 81 mutations, gonlodysgenesls, and clinic.al characteristics. Am 1 Ophtha/mo/ 2006;142:993-1 004. 4. Tanimoto SA. Brandt JD. Options In pediatric glaucoma after angle surgery has failed. Cutr Opin Ophthalmo/ 2006; 17:t 32-13 7. 5. Blglan AW. Glaucoma In children: Are we making progress? JAAPOS 2006;10:7-21.

ADDITIONAL READING • Papdopoulos M, Khaw PT. Advances In the management of paediatric glaucoma. Eye 2007;21:1319-1325.

.

CODES

ICD9 • 365.14 Glaucoma of childhood o 743.20 Glaucoma of childhood • 743.22 Buphthalmos associated with other ocular anomalies

CLINICAL PEARLS • Buphthalmos. corneal douding, blepharospasm, epiphora, and photophobia occurring in the first 3-4 years of life should alert the clinidan to the potentiaI diagnosis of congenital/infantile glaucoma. • Rapid myopic shift or asymmetric myopia in the infant and young child should lead the examiner ID consider the diagnosis of congenital glaucoma. • Amblyopia is the most common c.ause of visual loss. o Definitive management is surgical.

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CONGENITAL AND PEDIATRIC CATARACTS Harold P. Koller Christopher M. Fecarotta

~ BASICS DESCRIPTION • Any opacity of the crystalline lens is called a cataract • Can be congenital or developmental • Isolated or associated with anterior ocular segment dysgenesis • With or without systemic disease • Multitude of morphology including anterior polar, lamellar, nuclear, posterior lenticonus, persistent fetal circulation with vascularized plaque, anterior lenticonus, pulverulent. cerulean, sutural, total, and others - Known cause or inherited in approximately 6Q--70% of cases EPIDEMIOLOGY

lnddence In the US, the incidence is estimated to be 1.2-6 cases per 10,000.

RISK FACTORS • Intrauterine infections • Metabolic conditions • Family history • Trauma including birth trauma • Some genetic syndromes • Steroids • Uveitis

Genetia • The most common mode of transmission is autosomal dominant with variable penetrance. • Multiple genes are identified that, when mutated, can result in cataracts. Multiple additional loci are known without mapped genes. • Can also be autosomal recessive or X-linked recessive

GENERAL PREVENTION • Maternal vaccination can prevent certain infections that cause cataracts in newborns, but otherwise prevention is limited. • Prenatal ultrasound is unreliable. • Genetic testing not currently useful due to large number of possible genes but genetic counseling may be helpful in family planning. • Prevention of visual loss by early identification. All children born to a parent with known heritable cataract should be examined by an eye doctor in the first 2 days of life and followed serially thereafter.

188

PATHOPHYSIOLOGY Depends on the cause, but generally involves a loss of lens clarity in a specific region of the lens based on the time of intrauterine insult or the specific mutated gene. ETIOLOGY • Most commonly idiopathic • Most common known cause is genetic and many isolated otherwise idiopathic cataracts may prove later to be heritable • Other etiologies: Chronic corticosteroid use, genetic syndromes. metabolic disorders, and intrauterine infections are the most common COMMONLY ASSOCIATED CONDITIONS • Intrauterine infection - Rubella, varicella, toxoplasmosis, herpes simplex, bacterial, or fungal endophthalmitis, cytomegalovirus. • Metabolic disorders - Galactosemia, hypocalcemia, hypoglycemia, diabetes mellitus, mannosidosis, hyperferritinemia • Chromosomal -Trisomy 21, Turner syndrome, trisomy 13, trisomy 18, Cri du chat syndrome and many others • Renal disease - lowe syndrome, Alport syndrome, Hallermann-Streiff-Francois syndrome • Drug induced - Corticosteroids, chlorpromazine • Other -Microphthalmia, aniridia, retinitis pigmentosa, persistent fetal vasculature. retinopathy of prematurity, endophthalmitis

~ DIAGNOSIS HISTORY • History of parents seeing an abnormal pupillary reflex (leukokoria) directly or in a photograph • History of condition known to be associated with pediatric cataracts • Strabismus • Nystagmus • Cataract alone does not cause an afferent pupillary defect.

PHYSICAL EXAM • Visual assessment of each eye individually • Cycloplegic refraction • Slit-lamp biomicroscopy • Determination of the cataract's visual significance by quality of retinoscopy reflex, fundus view, and when possible, visual acuity • Examination of the optic nerve and retina • If unable to visualize the retina, B-scan ultrasonography is necessary to rule out persistent fetal vasculature, retinal detachment, and retinoblastoma • The size, location, density, and visual acuity are all considered in determination of therapy DIAGNOSTIC TESTS & INTERPRETATION Lab Initial lab tests • TORCH titers in bilateral congenital cases with systemic indicators • Consider galactokinase levels to rule out galactosemia in bilateral cases • Other tests as suggested by systemic or ocular examination Follow-up 1ft special considerations

Referral to geneticist if a systemic syndrome is suspected

DIFFERENTIAL DIAGNOSIS • Leukokoria - Retinoblastoma, toxocariasis, Coats disease, persistent fetal vasculature, retinal astrocytoma, retinochoroidal coloboma, retinal detachment, myelinated nerve fibers, uveitis, incontinentia pigmenti, toxoplasmosis

CONGENITAL AND PEDIATRIC CATARACTS

.

TREATMENT

MEDICATION • If the cataract is centJal but less than 3 mm, occlusion therapy over the opposite eye combined Ylith mydriatic drops (2.5% phenylephrine) can be an effective therapy. • A unilateral punctuatl! cataract often requires careful monitoring only.

ADDIT10NAL TREATMENT General Measures • If systemic disease is uncovered, referral to the appropriate pediatric subspecialist should be made. • Referral to genelidst if a systemit syndrome is suspected • Postoperative refractive correction and occlusion therapy are essential for visual rehabilitation. SURGERY/OTHER PROCEDURES • Larger, denser cenlr.!l cataracts that are more visually signifiCant require surgery • Pediatric cataracts are usually removed using mechanical a5piration tedlniques rather than phacoemulsification. • Primary posterior capsulotomy and anterior vitJectomy are indicated in any child not old enough to perform postoperative YAG laser. • Placing the IOL in ti1e capsular bag is best, but if that is not possible then sulcus fixation is acceptable. • Use of intJaocular lens implants in children under 1-2 years of age is rontroversial. • Contact lenses (usually silirone elastomer and rigid gas permeable lenses) or glasses In un!lateral or bilateral cases are acceptable alternatives to IOL implantation. Contact lens is the standard of care for children < 1 year old.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Amblyopia therapy is carried out in the standard manner depending on the density of visual loss. PATIENT EDUCAT10N

The Pedlat~c Glaucoma and Cataract Family Association: tmp:/M'Nw.pgcfa.org.

• Paries MM, Johnson DA. Reed GW. Long·term visual results and complications In ch lldren with aphaIda. A function of cata iclct type. Ophthalmology 1993;100(6):826-84(); disc p 8-W-1. • Awner S, Buckley EG, DeVaro JM, et al. Unilateral pseudophakia in children under 4 years. 1 Pediatr OphthalmoJ Str.Jbismus 1996;33(4):23o-236. • Huang Y, DalY, WU X. et al. TOldc anterior segment syndrome after pediatric cataract surgery. 1AAPOS 201 0;14(5):444-446.

PROGNOSIS Depends on the presence of roncomitant ocular disease, age of onset, length of time of visual axis occlusion, and density of amblyopia.

. . CODES

COMPUCATlONS

ICD9

• Most common romplications are posterior capsule/anterior vitJeous face opadfitation and aphaticlpseudophakic glaucoma. • Other complications lndude hyphema, l~s Incarceration In the Incision, pupillary distortion, vitreous hemorrhage, retinal hemorrhages. retinal detachment, intraocular lens subluxation, and endophthalmitis.. • Later complications induding aphakic or pseudophaklc glaucoma can a~se years later In up to 30% of cases. Highest risk if microphti1almia, nudear cataract or persistent fetal circulation. Average time of onset is 8 years postoperatively. Minimum annuaI lOP measurementeven if sedation/anesthesia required • TOldc anterior segment syndrome (TASS) causing postoperative romeal edema must be prevented with careful instJument and solution sterilization.

ADDITIONAL READING

• 366.00 Nonsenile cataract, unspecified • 743.30 CongenItaI cataract. unspedfled • 743.39 Other congenital cataract and lens anomalies

CLINICAL PEARLS • Congenital and pediatric cataracts can be caused by ocular developmental dysgenesis. intJauterine infections, metabolic syndromes, gene mutation, or as part of a muttlsystem syndrome. • Work-up for systemic disease or referral to a pediatric genetics speda list should be ronsidered as suggested by ocular and systemic evaluation. • Determination of a cataract being visually significant determines necessity for and method of treatment • Alter cataract surgery, patients should be followed closely for development of amblyopia, glaucoma, and other romplications..

• Taylor D, Hoyt CS.I'I!diatric ophthalmology and strabismus, 3rd ed. Philadelphia, PA: Elsevier Limited, 2005:441-457. • Wright KW. Lens abnormalities: Chapter 27 in pediatric ophthalmology and strabismus. In: Wright rYI, Spiegel PH (eds), 2nd ed. New York: SpringerVerlag, 2003:45G-480. • Tesser RA. Hess DB, Buckly EG. Pedlat~c cataracts and lens anomalies, Chapter 131n Harley's Pediatric Ophthalmology. In: Nelson LB, Olitsky SE (eds), 5111 ed. Philadelphia: Uppinrott Williams ll Wilkins, 2005:255-284.

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CONGENITAL HYPERPIGMENTED ABNORMAUTIES OF THE FUNDUS Ahmara V. Gibbons Alex V. Levin

~ BASICS DESCRIPTION • Congenital hyperpigmented lesions ofthe fundus are differentiated based on appearance, pattern, and distribution in the ocular fundus and are present at birth. • Includes: Grouped pigmentation (bear tracks), congenital hypertrophy of retinal pigmented epithelium (CH RPE), combined hamartoma ofthe retina, choroidal nevi, melanocytoma, chorioretinal scar (usually associated with hypopigmentation) EPIDEMIOLOGY • Grouped pigmentation: 1.2/100 (3)[C] • Congenital hypertrophy of Retinal pigmented epithelium (CH RPE): 5 per 1,000 (3)[C] • Combined hamartoma of the retina: Precise frequency in the general population is unknown (3)[C] • Choroidal nevi: 10-13 per 100 (4)[8[ • Melanocytoma: Frequency in population is generally unknown (4)[8] • Chorioretinal scar due to in utero toxoplasmosis: 1 in 10,000 live births (3)[C]

RISK FACTORS • CH RPE: Family history of Gardner syndrome (adenomatous polyposis coli) • Combined hamartoma of the retina and RPE: Family history of neurofibromatosis 2 Genetics • CH RPE lesions associated with mutations in the adenosis polyposis coli gene (APC. 5q21. autosomal dominant) if bilateral or >2 in one eye • Combined hamartoma ofthe retina and RPE is associated with mutations in the gene for NF2 (22q12.2, autosomal dominant}

190

GENERAL PREVENTION Genetic counseling (1 ,3) [B,C]

~ DIAGNOSIS

PATHOPHYSIOLOGY • Hyperpigmentation arises either from the neuroectodermal derived RPE or from melanocytes (neural crest) in the choroid -Grouped pigmentation, CHRPE, and combined hamartoma arise from RPE - Choroidal nevi arise from melanocytes in the choroid - Melanocytoma is a benign optic nerve tumor of melanocytes with abundant melanin • Migration and distribution of pigment containing cells may be dysfunctional during fetal development • Pigment-containing cells may be altered genetically and by systemic and external stimuli (e.g., trauma, infection)

HISTORY • History of prenatal infections (2)[C] • Family history of colon cancer, NF2

ETIOLOGY

DIAGNOSTIC TESTS lr INTERPRETATION Lab Initial lab tests None indicated Follow-up i special considerations • Genetic consult if genetic syndrome (2)[C]

• Mutated or abnormal genes (1 ,3)[B,C] • lnHammatory/infectious conditions causing chorioretinal scar • Idiopathic

COMMONLY ASSOCIATED CONDITIONS • CH RPE: Gardner Syndrome and Turcot Syndrome (adenomatous polyposis coli, tumors of the brain and spinal cord) Combined hamartoma of the retina and RPE is associated with iris hamartoma: Manifestations of NF2 include acoustic neuromas, meningiomas of the optic nerve, and presenile posterior polar cataracts. • Melanocytomas can be associated with iris melanocytomas, pupillary disfunction and corectopia, and secondary glaucoma (from spontaneous necrosis with the resultant pigment dispersion) (1, 5)[B,C] • Chorioretinal scar can be a manifestation of intrauterine infection, which may also affect central nervous system

• History of sarcomas, neurofibromas (1 ,2)[B,C] History about seizures. learning disabilities, and mental retardation • For chorioretinal scars inquire about maternal history of ingestion of contaminated raw or undercooked beef, lamb, or pork, blood transfusions, organ transplants. or exposure to cats.

PHYSICAL EXAM Full ocular examination including visual acuity, visual field testing (if age permits), and dilated funduscopic exam (3,4)[C,B].

• Choroidal nevi and melanocytoma require serial follow-ups (4)[8] and photo imaging for risk of malignant potential or advancement of disease. • Colonoscopy beginning at the age of 8 years if Gardner syndrome • Serial audiology if NF2

Imaging Initial approach • If combined hamartoma associated with NF2, MRl of brain - B-Scan and OCT may be used to evaluate hyperpigmented lesions Diagnostic Procedures/Other Molecular genetic testing as appropriate and available (2)[C[.

CONGENITAL HYPERPIGMENTEO ABNORMAliTIES OF TilE FUNDUS REFERENCES .

TREATMENT

MEDICATION None ADDITIONAL TREATMENT General Measures Amblyopia ltlerapy as indicated (1 )[B)

Issues for Refeml • If Gardner syndrome suspected: Gastroenterology (2)[C] • If NF2 suspected: O!Dminolaryngology and Neurosurgery (2)[C) • Activation of toxoplasmosis dlorioretinal scar: Consider Infectious Disease mnsultation • Progression of choroidal nevus or melanocytoma require referral to an OClllar Oncologist

1. Ellis FD. Selected pigmented fundus lesions of children. JAAPOS 2005;9(4):306-314. 2. lee DA. Higginbotham EJ. Clinical guide to comprehensive ophthalmology. New York: Thieme New York. 1999:478-485. 3. Taylor D. Paediatric ophthalmology. Oxford: Bladc.well Science Ltd, 1990:122-143, 153-154, 587-598, 61H20. 4. Shields CL. Furuta M, Mashayekhi A. et al. Clinical spectrum of choroidaI nevi based en age at presentation in 342 2 mnsecutM! eyes. Ophthamo/ogy 2008;115(3):546.e2-552.e2. 5. Yanoff M, Duker JS. Ophthalmology, 3rd ed. New York, NY: Mosby, 2008:511-516, 552-554,

935-936.

ADDITIONAL READING $

ONGOING CARE

FOLLOW-UP RECOM MENDA110NS Choroidal nevi and melanocytoma: Photo documentation and serial examination (4)[8] l'affenf Monitoring • Visual acuity • Phato dowmentation of tumor growth for potentiaI malignarn transformation

For more on Chorioretinal scars. see chapter Hypopigmented Lesions of ltle Fundus.

.

CODES

ICD9 • 224.0 Benign neoplasm of eyeball, except conjunctiva, cornea, retina, and choroid • 224.6 Benign neoplasm of choroid • 361.30 Retinal defect. unspedfied

CLINICAL PEARLS • If bilateral or multiple unilateral CHRPE, mnsider Gardner syndrome and inquire about fami~ history af mlon cancer. Consider colonoscopy. • If combined hamartomas of the retina and RPE, mnsider NF2. • If dloroidal nevi or melanocytoma, there is an extreme~ low chance of rna lignant transformation, however these lesions shou lei be observed with photodoCllmentatlon and se~al examinations. • In patients with chorioretinal scaring inquire about intrauterine infections. particularly Toxoplasma gondii exposure.

PA11ENT EDUCATION • Genetic counseling • VIsuaI acuity and low vision lrnerventlon as indicated - Report concerns regarding hearing or neurologic change if NF2

191

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CONGENITAL HYPERTROPHY OF THE RETINAL PIGMENTED EPITHELIUM [CHRPE] Hermann D. Schubert

~ BASICS DESCRIPTION • Congenital hamartiasJhamartomas: Placoid melanocytic lesions of ttle retinal pigment epithelium, solitary, grouped, or multiple in one or both eyes, the latter maybe associated with familial adenomatous polyposis (FAP) and - historically Gardner or Turcot syndrome (1). • Solitary lesions: Flat, well demarcated round, oval, or geographic wittl smooth or scalloped margins. The color is gray brown or jet black. with a surrounding halo of depigmentation and/or central depigmented lacunae which bare the underlying choroidal vessels. The depigmentation may progress to involve the entire lesion (1). The usual size is 1-2 disc diameters (DD). however. can occupy one entire quadrant of the fundus. Slow concentric enlargement has been noted and seems to be the rule (2) The most common location is superotemporal and equatorial. Macular involvement is rare. There are few. if any, systemic associations. (3). • Grouped lesions: Flat, well demarcated round, oval, or geographic smaller black spots (0.1-{).5 DD) arranged in groups reminiscent of "bear tracks". These are usually found in one sector. however can involve a large area of the fundus. Smaller lesions are found more posteriorly. larger ones are located peripherally. Bilateral involvement does occur. Cutaneous sectorial pigmentations. the lines of Blaschke, may be seen, suggesting patterns of pigmentary mosaicism in both eye and skin. There are no systemic associations (1-3). • Multiple small ovoid hyperplastic lesions associated wittl familial adenomatous polyposis (FAP): Slightly raised. oval. with irregular borders and fishtail shaped areas of depigmentation at one or both poles of the lesion. The lesions have a meridional orientation and haphazard distribution. Retinal invasion and glial, capillary and pigment epithelial proliferation and hypertrophy are typical. More than 4 widely spaced small ( 1 yea~. treatment dose. and pre-treatment morbidity (age. preexisting glaucoma or ocular hypertension and connective tissue disorders) (6)[C]. PATIENT EDUCATION • Crohn's and Colitis Foundation of Ame~ca- Patient lact sheet on eye diseases - http://Www.cda.orglframeviewernurl=.lmed ial pdi/FactSheetslt!jeS.pdf • A family history of IBD is an independent risk factor for the dM!Iopmem of Idiopathic weltls, scleritis, and lceratltls (7). PROGNOSIS • Good - Most patients with ocular manifestations of IBD are treatment-responsive at some IM!I and rna lntaln their 'llsual acuity. COMPUCATIONS o Glaucoma and cataracts secondary to long-term oraiJtopical steroids or prolonged intraocular inflammation • Marular edema secondary to inflammation o Phthisis bulbi in a chronically inflamed eye

REFERENCES

4. Ghanchi FD, Rembadrl!n BJ. Inflammatory bowel disease and the eye. Surv OphtiJalmol2003;

48:663-676. 5. Barrie 8, Regueiro M. Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel disease. lnffamm Bowel Dis

2007;13:1424-1429. 6. Chadhas V, Cruikshank I, Sw1ngler R, et al. Advanced glaucomatous visual loss and oral rortkosteroids. BMJ 2008;337:670. 7. Lin P, Tessler HH, Goldstein DA.. Family history of inflammatory bowel disease in patients with idiopathic ocular inflammation. Am J Oi/lthalmol

2006;141(6):1097-1104.

ADDITIONAL READING • Latkanlty PA. Jabs DA. OOJ lar manifestations of inflammatory bowel disease. In: Bayless TM, Hanauer SB, eds. Advanced therapy of irrflammatory bowel disease. Hamilton, Ontario: BC Dedcer Inc.,

2001:275-277.

.

CODES

ICD9 • 555.9 Regional enteritis of unspecified site • 556.8 Other ulcerative colitis • 558.9 Other and unspedfied noninfectious gastroenteritis and colitis

CLINICAL PEARLS • Antet1or uveitis Is the most common dlnlcally encountered ocular manifestation of IBD. • Treatment witll topical or systemic corticosteroids is usually effective in controlling oOJiar inflammation secondary to IBD. • Infection must be ruled out before starting topical oOJ lar steroid draps. • Glaucoma and cataract are long-1erm complications af inflammation and/or topical or systemic steroid therapy.

1. Bernstein CN, Blanchard JF, Rawsthome P, etal. The prevalence of extraintestinal diseases in inflammatory bowel disease: A population-based study. Am J Gastroentero/2001; 96(4):1116-1122. 2. McCannel CA. Holland GN, Helm CJ, et aI. Causes of uveitis in the general practice of ophthalmology. Am J Ophthalmol 1996; 121 :35-46. 3. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: Clinical features and the role of HLA genes. Gasrroenrero/ogy 2002;1 23(3):714-718.

227

c

CROUZON SYNDROME Deepak P. Grover

~ BASICS DESCRIPTION • Crouzon syndrome, a craniosynostosis disorder, is characterized by premature closure of calvarial and cranial base sutures, as well as those of the orbit and maxillary complex. • Distinctive malformations of the skull and facial region are its hallmark. EPIDEMIOLOGY lnddence 1 case per 60,000 live births.

Prevalence 1 case per 25,000 population.

RISK FACTORS

Genetia • It may be transmitted as an autosomal dominant disorder with complete penetrance and variable expressivity, or appear as a new mutation. Crouzon syndrome has no race or sex predilection. • Caused by mutations in the fibroblast growth factor receptor-2 (FGFR2) gene, which is mapped to chromosome locus 1Oq2 5-1 Oq26. • 50% of incidents are not inherited and are the result of new mutations.

GENERAL PREVENTION Genetic counseling. PATHOPHYSIOLOGY Premature closure of cranial sutures. most commonly the coronal and sagittal sutures. results in abnormal skull growth of the orbits and maxillary complex. The degree of deformity is dictated by the order and rate of suture fusion. Growth perpendicular to a fused suture is restricted promoting compensatory growth at the remaining open sutures (1)[B]. ETIOLOGY See "Genetics.· COMMONLY ASSOCIATED CONDITIONS • Acanthosis nigricans is the main dermatologic manifestation of Crouzon syndrome. -Characterized by thickened, velvety, light-brown to black markings on the neck, under the arms, or in the groin - Detectable after infancy

228

~ DIAGNOSIS HISTORY • Craniofacial abnormalities are often present at birth and may progress with time. • Headaches and loss of vision secondary to elevated intracranial pressure • Decreased mental function • Visual disturbance secondary to excessive exposure of cornea or conjunctiva leading to ocular redness and irritation or burning sensation • Unexplained loss of visual acuity or double vision • Hearing loss secondary to ear canal stenosis or atresia PHYSICAL EXAM • Common ophthalmic features - Proptosis secondary to shallow orbits - Divergent strabismus or exotropia - Ocular hypertelorism - Exposure keratitis or conjunctivitis • Common facial features - Midfacial hypoplasia secondary to small, underdeveloped maxilla - Beaked nose - Short upper lip -Relative mandibular prognathism secondary to protrusion of the lower jaw • Other manifestations - Upper airway obstruction - Obstructive sleep apnea which can often present in infancy - Papilledema or optic atrophy secondary to elevated intracranial pressure - Progressive hydrocephalus - Chronic tonsillar herniation - Hearing loss secondary to recurrent ear infections - Crowding of the upper teeth - V-shaped maxillary dental arch - Narrow, high, or cleft palate - Bifid uvula - Cervical vertebral body fusions

DIAGNOSTIC TESTS & INTERPRETATION

Lab • Molecular analysis for FGFR2 mutation -Although the mutation is present in more than 50% of patients with Crouzon syndrome, it may also be present in Apert syndrome, Pfeiffer syndrome, and Jackson-Weiss syndrome. -All patients with associated acanthosis nigricans have an Ala391 Glu mutation within the transmembrane region of the FGFR3 gene.

Imaging Initial approach • Skull radiography- to show synostosis, craniofacial deformities, digital markings on skull, widening of hypophyseal fossa, small paranasal sinuses. maxillary hypoplasia, and shallow orbits • Spine radiography- to show fusion of the vertebral bodies and posterior elements • limb radiography- to demonstrate subluxation of the radial head • CT head/orbits with 3-dimensional reconstruction to define pathologic anatomy • MRl brain -to show corpus callosum agenesis and optic atrophy Follow-up a spec:ial cansideretions Genetics evaluation.

Diagnostic Procedures/Other • • • • • •

laryngologic examination with audiography Sleep study to evaluate for obstructive apnea Ophthalmologic examination General physical examination with ECG Psychiatric examination and psychological testing EEG -low-voltage, increased convulsive excitability

Pathological Findings • Immunohistochemical analysis of cranial sutures, performed with labeled anti·FGFR2 antibodies, demonstrates that sutures obtain lower levels of FGFR2 activity in both stenosed and nonstenosed sutures. • Histological features of acanthosis nigricans demonstrate hyperkeratosis, acanthosis, and papillomatosis. There are increased pigment cells in the upper dermis of the basal layer.

CROUmN SYNDROME DIFFERENTlAL DIAGNOSIS • Apert syndreme -Craniosynostosis combined with s~actyly of t11e hands and feet involving second, tl1ird, and fourth digits • Heiffer syndrame -Craniosynostosis combined with broad thumbs and great toes, complex cardiovascular malformations and variable partial soft tissue syndactyly of the hands and feet • C111penter qrndrom•

-Craniosynostosis combill@d with craniofacial dysmorphism, finger and toe abnormalities. heart defects, growth and mentaI retardation. • Saethre-Chotzen syndrame - Cr.miosynostosis combined with low-set frontal hair Iine. deviated nasal septum, wriable facial asymmetry and partial cutaneous syndactyly

rJ

TREATMENT

ADDITlONAL TREATMENT General Meuutes • Early detection and management of amblyopia and refractive error • NasaI continuous positive airway pressure device to rei ieve obstructive sleep apnea • Nasopharyngeal airway as a better tolerated treatment modality in the management for obstructive sleep apnea (2)[BJ • Speech mana~ent Issues for Refetral • Neurosurgeon • Neuroradiologist • Neurologist • aphthaImologist • 0romaxillofacial surgeon • Genetic specialist • Psychiatrist • Stomatologist • L.aryngalogist

SURGERY/OTHER PROCEDURES • Cranlofadal and neurosurgical Intervention w1tl1 t11e goal to stage reconstruction to correlate witl1 facial growth patterns, visceral function, and psychosocial development (1)[BJ. -In the first year of life, it is preferable to release the synostotic sutures of the skull to allow adequate aanlaI volume to promote brain growth and expansion. This can be performed with fronto--contraction. This can be done in the absence of a deviation in primary gaze or adjusted to eliminate a deviation if present.

IN-PATIENT CONSIDERATIONS None

•

COMPLICA110NS o Recession of the medial rectus more than 6 mm may cause conserutlve exatropla. • Amblyopia

ADDITlONAL READING • Isenberg S, Urist MJ. Clinical observations in 101 consecutive patients with Duane's retraction syndrome. Am J Ophthi/mol1972;84:419. • Jampolsky A. Duane syndrome. In: Rosenbaum AI., Santiago AP, eds. Clinical srrablsmus matMgement: Ptindples and surgical techniques. Philadelphia: Saunders, 1999:325-346.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Follow the child for the development of amblyopia, strabismus in the primary position, or a face tum. l'atient Monitoring Periodic for assessment of vision and aIignment

.

PATIENT EDUCATION o http:Jtwww.expelienceproject.com/groups/Have· Duane-Syndrome/97737 • http:Jihealth.groups.yahoo.CDmfgroup/duanesl

CLINICAL PEARLS

PROGNOSIS o Surgery can help to reduce or eli minalE an assoda!Ed face tum. • Few patients show Improvement In abduction following surgery and some patients undergoing medial rectus recession may have a deaease in adduction. In patierrts with significant co-contraction, large over-corrections can occur following mediaI rectus recession. • Excellent prognosis for vision If amblyopia and refractive error addressed o Su ~ k:al results can be very sillisfactory.

CODES

ICD9 378.71 Duane's syndrome

• Most children with Duane syndrome have no strabismus in the primary straight ahead position. • Duane syndrome does not usually worsen with age.

259

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DYSLEXIA Michael D. Tibbetts

~ BASICS DESCRIPTION • Dyslexia is a primary reading disorder. It is characterized by difficulty in understanding and using alphabetic and logographic principles to acquire accurate and fluent reading skills - Results from a written word processing abnormality in the brain - Not explained by sensory deficits, cognitive deficits, lack of motivation or lack of adequate reading instruction - Historically termed "word blindness,· but most commonly due to deficit in auditory processing of language (phonological processing) and not visual processing -Word reversals and skipping words result from linguistic deficiencies rather than visual or perception disorders

EPIDEMIOLOGY Prevalence • In a population, reading ability and reading disability occur along a continuum, with reading disability representing the lower tail of the distribution • Depending on definition, 5-17% of children affected; boys more than girls -Similar rates across languages • Approximately 80% of people with learning disabilities have dyslexia

RISK FACTORS Genetics • Strongly heritable (54-75%) - 68% concordance in identical twins and 40% of individuals with affected parent or sibling - Heritability greater among children whose parents have higher education level • Polygenic inheritance -At least 9 associated loci

GENERAL PREVENTION Early identification and intervention key to improving outcomes

EnOLOGY • Disorder within the language system, specifically phonological processing: - Disruption of left hemisphere posterior brain systems while performing reading tasks - Increased reliance on ancillary brain regions including frontal lobes and right hemisphere posterior circuits • Vision problems can interfere with the process of learning. • However, vision problems are not the cause of primary dyslexia or learning disabilities.

260

COMMONLY ASSOCIATED CONDITIONS • Some children may have visual problems that contribute to primary reading or learning dysfunction -Treatable ocular conditions include: o Strabismus o Amblyopia o Convergence and/or focusing deficiencies o Refractive errors

~ DIAGNOSIS HISTORY • In young children, language delay or not attending to the sounds of words: -Trouble learning letters of alphabet or nursery rhymes - Confusing words that sound alike or mispronouncing words • In older children, slow and laborious reading and writing • Discrepancy between general intelligence (IQ) and standardized reading test scores

PHYSICAL EXAM • If a child has suspected learning disabilities, child should be evaluated for medical problems which could affect the child's ability to learn • Children with dyslexia should have hearing and visual screenings. according to national standards for all children -Visual screening with non-letter symbols may be necessary for testing children with dyslexia • Children with dyslexia have the same visual function and ocular health as other children (l)[A[ - Dyslexia is not caused by subtle eye or visual problems including (2)[A[: -Visual perceptual disorders - Refractive error - Abnonmal focusing - Jerlcy eye movements, - Binocular dysfunction - Misaligned or crossed eyes • Readers with dyslexia may have saccadic eye movements and fixations similar to beginning readers but show normal saccadic eye movements when content is corrected for ability - Saccadic patterns are result of reading disability but not the cause

DIAGNOSTIC TESTS & INTERPRETATION Imaging Currently, there is no indication for imaging in the standard evaluation of dyslexia or other learning disorders_

Diagnostic Procedure~th~r • Dyslexia as well as other learn1ng disorders should not be diagnosed by physicians but by educators. psychologists, or neuropsychologists with specialized, comprehensive assessments. • Standardized tests of reading including: -Comprehensive Test of Phonological Processing in Reading -Woodcock Johnson Tests for word decoding -Gray Oral Reading Test for fluency • In the future, the combination of standardized neurocognitive tests, neuroimaging, genetic and familial information may improve diagnosis and allow for earlier intervention.

Pathological Findings • Functional neuroimaging studies have revealed differences in brain function and connectivity that are characteristic of dyslexia: (3) - Reduced or absent activation of left temporoparietal cortex -Atypical activation in other regions including: o left prefrontal regions associated with verbal working memory o left middle and superior temporal gyri associated with receptive language o left occipito-temporal regions associated with visual analysis of words and letters. • Experimental functional neuroimaging studies have demonstrated brain plasticity associated with effective intervention for dyslexia - Neuroimaging studies have not revealed any differences in the brains of children who do and do not respond to treatment

DYSLEXIA DIFFERENTlAL DIAGNOSIS • Other Important reasons for reading failure on the population levellndude: - Reduced vocabulary and strategies needed for text comprehension - Reduced motivation to read - Both these reasons are often tied to sodoeconomlc factors at home and at sdlool • Attention deficit hyperactivity dborder (ADH D) • Aphasia • Auditory processing disorder • Less common reasons indude visual problems sud1 as strabismus, amblyopia, and refractive errors. • Other conditions such as convergence lnsufflclency and poor accommodation (both of which are rare in children under age 1Dyears) can interfere with the physical act of reading but not decoding and comprehension.

rl

TREATMENT

ADDITlONAL TREATMENT General Meuutes • Multidisciplinary evaluation and management • Explidt and systematic intensive instruction in small groups in phonologicaI awareness and decoding strategies -Improvements more likely ln younger children (ages 6-8 years) than in older children • Providing accommodations for older d1ildren including exllll time for reading. spell d1Kk computer programs. tape recorders • Vision training is not a primary or adjunctive ther.~py for dyslexia (4)[8 [ • Scientific evidence does nat support the following alternative therapies for improving the long-term educational performance efficacy: - Eye exerdses - BehavioJal vision theJapy - Spedal colored or tintl!d filtl!rs or lenses

lssllfls for llflfwral • Patients with suspected learning disabilities should be referred for funher educatlonaI, psychological, or other appropriate evaluation. • If vision problem is suspected, children should be referred to an ophthalmologist with experience in assessment and treatment of children.

COMPLEMENTARY & ALTERNATIVE THERAPIES Scientific evidence does not support alternative therapies aimed at visual training.

3. Shaywitz SE, Shayv.itz BA. Pugh KR, et al. Functional disruption In the organization af the bJaln for reading In dyslexia. Proc Nall ACildSd US A 1998;95(5~2636-2641. 4. Barrett B. A critical evaluation of the evidence supponing the practice of behavioural vision therapy. Ophthalmic Physio/ Opt 2009;29(1):4-25. 5. Schatschnelder C, Torgesen JK. Using our current understanding of dyslexia to support early identification and intervention. J ChUd Neurol 2004;19(1 0}:759-765.

•

.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Multidisciplinary management by educators PATIENT EDUCATION • The lntl!rnational Dyslexia Association (http:flwww. interdys.org) PROGNOSIS • Persistent ch ronlc condition, not a tr.~nslent developmental lag • A student who fails to read adequately in the 1st grade has a 90% probability of reading poorly in 4th grade and a 75% probability of reading poorly in high sd1ool • For students with dyslexia, early Intervention (before the 3rd glillie) is key to improving reading ability (5) [C]

CODES

ICD9 • 368.DO Amblyopia, unspedflecl • 378.9 Unspedf!ed dborder of~ movements • 784.61 Alexia and dyslexia

CLINICAL PEARLS • Dyslexia is a primary reading disorder from a word processing abnormality in the brain. • Dyslexia is not due to a llisual problem. • It Is Important to recognize the signs and symptoms of dyslexia earty so that affected children can receive appropriate instruction and improve their long·tl!rm reading ability.

REFERENCES 1. Helveston EM, Weber JC, Miller K. et al. Visual function and academic performanee. Am J Ophtha/moi 1985;99(3):346-355. 2. Polataj leo HJ. Visual-ocular control of normal and learning disabled children. Dev Med Child Neuro/ 1987;29(4):477-485.

261

I

EAI.B DISEASE P. KumarRao

~ BASICS DESCRIPTION An idiopathic obliterative vasculopathy. The classic triad is a retinal phlebitis, associated witf1 peripheral retinal nonperfusion and vitreous hemorrhage, typically in young adults. EPIDEMIOLOGY Incidence • Most commonly reported in India and the Middle East. • In India, it occurs in 1/2 50 patients witf1 eye disease. • It usually occurs in adults 2D-30 years old. • Prior studies suggested a higher incidence in men; however recent reports suggest a more even distribution between men and women.

RISK FACTORS Living in areas such as India and the Middle East. PATHOPHYSIOLOGY A nonspecific obliterative vasculitis. A hypersensitivity to tuberculin protein has been suggested, and tubercle bacilli have been identified in pathology specimens. COMMONLY ASSOCIATED CONDITIONS Myelopatf1y, ischemic stroke, hemiplegia, multifocal white matter abnormalities, and vestibuloauditory dysfunction have been reported.

262

~ DIAGNOSIS HISTORY The most common symptoms include decreased vision and cobwebs or floaters. PHYSICAL EXAM • Retinal phlebitis appears as vascular sheathing with adjacent nerve fiber layer hemorrhages and hard exudates. • Over half of patients will have bilateral disease. • Anterior chamber cell and flare with keratic precipitates may be present. Vitreous debris and cells, as well as vitreous hemorrhage, can be seen. • Cystoid macular edema may be present. • Non perfusion in the temporal periphery is typical and is associated with other microvascular changes such as microaneurysms, venous shunting, venous beading, hard exudates, and cotton wool spots. Neovascularization of the disc or elsewhere in the retina is present in up to 80% of patients. Neovascular glaucoma may also occur. DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests No specific testing can determine the diagnosis; however Eales disease is a diagnosis of exclusion and testing should be done to rule out causes of vasculitis (see Differential Diagnosis section). Follow-up & special considerations lumbar puncture (not routinely needed) shows pleocytosis of CSF. In addition, MRI and CT imaging may be used to identify CNS lesions.

Imaging Initial approach • Fluorescein angiography (FA) is helpful to analyze presence of active vasculitis, vascular damage, and to look for areas of nonperfusion and neovascularization. • OCT may reveal cystoid macular edema and/or epiretinal membranes. Follow-up & special considerations Patients should be monitored for neovascularization of tf1e retina, iris, and anterior chamber angle. Retinal neovascularization may lead to vitreous hemorrhage. Epiretinal membranes may develop after pan-retinal photocoagulation (but may also occur without laser photocoagulation).

Diagnostic Procedures/Other • Eales disease is diagnosis of exclusion and therefore entities in the differential diagnosis must be ruled out with appropriate history, physical exam, and ancillary testing. • MRl testing of the CNS may reveal multifocal white matter abnormalities.

DIFFERENTIAL DIAGNOSIS • Siclde cell disease. • Diabetes mellitus. • Branch retinal vein or artery occlusion. • Retinal embolization. • Retinopathy of prematurity. • Familial exudative vitreoretinopathy. • Hyperviscosity syndromes (e.g., leukemia). • Ocular ischemic syndrome.

EALES DISEASE • • • • • • •

• • •

• • • • •

Carotid-cavernous fistula. Multiple sclerosis. Toxemia of pregnancy. Sarmidosis. Collagen-vaswlar disease. vasculitis secondal) to infection. Uveitis. Blrdshot retlnoc:horoldopathy. Toxoplasmosis. Acute retinal necrosis. Long-standing retinal detachment Retinitis pigmentosa. Retinosch isis. Choroidal melanoma or hemangioma. lncondnenda plgmentl.

rl

TREATMENT

ADDITIONAL TREATMENT

lmle.s for Refe«al CNS findings warrant a referral to neurology.

COMPLEMENTARY 8t ALTERNATIVE THERAPIES Thyroid extract. osteogenic hormones. androgenic hormones, and .systemic steroids and antioxidant vitam ins A. C, and Ehave been suggested. None have been prt11151 effective in lt1e treatment of this disease. SURGERY/OntER PROCEDURES • Pa nretinal photocoagulation for neovascular complications is necessary. • VJtrectomy and membrane removal may be considered for eplretlnal membranes. • Both oral steroids and intrllvitreal triam(inolone has been used to stabilize vascular leakage. • lntravitreal bevacizumab has been used to induce regression of neovaswlarization.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Patient Monitoring Patients should been followed every 3 to 12 months, depending on the extent of nonperfusion and neovascularization. PATIENT EDUCATION Patients should be tauglrt the symptoms of vitreous hemorrhage. such as sudden onset of floaters. Early detection and treatment of vitreous hemorrhage and neovascularization can allow laser photocoagulation, which may prevent the tr.~ctional complications such as retinal detachment or neovascular glaucoma. PROGNOSIS The majority of patients maintains 20140 vision or better with disease stabilization. COMPLICATIONS Retinal neovascularization, rhegmatogenous retinal detachment.. vitreous hemorrhage, and traction retina I detachment can also OCOJr.

3. lshaq M, Feroze AH, Shahid M, et al.lntravitreal steroids may fadlltate treatment of Eales' disease (idiopathic retinal vasculitis): An interventional tase series. Eye (Lone/) 2007;21(11):1403-1405. E·pub Sept 15, 2006. 4. Therese ICI... Deepa P, Therese J, Bagyalakshmi R, Biswas J, Madhavan HN. Association of mycobacteria with Eales' disease. lnd 1 Med Res 2007;126(1):56-62.

f ; coDES ICD9 • 362.18 Retinal vasculitis • 379.23 Vrtreous hemorrhage

CLINICAL PEARLS • Suspect Eales disease in young men from India who have no other underlying systemic disease that could cause retinal neovaswlarization.

REFERENCES 1. Chanana B, Azad RV, Patwardhan~ Role of intravitreal bevadzumab in the management of Eales' disease. lnt Ophtha/mal 201 0;30(1):57-ii1. E·pub Jan 23, 2009. 2. Das T, Pathengay A. Hussain N, Biswas J. Eales disease: Diagnosis and management. Eye

2010;24:472-42.

263

I

ECTOPIA LENTIS Dorothy H. Hendricks

~ BASICS DESCRIPTION • Displacement of the lens. • This may be divided into subluxed lens, which is partially displaced, and luxated or dislocated lens, which is completely displaced. • May be an isolated anomaly, or associated with various systemic diseases or trauma. EPIDEMIOLOGY lnddence • Marfan disease 4-611 00,000 births (1) and approximately 6D-75% have ectopia lentis. • Homocystinuria 1/200,000 births (1) and approximately 80-85% have ectopia lentis.

Prevalence Unknown.

RISK FACTORS • Trauma. • Family history. • Marfan syndrome • Type 1 Ehlers-Danlos. • Weill-Marchesani • Homocystinuria. • Hyperlysinemia. • Sulfite oxidase deficiency. • Molybdenum cofactor deficiency. • Infantile glaucoma with buphthalmos. • Persistent ocular fetal vasculature. • Coloboma of ciliary body. Genetics • Isolated ectopia lentis can be autosomal dominant due to mutations in the fibrillin 1gene (FBN1, 1Sqll), the same gene involved in Marfan syndrome (1). • An autosomal recessive form of isolated ectopia lentis is associated with mutation in ADAMTSL4 gene (1 q2 1) (l). • Ectopia lentis et pupillae is autosomal recessive (3), gene unknown. • Weill-Marchesani may be autosomal dominant due to mutation in FBN 1 or autosomal recessive due to mutations in ADAMTS 10 (19p 13.3) or ADAMTS 17 (15q24) (4). • Type 1 Ehlers Danlos is due to mutations in collagens COLSA1, COLSA2, or COL1A1. • Homocystinuria is autosomal recessive and linked to the gene coding cystathionine beta-synthase (21 q22.3) (1). Other less common disorders of cysteine metabolism may also be associated with ectopia lentis. • Mutation in the sulfite oxidase gene (SUOX, 12q 13.1 3) cause autosomal recessive sulfite oxidase deficiency (5).

264

• Hyperlysinemia is caused by mutation in the alpha-aminoadipic semialdehyde synthase gene (AASS, 7q31.3)(6). • Virtually any form of glaucoma resulting in buphthalmus may rarely be a cause of ectopia lentis. The genetics of the underlying disorder determine the inheritance pattern. The same holds true for other rare syndromic causes of ectopia lentis and coloboma. • Persistent ocular fetal vascular is usually not genetic (see chapter).

GENERAL PREVENTION • Genetic counseling. • Some recommend restricted activity or protective polycarbonate lens in patients with systemic conditions associated with ectopia lentis. • Some forms of homocystinuria may respond to vitamin B6, methionine-restricted diet. betaine, or supplementary cysteine (1 ). -This treatment has been shown to reduce the incidence of lens dislocation.

PATHOPHYSIOLOGY

~ DIAGNOSIS HISTORY • Family history of ectopia lentis or any of the above-mentioned associated conditions. • History of ocular trauma.

PHYSICAL EXAM • Full ocular examination including slit lamp examination pre- and post-dilation. • Pupil position (e.g., corectopia). • Assess if zonules absent, broken, or stretched. • Assess if lens edge flat, round, crenulated. • Measurement of intraocular pressure. • Cycloplegic refraction and assessment of vision: Can refract through aphakic (with or without pharmacologic mydriasis) or phakic visual axis for best vision. • Full physical exam for systemic associations.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

• Traumatic rupture of zonules. • Congenital zonular deficiency (e.g., ciliary body coloboma). • Defective zonules that results in weakening. - Marfan-defect in fibrillin. - Eh lers-Danlos-defect in type V collagen. - Homocystinuria-zonules deficient in cysteine.

lnitiall111b tests • None if history of ocular trauma (ectopia always unilateral). • All patients without clear family history or diagnosis and no trauma should have urine/blood homocysteine levels as risk of stroke/death under general anesthesia. Follow-up 1ft special considerations • Genetic consult for further work up and evaluation if warranted. - Consider cardiology consultation.

COMMONLY ASSOCIATED CONDITIONS

Imaging

Weakening or stretching of the zonular attachments lens (1).

ETIOLOGY

• Marfan syndrome: Aortic root dilation, Marfanoid habitus, pectus excavatum/carinatum, and other features. • Eh lers-Danlos: joint laxity, •cigarette paper• scars of skin and other features. • Weill-Marchesani: short stature, cardiac abnormalities, abnormal hands • Homocystinuria: Developmental delay (50%), Marfanoid habitus, premature grey hair, hypercoagulability and other features. • Hyperlysinemia: Severe developmental delay. • Sulfite oxidase deficiency: Severe developmental delay.

Initial approach Consider echocardiogram if considering Marfan syndrome or Weill-Marchesani. Follow-up a special considerations • Follow for increased movement of lens, change in vision/refraction, and amblyopia. -Weill-Marchesani follow for progressive shallowing of anterior chamber and secondary closed angle glaucoma. -Glaucoma risk also in other forms of ectopia lentis (Marfan, persistent ocular fetal circulation, trauma).

ECTOPIA LENDS Diagnostic ProCIIrJu/WSIOthaT Molewlar genetic testing as indicated. Pathological Findings • Fibrill inopathy: Loss of periodidty in zonules with fibrillin staining. - Hamocystinuria and related disorders: PAS positive zonular material on lens edge and ciliary body. -Weill-Marchesani: Peripheral anterior synechia.

DIFFERENTlAL DIAGNOSIS Microspherophakia.

•

TREATMENT

MEDICATION • Hamocystinuria (see earlier}. • If lfns dislocared into anterior dlamber consider glaucoma treatment induding mannitol to shrink vitreous. topical steroids ID reduce inflammation, and short acting mydriatics with patient in supine position. After lens floats back. behind pupil, then pilocarpine. • Weill-Marchesani: Aggressive cydoplfgia (e.g., atropine) may deepen anterior chamber as short·term treatment. ADDITlONAL TREATMENT General Measures • Correction of refractive error (1 ). - Treatment of amblyopia if present Issues for Refet'l'81 • Genetic consultation. -Cardiology as indicated. - Metabolics consu Italion as indicated. ArlrJit:lonal Tllaraplfls Massage of mrnea may be needed to release lens dislocated Into anterior chamber. COMPLEMENTARY a ALTERNATIVE T11ERAPIE5 None. SURGERY/OTHER PROCEDURES • L.ensectomy and anter!or vltrectomy. - Typically poor zonule support prevents lens implantation in children (1). - Contact lens or spectades are then used for aphakic correction. -Weill-Marchesani: Early lensectomy advised if anter!or chamber deepening. - Use of argon laser iridoplasty or YAG laser lysis of zonu les has been reported.

IN-PATIENT CONSIDERATIONS Inftlel Stabilization • A.s needed for associated systemic diseases. - If lens in anterior chamber maintain supine position.

Admission Crltetffl • A.s indicated by systemic disease. -Admit all patients w1t11 homocystlnurla undergoing surgecy night before and after surgecy.

IV Fluids Hamocystinuria 1.5 x maintenance starting night before surgery and continuing through 1 night after.

Nursing Maintain supine position and strict bed rest as long as lens in anterior dlamber.

Discharge Criteria If lens is not returned to retropupillary position by medical means, lensectomy before discharge.

$

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Routine ophthalmic examination depending on degree of dislocation and presence of other pathology including amblyopia. l'lltient Monitoring • Cardiology, metabollcs, developmental services as needed. - Visual awity, intraocular pressure. DIET Methioni~nestricted diet in patients with hom~lnu~a.

PATIENT EDUCATION • Genetic counseling. • http://Www.marfan.cal and http://Www.marfan .o~marfanl. • http:/Jwww.mdjunctlon.comlhom~lnur!a. PROGNOSIS • Good visual prognosis with early intervention and routine follow-up. • Even in patients requiring lensectomy most achieve vision of 20/40 or better (1). -If not complicated by umreated amblyopia.

REFERENCES 1. Neely DE. Plager DA. Management of ectopia lentis

In children. Ophthalrnc/ Clln North America

2001 ;14(3):493-497. 2. Ahram D, Sato TS, Kohilan A, et al. Ahomozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis. Am J Hum Genet 2009;84:274-278. 3. Colley A. Lloyd IC, et al. Ectopia lends et pupillae: The genetic aspetts and differential diagnosis. J Med Genet 1991 ;Nov 28(11 ):791-794• 4. Faivre L Dollfus H. Lyon net 5, et al. Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am JMed Genet

2003;123A:204-207. 5. Kisker C, Schindelin H, Pad1eco A, etal. Molecular basis of sulfite oxidase defidency from the structure of sulfite oxidase. CeU 1997;91 :973-983. 6. Sacksteder KA, Biery BJ, Morrell JC, et al. ldentlftcatlon of the alpha-amlnoadlplc sem!aldehyde synthase gene, which Is defective In familial hyperlysinemia. Am J Hum Genet 2000;66:1736-1743.

.

CODES

ICD9 • 743.37 Congen itaI ectopic lens • 996.53 Mechanical complication of prosthetic ocular lens prosthesis

CLINICAL PEARLS • Trauma rarely cause bilateral ectopia lentis. • If considering surgery and diagnosis not clear, do urine and blood homocysteine measurement and ECG. • If cannot darify vision through phakic visual axis, consider aphakic correction with pharmacologic mydriasis as needed.

COMPUCATIONS Ambtjopia, glaucoma, retina I detachment (partiwlarly in patients with Marfan disease), lens dislocation.

265

E

ECTROPION Thaddeus S. Nowinski

~ BASICS DESCRIPTION • Outward turning/eversion of the upper eyelid margin. • Types: - Congenital. - Involutional (most common). - Paralytic. - Cicatricial.

EPIDEMIOLOGY lnddence

Pediatric Considerations Congenitai-Biepharophimosis, Downs, Ichthyosis, congenital eyelid eversion, facial dysmorphic syndromes.

ETIOLOGY

DIFFERENTIAL DIAGNOSIS • Thyroid ophthalmopathy. • Floppy eyelid syndrome.

COMMONLY ASSOCIATED CONDITIONS • Bells-Lyme

~ DIAGNOSIS

Bells palsy-25 per 100,000.

HISTORY • • • • • •

RISK FACTORS • • • • • •

Increased skin sun sensitivity. Lighter iris color. Diabetes. Hypertension. Stroke. Smoking.

PATHOPHYSIOLOGY • lnvol utional---florizontal eyelid laxity. • Cicatricial--skin contracture secondary to inflammatory or infiltrative dermatitis, tumor, previous eyelid, or facial surgery • Paralytic-Bell's palsy, herpes zoster, parotid gland surgery, surgery involving the 7th nerve. • Allergic-90% • High body mass index • Keratoconus on sleeping side

306

~ DIAGNOSIS HISTORY Chronic mucous secretion Foreign body sensation-worse upon awakening Eversion of upper eyelid during sleep Sleeps on affected side of face Snoring Smoking

• • • • • •

PHYSICAL EXAM • Downward pointing upper eyelashes-lash ptosis • Easily everted upper eyelid • Soft and rubbery consistency of upper eyelid tarsal plate • Horizontal laxity upper and possibly lower eyelids • Chronic papillary conjunctivitis of upper eyelid • Ptosis • Lagophthalmos with secondary corneal punctuate keratitis DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests Sleep study. Follow-up It special considerations

ALERT • Strong association of OSAHS and systemic sequelae. - Cardiovascular disease -Stroke -Obesity - Metabolic syndrome - Cognitive and emotional disorders - Drowsiness-related accidents

DIFFERENTIAL DIAGNOSIS Ptosis Chronic blepharoconjunctivitis Ectropion Vernal conjunctivitis Giant papillary conjunctivitis Superior limbic keratoconjunctivitis

• • • • • •

rJ

TREATMENT

MEDICATION First Line • Viscous ocular lubrication -Artificial tears, gel, ointment

Second Line Oral doxycycline 100 mg b.i.d.

ADDITIONAL TREATMENT General Measures • Bedtime patching/taping shut • Eye shield • (PAP unit

Issues for Refe"al Ophthalmologist 1-2 week.s.

FLOPPY EYELID SYNDROME Additional Tllfllilplfls

• OSAHS - Behavioral - Mandibular advancement di!Yice - Surgery induding UPPP, tonsillectomy, tracheostomy

SURGERY/OTHER PROCEDURES • Defer surgery If possible until after OSAHS treated • SurglcaI procedures -Full thickness eyelid resection (may also improvl! ptosis) -Horizontal eyelidfcanthal tightening • Recurrences and repeated surgeries common

(f) ONGOING CARE FOU.OW-UP RECOM MENDA110NS Ophthalmologist 1-2 weeks to monitor comea. PA11ENT EDUCATION Importance of treatment of obstructive sleep apnea is stressed to decrease OOJiar and systemic morbidity. PROGNOSIS Treatment of sleep apnea with CPAP unit may improve floppy eyelid syndrome and its associllled ocular and systemic pathologies.

REFERENCES 1. Pham T, Perry J. Floppy eyelid syndrome. CUlT Opin Ophtha/mo/2007;18:43o-433. 2. Cheung N, Wong TY. Obesity and eye diseases. Surv Of/ltha/mol 2007;52:180-195. 3. McNab A. The eye and sleep. Clin Exp 0/ilthalmol 2005;33:117-125. 4. Karakucuk S, Goktas S, Aksu M, et al. Ocular blood flow In patients with obstructive sleep apnea syndrome (OSAS). Graefes Arch Clin Exp 0/ilthalmol 2008;246:129-134.

a

Sea Alia (Tapic, Al1arithm, Electranic

~ Media Ele11en0

• W'IIWI.asaprs.org • Ectropion

.

CODES

ICD9 • 372.39 Other conjunctivitis • 374.10 Ectropion, unspedfied • 374.89 Other disorders of eyelid

ADDITIONAL READING • Ezra DG, Beamnsfield M, Sila M, et al. L.ong·term outcomes af surgical approaches to the treatment of floppy eyelid syndrome. Ophthalmology 201 0; 117:839-846. • Ezra DG, Beaconsfield M, Sira M, Bunce C, wormald R. Collin R. The associations af floppy eyelid syndrome: a case mntrol study. Ophthalmology 2010;1, 7:8314138.

CLINICAL PEARLS • Floppy eyeIid syndrome is associated with severe cardiovascular and cerebral sequelae of obstructive sleep apnea--hypopnea syndrome (OSAHS). • Floppy eyeIid syndrome may improvl! with CPAP therapy. • Floppy eyeIid syndrome is associated with severe ow lar sequelae including corneal, optic nerve, and glaucoma disorders..

COMPLICATIONS • Corneal abrasion, ulcet scarrtng, perforat!on • Optic neuropathy--nonarteritic • Glaummit-t'1ormaltension • Papilledema

307

f

FOREIGN BODY INTRAORBITAL Omaya H. Youssef

~ BASICS DESCRIPTION Intraorbital foreign bodies (IOFBs) occur as a result of a high-velocity penetrating injury or direct impalement of an object. EPIDEMIOLOGY The majority are male, typically of young age (less than 30 years old). GENERAL PREVENTION Education and protective eyewear. PATHOPHYSIOLOGY Traumatic insertion of a foreign body through the eyelid or conjunctiva. ETIOLOGY • Projectile, usually metallic, foreign bodies such as BB pellets and firearms • Penetrating trauma from nonmetallic foreign bodies, either organic (e.g., tree brandl, pencil) or inorganic (glass, plastic, or stone)

~ DIAGNOSIS HISTORY • A history of periocular trauma is usually elicited. • A delayed presentation from the time of injury is not uncommon, especially with children or patients who sustain trauma while under the influence of various substances. • A detailed history is essential in patients who present with orbital infections or inflammation.

308

PHYSICAL EXAM • Visual acuity can range from normal to complete loss of vision, depending on associated ocular and orbital injuries. • Afferent papillary defect may be present if optic nerve is involved. • Extraocular muscle underaction, if extraocular muscles are affected • Gaze-evoked amaurosis (with apical IOFBs) • Blepharoptosis • Proptosis • Orbital inflammation • Careful examination of the periocular skin and conjunctiva, especially the fornices, to identify entry wound DIAGNOSTIC TESTS & INTERPRETATION

Lab • Wound culture (aerobic, anaerobic, fungal) • Foreign body culture • CBC may reveal elevated serum white cell count secondary to chronic orbital inflammation

Imaging • Plain film radiographs for metallic IOFBs • CT - Excellent for identifying metal or glass - Safe in the presence of ferromagnetic metallic foreign bodies - lnorgan ic IOFBs (e.g., wood) can mimic air on CT - Quantitative CT with wide bone window settings can distinguish wood from low-density signals of air or fat

• MRl if CT scan is negative and non-metallic IOFB is suspected - MRl can be used to localize BBpellets, whidl are made of steel, and coated with copper or zinc • Ultrasound (US) can be used to localize the IOFB; however it does not image the orbital apex reliably. Follow-up ll special considerations • Orbitocranial extension should be ruled out, especially in children who have thinner orbital bones. - Coronal and parasagittal images should be obtained in suspected transorbital, intracranial penetration.

Diagnostic Procedures/Other Electroretinography (ERG) to assess for photoreceptor toxicity if iron or copper containing IOFB is adjacent to sclera.

Pathological Findings With organic IOFBs: Chronic inflammation with or without granulomatous reaction and fibrosis.

DIFFERENTIAL DIAGNOSIS • Orbital cellulitis • Idiopathic orbital inflammation • Orbital neoplasm (children)

FOREIGN BODY INTRAORBITAL

.

TREATMENT

MEDICATION • Broad-spectrum antibiotic tl1erapy wltl1 anaeroblc coverage. in Ulses of orbital cellulitis secondary to duonical~ retained IOFBs (more common witl1 organic IOFBs) • Antitetan us prophylaxis SURGERY/OTHER PROCEDURES • SurgiU!I removal depends on vtsual starus, composition of IOFB, and loti!ion within tl1e orbit o SurgiUII removal is ind lUlled for the following: - Neurological compromise - Ocular motility restriction - All organic IOFBs - Inorganic 10FBs if they are located in tl1e anterior orbit and are easily accessible o Inorganic 10FBs that are loti!ed posteriorly may be left in place, unless they are causing orbital complications. • l'!!rcutaneous US and fluoroscopy can be used intraoperatively to localize tl1e IOFB.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Ophthalmologist • Neurosurgeon (H intracranial involvement) PROGNOSIS • Vision loss is generally related to initial injury and not as a result of complications from IOFB or management. • Retained metallic IOFBs are usual~ well-tolerated and have a good vlsuaI prognosis. The exception Is metallic IOFBs containing copper, whid1 can cause a chronic suppurative orbital inflammation. • Organlc IOFBs have a higher Incidence of vision-t11reatening compliti!ions, and a higher risk of arbitaI and cerebral infections. COMPLICATIONS • Arutl! orbital cellulitis (usually from organic material such as wood)

• Ch ronlc suppurative arbltallnflammadon (from copper foreign bodies) • Sterile abscess o Orbitoartaneaus fistula • Orbital wall osteomyelitis • Cerebral infection

ADDITIONAL READING • Finlcelstein M,Legmann A. Rubin PA. Projectile metallic foreign bodies in the orbit: a retrospective study of epidemiological factors, management. and outcomes. Ophthalmolagy 1997;1 04:96-103. • Fulcher TP, McNab AA. Sullivan TJ. Clinical Features and Management of Intraorbital Foreign Bodies. Ophthalmology 2002;109:494-500. • Ho VH, Wilson MW, Fleming JC, et al. Retained Intraorbital Metallic Foreign Bodies. Ophthal Plast Reconstr Surg 2004;20:232-236. • Nasr AM. Haik BG. Fleming JC, et al. l'!!netrating Orbital Injury with Organit Foreign Bodies. Ophthalmology 1999;106:523-532. • Shelsta HN, Bilyk JR, Rubin PA. et aL Wooden Intraorbital Foreign Body Injuries: Clinical Charactet1st1cs and Outcomes of 23 Patients. Ophthal Plast lleconstr Surg 201 0;26:238-244.

.

CODES

ICD9 • 360.60 Rlreign body, intraocular, unspecified • 870.4 Penetrating wound of orbit witl1 foreign body

CLINICAL PEARLS • Rule out lntracranlallnvolvement of IOFB prior to removaL • All organic IOFBs should be removed. • Inorganic IOFBs that are easily accessible In the anterior orbit should be removed, while those in the posterior orbit can be left in place unless causing orbital com plicalions.

309

I

FOVEAL HYPOPlASIA Michael J. Bartiss

~ BASICS DESCRIPTION • Clinical condition characterized by an abnonnal funduscopic appearance of the macula and decrease or absence of tile foveal reflex and varying degrees of macular hypoplasia • Macular vessels often traverse near or across the normally avascular zone of the fovea. • Optic nerves and peripheral retina may appear normal. • Visual acuity typically in the 20/1 OQ-20/200 range but variable depending on degree of hypoplasia EPIDEMIOLOGY Unknown. RISK FACTORS • Commonly associated with albinism and aniridia • Family history

Genetics • When seen in combination with aniridia or albinism the genetics of those syndromes apply. Also reported with Axenfeld-Reiger spectrum. • Isolated autosomal dominant macular hypoplasia may be due to mutations in PAX6 (11 p13). • Autosomal recessive inheritance also reported including foveal hypoplasia with anterior segment dysgenesis (FHASD, 16q23.2-24.2).

GENERAL PREVENTION Genetic counseling and/or prenatal testing (if mutated gene known or syndrome recognized in family).

310

PATHOPHYSIOLOGY • Results from incomplete development of the fovea. • In albinism, the absence of melanin in the retinal pigmented epithelium leads to a failure of induction of proper macular development • In aniridia or isolated macular hypoplasia due to PAX6 mutation it is presumed that there is a failure of induction of a gene(s) downstream from PAX6, responsible for macular differentiation. ETIOLOGY Thought to result from incomplete embryologic development of the fovea, which typically develops in stages: • Stage 1: Indistinct pigmented area • Stages 2 and 3: Development of the annular reflex • Stage 4: Appearance of the foveal pit • Stage 5: Development of the foveal reflex COMMONLY ASSOCIATED CONDITIONS • Achromatopsia • Albinism • Aniridia • Less common: Axenfeld-Reiger • Nystagmus • Reduced vision

~ DIAGNOSIS HISTORY Poor vision, possible nystagmus. PHYSICAL EXAM • Full ocular examination including careful evaluation ofthe macula • Careful examination with indirect ophthalmoscope by noting presence or absence of annular ring and foveal light reflex and anomalous patterns of macular vessels • Assess vision, nystagmus DIAGNOSTIC TESTS 1r INTERPRETATION Lab

Initial lab tests None needed.

Follow-up a special considerations Consider molecular genetic testing where appropriate.

Imaging Initial approadl • OCT can be used for grading. -Widespread thickening of the retina ltlroughout the entire fovea with no difference in thickness from the surrounding macula - High reflectivity of the inner retina

FOVEAL HYPOPLASIA Diagnostic ProCIIrJu/WSIOthaT Visual f~eld, espedally Goldmann, may be helpful. Pathological Findings • Absence of foveal differentiation and red-free mne • Continuation of ganglion cell layer th roug holll mawIa • Associated with reduction in the th iclcness of the optic nerve and In the volume of gray matter In the vtsual cortex • Abnormalities in the length and mean surface area of the c:alcari ne fissure present in visual CDnex

DIFFERENTIAL DIAGNOSIS • Eplretlnal membrane • Macular drag (e.g.• retinopathy of prematurity, familial exudative retinopathy) • High myopia • Blonde fundus • Congenitally anomalous retinal vascular (e.g., macrovessel, tllrtl.lositv) • Optic atrophy with seCDndary macular neM! fiber loss • Optic nerve hypoplasia • Retinal/macular dystrophy

.

TREATMENT

MEDICATION None. ADDITIONAL TREATMENT

General Measures • Amblyopia therapy as indicated • Genetic CDunseling • If photophobia CDnsider Coming lenses

ArJtlltlonal Theraplu Maximization of vision potential with spectades. contact lenses. and/or low-vision aids.

COMPLEMENTARY a ALTERNATIVE THERAPIES None proven or indicated. SURGERY/OT11ER PROCEDURES • None for fovea I hypoplasia • Strabismus and nystagmus surgery as indicated (nystagmus surgery unlikely to yield great visual acuity improvement)

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • As needed for amblyopia and strabismus monlto~ng and treatment - Low-vision t'Villuation Patient Mot~lfDrlng • Monitor patients for associated conditions of aniridia and albinism and CDngenltal nystagmus • VIsual development and function • If asymmetric. amblyopia can ocwr. • Strabismus. PROGNOSIS • VIsual prognosis based on assodated conditions and degree of macular hypoplasia • Presence of anomalous blood vessels in macuIa (e.g., crossing midline raphe. extending close or through putative fovea) assodated with worse visual prognosis

ADDI110NAL READING • Brodsky MC, Baker RS, Hamed LM••Pediatric Neuro- 85%). Clinically correlates with ophthalmoplegia and ataxia.

Imaging • Consider MRI for differential diagnosis of brainstem infarction, Wernicke encephalopathy, brainstem encephalitis. • Rarely see brainstem signal changes in GBS. • May see enhancement of cranial nerves.

Pathological Findings Perivenular inflammatory infiltrate and demyelination

of peripheral nerves.

GUIUAIN-BARRE SYNDROME AIID ASHER SYNDROME YARIAIT DIFFERENTlAL DIAGNOSIS • Bralnstem encephalitis, Infarction, mass, or hemorrhage • Myasthenia gravis • DEmyelinating disease • Wem icke'sencephalopathy • Botulism • Cavernous sinus lesion

rl

TREATMENT

MEDICATION • For GBS

IN-PATIENT CONSIDERATIONS

REFERENCES

Initial Stabilization With typical GBS and ascending paralysis frequent

1.

monitoring of respiratory mtus and cardiac rhythm.

Admission Crit.eria All GBS patients except relatively stable F5 patients.

ALEIn • With GB5-ICU monitoring for potential respiratory failure or autonomic dysfunetion (arrhythmia). • Early intubation with progressive respiratory failure.

• Plasmapheresis (1)[A) • Intravenous immunoglobulin (2)[A] • No controlled trial of treatment in FS

Discharge Criteria

ADDITIONAL TREATMENT

•

GfHHH'illltiiNSUIWS

FOLLOW-UP RECOMMENDATIONS Continued follow up until recovery is complete or plateaued.

• ICU monitoring • Respiratory suppon • Monitoring for autonomic dysfunction

Additional Therapies • Physical therapy for weakness • Monorular ocd usion or prism for acute or nonresolving diplopia • Care for corneal exposure with fadal paresis

SURGERY/OlliER PROCEDURES With suboptimal recoveiY of ptosis or ophthalmoparesis-strabismus, or lid surgery.

Plateau in progression of weakness or improvement

ONGOING CARE

PROGNOSIS

• Gcod for signIllcant recovery wlthl n 3 months of onset with FS. Recovery often begins within 2 weeks. • Gcod for sign meant recovery with GBS. • A subgroup of GBS patients will have recurrent episodes or contln ued progression Into chronic im'lammatory demyelinating polyneuropathy (CIDP).

Guillain-Bar~ Study Group. Plasmapheresis and acute Guillain-BaiTI! syndrome. Neurology

1985;35:1096-1104. 2. Plasma ExchangeJSandoglobulin Guillain-Ba~ Syndrome Trial Group. Random lzed t~al of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barre syndrome. lancet 1997;349:225-230.

ADDITIONAL READING • Snyder LA, Rismondo V, Miller NR. The fisher variant of Gulli aln-Barre syndrome (Fisher Syndrome). 1 Neuro.()phthalma/2009;29:31 ~324. • Vucic: S, Kiernan MC, Cornblath DR. Guillain-Barre syndrome: An update. J Clin Neurosd 2009;16:

733-741.

.

CODES

ICD9 • 323.81 Other causes of encephalitis and encephalomyelitis

• 357.D Acute infective polyneuritis • 374.30 P1osls of eyelid, unspecified

I

329

GYRATE ATROPHY Avni Vyas

~ BASICS DESCRIPTION Gyrate atrophy is an autosomal recessive chorioretinal dystrophy that initially presents with nyctalopia and decreased peripheral vision during the first decade of life with progressive constriction of the visual field and eventual loss of central vision. EPIDEMIOLOGY Incidence • Rare disease • Most commonly reported in Finland with an incidence of approximately 1 in 50,000. • Generally, presents in the first decade of life

RISK FACTORS Has been diagnosed in several countries with the largest number of patients reported in Finland (l)IA]. Genetics • Autosomal recessive inheritance • Linked to chromosome 1Oq26, with more than 60 reported mutations PATHOPHYSIOLOGY • Patients have a deficiency of ornithine aminotransferase (OAn. which leads to a 10- to 20-fold increase in plasma ornithine levels. • It is proposed that high ornithine levels may be toxic to the retinal pigment epithelium (RPE). EnOLOGY Enzyme deficiency of OAT. COMMONLY ASSOCIATED CONDITIONS • EEG abnormalities and hair abnormalities have been reported in patients with gyrate atrophy. • Skeletal muscle changes have been reported on CT and MRI. • White matter lesions and atrophy have been noted on brain MRis.

330

~ DIAGNOSIS HISTORY • In the first decade of life. patients typically present with nyctalopia, decreased peripheral vision. myopia, and astigmatism. • In the second decade of life, patients develop posterior subcapsular cataracts. • Patients develop progressive constriction of their visual fields with advancing age. • Patients report a gradual decline in vision with loss of central visual acuity by the fifth decade. PHYSICAL EXAM • All patients with gyrate atrophy are myopic, generally with refractive errors-4.00 to -20.000. Many patients have astigmatism as well. • By adolescence, posterior subcapsular cataracts are evident. • Dilated fundus exam initially shows multiple round well-circumscribed areas of chorioretinal atrophy in the periphery and midperiphery of both eyes, generally in a symmetric pattern. • These areas coalesce with age and move towards the posterior pole, eventually involving the entire fundus. • Typically, there is a scalloped border between the remaining normal retina and the atrophic retina.

DIAGNOSTIC TESTS & INTERPRETATION

Lab Plasma ornithine levels should be checked and are generally 10 to 20 times higher than the general population.

Imaging • Fluorescein angiography typically shows hyperfluorescence of the atrophic areas with possible leakage at the margins between normal and atrophic tissue. - Optical coherence tomography may demonstrate cystoid macular edema or an epiretinal membrane.

Diagnostic Procedures/Other Early electroretinographic (ERG) testing shows reduced scotopic and photopic responses. By adulthood, ERG responses are nondetectable.

DIFFERENTIAL DIAGNOSIS Advanced choroideremia-This is an X-linked recessive disorder with atrophy of the RPE and choriocapillaris.

GYRATE ATROPHY

.

TREATMENT

MEDICATION FirstUne • Studies have suggesll!d that long-term tompliance with a low-protein, low-arginine dirt can slow the progression of chorioretinal degeneration (2)[A). However. even with good mmpi iance, there is still a progressive decline in retinal function. One study of sibling pairs showed that younger siblings with earlier mmmencement of arginine-restriction had slower progression mmpared with older siblings with later commencement of dietary modification (3)[A).

• Supplementation with vitam in 86 (pyridoxine) has also been suggested, with additional dietary protein restrittion based on ornithine levels. However, the majority of patients with gyrate atrophy are not pyridoxine responders. The dose of pyridoxine supplementation Is not well established. SecondUne Consider cataract extraction when the posterior subcapsular cataracts bel:orne vlsua lly slgnlflcant Patients should be educated that the poslllperative visual potential is limited by their retinal disease.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Gyrate atrophy is a chronic progressive disorder with progressive loss of vtsual arulty and peripheral vision. • Patients should be followed routinely for calllract and retina I evaluation. DIET See Treatment section. PATlENT EDUCATION Consider genetic munseling.

PROGNOSIS LDng-term visual prognosis is poor.

3. Kaiser-Kupfer ML. Caruso RC, Valle D. Gyrate atrophy of the choroid and retina. ArdJ Ophthlimo/ 2002;120: 1-46--153. 4. Talcki KK. Milton RC. The natural hi51ory of gyrate atrophy of the choroid and retina. Ophthalmology 1981;88:292--301.

.

CODES

ICD9 • 363.54 Central chorolda Iatrophy, tota I • 363.57 Other diffuse or generaliZ!!d dystrophy of dloroid, total • 368.60 Nlght blind ness, unspecified

REFERENCES

CLINICAL PEARLS

1. Potter MJ, Berson EL. Diagnosis and treatment of gyrate atrophy. lnt OphthaJmo/ Clin 1993;33: 229--236. 2. Kaiser-Kupfer ML. Caruso RC, Valle D, Reed GF. Use of an arginine-restricted diet to slow progresslonof visual loss In patients with gyrate atrophy.Arcfl Ofirtha/mo/ 2004;122:982--984.

• Early intervention with a low-protein, low-arginine dlet may help slow progression of the disease.

I

331

HAU.UCINATIONS, VISUAL Tulay Kansu

~ BASICS DESCRIPTION • Visual hallucinations are visual sensory perceptions wittlout external stimulation associated with ophthalmologic, neurologic, metabolic, toxic, and psydliatric diseases. • Charles Bonnet syndrome (CBS) is vivid, detailed, but nonthreatening hallucinations in visually deprived but cognitively unimpaired patients (1). EPIDEMIOLOGY lnddence The incidence of the Charles Bonnet syndrome varies among different population groups. Common in patients with dementia or confusional states secondary to metabolic insults. Prevalence The prevalence of visual hallucinations in a range of ophthalmological populations, is around 10%, varying between 0.4% and 63%, significantly associated with an age over 64 years and a visual acuity in the best eye of 0.3 or less (2,3). RISK FACTORS Dementia, psychiatric disorders, drugs, alcohol, social isolation, visual loss, female sex, and old age. PATHOPHYSIOLOGY • Visual loss due to certain conditions produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon-deafferentation). • Ictal hallucinations are caused by spontaneous or iatrogenic stimulation of the occipital or temporal cortex. • Hallucinogenic agents have effects on serotonergic and limbic system structures. • Migraine aura is caused by cortical spreading depression, which is a wave of electro-physiological hyperactivity followed by a wave of inhibition, usually in the visual cortex. EnOLOGY • Ophthalmologic diseases (Visual loss due to enucleation, cataract, glaucoma, optic nerve, or retinal disease) • Neurologic disorders (Epilepsy, migraine, narcolepsy, brainstem disorders, hemispheric lesions, Alzheimer, Parkinson, and Lewy body disease) • Toxic and metabolic conditions (encephalopathies, drugs, alcohol, and withdrawal syndromes) • Psydlosis

332

COMMONLY ASSOCIATED CONDITIONS Hallucinogenic agents Visual deprivation Psychosis Delirium, delirium tremens Dementia (Alzheimer disease, vascular dementia, Dementia with Lewy bodies (DLB), Creutzfeldt-Jakob disease)

• • • • •

~ DIAGNOSIS HISTORY Detailed description of seeing things Any clues to the cause anywhere in the body Neurologic or ophthalmologic symptoms Smoking, alcohol, illicit drugs Most patients are reluctant to admit hallucinations due to fear of being labeled with a psychiatric disease. Therefore, directed questioning of susceptible patients is essential. PHYSICAL EXAM • Visual acuity • Visual fields • Full neurologic examination • • • • •

DIAGNOSTIC TESTS & INTERPRETATION

Lab • Drug levels if patient is on medications • Electroencephalography (EEG) for seizure disorders and encephalopathy

Imaging MRI if brainstem or hemispheric lesion is suspected. DIFFERENTIAL DIAGNOSIS • Delusions are abnormal beliefs that are endorsed by patients as real. • Confabulations are fabricated facts or events and occur primarily in patients with memory disturbances. • Visual illusions are abnormal visual perceptions of a viewed object (metamorphopsia, cerebral diplopia, polyopia, and palinopsia). • Hallucinations are the visual sensation that does not correspond to a real object. - Simple (flashes, sparkles, haloes, lights, shapes, patterns, phosphenes) - Complex (flowers. animals. people)

• Release hallucinations represent images formed from memory traces which would ordinari ~ be blocked by incoming sensory data. • Charles Bonnet syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. • Ictal hallucinations are brief, stereotyped visual experiences. Ictal hallucinations tend to be unformed when associated with occipital lesions and formed when associated with temporal lobe lesions. • Peduncular hallucinosis is colorful, vivid images associated with midbrain, pontine, and thalamic lesions due to damage to the ascending reticular activating system. • Migraine aura is a disturbance of vision consisting unformed black and white flashes, multicolored lights, dazzling zigzag lines (scintillating scotoma); and fortifications (teichopsia). • ·Alice in Wonderland· syndrome is a rare form of migraine aura. The most distinctive symptom is metamorphopsia, a distortion of body image and perspective. • Hypnagogic hallucinations are dreamlike hallucinations associated with narcolepsy that occur as a person is falling to sleep. • Schizophrenia sufferers experience auditory, visual, tactile, olfactory, and taste hallucinations. Auditory hallucinations are more common. • Hallucinations are primarily visual in delirium which can be caused by drugs or metabolic diseases.

Pediatric Considerations • Children may have hallucinations associated with substance abuse, psychosis, night terrors, decongestant medications, and seizures. VIVid recall of visual images with hallucinatory character can occur in some children. • •Alice in Wonderland• syndrome can occur at any age, but is more common~ experienced by children.

Geriatric Considerations • Elderly people, especially who are suffering with dementia might see people, animals. complicated scenes, and other bizarre scenarios. • Hallucinations associated wittl: - 25% of Parkinson's disease - 25% of Alzheimer disease - 57% of patients with a variety of causes of visual loss (Charles Bonnet Syndrome) - Hallucinations and agitation are especially troublesome in dementia with Lewy bodies (DLB). Clinical characteristics include progressive dementia, persistent visual hallucinations, extrapyramidal syndrome, and severe sensitivity to neuroleptics.

HALLUCINATIONS, VISUAL

.

TREATMENT

Currerrt evidence of treatment comes from Cilse reports. No controlled eli nical trials have been reported. The treatment is dependent on the underlying cause.

MEDICATION FlmLine • Antipsychatics - Drug selection sl1ould be individualized to the patient's previous history of antipsychotic use, current medical conditions, potential drug interactions. and side effects of the medication. • In dementia with Lewy bodies. if symptoms are mild, no mediCi!I treatment may be necessary. -Therapeutic strategies include prescription of L-dopa and cholinesterase Inhibitors such as rlVastlgmlne, and avoidance of anticholinergic medications and neuroleptics. - Atypical neuroleptics are recommended such as clozapi ne, quetiapine, or aripipn!Zole when cholinesterase inhibitors are ineffective (4) - Caution Is also requIred when prescribing memantlne to patients with possible DLB. • Antiepileptics in seizure disorders SacondUna Selective serotonin reuptake inhibitors and tricyclic antidepressants (3). ADDITIONAL TREATMENT Generall'tfeiuutes Visual imprllVI!ment and rl!aS!iurance are the mainstays of treatment. Issues for Rmtral Ophthalmology, Psychiatry, Neurology consultations for related problems SURGERY/OTHER PROCEDURES Nat indicated except tumors causing ictal halludnations

IN-PATIENT CONSIDERATIONS Initial Stabilization Make sure that the metabolic status Is normalized. Admlulon Criteria Metabolic disorders. delirium, agitation.

REFERENCES 1. Ffytdle DH. Visual hallucinatol)' .syndromes: Past. present, and future. Dialogues Clin Neurosd

When the metabolic status Is normalized

2007;9:173-189. 2. Ffytche DH. Visual hallucinations in eye disease. Curr Opln Neuro/2009;22:28-35. 3. Schadlu AP, Schadlu R. Shepherd JB 3rd. Charles Bonnet syndrome: A review. Curr Opin Ophthii/mol 2009;20:219-222. 4. Gold G. Dementia with L.ewy bodies: CliniCill diagnosis and therapeutic approach. Front Neurol Neurosd 2009;24:107-113.

$

ADDITIONAL READING

IV Fluids Given as supplement and to correct the metabolic status.

Nuning Careful monitoring for agitation and seH-destruction.

Discharge crn.r1a

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Reassurance and regulation of medications l'atient Monitoring Metabolic side effects should be dosely monitored in this population.

DIET No spetific diet.. thiamine in alcohol withdrawal PATIENT EDUCATION Reassurance PROGNOSIS • Depends on the cause and complications • Most patlents are relieved by reassurance and medications but resol utlon of symptoms over time does nat always occur. COMPUCA110NS Halludnations may be persistent despite the treatment

• Cummings JL.. Miller HL Visual hallucinations. Clinical occurrence and use in differential diagnosis. West 1 Med 1987; 146:46-51. • Khan JC, Shahid H, Thurlby DA, et al. Charles Bonnet syndrome in age-related macular degeneration; The nature and frequency of Images in subjects with end-stage disease. Ophthii/mic Epidemio/2008;1 5:202-208. • Teeple RC, Caplan JP, Stem TA. Visual halludnations: Differential diagnosis and treatment. Plfm Care Companion J Clln Ps}f:lllatry 2009;11:

26-32.

CODES ICD!f 368.16 Psychophysical visual disturbances

CLINICAL PEARLS • VISual hallud nations can be caused by release phenomena, seizures, migraine. cognitive deficits, retina I disease, alcohol, drugs, halludnogens. or metabolic disturbances. • Charles Bonnet syndrome is vivid, detailed but nonthreatening halludnations in visually deprived patients. Patients are not cognitively impaired. • Ocdpltal seizures cause simple unformed halludnatlons. Temporal lobe seizures may lead to complex imagery or formed halludnations. Electroencephalography can be diagnostic. • Avoid neuroleptics such as haloperidol in a dementia patient with lew! body disease.

333

I

HARD EXUDATES Vikram J. Setlur

~ BASICS DESCRIPTION • Hard exudates in theundus represent leakage of lipid and protein from incompetent vessels in the retina, choroid, or optic disc. - Hard exudates are usually present in the oiJ!er plexiform layer of the retina but can dissect into the subretinal space as well as into other retinal layers. EPIDEMIOLOGY Incidence Difficult to quantify RISK FACTORS Underlying vascular diseases such as diabetes. hypertension, and dyslipidemia GENERAL PREVENTION Control of blood glucose, blood pressure, and blood lipid levels can reduc.e the risk of common causes of hard exudates. such as diabetic retinopathy, hypertensive retinopathy, retinal arterial macroaneurysm, and retinal vascular occlusion. PATHOPHYSIOLOGY Increased vascular permeability allows leakage of protein and lipid into the retina. EnOLOGY • Numerous retinal vascular diseases can cause hard exudates, including: - Diabetic retinopathy - Hypertensive retinopathy - Retinal vascular occlusion

334

-

Retinal arterial macroaneurysm Radiation retinopathy Coats' disease Capillary hemangioma of the retina (i.e., von Hippellesion) -Neuroretinitis - Choroidal neovascularization (e.g., age-related macular degeneration)

COMMONLY ASSOCIATED CONDITIONS Macular edema is often present with hard exudates.

~ DIAGNOSIS HISTORY • Decreased vision if hard exudates are present in the macula • Underlying medical diseases PHYSICAL EXAM • Fundus examination reveals discrete, yellow-white deposits most frequently in the posterior pole. • Can be globular, linear, circinate surrounding a leaking vessel, or large and confluent. A macular star can be seen with neuroretinitis or hypertensive retinopathy.

DIAGNOSTIC TESTS & INTERPRETATION DIFFERENTIAL DIAGNOSIS • Cotton-wool spots • Myelinated nerve fiber layer • Retinitis • Drusen • Chorioretinal atrophy • Hollenhorst plaque • Crystalline retinopathy (see the Talc retinopathy chapter)

rJ

TREATMENT

MEDICATION First Line Treatment of the underlying disorder is required. Second Line For diabetic retinopathy and diabetic macular edema. a common cause of hard exudates, treatment of the underlying macular edema with laser photocoagulation and/or injection of intraoular steroid or anti-VEG Fmedication can lead to resolution ofthe hard exudates (1,2)[C]. SURGERY/OTHER PROCEDURES Submacular surgery has been used to remove massive diabetic submacular hard exudates.

HARD EXUDATES

•

ONGOING CARE

COMPLICATIONS • Macular edema is often associated with hard exudates. • Patients with neuroretinitis may have an afferent pupillary defect, but this oftl!n resolves with time.

REFERENCES 1. Larsson J, Kifley A, Zhu M, et al. Rapid reduction of hard exudates in eyes with diabetic retinopathy after int~treal triamcinolone: Data from a randomized, placeb()-((lntrolled, dlnlcal t~al. Acta Ofi!thalmol2009;87:275-280. 2. Ciardella AP, Klancnik J, SchiffW, 1!1 al.lnt~treal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: Arl optical coherence tomography study. Br1 0/i!thalmo/2004;88: 1131-1136.

ADDinONAL READING

CLINICAL PEARLS

• Naito T, Matsushlt S, Sata H, et al. Results of submacular surgery to remove diabetic submacular hard exudates. 1Med Invest 2008;55:211-215.

• Discrete, yellow-white deposits of lipid and protein in the fundus from leaking vessels in the retina, choroid, or optic disc. • First-line treatment Is aimed at the underlying disorder, not the hard exudates themselves. • Macular edema is frequent assodation, and may need treatment Independent of underlying systemic diseases Of present).

f ; coDES ICD9 • 250.50 Diabetes mellitus with ophthalmic manifestations. type ii or unspecified type, not stated as uncontrolled • 362.01 Background diabl!lk retinopathy • 362.82 Retinal exudates and deposits

I

335

HEMANGIOMA IN CHILDREN Mary O'Hara

~ BASICS DESCRIPTION Rapidly growing benign blood vessel tumor of the periorbital tissues EPIDEMIOLOGY 1-2.6% of neonates (1)[C]

RISK FACTORS • Female sex (1 )[C[ • Caucasian race (1 )[C[ • Prematurity (1)[C] • Chorionic villus sampling (2)[C] • Family history Genetics • Most are sporadic without hereditary component - Familial form is a highly penetrant autosomal dominant trait with variable expression, linkage to chromosome 5q31-33 (2)[C] GENERAL PREVENTION Genetic counseling for familial form PATHOPHYSIOLOGY Increased local expression of vascular endothelial wowth. factor (VEGF) during proliferative stage. During mvolut1onal phase, VEGF expression decreases (2)[C]. EnOLOGY Hamanomatous growth of blood vessels. COMMONLY ASSOCIATED CONDITIONS • PHACES: Posterior fossa malformations hemangiomas (usually large facial), an~rial anomalies, coarctation of the aona and other cardiac defects, eye abnormalities (especially optic nerve malformation), sternal clefting and supraumbi lical raphe • Kasabach-Mellitt syndrome: Consumptive c~agulopathy with thrombocytopenia, associated With very large capillary hemangiomas • Diffuse neonatal hemangiomatosis • Maffucci syndrome: Endochondromas, bony deformities, and diffuse hemangiomas • Klippei-Trenaunay syndrome: Rare triad of capillary or cavernous hemangioma, venous malformations and soft tissue or bony hypenrophy '

336

~ DIAGNOSIS HISTORY • Rapid growth and proliferation of a vascular lesion in the first 6 months of life - Presentation is variable, may be red macule or no lesion noted • Spontaneous involution begins during second year of life and may continue for almost 10 years.

PHYSICAL EXAM • Full ocular examination with special attention to refraction (can induce myopia or astigmatism) • Measure size of lesion/photograph if possible • Systemic examination for other anomalies • Vascular nature of lesion gives it a reddish color if superficial and bluish-puiple color if subcutaneous • Lesion is compressible and blanches to touch • Mass may swell and become more violaceous when baby cries or when placed in Trendelenburg position. • ~ttention to obstruction of visual axis, preference of f1xation, and chin lift (indicating likely binocular fusion). • Assess for proptosis, optic nerve compression, or fullness of temporal fossa. DIAGNOSTIC TESTS & INTERPRETATION

Lab lnitialle~b tests • None if no systemic involvement • CBC with platelet count for large lesions or if other signs of small vessel bleeding (e.g., petechia) Follow-up It special considerations • Counsel.parents that wheezing may indicate airway hemangioma and to seek immediate medical care • Bleeding or petechia indicate consumptive coagulopathy (Kasabach-Merritt syndrome)

Imaging Initial approach • Ultrasound of the lesion demonstrates compressibility, internal reflectivity, and indiscrete borders - Computed tomography (CT) less favored because of radiation to the infant, but can determine if there is any associated bony erosion. - Magnetic resonance imaging (M Rl) demonstrates indiscrete margins and vascularity when comparing Tl- and T2-weighted images. - Orbital and brain imaging if proptosis, full temporal fossa, indication of optic nerve compression (e.g., afferent pupillary defect).

Follow-up It special considerations Close fo_llow-.up of the ophthalmic examination during the proliferative phase as astigmatism, anisometropia, and ptosis can cause profound amblyopia.

Diagnostic Procedures/Other • Doppler of lesion demonstrates vascularity - Biopsy may be necessary if cannot rule out rhabdomyosarcoma

Pathological Findings Proliferative phase marked by rapid proliferation of capillaries lined by endothelial cells with high mitotic rates and accompanying fibroblasts, pericytes, and mast cells. During involution there is drop-off of mitosis with apoptosis of endothelial cells.

DIFFERENTIAL DIAGNOSIS • Rhabdomyosarcoma (usually superior temporal or nasal) • lymphangioma • Cavernous hemangioma • Nevus flammeus (does not gain volume) • Port wine mark (does not gain volume until much later in childhood) • Arteriovenous malformation • Neuroblastoma • Encephalocele (usually superior nasal) • lacrimal sac mucocele (inferior nasal)

rJ

TREATMENT

MEDICATION Only indicated when visual axis obstructed and amblyopia unresponsive to penalization or occlusion of the contralateral eye.

First Line • Beta-blocker therapy is rapidly becoming first-line treatment modality (3)[C[ - Systemic treatment with 1-2 mg/kg/d of propranolol divided b.i.d has produced dramatic involution of lesions. There is no universally a~cepted protocol for initiation of therapy. A h1story of bronchospasm, cardiac disease, or CNS vascular anomaly may be a contraindication to therapy. • Topical treatment with timolol eyedrops or gel has produced results similar to systemic treatment in isolated cases but has not been rigorously studied (4)[CJ.

HEMANGIOMA IN CHilDREN SecandUne • Corticosteroid therapy has been the most commonly used treatment modality until recently (l)[C) - Oral therapy has a 3D-90% response rate. PartiaJlarly useful in treating deep orbital lesions.. Complications Include pltultaryfadrenal suppression, immunological suppression, and Cushing syndrome. Dose 1-2 mg/kg.ld. me have used as much as 4 mgfkgld - lntralesional steroid therapy has a 60-80% response rate. Potential complications: Central retina I artery occlusion, eyelid neaosis, eyelid depigmentation, and subclltaneous fat atrophy. Adrena I suppression also reported. -Topical steroid therapy may be helpful. Skin changes have been reported and ad renal suppression can be seen with high-dose. extended treatment. • Interferon alfa can be effective but rarely used because of high rate of toxicity in children. Efficacy may be increased if used with steroids. -Spastic diplegia, seizures. coma - Liver toxicity -Hematologic abnonnalitles

ADDITIONAL TREATMENT Ge~l MNsu,.s

• Observation if no obstruction of visual axis or significant astigmatism • Treatment of amblyopia wtth atropine penalization or occlusion of the contralateral eye along with spectade if indicated

lssws for Referral • Prompt ENT referral for airway hem angiomas • Genetic counseling if fami Iial form or assodated conditions • Hematology consu Italion if Kasabal:h-Merrin syndrome • Neurosurgical consultation if orbitaUbrain Involvement

Additional Therapt.s • Laser therapy may occasionally benefit superficial lesions. Several different types of laser have been used -Carbon dioxide (C02)

-Argon - Neodymium:Ynrium-aluminum-garnet (Nd:YAG) - Pulsed dye lasers

COMPLEMENTARY & ALTERNATIVE THERAPIES None proven or indicall!d SURGERY/OTHER PROCEDURES • Embolectomy usual~ not indicated for orbital and adnexal lesions. • Complete or partial excision of sight-threatening lesions resistant to other treatment modalities may be necessary on rare occasions. • Surgical excisions/facial plastic procedures may be done after involution.

IN-PATIENT CONSIDERATIONS

Initial Stabilization If airway concerns, this is primary consideration.

Admission Criteria Some hiM! recommended inpatient initiation of systemic beta-blocla!r treatment with appropriatl! monitoring.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Rebound recurrence of the lesion has been seen on cessation of aII forms of steroid and beta blocker therapy. • Close follow-up during proliferative phase as am blyopla Is common - Spectacles for significant astigmatism - Penalization/occlusion therapy as needed - Medically treat If nat responsive to conserwtlve therapy • Subsequent follow-up for appearance issues - Defer surgery until Involution complete. If possible Patient Monitoring • Visionfrefraction • Psychosoda llnll!ractlons

PATIENT EDUCATION Family support networlc: National Organization of Vascular Anomalies {NOVA): http:/flwlw.novanews. org PROGNOSIS • Approximately 40% of lesions spontaneously involute by 4 years old and 70% by 7 years old. • Astigmatic refractive errors are seen in 2D-46% of patients with eyelid or orbital capillary hemangiomas {5)[C). • One-third of patients with anisometropia had visual aoolty of 20160 or worse In the affected eye (5)(C].

mMPUCATIONS • Ud deformity • Scarring, hypopigmentation, or atrophy of skin • Fadal asymmetry • Psychosocial issues related to appea ranee

REFERENCES 1. Ceisler EJ, Santos L. Blei F. Periocular hemangiomas: What every physician should know. Pediatr Dermato/2004;21: 1-9. 2. Phung TL. Hochman M, Mihm MC. Current knowledge of the pathogenesis of infantile hemangiomas. Arch Facial Plart Surg 2005;7: 31~321.

3. Zimmerman AP, Wiegand S, Werner JA, et al. Propranolol therapy for infantile haem angiomas: Review of the literature. tnt JPedlatr Otolflinolaryngo/ 201 0; 74:338-342. 4. Guo s. Ni N. Topical treatment for capillal)' hemangioma of the eyelid using beta-block.er solution. Arch Ophfhalmol 201 0; 128:255-2 56. 5. Schwartz SR. ICodsi SR. Blei F, et al. Treatment of capi llal)' hemangiomas causing refractive and otduslonal amblyopia. 1AAPOS 2007;11: 577--583.

ADDITIONAL READING • http:l/emedicine.medscape.com/artide/1218805overview

.

CODES

ICD9 228.01 Hemangioma of skin and subcutaneous tissue

CLINICAL PEARLS • Follow dosely for amblyopia In the proliferative phase of the lesion. • Wheezing warTants evaluation for airway hemangioma. • Most lesions do not waiTant treatment and spontaneously resolve over the first decade of life.

337

I

HERPES SIMPLEX Peter R. Laibson

~ BASICS DESCRIPTION • Herpes simplex virus type 1causes ocular infection following introduction of the virus in childhood as a subclinical or mild systemic infection. The HSV becomes latent in ganglion around the eye (trigeminal). The virus or viral genome may remain latent for decades before reactivating to cause various forms of herpetic keratitis. • Conjunctival inflammation precedes corneal vesicles. Superficial Punctate Keratitis (SPK), and then branching epithelial ulcer, a classic dendritic ulcer which may enlarge to a geographic form. • Deeper corneal forms of herpes simplex virus keratitis (HSVK) may follow days/weeks later. Disciform keratitis is an immune form of HSV involving corneal endothelium leading to edema. With persistence, corneal scarring, thinning, and rarely, perforation. EPIDEMIOLOGY Incidence • HSV type 1 is the leading cause of blindness from an infectious corneal disease. By age 5 years, over 60% show antibody evidence systemic HSV. • About 1% of HSV infected patients develop ocular HSV. Prevalence • There are about 20,000 new primary cases of HSVK seen yearly. Most are dendritic keratitis. • About 30,000 recurrent HSVK cases are seen annually.

338

RISK FACTORS Fever, URI, ocular trauma, menses. high stress, CL use, all have been considered risk factors, but not proven. Genetics Probably exist but not defined. GENERAL PREVENTION Oral antivirals are useful to prevent recurrent HSVK. Most helpful with previous hx of multiple recurrences of HSVK. PATHOPHYSIOLOGY Systemic viremia of HSV early in life seeds ganglia around the eye. Later reactivation of latent virus causes infection. COMMONLY ASSOCIATED CONDITIONS Fever blisters around the mouth, nose, and eye often accompany ocular HSV.

~ DIAGNOSIS HISTORY Ocular inflammation and eye irritation (pain) often precede HSVK. Blurred VA when the infection is in the visual axis. PHYSICAL EXAM Slit-lamp examination is critical to diagnose ocular HSV. Vital dyes such as fluorescein, lissam ine green, or Bengal rose are very helpful.

DIAGNOSTIC TESTS & INTERPRETATION Lab Most often lab tests such as culture are not necessary as slit-lamp diagnosis of dendritic keratitis is very specific. With more complicated, deeper forms of HSVK, culture, PCR, or immune tests are used.

Imaging None.

Pathological Findings Pathological studies are rarely performed.

DIFFERENTIAL DIAGNOSIS Can be confused with herpes zoster keratitis, Epstein Barr, acanthamoeba, fungal keratitis, and other persistent unusual deeper corneal infections.

.

TREATMENT

MEDICATION First Line Dendritic keratitis responds well to trifluridine drops topically and third generation topical gels such as gancidovir. Oral antivirals, acyclovir and valacydovir are useful. Steroids should be avoided for ocular surface HSVK, but are used with antivirals for stromal HSVK, disciform, necrotizing and uveitis.

SURGERY/OTHER PROCEDURES Penetrating keratoplasty for severe stromal scarring, thinning, or perforation is helpful.

HERPES SIMPlfX

•

ONGOING CARE

FOU.OW-UP RECOMMENDA110NS l'atlent Monltotlng With HSV dendritic keratitis fnllow-up. slit-lamp exams as necessary until resolution, with stromal disease, very long term follow-up Is altlcaL Herpes Is fnrever. PA11ENT EDUCATION Discussion of long-term therapy. Not ID seH-med icate with recurrences, but to ellpl!dite office examination. PROGNOSIS Good for lniUaI and ea~y recurrent dendritic keratitis with topical Rx. Or oral Rx. Guarded for stromal HSV.

ADDITIONAL READING • Young RC, Hodge DO, Liesegang TJ, et al. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976--2007: The effect of oral antiviral prophylaxis. Ardr Ophthalmo/ 201 0; 128(9):1178--1183. • Kn ickelbein JE, Hendricks RL, Charublm noetkanok P. Management of hsv stromal keratitis: An evidence-based review. Suw Ophtha/2009; 54(2):226--234.

.

CODES

ICD9 • 054.42 Dendritic keratitis • 054.43 Herpes simplex disciform keraUtls

CLINICAL PEARLS • Always suspect possible ocular HSV in patients. With acute red eye and do slit-lamp examination with vital dye to avoid treating HSV with topical steroids especially in children.

COMPLICATIONS Significant morbidity and visual los.s with stromaI HSV: Pediatric ConsideratioM Infants and children can develop HSVK after loss of maternal antibodies. Steroids should never .be used for a red eye in this group unless a slit-lamp examination is done.

I

339

HERPES ZOSTER OPHTHALMICUS Neelofar Ghaznawi Kristin M. Hammersmith

~ BASICS DESCRIPTION • Acute, painful, vesicular eruption distributed along the ophthalmic branch of the trigeminal nerve (1 ). • Ocular inflammation without characteristic rash: Zoster sine herpete (2). EPIDEMIOLOGY lnddence • 200,000 new cases per year in the US. • 1% life time ris~ (3).

RISK FACTORS • Increasing age. • Immune compromise (i.e., HIV. cancer, immunosuppression) (4). GENERAL PREVENTION • CDC recommendation (2008}--routine vaccination of all individuals 60 years or older with Varicella Zoster Vaccination (Zostavaxlll>), including those with prior history of herpes zoster or chronic medical conditions. • The vaccine is not licensed for the treatment of acute HZ or post herpetic neuralgia (PH N), or for the prevention of HZ in patients aged younger than 60 years (5). PATHOPHYSIOLOGY • Reactivation of latent virus from trigeminal ganglia with viremia and spread of virus from sensory axons to skin. • Age-related decline in varicella-zoster virus specific cell mediated immunity increases susceptibility to viremia (5).

~ DIAGNOSIS HISTORY • Painful vesicular eruption in a single dermatome. • Fever, malaise, headache, and pain in the affected dermatome. • Affective disorder: Anorexia, lassitude, mood changes, antisocial behavior, depression, and insomnia (6). PHYSICAL EXAM • Rash involving the V1 dermatome evolving from an erythematous lesion with macules, papules and vesicles with pustules and crusts developing subsequently. • Slit-lamp examination. -Ear~: o Eyelid: Hyperemia, edema, ptosis. o Conjunctiva: Hyperemia, petechial

hemorrhages, vesicles, pseudodendrites, papillae, follicles, pseudomembranes. o Sclera/episclera: Limbal vasculitis, sclerokeratitis, posterior scleritis. o Cornea: o Epithelium: Pseudodendrites, punctate epithelial keratitis. o Stroma: Nummular stromal keratitis, disciform keratitis (7).

340

Iris/uvea: Segmental iris edema, granulomatous keratouveitis with keratic precipitates (8), secondary glaucoma (9). o Retina/optic nerve: Retinal perivasculitis, ischemic optic neuritis, necrotizing retinopathy. -late (1 month after rash): o Eyelid: Cicatricial entropion/ectropion, trichiasis. o Conjunctiva: Hyperemia, pseudomembranes. o Sclera/episclera: Limbal vasculitis, sclerokeratitis, posterior scleritis. o Cornea: o Epithelium: Delayed pseudodendrites (mucous plaque keratitis). punctate epithelial keratitis, neurotrophic ulceration, band keratopathy (1 0). o Stroma: Nummular stromal keratitis, disciform keratitis, lipid deposition, anterior and posterior stromal scarring, chronic edema (7). o Iris/Uvea: Segmental iris atrophy, granulomatous keratouveitis with KP. secondary glaucoma. o Retina: Acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN). • Neuroophthalmic examination. - Extraocular muscles: Transient EOM palsy and diplopia (11). -Cranial nerves: CN Ill, IV. or VI can be involved indicating vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction (12). -Acute pain: Characterized as lancinating, burning, aching, andlor itching. -Post-herpetic neuralgia (PHN}-pain lasting more than 1 month after disease onset. Characterized as constant or intermittent aching or burning, sudden lancinating pain, allodynia (pain from nonpainful stimuli), and/or a constant or intermittent itch (13). o

DIAGNOSTIC TESTS & INTERPRETATION

Lab No laboratory work up is necessary unless there is a high index of suspicion for HIV.

Imaging Initial approach Slit-lamp examination including intraocular pressure assessment, corneal sensation, and dilated funduscopic examination.

Follow-up It special considerations • Starting oral antiviral therapy shortens the duration of acute pain, virus shedding, rash, acute, and late-onset anterior segment complications, and the incidence and severity of PHN (12). • Depending on severity of ocular inflammation, patient should be re-evaluated within 5-7 days and frequency of follow-up visits should be dictated by severity of slit-lamp findings.

ALERT Treatment with valacyclovir in severe immunocompromise has been associated with thrombocytopenic purpura/hemolytic uremic syndrome and is therefore not FDA approved for use in this subset of patients.

Diagnostic Procedures/Other • PC Rcan be used to document the presence of VN DNA in aqueous samples in patients with evidence of uveitis but without clinical eruption (14). • Evolution of lgG antibo~ titers between acute and convalescent phase specimens demonstrating a 4-fold increase can confirm evidence of HZO in the absence of skin involvement (15).

DIFFERENTIAL DIAGNOSIS Orbital cellulitis, poison ivy, herpes simplex keratitis.

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TREATMENT

MEDICATION First Line • Oral antiviral therapy starting with 72 hours of rash onset. Duration of therapy-1 0 days. -Acyclovir 800 mg PO, 5 times dailyt - Valacyclovir 1000 mg PO, 3 times dai~t· - Famciclovir 500 mg PO, 3 times dailyt• t Acute renal failure: May occur in elderly patients (with or without reduced renal function) Use with caution in elderly patients and reduce dosage in patients with renal impairment (16). • Note: Use of valacyclovir and famciclovir has been associated with decreased occurrence of PHN. Second Line There are no FDA-approved alternative therapies. ADDITIONAL TREATMENT Additional Therapifls • Acute HZO: - Rash: Topical antibiotic ointment for areas of pustule and crust formation. - Pain: Prednisone 60 mg/day for the first 7 days, 30 mg/day on days 8 to 14, and 15 mg/day on days 15 to 21 for moderate to severe pain (17). -Anterior segment complications: - Dry eye syndrome (DES): Frequent lubrication with topical artificial tear formulations. - Stromal scarring: Cautious use of low potency topical steroid to control inflammation. -Iritis: Topical steroids (7). • Chronic HZO: - PH N: Tricyclic antidepressants, opioids, anticonvulsants, and topical analgesics have proven benefit. Refer to neurologist/pain specialist for further management (13). -Anterior segment complications: - DES: lubrication, punctal occlusion, autologous serum. -Neurotrophic ulceration: autologous serum, conjunctival flap, amniotic membrane transplant, tarsorrhaphy. - Keratouveitis/lnterstitial keratitis: Topical steroid therapy (7). - Pseudodendritiform keratitis (mucous plaque keratitis): lubrication and off label use of topical antiviral ointment (acyclovir, vidarabine, or ganciclovir) has demonstrated potential benefit (10). - ARN/PORN: lntravitreal and intravenous antiviral therapy. Seek retina consult immediately.

HERPES ZOSTER OPKTHALMICUS SURGERY/OTHER PROCEDURES • Tarsorrhaphy: Neurotrophlc ulceration not responsive to Iubr1catlon. • Corneal glue: Perforations I mm or less in diameter. • Amniotic membrane transplant/Gunderson flap: Neurotrophic ulceration and thinning. • Penetrating ker.rtoplasty (PIC): Visually significant scarring or ulceration not responsive to tarsormaphy alone (7). ALERT Taoorrhaphy should be s1rongly considered in patients undergoing PK. IN-PATIENT CONSIDERATIONS Admission Criteria • Pediatric patlenu requiring Intravenous antM ral therapy • Elderly patients unable to self-admi nistl!r oraI medications or those with zoster in muhipie dermatomes • Patients witl1 severe immune compromise at risk for disseminated disease

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ONGOING CARE

PATIENT EDUCATION

Immunization with varicella zoster vaccine Is recommended after resolution of disease.

PROGNOSIS New lesion formation in the primary dermatome frequently stops In 3-7 days In the healthy Individual and the affected dermatome often heals within 2 weeks, but may not resolve for 4 to 6 weeks (1). COMPLICATIONS • Chronic disease ottUrs in 30% of patients over 60 and approaches 70% in patients older than 80 years (18) • OphthaImic complications indude the following: -Stromal scarring -Cataract - Corneal perforation -Glaucoma - Neurotrophic ulceration - Secondary infectious keratitis - Necrotizing retinitis - Optic neuritis • Systemic complications -PHN - Stroke (19)

REFERENCES 1. llesegang TJ. Herpes zoStl!r ophthalmlcus: Natural history, risk factors. dinical presentation and morbidity. O,JJthalmaiD!fY 2008;115:S3-S12. 2. lewis GW. Zoster sine herpete. Br Med J 2958;2: 418-421. 3. Ragozzlno MW. Population based study of herpes zoster and 113 sequelae. Medldne 1982;61: 31D-316. 4. Cohen PR, Grossman ME. Clinical feab.ues of HIVassociated disseminated HZV infection-A review of literalure. Clin Exp Dermvto/1989;14: 273-276. 5. Harpaz R. Ortega-Sanchez IR, Seward JF. AdviSOIY Committee of Immunization Practices (ACIP) Centers for Disease Control and Prevention. Prevention if herpes zostl!r: recommendations of the Advisory Committee of 1mmunization Practices (ACI P). [published correction appears In MMWR Recomm Rep. 2008;57(28):779; MMWR Recomm Rep 2008;57(RR-5):1-30; http:llwww.cdc.gov/ mmwr/preview/mmwrhtmllrr5705a1.htrn. Accessed July 10, 2010. 6. Burke BL. Immune response to varkella-zoster In the aged.Ard! lntem Med 1982;142:291-293 7. Liesegang TJ. Comeal complications from herpes zoster ophthalmicus. Ophtha/mol 1985;92: 316-324. 8. Yamada 1:. Cutaneous eruption with or without ocular complications In patients w1th herpes zoster involving the trigeminal neM. Graeles Arch Clin Exp Ophtha/moi19!Kl;228:1-4. 9. Cabo M. Observations on the natural history of herpes zoster ophthalmirus. Cu" Eye Res 1987;6:195-199. 10. Pava n-L.angston D. Dela~ herpes zOStl!r pseudodendrites. PCR detection of viral DNA and a role for antM ral therapy. Arch Ophthalmal 1995;13: 1381-1385. 11. Marsh RJ. Extraocular motor palsies in ophthalmic zoster: a review. Br J Ophtha/mol 1977;61: 677-682. 12. Kattah JC, Kennerdel JS. Orbital apex syndrome secondaIY to herpes zoster ophthalmicus. Am J Ophthalmol 1978;85:378-382. 13. Pava n-L.angston D. Herpes zoStl!r: AntMrals and pain management. Ophtha/mo/2008;115: S13-S20.

14. Starrou P. Detection of varicella zoster virus DNA In ocular samples from patients with uvletis but no cutaneous eruption. Eye 1994;8:684-687. 15. GiIden DH. Varicella zoster virus reactivation without rash.J lrrkctOis 1992;166:S3D-S34. 16. http:/ldailymed.nlm.nih.govfdailymed/archivesl fdaDrugl nfo.cfm1archiveid=13284. Accessed 7126/10. 17. Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zostl!r. A randomized, placebo-controlled trial. The Na1ional Institute of Allergy and Infectious Diseases Collaboralive Antiviral Study Group. Ann lntem Med 1996;125:376-383. 18. Harding SP. Management of ophthalmic zostl!r. J Med Viro/ 1993;5 97-101. 19. Un HC. Herpes zoster ophthalmkus and the risk of stroke: A popula1ion-based follow-up study. NeuroiD!fY 201 0;74:792-797.

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CODES

ICD9 • 053.21 Herpes zoster keratoconjunctivitis • 053.22 Herpes zoster l~docydltls • 053.29 Herpes zoster with other ophthalmic complications

CLINICAL PEARLS • Recognition and prompt trea1ment of HZO is necessary to reduce the inddence of complications. • HZO can have a chronic and complicated course and therefore req ulres frequent foil ow-up. • Herpes zoster vaccination should be recommended to all individuals meeting immunization criteria.

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H

HIV/AIDS-REIATED RETINOPATHIES Brad Ballard Mark L. Nelson

~ BASICS DESCRIPTION • HIV retinopathy and CMV retinitis are by far the most common ocular manifestations of HIV. • Cytomegalovirus (CMV) retinitis is the most important AIDS-associated illness to affect the eyes. It is a full thickness retinal infection that can lead to necrosis and to retinal tears and detachments. • Other ocular manifestations of HIV infection include HIV retinopathy, various opportunistic infections including toxoplasmosis. syphilis. pneumocystis carinii, cryptococcus. and herpes-family virus infections. especially CMV retinitis and progressive outer retinal necrosis. Kaposi Sarcoma, intraocular lymphoma, and conjunctival squamous cell carcinoma also occur. Pediatric Considerations Congenital CMV infection can cause significant neurological and developmental abnormalities. Pregnancy Considerations Mothers with CMV primary infections can pass the virus on to fetus transplacentally causing congenital CMV infection. EPIDEMIOLOGY Incidence In the pre-HMRT era, CMV retinitis had a cumulative lifetime incidence of 25--40%. The incidence has decreased considerably in recent years.

Prevalence • HIV retinopathy occurs in 50--60% of patients infected with HIV. • Historically, CMV retinitis occurred in up to 40% of patients with HIV and is an AIDS-defining illness; however, it is much less common in the HMRT era.

RISK FACTORS The main risk. factor for development of CMV retinitis is a low CD4 count, typically below 50. GENERAL PREVENTION HMRT therapy has shown great benefit for reduction in CMV retinitis, as it often maintains a CD4 count above 50.

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PATHOPHYSIOLOGY • CMV reaches the retina hematogenously. It then infects the retinal vascular endothelium. • On histopathology, infected cells show pathognomonic cytomegalic inclusions with large eosinophilic intracellular bodies. • Electron microscopy can show CMV particles within infected cells. • Histopathology shows full thickness retinal necrosis. coagulative vasculitis, and choroiditis. ETIOLOGY • Cytomegalovirus (CMV) is a member of the herpes virus family. • There is a high prevalence of CMV antibodies in the general population and most people are thought to have been infected at one time or another. • In healthy people, CMV infection may manifest as a mild mono-lik.e illness, or may be asymptomatic. COMMONLY ASSOCIATED CONDITIONS • Although CMV retinitis occurs most commonly in patients with AIDS, it can also occur in severely immunocompromised individuals, such as those receiving chemotherapy. • Before HMRT. a diagnosis of CMV retinitis was associated with a median survival time of 6 months.

~ DIAGNOSIS HISTORY • Patients may present with decreased visual acuity, flashing lights (photopsias), or blind spots (scotomata). • One study found that 54% were asymptomatic. PHYSICAL EXAM • Physical exam shows yellow--white areas of retinal necrosis with some retinal hemorrhages that often start in the periphery and follow the vasculature centripetally. • There may also be hard exudates, and mottling of the retinal pigment epithelium. • Each lesion is most active at the borders. • As most patients are severely immunocompromised, there is usually minimal vitreitis. • Very early CMV may resemble cotton wool spots, but with lesions larger than 750 11-m, CMV must be considered. • Funduscopy may show a granular pattern, a fulminant/hemorrhagic appearance, or "frosted branch" angiitis.

DIAGNOSTIC TESTS & INTERPRETATION

Lab • C04 count and viral load are important lab tests to follow. It is not necessary to draw CMV blood serology as CMV has a high prevalence in the population. • Aqueous sampling with PCR analysis can be used to identify CMV DNA.

Imaging • Serial fundus photographs are helpful to document progression of disease. • Fluorescein angiography is not usually helpful in diagnosis.

DIFFERENTIAL DIAGNOSIS The differential diagnosis includes cotton wool spots from other causes. herpetic retinitis syndrome such as ARN and PORN, and toxoplasmosis.

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TREATMENT

MEDICATION First Line • In all FDA approved treatments of CMV retinitis, there is an initial period of high-dose antiviral induction followed by continuous maintenance. Initially, oral valgancidovir (the oral pro-drug of ganciclovir) 900 mg b.i.d for 21 days of induction followed by 900 mg q day for maintenance therapy can be used. The major side effect of valganciclovir/ ganciclovir is bone marrow suppression. - However, in eyes with macula threatening disease, IV gancidovir should still be considered. • IV ganciclovir can be administered 5 mg/kg IV b.i.d for 2 week.s followed by 5 mg/kg IV for maintenance therapy. The major toxicity of ganciclovir is myelosuppression. Granulocyte-macrophage colony stimulating factor should be used concomitantly to avoid myelosuppression. • Oral ganciclovir can be used as maintenance therapy, but recurrence is more frequent than with valganciclovir or IV ganciclovir, and the fellow eye is at greater risk of developing CMV retinitis.

HIVIAIDS-RELATED REnNOPAlliiES • IV fesc:arnet at 90 mglkg b.i.d for 2 weeks foiiOWI!d by 90-120 mglkg dally for maintenance Is another option. The principle toxicity of foscamet Is rena I dysfunction, electrolyte abnormalities, and possibly seizures. • Institution of HAART therapy is critical. It has raised the survival time from 0.65 years to>1 year, it has reduced the odds of CMV prog resslon, and the number of new CMV cases has declined. • Maintenance therapy may be discontinued in patients with CD4 > 100 cells/p.L who show no signs of progression AND who are on HAARJ:

Second Une • lntravltreal administration of gandclavlr 200 P.!r-2 mg weekly and fcscarnet 2.4 mg weekly. Induction with intravitreal injections is twice a week for 2-3 weeks. Intravitreal injection ID one eye obviously does not protect the other eye from developing CMV retinitis. • A gancldovlr lntravttreallmpia nt (VItrasert) may be considered in piltients who do not tolerate systemic treatment. but it does not provide systemic protection against CMV nor does it protect the other ~ from CMV. It typically lasts 2 years if CMV reslsta nee to gancldovlr does not develop. • lhe risks of intravitreal injections indude cataract, vitreous hemorrhage, retinal detachment, and infectious endophthalmitis. • IV cidofovir at 5 mg/k:g weekly for 2 weeks, then 5 mglkg Mf'l other week for maintenance. Cldofovlr may cause hypotony and anterior uveitis.

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ONGOING CARE

COMPUCATlONS • Immune Recovery Uveitis (IRU) Is a potential compllci!tlon of recovery from low CD4 counts. Patients who had CMV retinitis, who then have reconstitution of their immune system. may develop anterior or intermediate Mitis, cystoid macular edema, and epiretinal membranes. Patients com plain of vision loss, pal n, photophobia. and floaters. • Other complications of IRU indude posterior subcapsular cataracts, proIiterative vitreoretinopathy, and optic nerve neovascularizalion. • CMV retln ltls can cause retinal detachments. Regular monitoring is needed.

• Holland GN. AI OS and Ophthalmology: The first quarter century. Am I Ophthalmo/ 2008; 14S(3):

397-408. • Musch DC, Martin DF, Gordon JF, et al. Treatment of cytomegalovirus retinitis with a sustained-release gancidovir implant lhe Ganciclovir Implant Study Group. N Enrl J Med. 1997;337(2):83-90.

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CODES

ICD9 • 078.5 Cytomegaloviral disease • 363.20 Chorioretinitis, unspecified

ADDITIONAL READING

CLINICAL PEARLS

• Marlin DF, Sierra·Madero J, Walmsley S, et al; Valganciclovir Study Group. A controlled trial of valgancidovir as induction therapy for cytomegalovirus retln!tls. NEnrl J Med. 2002;346(1 S):1119-1126. Erratum In: N EnfiJ Med 2002;347(11 ):862. • Goldberg DE, Smithen LM, Angelilli A, et al. HIV· assodated retinopathy in the HAART Era. Retina

• After HIV retinopathy, CMV retinitis Is the most common ocular manlfestatlon of AIDS. It Is an AIDS defining illness. • Patients may be asymp!Dmalic or may have vision less, floaters, flashes, or blind spots. Retinal findings of vaso.dar angiitis, yellow-white retinitis with a granular appearance, and hemorrhage can be seen. • Treatment is usually started with oral valganddovir and HAART treatment is necessary to achieve any lasting rem ission. • Prognesis is improved since HAART, but is still poor.

2005;25(5):633~9.

• Thome JE, Jabs DA, Kempen JH, et at Studies of Ocular Complications of AIDS Research Group. lnddence of and risk factors for visual acuity less among patients with AIDS and cytDmegalovirus retinitis in the era of highly active antiretroviral therapy. Ophtflalmolagy 2006 Aug;113

I

(8):1432-1440.

FOU.OW-UP RECOM MENDA110N5 Patients should be followed dosely, especially if they have discontinued therapy as CMV retinitis has a high recurrence nate in patients with a CD4 count < 100. PROGNOSIS • lhe prognosis was almost uniformly fatal prior to the advent of HAARJ: • Now it carries a much better prognosis, but even with HAART, and anti·CMV therapy, mortality is still increased after CMV retinitis develops.

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HOMOCYSTINURIA Douglas M. Wisner

~ BASICS DESCRIPTION • Homocystinuria compromises a group of inborn errors of methionine metabolism tf1at result in elevated levels of homocysteine in the urine (homocystinuria) and blood (homocysteinemia). • Cystathione ,6-syntf1etase deficiency (classic homocystinuria) is the most common cause and is discussed here. • Other defects leading to elevated levels of plasma and urine homocysteine include defects in methylcobalamin formation and methylenetetrahydrofolate reductase deficiency. • Signs and symptoms of classic homocystinuria are systemic, primarily involving the ocular, nervous, cutaneous, skeletal, and hematologic systems. • Ocular involvement is marked by progressive myopia (nearsightedness) and ectopia lentis (dislocation of the native lens). EPIDEMIOLOGY

Incidence • Varies by region; the highest incidence in the world, a ratio of about 1:3000 live births, is found in Qatar. Other nations with high incidence include Norway (1:6400), Germany (1:17,800), and Ireland (1 :65,000). • General incidence is estimated to be 1:200,000 to 1:300,000 live births.

RISK FACTORS

Genetics • Classic homocystinuria is autosomal recessive. • The gene for cystathionine ,6-synthetase is located on chromosome 21q22.3. • Patients typically harbor 2 different mutations in the gene for cystathionine p-synthetase (i.e., compound heterozygotes). • Varying disease manifestations are felt to be related to the particular mutations inherited.

GENERAL PREVENTION • Newborn screening - Not available in all states -Tests for methionine levels o High false-negative rates secondary to normal neonatal levels during the first few days of life • Genetic counseling

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PATHOPHYSIOLOGY • Progressive lenticular myopia and eventual ectopia lentis • Acute glaucoma secondary to pupillary block • Thromboembolism secondary to increased vascular endothelial adhesiveness and platelet activation ETIOLOGY • Incompetence and disruption of the zonular fibers • Ischemia to brain and vital organs COMMONLY ASSOCIATED CONDITIONS • Developmental delay (common) • Thromboembolic disease (common)

~ DIAGNOSIS HISTORY • Birth history - Neonatal screening performed? • Development -Speech delay - Mental retardation - Behavioral/psychiatric disturbances • Family history - Consanguinity -Thromboembolic death at an early age • Ocular history - Poor vision - Profound nearsightedness (reading material held very close to face) -Eye pain PHYSICAL EXAM • General - Poor speech/interaction for age - Marfanoid habitus -Scoliosis - Pectus excavatum or carinatum - Genu valgum -Pes cavus - High arched palate - Dental crowding - Malar flush - Generalized osteoporosis • Ocular -Thick glasses/progressive and severe myopia - Increased intraocular pressure -Red eye - Ectopia lentis with disrupted zonular fibers o Usually after age 2 -Cataract - Retinal detachment - Optic atrophy - Staphyloma

DIAGNOSTIC TESTS & INTERPRETATION

Lab • Classie homocystinuria is a clinical diagnosis affirmed by laboratory and genetic testing. • laboratory testing reveals elevated levels of plasma metf1ionine and plasma homocysteine. • Urinary levels of homocysteine are elevated. This should be a freshly voided specimen as the compound is unstable. • Pyridoxine (86 ) challenge differentiates 86 responders from nonresponders and dictates treatment. - 100 mg pyridoxine PO x 1. - Plasma amino acids measured in 24 hours. -A reduction of 30% or more in plasma homocystine and/or plasma methionine concentration suggests B6 responsiveness. a If no significant change occurs, 200 mg pyridoxine PO x 1, then reassess as above. o If still no change has occurred, 500 mg of pyridoxine is given in a child or adult. - If plasma homocystine and methionine concentrations are not significantly decreased after the last dose of pyridoxine, it is concluded that the individual is 85 -nonresponsive. o Note: Infants should not receive more than 300 mg of pyridoxine. This can lead to ventilator-dependent respiratory failure.

Imaging • MRl with stroke protocol if any suggestion of focal CNS lesion on examination. • DEXA scan for osteoporosis monitoring.

Diagnostic Procedures/Other • Prenatal diagnosis possible with amniocentesis. • Molecular genetic testing is available to isolate the genetic mutations. • liver biopsy can be used to assay for cystathionine ,6-synthetase.

Pathological Findings • Disrupted zonular fibers (as opposed to Marfan syndrome where fibers tend to be stretched). • Ectopia lentis in homocystinuria can occur in any direction (contrary to classical teaching).

HDMDCYSTINURIA DIFFERENTlAL DIAGNOSIS • Trauma • Isolated OOJiar disease - Buphthalmos -Aniridia - Ectopia lentis et pupillae - FamiIial ectopia lentis - P'erslstent hyperplasia of the primary vitreous/persistent fetal vasculature -Coloboma • Infectious -Syphilis • Metabolic/syndromit - Marfan syndrome -Weill-Marchesani syndrome - Sulfrte oxidase defidency - Xanthine oxidase defidency - Molybdenum tofactor deficiency - Hyperlyslnemla - Methylenetetrahydrofolate reductase defldency

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TREATMENT

MEDICATION • 8(;fpyridoxi ne - 200-1 000 m!f-!4 hr Bti - 1-5 m!f-!4 hr py~daxlne o Drives methionine metabolism forward o Patients with some residual enzyme activity (40% of affected) will respond. • Bu supplementation • Betaine (1)[C] - 200-250 mg/kg/day - Remethylates homocysteine to mflhionine ADDITIONAL TREATMENT General MHSIII'eS • Address refractive error with glasses or contact lens. • Treat amblyopia, which can result from anisometropia. • Hydration to prevent thromboembolism.

SURGERY/OTHER PROCEDURES • Patients are at extremet,o high risk of lntraopetatlve stroke and thrombosis. • Urgent lens extraction for acute glaucoma caused by ectopia lentis • Elective lens extraction for extreme myopia or to prevent arute glaucoma - Accomplished via pars pia na lensectorny with successful lang-term outcome {2)[C]. • Thrombolysis for acute stroke

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ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Pediatric aphthalmologist • Contact lens speda list Uf aphaldc) • P'edlatrlc mftabollc dlsease spedalist • Hematology evaluation Patient MonltDrlng • Special intraopellltive antithrombotit measures are indicated if patients require a surgical procedure (3)[C]. • See " Follow-up· section. DIET Meth iani~restricted diet. PATIENT EDUCATION • Genetics Home Reference: Homocystlnu~a (http:l/gh r. nlm.nih.gov/condition=homocystinuria) PROGNOSIS • Usually limited lifespan (thromboembolism) and intelligence. • If ~ therapy Instituted at an eart,o age In a responsive patient, developmental delay and ectopia lentis can be prevented (4)[C].

REFERENCES 1. Lawson·Yuen A. l..l!'ly HL. The use of betaine in the treatment of elevaled homocysteine. Mol Genet Metab 2006;88(3):201-207. 2. Wu-Chen W, Letson R. Summers C. Functional and structural outcomes following lensectomy for ectopia lentis. JAm Assoc Pediatric O{irtha/

Strabismus 2005;9(4):353-357. 3. Lowe S, Johnson D, Tobias J. Anesthetic implications of the child with homocystinuria.J Clin Aneslh 1994;6(2):142-144. 4. Bulla! JP. O'Keefe M, Bowell R. Naughten ER. Ocular complications in homocystinuria-early and late treated. Br J Of/ltha/mo/1989;73:427-431.

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CODES

ICD9 • 270.4 Disturbances of sulphur-bean ng amino-add metabolism • 367. 1 Myopia • 743.37 Congenital ectopic lens

CLINICAL PEARLS • NeM!om screening currently has high fa Jse.negative !lites.

• Early treatment can reduce long-term complications. • Patients are at extremely high 11sk. of Intraoperative stroke and thrombosis. • Parents of patients with classic homocystinuria are at increased risk for thromboembolism as heterozygotes.

COMPUCATIONS • VIsual loss • Death (thromboembolism) • Fractures (osteoporosis)

345

H

HORNER SYNDROME Deepak P. Grover Ann P. Murchison Jurij R. Bilyk

~ BASICS DESCRIPTION • Horner syndrome {HS) refers to the clinical triad of ptosis. miosis. and at times anhydrosis. which results from an interruption in the oculosympathetic pathway. • May have iris heterochromia if congenital. • Transient conjunctival hyperemia • Congenital or acquired. EPIDEMIOLOGY

lnddence • Pediatric HS: 1.42 per 100,000 patients. • Acquired adult HS: Unknown.

Prevalence • Congenital HS: 1 in 6,250 births. • Acquired adult HS: Unknown.

RISK FACTORS • Head and neck trauma • Brainstem or cervical spine pathology • Neck or lung apex pathology, including benign tumors. malignancy. and inflammation

Genetics A rare genetic form is likely an autosomal dominant trait. The vast majority of HS is sporadic and acquired from a localized abnormality.

GENERAL PREVENTION None PATHOPHYSIOLOGY • First-order central sympathetic fibers descend from the hypothalamus through the midbrain and pons, and terminate in the intermediolateral cell column of the spinal cord (ciliospinal center of Budge) at the level of C8-T2. • Second-order preganglionic sympathetic fibers exit the spinal cord at the level of T1, enter the cervical sympathetic chain near the pulmonary apex and the subclavian artery, then travel up the sympathetic chain and synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery {CH4). • Third-order postganglionic fibers exit the superior cervical ganglion, ascend along the internal carotid artery and enter the orbit through the optic canal and cavernous sinus/superior orbital fissure. lntraorbitally, the fibers travel with sensory nerves and arteries to innervate the iris dilator and Milller muscle. EnOLOGY • First-order neuron lesions: Intracranial or cervical spine pathology. • Second-order neuron lesions: Lung apex and neck to level of carotid bifurcation. • Third-order neuron lesions: Carotid bifurcation to cavernous sinus.

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• N. B.: Although migraine and cluster headaches may rarely present as HS, carotid dissection must be ruled out in any patient presenting with pain (including headache). • N. B.: Cavernous sinus lesions rarely present as an Isolated HS. Typically cranial neuropathy {e.g., abducens nerve palsy) is also present. • N. B.: Orbital lesions never cause an isolated HS.

COMMONLY ASSOCIATED CONDITIONS See Table 1 in • Online Resources •.

~ DIAGNOSIS HISTORY • By far, the most frequent complaint is new onset, unilateral ptosis. • Patients rarely complain of visual problems secondary to miosis. • Transient redness of the affected eye. • Forehead anhydrosis is an infrequent complaint. • Duration of symptoms is important to elicit. • The most important symptom to obtain from the patient is the presence of any head, periorbital, or neck pain {sometimes described by the patient as a dull ache). • Additional history may be obtained on directed questions • Associated neurologic symptoms: - Hem isensory loss -Dysarthria -Dysphagia -Ataxia -Vertigo -Nystagmus • Recent or distant head, neck. or chest trauma, including surgery. • Any history of respiratory disease, including smoking. • Any history of cancer. PHYSICAL EXAM • 1-3 mm of upper eyelid ptosis secondary to MUller muscle paresis • Reverse ptosis (slight elevation) of the lower lid secondary to denervation of the inferior tarsal muscle. This finding is not always present, but is highly specific. • Miosis • Anisocoria that increases in the darlc. Dilation lag is usually present (the affected pupil dilates slowly in a dark room). • Anhydrosis is variable and difficult to test. • Conjunctival hyperemia may be noted in the first 2 weeks of onset. but is usually a transient phenomenon. • Iris heterochromia (hypopigmented iris) can be seen in congenital HS or in acquired pediatric HS (within a few months of birth).

DIAGNOSTIC TESTS 8r INTERPRETATION

Lab Initial lab tests • Initial lab studies are not necessary in the diagnosis ofthe HS. • Lab tests may be considered depending on localization and suspected etiology: -ACE and PPD placement if chest imaging is abnormal. -Urine test (vanillylmandelic acid [VMA]. homovanillic acid [HVA]) to rule out neuroblastoma in pediatric HS. Fallow-up ll special considerations Inspect old photographs for evidence of HS.

Imaging Initial approadl • Correct imaging is critical in the management of HS. • In many cases of HS, the history will provide important clues as to the etiology of the HS. • Any acute HS ( 1 episode (6). COGAN'S DISEASE • Topical corticosteroids and cycloplegics • Prednisone 2 mglkg for first week; slow taper • System1c Immunosuppression for underlytng systemic disease or disease unresponsive to mrticosteroids alone. • Check MRIInner ear, audiogram, and ed1oca rd iogram if diagnosis is suspected and start high-dose steroids.

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ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Patient Monitoring • Follow patients weekly until inffammation is controlled. o Go.a I is to haw patients on least amount of topica I corticosteroid tD control Inflammatlon and permanent corneaI scarring o Infectious Disease consult when indicated

REFERENCES 1. Knox Mc, Holsdaw DS. Imerstltlal keratltls./nt Ophtha/md Clin. 1998;38:183-195. [A] 2. Schwartz GS, Harrison AR, Holland EJ. Etiology of Immune stromal Onterstltlal) keratitis. Comea 1998

May;17:271-281. [A) 3. Liu E. SlomD'Iic AR. Indications for penetrating keratoplasty In canada. 1986--1995.Comea

1997;16:414-419. [A) 4. Dorrepaal SJ, Cao KY. Slomovic AR. Indications for penetrating keratoplasty in a tertiary care referral centre In Canada, 1996--2004. Can 1 Ophtha/mol 2007;42:244-250. [A) 5. Wilhelm us KR, Gee L, Hauck 'IN/, e1 al: Herpetic eye disease study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology 1994:1 01 :1883-1895: discussion

95-96. 6. Herpetic Eye Disease Study Group: Oral Acyclovir for herpes simplex virus:effect on prevention of epithelial keratitis and stromal keratitis. Arch Ophtha/md 2000; 118:1 030-1036. 7. Samicola V, Toro P. Oeep anterior lamellar keratoplasty in herpes simplex mrneal opacities. Cornea 2010;29:60-64. 8. Tambasco FP, Cohen EJ, Nguyen LH, et al. Oral acyclovir after penetrating keratoplasty for herpes simplex keratitis.ArdJ Ophtha/mo/1999;117:

445-449.

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CODES

ICD9 • 053.21 Herpes zoster keratoconjunctivitis • 090.3 Syphilitic interstitial keratitis o 370.50 InterstitiaI keratitis, unspecified

CLINICAL PEARLS • Unilateral: Acquired syphilis, TB, mumps, herpetic disease, and Cogan's syndrome • Bilateral: Congenital syphilis, leprosy, EBV. Lyme's disease, Cogan's syndrome, and ond1ocerciasis

SURGERY/OTHER PROCEDURES • Penetrating keratoplasty (PKP) • Deep anterior lamellar keratoplasty (DAL.K) (7) • Hlgh-rtsk. of graft rejection wtltl active corneal neovascularization • Consider antiviral prophylaxis in herpetic disease and PKP (8).

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INTRAOPERATIVE ROPPY IRIS SYNDROME [IRS] Brad H. Feldman Mark H. Blecher

~ BASICS DESCRIPTION • An iris abnormality that may manifest preoperatively with poor pupil dilation and may manifest intraoperatively with some or all of the following findings: - Billowing ofthe iris stroma during normal irrigation - Iris prolapse to corneal incisions - Poor maintenance of dilation with progressive miosis (pupil constriction) - Ineffectiveness of pupillary stretching to maintain pupil expansion EPIDEMIOLOGY Occurs in males > females

Prevalence In the US, occurs in

~2-3%

of cataract surgeries

RISK FACTORS • Most frequent and severe in patients exposed to selective a,-antagonists Associated a,-antagonists: - 1A selective o Tamsulosin (Fiomax): up to 90% of patients taking this drug may have IFIS o Alfuzosin (Uroxatral): up to 15% of patients taking this drug have IFIS o Silodosin (Rapaflo): unknown% - Nonselective: lower risk o Terazosin (Hytrin) o Doxazosin (Cardura) o Naftopidil (Fiivas) Use of other medicinesfsupplements: lowest risk - 5-alpha reductase inhibitors o Finasteride o Dutasteride (Avodart) - Saw palmetto -Antipsychotic drugs

364

GENERAL PREVENTION Avoidance of associated medications

~ DIAGNOSIS

PATHOPHYSIOLOGY • Alpha 1A iris smooth muscle adreno receptor may be blocked by associated antagonists. • Blockage may lead to loss of dilator muscle tone. • Decreased dilator tone may lead to poor dilation and intraoperative floppiness.

HISTORY Important to screen all patients for current or past use of all associated agents

ETIOLOGY IFIS may occur even with short-term exposure to associated medications (~2 days reported) or use in the distant past COMMONLY ASSOCIATED CONDITIONS Any condition treated with associated medications • Benign prostatic hypertrophy • Prostate cancer • Urinary retention (menfwomen) • Hypertension • Hair loss • Psychiatric disturbances

Geriatric Considerations The incidence of benign prostatic hyperplasia (BPH) is ~50% in men >50 years and 90% in men >85 years of age.

PHYSICAL EXAM Poor or slow dilation preoperatively may suggest IFIS DIFFERENTIAL DIAGNOSIS • Poor preoperative dilation -Prior injury, inflammation, infection, or topical miotic use • Iris prolapse - Short or inadequately constructed wounds - High intracameral pressure

.

TREATMENT

MEDICATION • Stopping associated agent preoperatively - May improve dilation but will not typically decrease IFIS severity - Most surgeons do not stop these agents • Preoperative atropine - Improves dilation but does not reliably decrease IF IS severity • lntracameral a 1-agonist injections (preservative-free only) -Epinephrine 1:1000 mixed 1:3 or 1:4 with balanced salt solution to buffer - Phenylephrine (not available in the US)

UITJIAOPERATIVE FLOPPY IRIS SYNDROME (IRS) ADDITIONAL TREATMENT

General M"sures

• Highly cohesive ophthalmic vismelastic devices (OVD)

- Sodium hyaluronate 2.3% (Healon 5) may fadIitate pu pll expansion and prevent Iris movement • Other specialized viscoelastics - Hyaluronic acid 1.6% and chondroitin sulfate 4.0% (DisCoVIsc) may remal n In the eye longer with higher flow rates

SURGERY/OTliER PROCEDURES • Longer, more stable, wound tunnels may decrease iris prolapse • Pupil expansion -Pupillary rings: Malyugin (Microsurgical technology), Graether silicone ring (Eagle Vision), 55 Pupil Ring (Mordter GmbH), Perfect Pupil (Milvella Ltd.) - Iris retractors/hooks: Disposable 6-0 nylon (Akon) or reusable 4-0 polypropylene (Katena Products. FCI, Oasis Medical)

•

ONGOING CARE

PATIENT EDUCATION • Patients should be infonned of risks of associated medldnes. • Prescribing physicians should consider referring patients to an ophthalmologist for consultation before start!ng these medldnes. • Patients must inform their ophthalmologists if they are currently or have ever taken these medidnes. COMPLICAnONS • IFIS is associated with a higher rate of posterior capsule rupture, vitreous loss, and iris damage. • The rate of complication Is highest when the ophthalmologist is unaware of patient use of associated medicines.

ADDITIONAL READING • Chang OF, Braga·M ele R. Mamalis N, et al. ASCRS white paper: Clinical re¥iew of floppy-iris syndrome. 1 Cataracr Refract Surg 2008;34:21 53-2161. • Chang OF, Campbell JR. Intraoperative floppy-iris syndrome assodated with tamsu losin. 1Cataract Refract Surg 2005;31 :664-673. • Chang OF, Osher RH, Wang L, et al. Prospective multicenter evaluation of cataract surgery in patients taking tarnsulosln (Fiomax). Ophthalmology 2007;114:957-964.

.

CODES

ICD9 364.81 Floppy iris syndrome

CLINICAL PEARLS

a,

• IFIS Is associated with -antagonist use. • Outcomes are best if IFIS risk. is identified preoperatively. • Several strategies can be used to successfully manage IFIS intraoperatively. • Patients and physida ns should be educated about IFIS risks.

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365

IRIDOCORNEAL ENDOTHELIAL (ICE] SYNDROME Michael J. Pro

~ BASICS DESCRIPTION An acquired and usually unilateral condition affecting young and middle-aged women. The condition causes various degrees of iris abnormalities, corneal edema, and glaucoma in affected individuals. The etiology is unknown, but is thought to be due to a viral infection. It affects all races. The hallmark of the c.ondition is an abnormal c.orneal endothelium, which advances onto the anterior chamber angle and iris.

Pediatric Considerations It rarely affects children. A case of an 11-year-old girl with ICE syndrome and glaucoma was reported (1 ).

Geriatric Considerations Older patients may have limitation in vision in the affected eye due to corneal disease and/or glaucomatous optic neiVe damage.

Pregnancy Considerations Glaucoma medications may need to be adjusted during pregnancy and nursing.

EPIDEMIOLOGY ICE syndrome is a very rare condition with no known genetic risk factors. GENERAL PREVENTION There is no known preventive measure ICE syndrome. ETIOLOGY Thought to be due to a viral infection. In one study 5 out of 9 c.omeal specimens were positive for herpes simplex virus (HSV} DNA in the c.omeal endothelium. The specimens were negative for herpes zoster virus or Epstein-Barr virus DNA (2).

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COMMONLY ASSOCIATED CONDITIONS • There are 3 variants that have slightly different presentations and courses. All 3 variants are associated with corneal disease and glaucoma. • Essential or progressive iris atrophy is notable for corectopia (distorted pupil) or pseudopolycoria (a "sec.ond" pupil). Marked iris atrophy is a hallmark of this variant. Severe anterior segment abnormalities may include extensive peripheral anterior synechiae (PAS). PAS formation is progressive, leading to angle closure and frequently elevated intraocular pressure (lOP). Sec.ondary angle-closure glaucoma is present in at least 50% of individuals. • Iris nevus syndrome (Cogan Reese) is notable for the presence of a large nevus c.overing a large part of the iris or multiple iris nodules. Specimens from eyes enucleated for presumed malignancy demonstrated iris tissue in these nevi. • Chandler's syndrome is notable for a corneal endothelium with a characteristic "hammered silver• appearance. Chandler's syndrome variant has a lower incidence of glaucoma and a higher incidence of corneal edema due to dysfunction of normal endothelial function.

~ DIAGNOSIS HISTORY Signs and symptoms: • Almost always has a unilateral presentation • Decreased vision due to c.orneal edema. which is frequently worse in the morning upon awakening • Pain is usually due to corneal edema, but may be from elevated lOP later on in the c.ourse of the disease. • Iris abnormalities noticed by patient or family and friends • Decreased visual function due to glauc.oma is present in advanced disease. PHYSICAL EXAM Slit lamp exam can demonstrate corneal edema and abnormal corneal endothelial appearance. Areas of abnormal corneal endothelium may be seen in the fellow eye. Iris atrophy and pupillary irregularity or decentration are hallmarks of progressive iris atrophy. Gonioscopy can reveal complete angle closure, especially in essential iris atrophy. DIAGNOSTIC TESTS It INTERPRETATION • Visual acuity may be reduced in the affected eye and may fluctuate with varying degrees of c.omeal edema. • Visual field may be abnormal if there is co-existing glaucomatous optic neuropathy.

IRIDOCORNEAL ENDDTHEUAL (ICE) SYNDROME Imaging • Optic nerve Imaging can be helpful In establishing diagnosis of glaucoma or assisting In detection of glaucoma progression. Imaging devices indude optic nerve photography, opticaI coherence tomography (aen, confocal scanning laser ophthalmoscopy (Heidelberg Retina TomographHRll, and scanning laser pola~metry (GDx). • Corneal disease is mostly followed dinically, but specular microscopy can demonstrate characteristic endothelial cell abnormality with variability in cell size and shape as well as loss of the normaI clear hexagonal margins. • Pachymetry can be useful to quantify ccmeal thicken ing.

DIFFERENTlAL DIAGNOSIS • Fuch's dystrophy may have a similar corneal appearance, but with no anterior dlamber abnormalities. • PPMD--may appear similar, but Is familial and bilateral • Axenfeld Riegers is congenillll and bilateral and may have systemic findings. sud1 as denllll abnormalities. • Iris melanomas can appear similar to pure Cogan-Reese syndrome.

.

TREATMENT

ADDITlONAL TREATMENT General NleasUNS • Corneal edema can be treated with hypertonic saline drops or ointment (sodium chloride solution ar ointment 5%}. • Elevated lOP and glaucoma can be treated with anti-gIaucoma drops. • Laser trabeculoplasty is not usually beneficial in this cype of chronic angle-dosure glaucoma. • Laser pe~phera I lrldotorny does nat halt the progression of progressive angle closure tl1at is a hallmark of this condition.

SURGERY/OTHER PROCEDURES

PROGNOSIS

• Cataract surgery can be complicated by poor papillary dilation and tl1e presence of an IcE membrane over the anteriar capsu Ie. • CorneaI transplants are performed for chronically edematous and hazy corneas. Newer partial-thickness corneal transplant procedures may reduce the Incidence of rejection. Descemet Stripping Automated Endotl1elial Keratoplasty (DSAEK} involves Descemet's and endothelial membrane transplant. • Iris reconstruction surgery for improved cosmetic appearance or to ameliorate glare can be undertaken alone or at the time of cataract surgery. The iris tissue is often friable and difficult to suture. ArtifidaI iris implantation can be usfluI (3). • Glaucoma in ICE syndrome may be more severe and refractory to surgical management Traber:ulectomy may fall more frequently, and tl11s Is thought to be partially due to growth of abnormal corneal endothelium over the internaI sderal ostium. Trabeculectorny in patients with Chandler's syndrome may be more successful than in the other variants. • Trabeculectorny may be more successful If performed with an anti-metabolite sud1 as mitomycin C • Glaucoma drainage implants (tube shunts} may be more successful than trabeculectomy as they may be less likely to be blocked with an endotheliaI membrane (4}.

• VIsual prognosis Is mostly related to seve~ty of glaucoma but may be affected by success In restoration of corneal clarity. • Compi ications from calllract surgery can also affect visuaI prognosis. • VISual prognosis is generally more poor for Individuals who reject multiple corneal transplants. • Irregular refractive errors after corneaI surgery may require use of specialty contact lenses.

$

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS l'atient Monifloring • Affected individuals should be followed up periodically for routine eye care. Mild cases without glaucoma may be seen yearly. • Monilllring for di!W!Iopment of glaucoma indudes evaIuation of optic nerve appearance with either direct or lndlrect ophthalmoscopy. VIsual fleld testing and op1ic neM imaging may also be appropriate. • Individuals with glaucoma or corneal disease may need mare frequent monitoring • CorneaI decompensation and glaucoma may require sub-specialty referral.

REFERENCES 1• Salim S, Shields MB, walton D. lridocomeal endothelial syndrome in a d1ild. 1 Pediw Oi/lthlllmo/ Strabismus 2006;43:308-3 t D. 2. Alvarado JA. Underwood JL, Green WR, et al. Detection of herpes simplex viral DNA In the lrldoccmeal endothelial syndrome. Aid! Oi/lthalmo/ 1994; 112: 1601-1609. 3. Kh ng C, Snyder ME. Iris reconstruction with a multipiece endocapsular prosthesis in iridocomeal endothelial syndrome. J Cataract Refract Surg 200 5;31 :2051-2054. 4. Doe EA. Budenz DL, Gedde SJ, lmaml NR. Long-term surgical outcomes of patients with glaucoma secondary to the iridocomeal endothelial syndrome. O,dJ thalmology 2001; 108:1789-179 5.

.

CODES

ICD9 • 365.43 Glaucoma associated with other anterior segment anomalies • 371.20 Corneal edema, unspecified

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367

IRIS ATROPHY Anita P. Schadlu Ramin Schad/u

~ BASICS DESCRIPTION • Iris atrophy can be caused by a myriad of ocular disorders. -The etiology can be determined by careful history taking and physical examination.

Pediatric Considerations Iris atrophy in the pediatric population may indicate syndromes such as ocular albinism or Axenfeld-Rieger syndrome.

ETIOLOGY • • • • • • •

Pregnancy Considerations Iris atrophy with uveitis in a pregnant patient may suggest a diagnosis of herpes simplex, herpes zoster, or Fuchs' heterochromic iridocyclitis (lin ked to rubella virus). All of these infectious etiologies should be addressed.

EPIDEMIOLOGY Incidence The incidence varies depending upon the etiology and the population in question. lridocomeal endothelial (ICE) syndrome is quite rare, whereas herpes zoster iritis occurs in ~43% of patients with herpes zoster ophthalmicus, a fairly common condition (1).

Prevalence The prevalence varies depending upon the etiology of the iris atrophy. In patients with Fuchs' heterochromic iridocyclitis, the prevalence of iris atrophy approaches

90%(2).

RISK FACTORS History of common causes of iris atrophy such as chronic or recurrent uveitis and certain types of glaucoma

Genetics • Axenfeld-Rieger syndrome is autosomal dominant. The responsible gene has been isolated to chromosome 4q25. • Ocular albinism follows all of the inheritance patterns, including X-linked recessive pattern.

PATHOPHYSIOLOGY • In cases of chronic inflammation, iris atrophy manifests as loss of detail and density of the anterior iris as the iris stroma breaks down. • In Axenfeld-Rieger syndrome, iris atrophy results from abnormal embryologic development of the iris and anterior chamber angle. • In ocular albinism, the number of melanosomes in the iris pigment epithelium is decreased, resulting in transillumination defects.

368

• • •

Herpes simplex uveitis Herpes zoster uveitis Fuchs' heterochromic iridocyclitis Pigment dispersion syndrome and secondary glaucoma Pseudophakic pigment dispersion from iris chafing Traumatic or iatrogenic ICE syndrome - Essential iris atrophy subtype - Minimal iris atrophy may also be seen in Chandler's syndrome and Cogan-Reese syndrome subtypes. Axenfeld-Rieger syndrome Ocular albinism Ischemic iridopathy -Diabetic - Ocular ischemic syndrome - Systemic cryoglobulinemia

COMMONLY ASSOCIATED CONDITIONS • Chronic uveitis • Glaucoma • Cataract

~ DIAGNOSIS HISTORY Patients may be any age. They should be questioned for a history of recurrent red eye, pain, glaucoma, and visual loss.

PHYSICAL EXAM • The patient's visual acuity and intraocular pressure should be accurate~ determined. - Increased intraocular pressure can be seen in: o Herpes simplex uveitis, herpes zoster uveitis, Fuchs' heterochromic uveitis, any form of chronic uveitis. ICE syndrome, Axenfeld-Rieger syndrome. and pigment dispersion glaucoma • Laterality of the iris atrophy is important in making the diagnosis of the underlying disease. • Fuchs' heterochromic iridocyclitis and herpetic uveitis are typically unilateral, but can be bilateral. ICE syndrome is unilateral, whereas Axenfeld-Rieger syndrome is bilateral. • Iris atrophy can be subtle. It is best detected by performing transillumination in the slit-lamp exam.

• Different patterns of iris atrophy may suggest the underlying disorder - Iris atrophy at the pupillary margin and/or persistent pupillary dilation suggests herpes simplex uveitis (3). - Sectoral iris atrophy suggests herpes zoster uveitis or herpes simplex uveitis (4). - Diffuse atrophy suggests Fuchs' heterochromic iridocyclitis. - Radial iris atrophy suggests pigment dispersion syndrome (which can cause secondary glaucoma). This pattern results from the lens zonules eroding the iris pigment epithelium. - Iris corectopia, ectropion uveae, and/or iris hole formation can be seen in ICE and Axenfeld-Rieger syndromes. • The corneal exam can also aid in diagnosis. - Corneal edema can be seen in ICE syndrome. - Keratic precipitates on the corneal endothelium suggest prior or current anterior uveitis. Diffuse keratic precipitates are seen in herpetic uveitis and Fuchs' heterochromic uveitis. • Gonioscopy should be performed. - Peripheral anterior synechiae suggest prior uveitis or ICE syndrome. - Heavily pigmented trabecular meshwork suggests pigment dispersion syndrome. • The presence of a cataract can suggest chronic uveitis. • The posterior segment examination is important in the workup of iris atrophy. -The optic nerve should be evaluated for glaucomatous cupping. -The retina should be examined for signs of ocular albinism as well as ischemic processes.

DIAGNOSTIC TESTS & INTERPRETATION Lab Initial lab tests • laboratory testing is not often indicated, but can be directed by the suspected underlying diagnosis. - PCR can be performed on aqueous samples to detect herpes simplex, varicella zoster, or rubella virus. Follow-up & special considerations Patients with iris atrophy from any etiology should be monitored for glaucoma, cataract formation, and visual loss.

IRIS ATROPHY Imaging • Slit-lamp photographs with and w!thout transillumination may be obtained to document the degree of iris atrophy. • In cases whel'l! iris-3 prism diopters). • Patients with 4th nerve palsy should not have ptosis, but may volitionally close 1 eye to avert diplopia.

DIAGNOSTIC TESTS & INTERPRETATION

Lab In adults. worl;-up for diabetes, hypertension and hypercholesterolemia should be considered. Imaging If a suspected 4th nerve palsy does not improve after a few months, neuroimaging should be perfonmed.

DIFFERENTIAL DIAGNOSIS • Bilateral 4th nerve palsies can occur, especially after trauma. Myasthenia gravis, Graves ophthalmopathy, and skew deviation may mimic a 4th nerve palsy. Patients with ocular myasthenia often have variable ptosis and variability in their eye misalignment with diurnal variation. Patients with Graves ophthalmopathy may show lid retraction, proptosis, conjunctival chemosis, and often have abnormal TSH. It is difficult for a non-specialist to differentiate 4th nerve palsy from skew deviation. Patients with skew deviation may have stroke history or brainstem findings, show incyclotorsion on Maddox rod testing, and often have less vertical strabismus in the supine, compared to uprigh~ position. • Rarely giant cell arteritis may mimic or cause 4th nerve palsy -Patients with superior oblique myokymia (due to neurovascular compression of the 4th cranial nerve root exit zone, multiple sclerosis, or posterior fossa tumor) may complain of episodic tilting.

ISOLATED TROCHLEAR NERVE (CRANIAL NERVE IV) PALSY

.

TREATMENT

ADDITIONAL TREATMENT General Measures Patients may find it helpful to tiIt their head away from the side of the palsied nerve. Pr1sm glasses are often helpful If there Is vertical or diagonal diplopia. If the patient has intolerable torsional diplopia, patching or translucent tape over a glasses lens can be of help. Issues for Referral Airy non·resoMng 4th nerve palsy should be referred for ophthalm k: assessment. SURGERY/OTHER PROCEDURES If new-onset diplopia does not impl'lM! after a year, and prism glasses do not help the patient. strabismus surgery can be considered.

•

ONGOING CARE

.

CODES

PROGNOSIS Many patients with microvascular or traumatic 4th nerve palsy have some improvement 3-9 months after presentation.

ICD9 • 368.2 Diplopia • 378.53 Fourth nerve palsy

REFERENCES

CLINICAL PEARLS

1. Lanning B. Kline. NeurrHJphtha/mo/ogy ll!Mew manual, 6th ed. Slack Incorporated: Thorofare. NJ, 2008. 2. Lanning B. Kline. Neuro-cphtha/mo/ogy. Seaion 5. Basic and Clinical Sdence Course. American Acaderrry of Ophthalmology: San Ffandsco, CA, 2009. l Burde RM, Savino PJ, Trobe JD. COnical decisions In MJurcrophthalmology, 3rd ed. Mosby; St Louis, M0,2002.

• With 4th nerve palsy, there is a characteristic head tilt to the side opposite to the palsy. Review of old photos (e.g., photo I.D.) may help determine chron icily of 4th nerve palsy. • 4th nerve palsy can occur even after relatively minor head trauma.

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379

JUVENILE IDIOPATHIC ARTHRITI5-RELATED UVEITIS Darrell E. Baskin

~ BASICS DESCRIPTION • Juvenile idiopathic arthritis (JIA)-related uveitis is a group of idiopathic arthritides with an onset before 16 years of age that persists longer than 6 weeks. • There are 7 subtypes of JIA -Systemic arthritis: Arthritis in one or more joints accompanied or preceded by fever and accompanied by one of the following: Evanescent, erythematous rash, generalized lymph node enlargement, hepatomegaly and/or splenomegaly, or serositis - Oligoarthritis: Arthritis in 1--4 joints in the first 6 months of disease. Oligoarthritis is further subcategorized as persistent oligoarthritis (affecting not more than 4 joints throughout the disease course) or extended oligoarthritis (affecting a total of more than 4 joints after the initial 6 months) - Polyarthritis (RF negative): Arthritis in 5 or more joints in the initial 6 months and a negative test for rheumatoid factor (RF) - Polyarthritis (RF positive): Arthritis in 5 or more joints in the initial 6 months and a positive test for RF on 2 occasions at least 3 months apart during the first 6 months of disease - Psoriatic arthritis (PsA): Arthritis and psoriasis or arthritis and at least 2 of the following: Dactylitis, nail-pitting or onycholysis, or psoriasis in a first-degree relative - Enthesitis-related arthritis (ERA): Arthritis and/or enthesitis (tenderness at the insertion of a tendon, ligament, fascia, or capsule to bone) with at least 2 of the following: Presence or history of sacroiliac joint tenderness, HLA-B27 antigen, onset of arthritis in male over 6 years of age, acute (symptomatic} anterior uveitis, or history of ankylosing spondylitis, ERA, sacroiliitis with inflammatory bowel disease, Reiter syndrome or acute anterior uveitis in a first-degree relative - Undifferentiated arthritis: Arthritis that fulfills criteria in no category or in 2 or more of the above categories EPIDEMIOLOGY

Incidence The exact incidence of JIA is unknown. The reported incidence varies from 0.008-0.226 per 1,000 children per year.

Prevalence • The exact prevalence of JIA is unknown. The reported prevalence varies from 0.07--4.01 per 1,000 children. • The prevalence of uveitis within known JIA populations varies from 4-38% worldwide. Analysis of pulled data suggests a cumulative prevalence of uveitis of 8.3% of JIA patients.

380

RISK FACTORS Risk factors for developing JIA uveitis include ANA positivity, early age at onset of arthritis (90% with surgery (3)[8], (4)[C] Postoperative visual acuity variable but can be good with successful hole dosure

COMPUCAnONS o Surgical complications - Cataract (common) - Retinal tear or detachment (uncommon) • Macular hole associated retinal detachment (rare)

.

CODES

ICD9 362.54 Macular cyst. hole, or pseudohole al retina

CLINICAL PEARLS • Macular pseudohole can often be differentiated from macular hole by a negative Watzke-AIIen sign and relatively good visual acuity. • Patients with suspected macular hole should be referred to a vltreored nal surgeon for evaluation and consideration of surgery. o V'ISual prognosis variable but often good with limely

surgeI)'.

I 413

MAUGNANT GlAUCOMA Anand V. Mantravadi

~ BASICS DESCRIPTION • An uncommon form of secondary glaucoma occurring post intraocular surgery characterized by a flat or shallow anterior chamber, absence of pupillary block, and elevated intraocular pressure. Expansion in vitreous volume due to sequestration of aqueous in the posterior segment with resultant anterior shift in the lens iris diaphragm. • "Malignant glaucoma" -named by Von Graefe in 1869- refers to the likelihood that this progressive condition will not improve spontaneously. -Synonyms: Aqueous misdirection syndrome, ciliary block glaucoma, and dliovitreal block. EPIDEMIOLOGY

Incidence • 2-4% in eyes undergoing glaucoma filtration surgery for angle closure glaucoma (1) • Can occur at any time following surgery • No established racial, sexual predilection

RISK FACTORS • Small eyes with small anterior hyaloid surface • Filtering surgery in eye with history of angle closure such as shallow chamber and peripheral anterior synechia • History of malignant glaucoma in fellow eye

Genetics Unknown for malignant glaucoma - but smaller eyes with angle closure have predisposition to development of malignant glaucoma, and eye size has a genetic basis with many genes associated with angle closure (2).

GENERAL PREVENTION Involves preoperative identification of high risk. eyessmall eyes with a history of angle closure or that of malignant glaucoma. PATHOPHYSIOLOGY • Under homeostatic conditions, aqueous volume flows predominantly anteriorly exiting through trabecular and uveoscleral outflow pathways and, to a lesser degree, aqueous circulates posteriorly into and around the vitreous body. • Under pathologic conditions, a shift to greater aqueous flow posteriorly occurs incited by sudden anterior chamber decompression (i.e., anterior chamber entry, overfiltration). When combined with a fundamentally decreased rate of aqueous exchange from the ciliary processes both across the anterior hyaloid and through the vitreous gel, the result is vitreous volume expansion through aqueous sequestration, and an anterior shift of the lens-iris diaphragm axis. The anterior chamber space is consequentially shallowed or flattened, further obstructing aqueous outflow through angle closure resulting in elevated lOP.

414

ETIOLOGY • The exact initiating event is not known but appears strongly related to an abnormal interaction between the ciliary processes, the lens, and the anterior vitreous face, seemingly induced by postoperative anterior chamber decompression leading to an anterior shift in the lens-iris diaphragm and diversion of aqueous into the vitreous cavity (3). • Smaller/hyperopic eyes- with tendency toward angle closure glaucoma, have correspondingly smaller anterior hyaloid surface area, and less space between the ciliary processes and the anterior hyaloid. Consequentially, if a shift in the lens-iris diaphragm occurs abruptly, contact between the ciliary processes and anterior hyaloid occurs. Aqueous is then disproportionately circulated posteriorly with resultant vitreous volume expansion and further flattening of the anterior chamber with elevation in intraocular pressure. COMMONLY ASSOCIATED CONDITIONS • Chronic angle closure • Hyperopia • Nanophthalmos

~ DIAGNOSIS HISTORY Malignant glaucoma can present any time after any intraocular surgery in phakic, pseudophakic:. or aphakic eyes, but most typically arises in eyes with a history of angle closure undergoing glaucoma filtration surgery. It has been reported rarely after laser iridotomy and miotic administration. PHYSICAL EXAM • Shallow anterior chamber: Uniform decrease in anterior chamber depth centrally and peripherally. • Absence of pupillary block.: Reflected by presence of patent iridotomyliridectomy. • Elevated intraocular pressure (lOP) - lOP may not be present, or only modestly elevated in the early stages of ciliary block in the presence of a filtering procedure. • Absence of simulating conditions causing posterior volume expansion: Choroidal effusion, hemorrhage: As visualized with indirect ophthalmoscopy. DIAGNOSTIC TESTS & INTERPRETATION

Lab • Slit-lamp exam may reveal elevated bleb initially with gradual flattening and disappearance upon further posterior misdirection and sequestration of aqueous. • Gonioscopy may reveal closed angle or obscured angle structures. and possibly visualization through the iridotomy of ciliary processes pushed forward.

Imaging • Ultrasound biomicroscopy (UBM) can demonstrate irido-corneal contact, decreased anterior chamber depth, forward displacement of the lens-iris diaphragm, and ciliary processes. • B-mode ultrasound can confirm absence of posterior space-occupying mechanism such as choroidal hemorrhage or effusion if visualization is poor with indirect ophthalmoscopy.

Diagnostic Procedures/Other • Anterior-segment optical coherence tomography (AS-OCT): Can noninvasively demonstrate anterior chamber angle structures and quantitatively assess the anterior chamber angle • laser iridotomy: Must be performed if not already present to diagnostically exclude pupillary block, and therapeutically relieve block if present • Fluorescein injection through peripheral vein, with visualization of fluorescein-tinged aqueous fluid flowing posteriorly shortly thereafter can confirm diagnosis

Pathological Findings • Smaller eyes have thicker sclera with a reduced ability to remove suprachoroidal fluid. • Malignant glaucoma has been proposed to involve a pathologic behavior of the vitreous gel with poor vitreous conductivity of fluid (4).

DIFFERENTIAL DIAGNOSIS • Pupillary block -Will typically demonstrate elevated lOP, preserved central anterior chamber depth, closed angle, and iris bomM of variable degrees. If patency of iridotomy is doubted, then another should be performed to exclude pupillary blade • Choroidal effusion - Serous: Gray-light brown choroidal elevation directly visualized or observed with B-scan ultrasound. Typically associated with low lOP, and shallow anterior chamber. Must consider overfiltration or wound leak if following filtration surgery. - Hemorrhagic: Dark-brown or red effusion directly visualized or observed with B-scan ultrasound. Typically associated with uniform anterior chamber shallowing or flattening, increased lOP. and frequently preceded by pain. • Overfiltration • Shallow anterior chamber associated with low lOP. If low lOP is accompanied by high/diffuse bleb morphology: likely overfiltration. If low lOP is accompanied by lowtflat bleb: Must exclude bleb leak. • Lens related angle closure: With anterior shift of lens-iris diaphragm and resultant angle closure. - Phacomorphic glaucoma: Anterior shift due to intumescent lens - Lens dislocation: Anterior shift due to zonular laxity as in pseudoexfoliation or other predisposing condition (i.e., Marfan's, trauma, etc.) • Infusion misdirection syndrome - Intraoperative condition due to misdirection of irrigating fluid posteriorly, potentially through iridotomy or zonular dehiscence -expanding vitreous volume and resultant anterior shift of iris/posterior capsule.

MALIGNANT GLAUCOMA

.

TREATMENT

MEDICATION • Cycloplegia/mydriasis: Widens dliary body diamell!r through contraction of dllator muscle of!~s Increasing diffusional area for aqueous; pulls lens posteriorly by tightening zanules through unopposed action of longitudinal muscle with circular musde paralysis. • lOP rna nagement -Aqueous suppression: Beta-blockers. carbonic anhydrase inhibitors. and alpha-agonist - Osmotic agents (Mannitol, lsosorbide): Decrease vitreous volume by increasing osmotic grc~d ient between blood and ocular fluids causing fluid to be drawn intrawscular Geriatric Considentfions Osmotics are relatively contraindical!!d in patients with renal or candiovasaJiar compromise. Signs of atropine tnxicity should be monitored in elderly patients. Pediatric Conside1'8fions AI pha agonlsts have potentially serious adverse effects in children and are contraindicated in children < 2 years old. Plwgnency Conslderetlons Aqueous suppressants and osmotic agents are classified as dass Cin pregnancy - with letaI risk revealed in animaI studies, but nat established or studied in humans. ADDITIONAL TREATMENT Genelal Measures • Miotics Clllltraindicated • If attack broken medically (chamber deepening, nomnalization of lOP}, can taper off hyperosmotics, and aqueous suppressants with long-term use of cydoplegialmydriasis due to risks of reoccurrence Issues for Refetral • Patients nat adequately responding to medicaI therc~py require surgical inl!!rvention. • Response may develop days after initiating medical thelllpy. SURGERY/OTHER PROCEDURES • Nd: YAG laser disruption of anterior hyaloid face: Can be attempl!!d in typically aphakic or pseudophakic patients not responding to medical thelllpy (5)[C]. Response can be observed as progressive deepening of anterior dlamber over hours--SO years and in all diabetics to improve prognosis with early diagnosis and treatment.

4. Nedand PA. The Ahmed glaucoma valve in neovascular glaucoma (An AOS Thesis). Trans Am Ofi!thalma/ Soc 2009;107:325-342. 5. Sidoti PA, Dunphy TR, Baerveldt G, et al. Experience with the Baerveldt glaucoma implant in treating neovascular glaucoma. Ophthalmology 1995;102(7):1107-11 18.

PROGNOSIS Guarded prognosis: Suc.cess depends on prevention and treatment of neDYiiSCular glaucoma early in its course and the ability to control the underlying disease

.

process.

COMPUCATlONS Chronic pain Complete loss of vision Choroidal effusions Suprachoroidal hemorrhage Phthisis • Loss of eye • • • • •

Admwlon Crlterla Inpatient admission required only in those patierrts who have uncontrolled systemic medicaI conditions.

REFERENCES

Nursing IV lnsenlon and EKG manItoring perloperatlvely and when IV mannitoI is used to decrease vitreous

1. Sivak.-Callcott JA, O'Day DM, et al. Evidence-based

volume.

Discharge Criteria Once systemic medical conditions ane controlled

•

ONGOING CARE

FOLlOW-UP RECOM MENDA110NS • Frequent follow-up is sdleduled depending on the patient's response to medical glaucoma therapy. • If guarded filtration surgery or tube shunt is indicated, then standard postoperative care is followed depending on the patient's dlnlcal response and amount of filtration.

recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalma/ogy 2001; 1DB(1D):1767-1776. 2. Fakhraie G, Katz U, Prasad A. et aI. SUrgical outcomes of lntravltreal be>.'aclzuma.b and guarded filtration surgery in neDYiiSCular glaucoma. J GlaiKDfTla 2010;19(3):212-218. 3. The Central Vein Ocdusion Stuely Group. A randomized dinicaI trial of early pan retina I photocoagulation for ischemic central vein ocduslon. The Cerrtral Vein Ocduslon Study Group Nrepon. Ofi!thalma/ogy 1995;102(10): 1434-1444.

CODES

ICD!t • 362.02 Proliferative diabetic retinopathy • 362.35 Centli!l retinal vein occlusion • 365.63 Glaucoma assodated with vascular disorders of eye

CLINICAL PEARLS • Gonioscopy Is keyI Diagnose early by perfonmlng gonioscopy and identify early signs of neOYaSCUiarization. • Conlin uity of care and communication between the glaucoma and retinal specialists and the patient's primary care pl1ysician is imponant to maximize the patient's general health and visual potential. • Arrti-VEGF irrtravitneal injections and PRP are the mainstay5 of treatmerrt of neovascularization. • If the intraocular pressure fails to he controlled with aqueous suppressants. guarded filtr.rtion procedures or tube shunts can be performed with a decreasing success rate over a 5 year period. • More, larger studies need to be done regarding the long-tenm success rate of guarded filtration procedures and tube shurrts in the era of anti-VEGF medications.

DIET • Blood pnessure, blood glucose. and d1olesterol control • Anticoagulation and antiplatelet agerrts in those at ~sk for stroke

I 451

NEUROFIBROMATOSIS Deepak P. Grover

~ BASICS DESCRIPTION • Neurofibromatosis (N F) consists of 2 neurocutaneous genetic disorders that can involve the bones, the nervous system, soft tissue, and the skin. It is the most common hereditary disorder belonging to the group of hamartoses. - NF1, also known as von Recklinghausen's NF, is the most common subtype. - NF2 is also referred to as central NF. EPIDEMIOLOGY Incidence • NF1: 1 case per 3,500 population • NF2: 1 case per 37,000 population RISK FACTORS Genetics • Neurofibromatosis is an autosomal dominant disorder with complete penetrance and high variability in its expression. Roughly half tend to be familial and the other half sporadic. It is independent of sex or race. - NF1 -The NFI gene has been mapped to chromosome 17q11.2. The gene encodes the protein neurofibromin. - NF2 - The NF2 gene has been mapped to chromosome 22q 11. The gene encodes the protein merlin. GENERAL PREVENTION Genetic counseling PATHOPHYSIOLOGY The gene products of the respective NF genes. neurofibromin for NF1 and merlin for NF2, act as tumor suppressors. A decrease in function of these proteins predisposes one to develop a variety of tumors involving the central and peripheral nervous systems. EnOLOGY Many different mutations in the neurofibromatosis genes have been described respectively for both the NFI or NF2 genes. COMMONLY ASSOCIATED CONDITIONS • Moyamoya disease -A progressive occlusive disease of the cerebral vasculature with particular involvement of the Circle of Willis - Linkage studies have linked one of the genes for familial Moyamoya disease to chromosome 17q25, which is in close proximity to the NFI gene. - Children often present with signs and symptoms of cerebral ischemic events, whereas. adults may present with signs and symptoms of subarachnoid or intracerebral hemorrhage.

452

~ DIAGNOSIS HISTORY • Neurofibromatosis Type 1 (NF1) - Parents may notice their children to have cutaneous discoloration or pathologic fractures. - Patients may complain of pain caused by neurofibromas or develop hypertensive headaches caused by a pheochromocytoma. • Neurofibromatosis Type Z (NFZ) - Patients may present with gradual hearing loss, tinnitus, or vestibular dysfunction secondary to vestibular schwannomas. -A visual decline secondary to optic nerve sheath meningioma, posterior subcapsular cataract, combined hamartoma ofthe retina and RPE, or epiretinal membrane may often be a presenting complaint. PHYSICAL EXAM • Neurofibromatosis Type 1 (Z of 7 aiteria needed) - 6 or more cafe-au-lait spots or hyperpigmented macules :::5 mm in diameter in children younger than 10 years and to 15 mm in adults -Axillary or inguinal freckles - 2 or more typical neurofibromas or 1 plexiform neurofibroma involving the upper eyelid - Optic nerve glioma (seen in 15--20% of patients) - 2 or more Lisch nodules (iris hamartomas) - Sphenoid dysplasia or pseudarthrosis of long-bones -First-degree relative (parent or sibling) with NF1 • Other manifestations of NF1 - Neurological manifestations o Seizure disorder o Pilocytic astrocytoma, meningioma, intramedullary glioma, and ependymoma o Vascular ectasias o Aneurysms o Chiari type 1 malformations o Malignant peripheral nerve sheath tumors o Dumbbell-shaped tumors of spinal cord -Ophthalmic manifestations o Proptosis, strabismus -Bone manifestations o Scoliosis, osteoporosis - Other disorders o Essential hypertension o Pheochromocytomas o Renal artery stenosis o Precocious puberty o Gastrointestinal stromal tumors o Learning disabilities or mild/moderate mental retardation o Vitamin D deficiency • Neurofibromatosis Type Z (1 of Z aiteria needed) - Bilateral cranial nerve eighth masses visualized on MRI -First-degree relative (parent or sibling) with NF2 and either: o A unilateral eighth nerve mass or, o 2 of the following: Neurofibroma, schwannoma, glioma, meningioma, or juvenile posterior subcapsular cataract

• Other manifestations of NF2: - Neurological manifestations o Nonvestibular schwannomas usually involving cranial nerves 3 and 5 o Dumbbell-shaped spinal cord schwannoma o Spinal cord ependymoma, astrocytoma, and meningioma o Cranial nerve palsies from compression by expanding vestibular schwannoma or nonvestibular cranial nerve schwannoma -Ophthalmic manifestations o Optic nerve sheath meningioma o Combined hamartoma of the retina and RPE o Epiretinal membrane o Proptosis, strabismus

DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests Gene sequencing, molecular testing, linkage analysis Follow-up & special considerations • For a suspected pheochromocytoma: - Plasma catecholamines and free plasma metanephrine - 24-hour urine collection to measure urinary free catecholamines (norepinephrine and epinephrine) and their metabolites (normetanephrine, metanephrine, and vanillylmandelic acid)

Imaging Initial approach • Radiography - Plain films of long bones, spine, and ribs • MRVCT - NF1 is associated with optic pathway gliomas and astrocytomas. Focal lesions of high signal intensity on T2-weighted MRI are also noted in cerebellar peduncles, basal ganglia, brainstem and optic radiations. - Spinal cord tumor, mediastinal mass, deep plexiform neurofibromas, pheochromocytoma - MRl using 3D volumetrics is the preferred method for following vestibular schwannoma growth for NF2 (1)[81 Follow-up & special considerations • Metaiodobenzylguanidine (M IBG) scintigraphy for pheochromocytoma if MRI/CT is not conclusive • Positron emission tomography (PED scan for tumor surveillance • Gallium-67 scintigraphy for malignant large plexiform neurofibromas • Electroencephalogram (EEG) Diagnostic Procedures/Other • Neurofibromatosis Type 1 -Slit-lamp examination for Lisch nodules • Neurofibromatosis Type 2 -Dilated fundus examinations for inspeaion of juvenile cataracts or retinal lesions - Brainstem auditory-evoked response (BAER) for early hearing loss

NEUROFIBROMATOSIS Patholog/GIJ Findings • Neurofibromatosis '!We 1

• Neurofibromatosis ~~~ Z - SurglcaI resection and stereotactic radiotherapy are the mainstay of treatment for vestibular sd1wan nomas. -Single fraction radiosurgery for spinal cord sd1wan nomas may be used In addition to surgery or as primal'/ ther.~py. - Tomolherapy is able to treat a range of neoplasms using a single helical beam with 360 degrees of rotational radiation.

- Neurofibromas are composed of well-i:lifferentiatl!d tumoo that mntain spindltHhaped cells, Schwann cells, fibroblasts. and mast cells. • NeunrfibrornatDiis Type l -Tumors of NF2 may consist of Schwann cells, glial cells, or meningeal cells.

DIFFERENTlAL DIAGNOSIS • Naunrfibromatasis 'fWHI1 - Bralnstem gliomas - Cauda equina and conus medullaris syndromes -Law~~ean~ma

-Meningioma -NF2 - Spinal cord hemorrhage/infarction - Spinal epid uraI abscess - Leglus syndrome (SPRED1gene mutation) - McCune-Albright syndrome • NaunrfibrornatDiis '~We 2 - Bralnstem gliomas -Epend~oma

- Meningioma -NF1

•

TREATMENT

MEDICATION • Carbopl atin and vincrinine for optic nerve gliomas • Under dinical study are tl1erapeU1it uses of erlotinib, bevadzumab, and imatinib mesylate for unreseclllble, progressive vestibular sdlwannomas • Vrta min Dsupplementation - May be of benefit In patients with deficiency or oneopenia

•

ONGOING CARE

PATlENT EDUCATION Patients should be made aware of symptoms of worsening vision, dnnltus, hearing loss, or sensol'f changes that might suggest tumor growth. PROGNOSIS

• Neurofibromatosis ~e 1 - NF1 has a better prognosis due to a lower inddence of CNS tumors than NF2. -Clinical manifes1ations often increase over time with a development in a malignancy or neurological detelioration oftl!n ensuing. - Due to the malignant tr.msfomnation of diseased tissues or development of neurofibrosarcoma, patients have a higher mortality/morbidity than the general population. A reduction of life expectancy by up to 15 years may result. - 3-1 S% additional risk of maIignant disease during Iifetime.

• NeuroflbrornBtosls ~~ l - NF2 Is associated with significant morbidlty and decreased lifespan. - As the tumors themselves are relatively indolent, prompt dlagnosls and treatment may Improve life expectancy to more than 15 years following diagnosis.

ADDITIONAL TREATMENT General Measutes • Cutaneous examination for documentation of new neurofibromas or progression of preexisting lesions • Blood pressure monltorlng

• Neunrfibi'CIITIIItosii T~e 1 - Visual loss secondary to optic nerve gliomas - Seizures. spinal cord tumors, scoliosis

lssws for Referral

• Neurofibromatosis T~e l

• Neurology- monitor changes in neurological status • Ophthalmology-annual eye examinations for detl!ction of optic nerve lesions, resection of orbital plexifomn neurofibroma, slit-lamp examination, and dilated fundus examInation • Neurosurgel'f - resection of spinal cord or brain tumor • Orthopedic- progressive scoliosis. pseudoarthrosis • Plastic surgel'f - resection of neurofibromas • Geneticist - family planning options and prenataI diagnosis

SURGERY/OntER PROCEDURES

• NaunrfibrornatDiis 'JWe 1 -Radiotherapy may be utilized in children over 5 years of age as an adjunct or as an altet'native to surgel'f for optic nerve gliomas; however, is generally avoided due to an increased risk of secondary malignancy.

COMPLICAnONS

- Visual loss from optic nerve meningiomas, cataracts, or combined hamartomas of the retina and RPE - Hearing loss, tinnitus, seizures

i'regMncy Considerations • Increase In size of existing neurofibromas and the appearance of new neurofibromas occur commonly in women with NF1 during pregnancy. • Neuroflbromatosls du ~ ng prenatal pe~od may be diagnosed by: - Linkage analysis can track the NF genes in a family with multlple affected members to determine whid1 chromosome the fetus received. - Gene sequencing to identify spedfic gene mutation in affected parent This would permit prenatal diagnosis by amniocentesis or d1orlonlc viii us sampling.

REFERENCES 1. Harris GJ, Plotkin SR, Maccollin M, et al. Three-dimensional volumetrics for tracking vestibular sthwannoma graw1h in neurofibromatosis type II. Neurosurgery 2008;62(6):1314-1319. 2. Nicolin G, Parkin P, Mabbott D, et al. Natural hinDI'f and outmme of optic pathway gliomas in children. Pedlatt Blood Cancer 2009;s3m: 1231-1237•

ADDITIONAL READING • Lee HH, Uan SL. Huang CJ, et al. Tomotherapy for neurofibromatosis Type 2: Case report and review of lill!rature. Br J Rarlio/2010;83(9811):e74-i!78. • Mukherjee J, Kamnasaran D, Balasubramaniam A, et aI. Human schwannomas express activated platelet-derived growth factor receptors and c-kit and are inhibited by Gleevac (lmatinib Mesylate). Cancer ReseardJ 2009;69(12):5099--51 07_ • Plotkin SR, Singh MA. O'Donnell CC, et al. Audiologic and radiographic response of NF2-related vestibular sdlwannoma to erlotlnlb therapy. Nat C/in Pracr Onco/ 2008;5(8):487-491 . • Plotkin SR, Stemmer-Rachamimov AO, Barker F6 II, et al. Hearing improvement after bevadzumab in patients with neuraflbromatosls type 2. NEJM 2009;361(4):358-367.

.

CODES

ICD9 • 216.1 Benign neoplasm of eyelid, indudingcanthus • 237.9 Neoplasm of uncertain behavior of other and unspecified parts of nervous system • 237.70 Neurofibromatosis, unspecified

CLINICAL PEARLS • Neurofibromatosis 1 and 2 are neurocutaneous genetic disorders diagnosed by spedfic dinical altet'la. • Remember the association between NF and optic nerve glioma, schwannoma, pheod1 romocytoma, and other tumors.

- Surgical resection is reserved for large tumors causing mass effect or hydrocephalus and optic pathway gliomas confined to the orbit or optic nerve (2)[B).

I 4S3

NEUROPROTECDON IN GlAUCOMA M. Reza Razeghinejad L. Jay Katz

~ BASICS DESCRIPTION Neuroprotection is the use of therapeutic agents to prevent, retard, and in some instances, reverse retinal ganglion cells (RGCs) death in glaucomatous patients. PATHOPHYSIOLOGY lOP dependent RGCs loss • Elevated lOP induces optic neuropathy by: - Mechanical theory. posterior bowing of lamina cribrosa. and damaging axon bundles passing through its pores -Vascular theory, low perfusion pressure, defined as tile difference between systemic blood pressure and lOP • lOP is no longer regarded as tile only causative factor in glaucomatous optic neuropathy because some patients with elevated lOP never develop glaucoma, in normal tension, glaucoma lOP is witllin normal limit, and some patients continue to progress with controlled low lOP. Non-lOP dependent RGCs loss • Excitotoxicity - RGCs die by apoptosis (programmed cell death) because of the presence of excessive amounts of glutamate, an excitatory neurotransmitter. - Glutamates binds onto postsynaptic receptors, NMDA (N-metllyl-d-aspartate) channels, and keeps them open for a long period of time, thereby allowing influx of Ca2+ and Na+ ions and initiating apoptosis.

454

• Mitochondrial dysfunction - Induced by glaucoma-related stimuli such as tumor necrosis factor and hypoxia • Oxidative stress - load of reactive oxygen species and lipid peroxides outweigh the antioxidant capacity of cells • Inflammatory and autoimmune mechanisms -Complement system: Several components are upregulated. - Heat shock proteins - Under physiological conditions act as molecular chaperones and/or have anti-apoptotic activities. -Glaucomatous patients have antibodies against HSP. - TNF, as a mediator of RGC death is upregulated. -Nitric oxide: It is a gaseous second messenger and appears to have physiologic role in optic nerve function. Excessive production of nitric oxide in glaucoma leads to RGCs loss.

~ DIAGNOSIS DIAGNOSTIC TESTS & INTERPRETATION Imaging • Establishing neuroprotective effect of drugs is difficult because glaucoma is a slow, progressive disease and the current method of measuring progression, a computerized visual field assessment, is highly variable. • Optic nerve and nerve fiber layer analyzers (Optical Coherent Tomography, Scanning laser Polarimetry, and Ophthalmoscopy) may lead to more meaningful assessment. • Detection of apoptosing retinal cells (DARC), an in vivo method, may become a precise tool to assess the effect of neuroprotective agents.

.

TREATMENT

MEDICATION • To be deemed a neuroprotective agent should have 4 criteria: (1) Possessing receptors on the optic nerve or retina, (2) Adequate penetration into the vitreous and retina at pharmacologic levels, (3) Triggering intracellular signals tllat enhance neuronal resistance to apoptosis (4) Demonstration of efficacy in clinical trials. • No neuroprotectant drug has ever been approved for an optic nerve disorder. Despite successful preclinical cell culture and animal model experiments, most of the phase 2 and virtually all of the phase 3 clinical trials of more than 100 neuroprotective drug candidates have failed to demonstrate efficacy and safety. Following are some of neuroprotectants that are categorized into 2 groups. Promoters of cell survival and inhibitors of cell death. • Inhibitors of cell death - Memantine,. a derivative of amantadine, which was used as an anti-influenza compound. As a NMDA receptor antagonist, is currently the only available clinical glutamate modifier (the first phase 3 trial did not confirm a neuroprotective effect). - Nitric oxidesynthase inhibitors: Had a neuroprotective effect in animal studies. - Infrared light. has metabolism-enhancing, antioxidant. and anti-apoptotic properties. A phase 0 clinical trial is currently announced to be in preparation.

NEURDPRDTECTlONIN GLAUCOMA - Vrtamin E, scavl!nger of peroxyl radicals:

- Neurotraphins, Nerve growth factor (NGF) and

Glaucoma patients reO!iving vitamin Ehave displayed lmproved visual fields In some studies. - cald~rt~channel blockers: In addition to anti-vasDSpastic effect, that is an important mechanism in optic nerve damage in some glaucoma patients (i.e., normal tension glaucoma), Its topical form may reduce lOP.

brain-derived neurotrophic factor (BDNF), have been tested extensively In animal studies, bath reduce RGCs deatl1. They activate toxic pathways as well as neuroprotective ones. - Geran,tgera,lacetone,. in animal studies, upregulated HSP-72 expression in RGCs and protected them from glaucomatous damage.

• Promoters crf neuronal survival - Brimonidine(a-2 agonist): Its mechanism of action is similar to an NMDA channel blocket MK-801. It also causes upregulation of BDNF (brain~erived neurotrophic factor) in the RGCs. Neuroprotective effect in experimental studies, but In clln leal t~als failed to translate Into similar efficacy in humans.

- Cop-1 (gla11ramer ace1ate; copolymer-1; copax·1 J: FDA approved drug for multiple sclerosis. In animal studies, Cop-1 reduced optic nerve damage caused by mechanical injury or intravitreal glutamate injection. - CoanZJITIB Q10, plays a audal role in energy production by the mitochondrial electron transport chain. Topical CoQl 0 has been effective in experimental glaucoma.

- Betaxoloi(.B1-blocker): Alters excitotoxic/h~ic pathway to exert its neuroprotective effect. No definite clinical proof for having neuroprotective effect - EmactGinkgo bilolla, an extract from leaves of Ginkgo biloba, has been effective in models of experimental glaucoma.

ADDITIONAL READING

.

CODES

ICD9 • 365.9 Unspedfled glaucoma • 365.12 Low tension open-angle glaucoma

CLINICAL PEARLS • No evidence that neuroprotective agents are effective in preventing retinal ganglion O!ll death, and thus preserving vision in patients with glaucoma has been demonstrated. Long-term randomized dinical tria Is with long-term follow-up are needed to determine if tl1ey may be benefidaI in this regard. • Mernantine is the only neuroprotective agent assessed in randomized dinicaltrials (phase 3) without showing a neuroprotective effect compared to placebo-treated patients.

• Bessero AC, Cia ria! PG. Neuroprotection for optic nerve disorders. Cu" Opn Neuro/20 10; 23:1 G-1 5. • Sena DF, Ramchand K. Lindsley K. Neuroprotectlon for treatmem oi glaucoma In adults. CodJrane Diltaba5e S;yst Rev 201 0;2:CD006539. • Cheung W, Guo L. Cordeiro MF. Neuroprotection in glaucoma: Drug-based approaches. Optam V'IS Sd

20Da;8S:.W6-416

I 455

NEURORETINITIS David B. Auerbach

~ BASICS DESCRIPTION Neuroretinitis is a unilateral, or more rarely, bilateral inflammation of the optic nerve and retina with macular exudate formation and associated visual loss. Originally termed "Leber's idiopathic stellate Neuroretinitis, • it is now known to have infectious etiologies. Although the most common association in the US is with cat scratch disease, various other causes need to be completely investigated as multiple infectious and inflammatory etiologies exist (1 )[A]. EPIDEMIOLOGY Incidence • 6 per 100,000 secondary to cat scratch disease • Cat exposure is seen in 90% of patients who are serology positive for Bartonella henselae. Prevalence • Exact prevalence remains unknown • Affects all ages • No sex predilection • Right and left eyes equally affected RISK FACTORS • May follow a recent upper respiratory viral illness in up to 50% of cases • Inquire about any recent exposure to cats • Important to take a sexually transmitted disease history GENERAL PREVENTION As disease is idiopathic or secondary to infectious etiology, no general prevention is known.

456

PATHOPHYSIOLOGY • Optic nerve edema • Macular edema with star formation

ETIOLOGY • Infectious or immune mediated • May be viral in up to 50% of patients COMMONLY ASSOCIATED CONDITIONS Bartonella henselae infection

~ DIAGNOSIS HISTORY • Blurred vision. Visual acuity can range from 20120 to light perception. • Usually painless • Flu-like symptoms • Regional lymphadenopathy • Ocular erythema • Decreased visual field

PHYSICAL EXAM • Optic disc edema (if bilateral, may be papilledema and neuroimaging and LP may be needed to rule out compressive lesion and/or elevated intracranial pressure). • Macular star formation (usually starts to appear 2-4 weeks after visual symptoms) • Regional lymphadenopathy • Afferent pupillary defect • Visual field defect (most common is cecocentral. however, arcuate and altitudinal defects can be seen) • Acquired dyschromatopsia • Small chorioretinal lesions

DIAGNOSTIC TESTS & INTERPRETATION Lab • • • • • • • • • • • • • • • •

MRI brain and orbits with and without gadolinium Bartonella hense/ae titer CBC ESR ANA ACE RPR lymetiter HIV Toxoplasmosis Toxocariasis Hepatitis B& Cantibodies Brucellosis Epstein Barr titers TB skin test leptospirosis

Imaging Initial approach • Visual field with central or cecocentral defect • Fluorescein angiogram shows leakage of disc vessels and late disc staining • MRl brain and orbits to rule out a compressive lesion Follow-up It special considerations Macular exudates usually resolve within a few months but may be present for up to a year.

NEURORETINITIS DIFFERENTlAL DIAGNOSIS • • • • • •

• • • • • •

.

Cat scratch disease L,yme disease Lupus Sarcoidosis Syphilis Toxoplasmosis Toxocarlasls Hypertensiye retinopathy Tuberculosis Pseudotumor Cerebri Leub!mia HIV

TREATMENT

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Patient should be seen every 2 weeks for the first 2 months to assess any change in visual function (visual acuity, visual field, mlor vision, and any change in optic nerve and/or retinal edema)

PATIENT EDUCAnON If patient is Bartonella positive, education regarding cat handling should be suggested.

PROGNOSIS • Self-1 imited in immunocompet:ent individuals • Good prognosis

FitstLine • Continues to be controversial. Usually a benign self-limited mndition. Medical therapies may shorten the recovery lime. • Alllmmunommpromlsed Individuals should be treated (A)[2]. • Treat accordingly if any serologic tests are posili¥e.

• Permanent deaease In visual acuity and visual field • Optic atrophy o Metamorphopsia o Dyschromatopsia

• • • •

Rlfampln Azithromydn Ciprofloxacin Trimethoprim-sulfamethoxazole

ADDITlONAL TREATMENT

12(3--4):155-159.

Regular diet

COMPUCAnONS

• Doxycycline (3)[A]

• Reynolds MG, Holman RC, Curns AT, et al. Epidemiology of cat-scratch disease hospitalizations among children in the United States. Pediatr Infect Dis J 2005;2-4(8):70D-704. • Rost Monahan S. Neuroretinitis: Ad inical syndrome at cat-scratch disease. Gin Eye VIs Care 2000:

DIET

MEDICATION

Second Un•

ADDI110NAL READING

.

CODES

ICD9 o 078.3 Cat-scratth disease • 363.05 Focal retinitis and retin odlaroiditis, Juxtapaplllary

CLINICAL PEARLS • No association with multiple sderosis o If suspected cat-scratch disease, treat empirically as liters may take about H weeks to seromnvert

REFERENCES 1. Williams N, Miller NR. Neuroretinitis. In: Pepose JS, Holland GN, Wilhelmus KR, editors. Ocular /rrfectlon and Immunity. St Louis: Mosby Year Book,

1996:601-608. 2. Cunningham ET, Ko!!hler JE. Ocular bartonellosis. Am J O{ilthal2000;130(3):340-349. 3. RayS, Gragoudas E. Neuroretinitis. lnt O{ilthalmol

cnn 2001:41(1):83--102.

Issues for Rmm~l • Should be evaluated by an ophthalmologist • Consider neuroophthalmologist and/or retinal specialist

IN-PAnENT CONSIDERATIONS

Admission Critwia Treated as an outpatient

I 457

NON-ARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY (NAION] Robert J. Granadier

~ BASICS DESCRIPTION Sudden, pain less. unilateral visual loss, associated with swelling of the optic disc secondary to vascular insufficiency. EPIDEMIOLOGY Incidence

PATHOPHYSIOLOGY lschem ia secondary to vascular insufficiency related to small vessel perfusion at the optic nerve head. (Indirect evidence, no causative factor in a pathologic specimen identified to date). ETIOLOGY Anatomic theory: Condition noted to be associated with small, crowded optic disc with small cup to disc ration in fellow eye (so called disc at risk).

2-10 individuals per 100,000 over 50 years old

COMMONLY ASSOCIATED CONDITIONS

Prevalence

• Diabetes • Hypertension • Migraine

1, 500-6,000 new cases per year in the US.

RISK FACTORS • Small vessel disease (1 liB] • Hypertension • Diabetes - Hypercholesterolemia -Migraine - Sleep apnea - Hypoperfusion - Amiodarone - Erectile dysfunction medication (unproven)

Genetics None recognized.

GENERAL PREVENTION Recommended: Patients who have suffered NAION in one eye should control risk factors and be cautioned in regard to potential nocturnal or anesthesia related hypotension/hypo-perfusion.

458

~ DIAGNOSIS HISTORY • Sudden, painless, unilateral vision loss • Often noted upon awakening

PHYSICAL EXAM Decreased visual acuity Reduced color vision Sluggish pupil with afferent pupillary defect Visual field deficit (altitudinal) Optic disc edema, segmental with peri-papillary intra-retinal hemorrhage

• • • • •

• Crowded optic disc in fellow eye with small cup to disc ratio, (disc at ris ~

ALERT Must distinguish from arteritic formof ischemic optic neuropathy secondary to giant cell arteritis, because if left untreated, there is a 70% incidence of the second eye being involved within 10-14 days. resulting in bilateral visual loss. DIAGNOSTIC TESTS & INTERPRETATION Diagnostic Procedures/Other • Visual fields: Static or kinetic • Most frequent visual field defect is an altitudinal loss of the inferior or superior field

Pathological Findings Ischemic infarction of the retro-laminar optic nerve. DIFFERENTIAL DIAGNOSIS • Arteritic anterior ischemic optic neuropathy secondary to GCA, see Alert. -Optic neuritis with optic disc swelling - Papillophlebitis - Amiodarone optic neuropathy

NON-ARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY (NAION)

.

TREATMENT

MEDICATION None prOYI!n. ADDITIONAL TREATMENT General Measures • Blood pressure • Blood sugar ISsues for Referral

Refer to Internist for general medical evaluation with attention ID potential WISOJiopathic risk factors (l)(B].

Additional Thetaples ProphylacticASA studied: Unproven (2)[C] COMPLEMENTARY & ALTERNAnYE

ntERAPIES • Anti-Coagulation Studied: Unproven (2)(A( • Steroids: Studied: Unproven {2)(B] • Hyperbaric Oxygen: Studied: Unprown (2)[B]

SURGERY/OTHER PROCEDURES Optic nerve sheath decompression: potentially harmfuI (3)(A]

•

ONGOING CARE

ADDI110NAL READING • Arnold AC. In Miller NR, Newman NJ, Biousse V, et al. Clinical Neuro-Ophthalmology, Ischemic Optic Neuropathy. Vol. 1Philadelphia PA. Uppincott, Williams & Wilkins, ed 6, 2005, 349-384.

FOLLOW-UP RECOMMENDATIONS • 1 week, 1 month, 3 months. • Disc edema resolves over 6-10 weeks. PlJtient NIOI'IitDring Uncommon: 24-hour blood pressure monitoring, In Individual cases when hypotension Is of concern.

.

PATIENT EDUCATION Educate patients with respect ID general health considerations. and potential risk faclllrs related to individual cases (i.e., erectile dysfunction medication, obstructive sleep apnea).

ICD9 • 377.00 Papilledema, unspecified • 377.30 Op11t neu ~tis. unspedfled • 377.41 lschemlc optic neuropathy

PROGNOSIS • Stablevisuallosslikely in BD-85%

CLINICAL PEARLS

• Spontaneous recovery of 3 lines of visual acuity approximately 15-20% (3)[A] as high as over 40%. (4)[8] • Fellow eye risk 15% over 5 years in patients over 50 years. (3)[A]

• Risk. moderately increased in younger p;~tients.

REFERENCES 1. Arnold AC. Pathogenesis af nonarterttic anterior Ischemic op11c neuropathy. J Neuroophfhillmol 2003; 23(2): 157-163. 2. Atldns EJ, Bruce BB, Newman NJ, e1 al. Treatment of nonarterttic anterior ischemic op1ic neuropathy. Surv Ophfha/mol 2010; 55{1): 47~3. 3. Optic Nerve decompression surgery for nonarterltlc ante~or lschem lc optic neuropathy (NAION) Is not effective and may be harmful. The Ischemic Optic NeuropathyDecompression Trial Research Group. .lAMA 1995; 273(8): 625-632. 4. Hayreh SS.Ischemit optic neuropathy. Prog Retin E~ Res 2009; 28(1 ): ~62.

CODES

• Anterior ischemic optic neuropathy should be accomp;~nied by swelling of the visible portion af the intraocular op1it nerve or 1he optic disc. Absence at assodated disc swelling should cause one to seek: an alternate diagnosis. • AIR!rent pupillary defect in the eye af concern may be absent in cases in which the fellow eye has previously sustained optic nerve damage. • Foster-Kennedy Syndrome: Skull based tumct' obstructing the foramen of Monroe must be suspected in patients presenting with optic disc swelling in one eye and optic atrophy in the fellow eye. Once a tumor has been ruled out, the more common diagnosis of pseudo Foster-Kennedy syr1drome secondary to remote NAION in the fellow eye and arute NAION In the affected eye may be considered.

I 459

NON-GRANULOMATOUS ANTERIOR UVEmS Nicole R. Fram Eliza Hoskins

~ BASICS DESCRIPTION • Non-granulomatous anterior uveitis (NGAU) is a broad classification for various inflammatory conditions localized to the iris (iritis), dliary body (cyclitis), or both (iridocyclitis) tflat typically present witfl pain, redness. and photophobia. - Etiologies can be infectious or immune·mediated -Systemic involvement or isolated to the eye - NGAU is characterized by small punctate or stellate keratic precipitates (KP) versus granulomatous anterior uveitis with large greasy mutton fat KP with iris nodules or choroidal granulomas.

EPIDEMIOLOGY lnddence • 8-17 cases per 100.000 population (1,2) • HLA-827 more common in Caucasian males • 8eh~et's disease is more common in Asian and Middle- Eastern males • Juvenile idiopathic arthritis (JIA) more common in females.

RISK FACTORS • Trauma • Genetic predisposition (HLA-827, HLA-851) • Smoking (3)

Genet/a • HLA-827 (ankylosing spondylitis (AS)), reactive arthritis (formerly Reiter's syndrome), Inflammatory bowel disease (lBO), psoriatic arthropathy • HLA-851 (Beh\et's disease)

GENERAL PREVENTION No prevention of idiopathic NGAU. ETIOLOGY • Idiopathic (50%) • 30% AS patients have NGAU

COMMONLY ASSOCIATED CONDITIONS See Review of Systems (ROS).

~ DIAGNOSIS HISTORY Targeted history onset. duration, location, quality of symptoms, and associated conditions. Clinical course (acute, chronic, or recurrent) laterality and previous treatments/trauma. • Standardization of uveitis nomenclature (SUN) (4) - Acute: Sudden onset with limited duration. - Recurrent: Repeat episodes separated by periods of inactivity without treatment > 3 montfls in duration -Chronic: Persistent uveitis with relapse 3 months, then annually. Risk of aseptic necrosis of bone 10-15% If on 60 mg In first month and >20 mg for first 6 months. 5) Children < 1s years may have delayed puberllll growth (S). 0 Steroid-sparing innulosuppressiveS if clw'onic and cannot taper systemic prednisone common > external carotid. - 5% lifetime risk for patients with internal carotid artery (ICA) stenosis to develop 015 - Less common: ophthalmic artery disease, systemic vasculitis (giant cell arteritis [GCAJ), vasa-occlusive disease (i.e., aortic arch syndrome), Takayasu arteritis COMMONLY ASSOCIATED CONDITIONS • Systemic vascular disease -Systemic arterial hypertension (HTN) - Diabetes mellitus (DM) - Coronary artery disease (CAD) - Previous cerebrovascular accident or transient ischemic attack. - Peripheral vascular disease

478

~ DIAGNOSIS HISTORY • Loss of vision - Most frequent symptom: present in 70% or above at presentation. absent in less than or equal to 10% -Variable in severity and onset-more than 2/3 are less than 20/60 at presentation; most experience vision loss over week.s to months, although some have abrupt vision loss • Pain-40% present with pain due to increased intraocular pressure (lOP) or ischemia ("ocular angina •--{jull, constant ache over the brow) • Transient vision loss/amaurosis fugax - Present in 10-15% of patients • Afterimages or prolonged recovery of vision after light exposure PHYSICAL EXAM • Anterior segment - Conjunctival and episcleral injection - Corneal edema and/or Descemet's folds - Iris atrophy and neovascularization (66%) -Anterior and posterior synechiae - Fixed and semidilated pupil or afferent pupil defect (APD) - Mild iritis in 20% (flare > cell) -Cataract - Neovascular glaucoma in 113 of patients - lOP may be low/nonmal second to decreased ciliary body perfusion. - Hypotony can further exacerbate corneal decompensation, cataract. and maculopathy. • Posterior segment (more frequent) - Narrowed retinal arteries -Veins dilated but not tortuous - Retinal hemorrhages in 80% of patients, mostly dot-blot and in midperipheral retina - Microaneurysms common in midperipheral retina· more visible on fluorescein angiogram ' - Spontaneous retinal arterial pulsations - Cherry-red spot (1 2%) from embolic or increased lOP induced occlusion of central retinal artery -Cotton-wool spots (6%) - Choroidal ischemia and peripheral wedge-shaped chorioretinal atrophy - Neovascularization of disc (NVD) in 35%, neovascularization elsewhere (NVE) in 10% • Orbital infarction syndrome - Ischemia of intraocular and intraorbital contents - Corneal hypoesthesia, intraocular inflammation, hyp~tony•. ophthalmoplegia, ptosis, proptosis, orb1tal pam • Systemic exam - Pulses, carotid and cardiac auscultation

DIAGNOSTIC TESTS & INTERPRETATION Lab

Initial lab tests • Fluorescein angiography (FA) - Delayed or patchy choroidal filling in 60% of patients; most specific FA sign - Prolonged arteriovenous transit time in up to 95% of patients: most sensitive -Staining of retinal vessels in 85%; arterial more than venous staining - Leading edge of arterial dye - 15% with macular edema (noncystoid pattern) often with disc leak.age ' - Retinal capillary nonperfusion • Consider ESR or C-reactive protein (C RP) if suspected GCA

Follow-up & special considerations • lndocyanine green angiography (ICG) - Prolonged arm- 10 years) necessary because of high recurrence, but most occur within the flrst 2 years. -Up to 30% with negative surgical margins - More than SO% with positive surgical margins - Recurrence is now mud11ess with the use of adjunctive topical chemother.~py and IFN. PA11ENT MONITORING Follow-up every 2--4 mllllths until clinical resolution if using topical agents

PROGNOSIS • Overall prognosis is good with extremely rare OSSN-related mortality. - Assodated with local invasion • lntraocular invasion via Iimbal perforating vessels gaining access to Schlemm's canal, trabecular meshwork, anterior chamber, suprachoroidal space, and d1oroid. - Assodated with large (>2 em) OSSN - Manifest as uveitis and glaucoma • Can metastasize to preauricular, submandibular, and cervical lymph nodes; paratld gland; lungs; and bone in advanced disease • lmmunosuppressed patients are at highest risk for lymph node metastasis. COMPUCAnONS

REFERENCES 1. Lee GA, Hlrst LW. Ocular surface squamous neoplasia. Surv Ophlhalmo/199 5;39:42!1--450. 2. Shields CL. Manchandia A. Subbiah R, et al. Pigmented squamous cell cardnoma of the conjunctiva in 5 cases. Ofilthalmo/ogy 2008;115:1673-1678. 3. Hlrst LW. Randomized controlled trial of topical mitomycin Cfor ocular surface squamous neoplasia. Ot/lthalmo/ogy 2007;114:976--982. 4. Shields CL. Naseripour M, Shields JA. Topical mitomydn C for extensive, recurrent mnjunctival squamous cell carcinoma. Am J Ophthalmol 2002;133:601~6.

5. Shields CL. Demirci H, Marr BP, et al. Chemoreduction with topical mitomydn Cprior to resection of extensive squamous cell cardnoma of the conjunctiva. AldJ Ofilthalmo/ 2005; 123: 10~113.

6. Yeatts RP, Engelbredlt NE, Curry CD, et al. 5-Fiuorouracil for the treatmem of intraepithelial neoplasia of the conjunctiva and cornea. Ophthalmology 2000;1 07:2190--2195.

or surglcaI excision for the management of p~ mary ocular surface squamous neoplasia. Ophlha/mology 2008;11 5:1297-1302. 8. Shields JA. Shields CL. De Potter P. Surgical management of conjunctival tumDil.. The 1994 Lynn B. McMahan Lecture. Ardl Ophthalmol 1997;11 5:8011--815.

ADDI110NAL READING • Shields CL. Demlrcl H, Karatza E, Shields JA. Clinical survey of 1643 melanocytic and nonmelanocytic tumors of the conjunctiva. Ot/lthalmology 2004; 11,:1747-1754. • Shields CL. Shields JA. Tumors of the conjunctiva and cornea. Surv Ophtha/mof 2004;49:3-24. • Shields JA. Shields CL Premalignant and malignant lesions of the conjunctival epithelium. In: Eyelid, Conjunctival, and Orbital Tumors. An Atlas and Textbook, 2nd ed. Philadelphia: Lippincott Williams &Wilkins, 2008:284-305. • Spencer WH. Conjunctiva. In: Spencer WH, ed. Ophlhalmic pathology. an atlas and textbook, 4th ed. Philadelphia: WB Saunders, 1996:38--125. • Yanoff M. Conjunctiva. In: Yanoff M, Sassani JW, ed. Ocular palho/ogy. 6th ed. Amsterdam, Netherlands: Elsevier, 2009:223-254.

CODES ICD9 • 190.3 MaIignant neoplasm of conjunctiva • 190.4 Malignant neoplasm of cornea • 234.0 Carcinoma in situ of eye

CLINICAL PEARLS • Most common epithelial neoplasm of the cornea and conjunctiva • Associated with age. sun e11posure, smok:i ng. HPV. and immunosuppression • Clinically appear as a fleshy mass or let~koplakia, usually located at or near the limbus. with feeder vessels and possible comeallnvolvemem • A complete excision with negative margins preferred, whenever possible • Adjunctive topical d1emotherapy and IFN assodated with lower recurrence rate

481

I

OCUlAR SYPHIUS Alok S. Bansal

Jeremy D. Wolfe

~ BASICS DESCRIPTION • Chronic, multiorgan, systemic bacterial infection caused by spirochete Treponema pa/lidum. • Responsible for 1-2% of all uveitis cases. • Ocular syphilis is considered a variant of neurosyphilis (see below). • Congenital syphilis (systemic findings): - Early (2 years of age): Frontal bossing, saddle-nose deformity, saber shins, Hutchinson teeth, deafness • Acquired syphilis (systemic findings): - Primary: Self-limited painless genital chancre - Secondary: Maculopapular rash an palms and sales, generalized lymphadenopathy, fever, malaise - Early latent (exposure within the last year): Seroreactivity without clinical manifestations - Late latent or latent syphilis of unknown duration (exposure > 1year): Seroreactivity without clinical manifestations -Tertiary: Gummas. neurosyphilis. cardiovascular abnormalities (aortitis) EPIDEMIOLOGY Incidence • Congenital: 10.1/100,000 in 2008 (1)[A] - Increased 23% from 2005 • Primary & Secondary: 15.3/1 00,000 in 2008 - Increased 37% from 2005 • Regional: Highest rates (50%) in Southern U5 • Age: Highest rates in 20-24 year olds • 63% of cases in US among men who have sex with men

Prevalence Due to the rarity of ocular syphilis and incomplete reporting to the CDC, true prevalence data (i.e., total cases) is not well known.

RISK FACTORS • High-risk sexual behavior • HIV coinfection • Intravenous drug abuse GENERAL PREVENTION • Prenatal care to prevent congenital syphilis • Safe sexual practices

482

PATHOPHYSIOLOGY • Transmission of acquired syphilis may occur through direct contact with syphilis sore on external genitals. vagina, anus, rectum, or lips and mouth during vaginal, anal, or oral sex. • Transmission of congenital syphilis occurs by transplacental contact. • Ocular inflammatory response to infection caused by bacteria Treponema pallidum. ETIOLOGY Treponema pallidum, spirochete COMMONLY ASSOCIATED CONDITIONS • HIV • Other sexually transmitted diseases

~ DIAGNOSIS HISTORY • Maternal syphilis • HIV • High risk sexual behavior • Pain, redness, photophobia, blurred vision, floaters PHYSICAL EXAM • Syphilis may affect any or all ocular structures (2)[A[ • Congenital Syphilis: - Early: Chorioretinitis, retinal vasculitis, •salt·and·pepper" retinal pigment mottling - late: Interstitial kl!ratitis with corneal vascularization, ghost vessels • Acquired Syphilis: - Primary: Ocular manifestations rare - Secondary: Anterior uveitis (granulomatous or non-granulomatous), iris nodules. scleritis, vitreitis, retinal vasculitis, retinal vascular occlusion, chorioretinitis (focal or multifocal), posterior placoid chorioretinitis, neuroretinitis, exudative retinal detachment optic neuritis, cranial nerve palsies - latent: Asymptomatic with recurrences -Tertiary: Argyii-Robertson pupil (pupil reacts to near target not to light stimuli), cranial nerve palsies. other ocular findings similar to those with secondary syphilis.

DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests • Non-treponema!: Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VORL) - Fourfold decrease in antibody titer used to monitor response to therapy - False-positives (collagen-vascular disease) and false-negatives (prozone phenomenon)

• Treponemal-specific: Fluorescent treponema! antibody absorption (FTA-ABS) or microhemagglutination-T. pallidum (MHA-TP) - Remain reactive from time of infection, thus should not be used to monitor therapeutic response. • lumbar puncture with cell count, protein, glucose, and CSF-VDRL to evaluate for neurosyphilis. - CSF-VDRL is highly specific. but not sensitive - 2006 CDCguidelines recommend lumbar puncture in all cases of ocular involvement, although practical indications for lumbar puncture are controversial (3)[A] - Isolated syphilitic anterior uveitis without neurologic signs/symptoms may not require lumbar puncture Follow-up & special considerations • HIV serology due to high rates of coinfection • False-positive and false-negative rates of syphilis serologic testing may be higher in HIV patients.

Imaging Consider MRI for any suspected case of optic nerve involvement and/or neurosyphilis.

Diagnostic Procedures/Other lumbar Puncture with CSF-VDRL

Pathological Findings Corlcscrevv morphology on darkfield microscopy (not commonly performed).

DIFFERENTIAL DIAGNOSIS • Ocular syphilis carries a broad differential diagnosis due to its protean manifestations - Sarcoidosis -Tuberculosis -Toxoplasmosis - Vogt-Koyanagi-Harada syndrome - HLA-B27 associated uveitis - Pars planitis -Acute retinal necrosis - CMV retinitis - Fungal endophthalmitis -White dot syndromes (e.g., APM PPE) - Lyme disease - Beh~et's disease - Diffuse unilateral subacute neuroretinitis - Toxocariasis - Presumed ocular histoplasmosis

OCUlAR SYPIIIUS

.

TREATMENT

MEDICATION RrstLine • Congenital: Aqueous ci}'Stalllne penicillin G 50,000 untts/kgfd r.l q12 hrs for flrst 7 days of life. and q8h thereafter for total of 10 days OR Proc:ai ne pen idllin G 50,000 unitslkgfd IM x 10 days (3)[A) • Primary, semndary, or early lall!nt syphilis: Ben2athine penicillin G 2.4 MU IM in single dose (3)[A] • Late latent or ll!rtiary withcut evidence of neurosyphilis: Benzathine penicillin G 2.4 MU IM, weekly x 3 doses (3)[A] • Neurosyphilis: Aqueous penidllin G3-4 MU r.l q4h x 1o-14 days OR Procaine penicillin G2.4 MU IM q day PLUS Probenedd 500 mg PO q.i.d x 10-14 days, followed by Benzathine penicillin G 2A MU IM, weekly x 3 doses (3)[A) • Manage oa.!lar inflammation with cyclopleg ics, and topical, periocular, and/or oral corticosteroids • Note: Pe~oaJ lar (depot) steroids shoold not be employed until other infectious etiologies for inflammation are eliminated from differential diagnosis or identified and treated concurrently.

SecondUne ALERT • Penicillin Allergy: -For congenital syphilis, neurosyphilis, pregnancy, or HIV+. patients should undergo de-sensitization and be treated with penicillin (see above) - For primary, secondary, lall!nt, or tertiary syphilis wltt1out neurosyphilis. see below: - Primary, secondary, or ea ~Y larent: Doxycydine 100 mg PO b.i.d x 2 weeks OR Tetracycline .500 mg PO q.i.d x 2 weeks (3)[A] - Lata lall!nt or ll!rtiary without avidanca of neurosyphilis: Doxycydine 100 mg PO b.i.d x 4 weeks OR Tetracycline 500 mg PO q.l.d x 4 weeks (3)[AJ - See also AltematiYl! Thera pies. ADDITIONAL TREATMENT General Measures ALERT • Monitor for Jarisch·Helllheimer reaction: - Acute febrile reaction that occurs within 24 hours of treatment due to penicilli n·induced spirodlete death. -Treat with supportive care

lssllfls for llfl,.,ral • Prompt referral to ophthalmologist for any suspected case of Intraocular Involvement • Prompt referral to infectious disease spedaIist for mnmmitant HIV minfection • Prompt referral to neurologist for suspected neurosyphilis

COMPLEMENTARY & ALTERNATIVE THERAPIES • Bicillin C-R (combination benzathine and procaine penicillin) should ba avoided as altllrnata b'Ntmant because it tonta ins haIf the dose of benzathlne penicillin G (3)[C). • P~mary, secondary, or ea~ larent Ceft~axone 1 gm 1M/IV x 8-1 0 days (3)[C] or Azithromycin 2 gm PO x 1 dose (3)[C) • Lall! latent or tartiary without evidence of neurosyphilis: Ceftriaxone (unknown dose or duration) (3)[C) • Neurosypllilis: Ceftriaxone 2 gm 1M/IV x 1D-14 days (3)[C) • Penicillin·allergic patients may exhibit aoss-reactivity to celtriaxone (~ 10%) • The use of alternative therapies In HIV+ patients has not been well srudied, and should be managed with (aution.

$

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Quantitative non-treponema! (RPR, VORL) titers should be repeated every 6 months for 2 years (every 3 months for 2 years if HIV+) to monitor for ri!SJXlnse to treatml!nt (i.e., fourfold dedine in titl!rs) (3)[A] - Follow either RPR or VORL because tests are not directly comparable - A VORL till!r > 1:8 should dedine at least fourfold within 1 year of appropriate treatment - A VORL titer < 1:8 often does not decrease fourfold • Consider re·treatrnent for: - Persistent or recurrent signs/symptoms of syphilis - Fourfold increase in antibody till!rs - l.l!ssthan "fourfold decrease in antibody till!rs

PROGNOSIS Visual prognosis dependent on severity of ocular Inflammatlon COMPLICAnONS Corneal scarring Cataract Glaucoma Macular Edema Retinal detachment

• • • • •

REFERENCES 1. Centers for Disease Control and Prevention. Sexually Transmitted Diseases SuM!illance 2008. Atlanta, GA: U.S. Department of Health and Human Services; Nov 2009. 2. Aldave AJ, King JA, Cunningham ET Jr. Ocular syphilis. CuffOpn Ophtha/mol 2001;12:433-441. 3. Center for Disease Control and PreYl!ntion.Worknwski KA, Berman SM. Sexually transmitll!d diseases treatment guidelines 2006. MMWR Recomm Rep 2006;55:1-94.

.

CODES

ICD9 • 091.50 Syphilitic lM!itis. unspedfied • 091.51 Syphilitic chorioretinitis (secondary) • 095.8 Other spedfled forms of late symptomatic syphilis

CLINICAL PEARLS • Syphilis should be on the differential diagnosis of any case of intlliDrular inflammation. • Ocular syphilis is a manifestation of neurosyphilis. • Treatment regimen for oaJ lar syphilis should be the same as for tertiary neurosyphilis. • All patients with syphilis should be tesll!d for HIV.

PATIENT MONITORING Serial ophthalmic examinations for resolution of DC\Jiar inflammation PATIENT EDUCATION • Coonseling for safe sexual practices • Coonsellng for partners of affected patients

483

I

OPEN-ANGLE GlAUCOMAS Patrick Tiedeken

~ BASICS DESCRIPTION • A diverse group of neurodegenerative eye diseases that result in a typical excavated appearance of the optic nerve (ON) • Associated with midperipheral and central visual field defects with the intraocular pressure (lOP) as a major risk. factor • Glaucomas are divided into open-angle glaucoma (OAG) types if the trabecular meshwork can be visualized, or closed-angle glaucoma if the meshwork cannot be visualized. • OAG is further subdivided into primary OAG if there are no other ocular or systemic diseases present. Secondary OAG if associated with an ocular cause (i.e., exfoliative or pigmentary glaucoma) or a systemic disease (i.e., amyloidosis). EPIDEMIOLOGY lnddence • 2 million patients in the USA (50% undetected) • Glaucoma is the second leading cause of blindness in the USA. Prevalence 10 million patients at risk. as ocular hypertensives (elevated lOP with normal ONs and visual fields)

RISK FACTORS • High lOP (major risk factor) • Old age - 4(}-49 years = 0.22% prevalence -80 years= 14% prevalence • African American-3 times increased prevalence (vs. Caucasians) and more severe disease • Family history (5-19% increased risk) • Migraine headaches, myopia, hypertension

484

GENERAL PREVENTION Screening for glaucoma is most effective if aimed at high-risk groups: elderly and African Americans PATHOPHYSIOLOGY • Final pathway is damage to the retinal ganglion cells. • 1 Million ganglion cells in each ON • Ganglion cell axon travels from the retina to the lateral geniculate body of the thalamus. • 2 General theories of glaucoma ON damage: (1) VASCULAR-abnormality of blood flow damages ganglion cells. (2) MECHANICAL-weakness of lamina cribrosa (specialized connective tissue at the level of the ON canal) causes damage to the gangIion cell axons. ETIOLOGY • lOP is the most significant and treatable risk factor. • Degree of glaucomatous ON damage is directly related to the lOP level. • lOP 25-29 mm Hg = 7% prevalence ON damage. • lOP 35-39 = 52% prevalence ON damage ON damage can occur at normal lOP (>21 mm Hg): Baltimore Eye Study demonstrated that 50% of all OAG patients had screening lOPs of ften involves anterior portion of orbit. which appears as grape-like lesion beneath the conjunctiva

DIFFERENTIAL DIAGNOSIS • Neuroblastoma • lymphangioma • Hemangioma • Dermoid cyst • Inflammatory conditions -Cellulitis - Nonspecific inflammatory diseases

rJ

TREATMENT

MEDICATION First Line Chemotherapy is delivered by a pediatric oncologist. According to the Intergroup Rhabdomyosarcoma Study Group, the chemotherapy agents include vincristine, actinomycin-D. dactinomycin, cyclophosphomide, ifosfamide, and etoposide.

Second Line Phase 1/11 trials include the use of chemotherapy agents such as doxorubicin (Adriamycin), melphalan, methotrexate, topotecan/irinotecan, taxol/docetaxel (Taxotere). These drugs are used alone or in combination with first-line agents.

ORBITAL IUIABIIOMYOSJIICOMA ADDITIONAL TREATMENT General IIAHsUI'eS • Referto pedlat~c oncologist • Staging--most orbital disease are group II or g1'0\JP Ill. - GI'OI.Ip 1-tumor completely resecll!d -Group ll-micrD5COpit residual - GI'OI.Ip Ill-gross residual - GI'OI.Ip IV--flletastasls • According to Intergroup Rhabdomyosarcoma Study Group IV recommendiltions - Group I istreall!d with chemotherapy for 32 weeks. - GI'OI.Ip Ills treated wltl1 chemotherapy for 32 weeks and oibitalr.~diotherapy (4,140 cGy). - Group Ill is treated with dlemotherapy for 52 weeks and oibitalradiotherapy (5,040 cGy).

Issues for Refeml Any suspldous orbital lesion In a young pat!ent should raise suspldon and prompt referral to an ocular oncologist.

Additional Thetaples See next item

COMPLEMENTARY & ALTERNATIVE THERAPIES • Adjuvant dlemotherapy • 0ibitaI radiotherapy - Miaoscopic residual--4,000-4,500 cGy -Gross residual-s,ooo-s,soo cGy SURGERY/OTHER PROCEDURES As indicall!d above, orbitotomy with excisional biopsy complete remowl if possible is the first goal of therapy. Then further dlemotherapy and radiotherapy depend on the staging. IN-PATIENT CONSIDERATIONS Initial Stabilization lnpiltient hospitalization might be necessary for dlemotherapy.

Admission Crit.eria Inpatient hospitalization might be necessary for dlemotherapy.

IV Fluids May be necessary for inpatient hydration Nursing Per floor routine for chemotherapy patients

Discharge Criteria Once medically stable

•

ONGOING CARE

3. Hayes-Jordan A. Andrassy R. Rhabdomyosarcoma In children. Cu" Olin Pedlatr. 2009;21 (3): 373-378. 4. Shields JA. Shields CL. Rhabdomyosarcoma: Review for ophtl1almologist. Surv Ophthalma/. 2003; 48(t ):39-57. 5. Karcioglu 'ZA, Hadjistilianou D, Rozans M, et al. Orbital rhabdomyosarcoma. Can~r Control. 2004;11 (5):328-333.

FOLLOW-UP RECOMMENDATIONS • Every 2-3 months for the first year then every 6 months - Repeat imaging every 6 months. Patient Monitoring • Watch for radiation side effects to ~ and in field of treatment • Based on a comprehensive review of oibital RM Sby Shields et al., the findings indude the following: - Cataract in 55% - Oibital hypoplasia in 24% - Dry eye in 36% - Chronic keratoconjunctivitis In 9% - Retinopathy in 9% - Rl!tllrrence can occur years after treatment. - lall! side fflects of chemotherapy such as leukemia

fr:3 Media El1111ntl

DIET No dietary restrictions

.

PATIENT EDUCATION See Additional Readings.

ICD9 190.1 Malignant neoplasm of orbit

PROGNOSIS • Historically there was about 30% survtva ~ but wtth adjuvant r.~diationfchemotl1er.~py there is a 95% sunrival rate. - Favorable prognosis in oibit because of ea~ presentation and lack of lymphatic drainage COMPUCATIONS Side effects of radiationldlemotherapy

ADDITIONAL READING • Shields JA. Shields CL. Eyelid, conjunctival, and otbiW tumotS. An atlas and textbook, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2008.

Q

• • • • • •

See Also -251.

.

CODES

ICD9 • 362.14 Retinal microaneurysms nos • 362.81 Retinal hemorrhage • 362.83 Retinal edema

611

I

RFnNALVASCULARTUMDRS Emil Anthony T. Say Carol L. Shields

~ BASICS DESCRIPTION • Retinal vascular tumors are uncommon and diverse hamartomas or malformations of the neurosensory retina. • They may have systemic associations involving the central nervous system (C NS) and other organs that may be life-threatening. • They may be familial or sporadic. • Types (and synonyms): - Retinal hemangioblastoma (RH B, capillary hemangioma, angiomatosis retinae) - Retinal cavernous hemangioma (RC H) - Retinal racemose hemangioma (RRH, congenital arteriovenous anastomoses, cirsoid aneurysm, arteriovenous aneurysms) - Retinal vasoproliferative tumor (VPT; see the chapter on this topic) ALERT Retinal vascular tumors are associated with both vision-threatening and life-threatening conditions.

Pediatric Considerations Genetic testing and systemic work-up is advised for affected patients. Pregnancy Considerations Genetic counseling is recommended for affected pregnant women EPIDEMIOLOGY Incidence • RHB: Incidence is unknown; however, its associated syndrome, von Hippei-Lindau's disease (VHL), occurs in 1 in 40,000 live births. • In a report by Singh, Shields, and Shields, a solitary RHB in ayoung patient (~ 10 years) is associated with 45% risk for VHL compared to 0.5% when diagnosed in older patients (6 1-70 years) (see ·Additional reading· below). • RCH: Incidence of RCH is unknown. • RRH: Incidence of RRH is unknown. Prevalence • RHB: Prevalence unknown • RCH: Prevalence unknown • RRH: Prevalence unknown • No definite racial or gender predilections for any retinal vascular tumor RISK FACTORS None Genetics • RHB: Currently accepted mechanism follows Knudson's two-hit hypothesis affecting the VHL gene (chromosome 3p2 5-26) • RCH: Two-hit mechanism in the cerebral cavernous malformation (CCM) gene on chromosome 7q1 1.2-q21 • RRH: No genetic mutation

612

GENERAL PREVENTION None PATHOPHYSIOLOGY • RHB: VHL gene is a tumor suppressor gene that controls proliferation of blood vessels and mutation causes elevation of hypoxia inducible factor (H IF) and vascular endothelial growth factor (VEGF) with formation of hemangioblastomas in the brain and retina. • RCH: Mutation in the CCM gene leads to loss or decreased expression of CCM protein and malformation of endothelial cells in utero. • RRH: Characterized by congenital arteriovenous malformations (AVMs) without capillary interposition producing turbulent blood flow and dilation of blood vessels. ETIOLOGY • RHB: Sporadic or germline mutation in the VHL gene leads to formation of hemangioblastomas. • RCH: Sporadic or germ line mutation in the CCM gene leads to cavernous malformations. • RRH: It is presumably caused by a local defect in maturation of retinal mesenchyme that gives rise to vascular tissue at the 7th week of gestation. COMMONLY ASSOCIATED CONDITIONS • RHB: VHL disease -Autosomal dominant inheritance -Associated with RH B(57%), cerebellar hemangioma (55%), spinal cord hemangioma (14%), renal cell carcinoma (24%), and pheochromocytoma (19%) • RCH: Familial cavernous malformation (FCM) -Autosomal dominant inheritance - Cavernous malformations in the brain, skin, and retina (RC H) • RRH: Congenital retinocephalic (CRC) vascular malformation syndrome (Wyburn-Mason or Bonnet-Dechaume-Bianc syndrome) - Unilateral, progressive, and nonhereditary - AVMs involving the skin, brain, and retina (RRH)

~ DIAGNOSIS HISTORY • RHB: Asymptomatic early but may cause severe pain and blindness from neovascular glaucoma when advanced • RCH: Mostly asymptomatic and are detected only during routine examination • RRH: Presents as a unilateral blind eye in 48% when associated with CRC but are mostly asymptomatic when isolated • Family history is extremely important, especially in cases of RH Band RCH, to rule out familial disease or germ line mutation.

PHYSICAL EXAM • Retinal hemangioblastoma (RH B): - Orange-red circumscribed retinal lesion typically with dilated feeder vessels - Peripheral (B 5%) or juxtapapillary (15%) - May be associated with localized or remote retinal exudation, retinal detachment, glial proliferation with traction detachment, macular pucker, twin vessels. or neovascular glaucoma • Retinal cavernous hemangioma (RCH) -Dark-red, grapelike, saccular aneurysms - May occur in the retina or optic disc - May be associated with overlying fibrosis with macular traction, vitreous hemorrhage, and vascular occlusion - Not associated with leakage and exudation • Retinal racemose hemangioma (RRH) - Dilated arteriovenous communications without capillary interposition - Extensive retinal involvement in cases with systemic associations and localized or sectorial involvement when isolated - Rarely located in the macula - May be associated with neovascular glaucoma, vitreous hemorrhage, vascular occlusion, and conjunctival injection - Not associated with leakage and exudation - Pulsating exophthalmos or visual field defects when AVMs are present in the orbit or visual pathway, respectively DIAGNOSTIC TESTS lr INTERPRETATION Lab

Initial lab tests Genetic testing to rule out systemic disease

Follow-up a special considerations • Genetic counseling is recommended when germline mutations are found. • Patients with systemic associations should be promptly referred to a pediatric oncologist, oncologist, neurologist, or neurosurgeon.

Imaging Initial approach • Fluorescein angiography (FA) is most helpful: - RHB (peripheral): Rapid filling of dilated feeder arteriole in arterial phase, intrinsic fine capillaries, with prominent draining vein and leakage on later films - RHB Ouxtapapillary): Diagnosis is established by the fine vascular pattern visualized on the angiogram - RCH: Slow filling of the aneurysms with hyperfiuorescent caps superiorly and hypofluorescence inferiorly due to settling of red blood cells under the supernatant plasma, typically without leakage of dye - RRH: Rapid filling of high-flow retinal AVMs with adjacent capillary dropout Follow-up a special considerations • Asymptomatic patients with exudates or retinal detachment threatening vision should be followed closely and offered treatment. • Early treatment is needed for symptomatic patients. • Frequency of follow-up is determined by severity of the condition and degree of visual impairment.

RETINAL VASCULAR TUMORS Diagnostic ProCIIrJu/WSIOthaT • MRl, MRA. CTA. or anglography may be requIred to rule out assodated systemic disease.

l'athological Findings • RHB: Composed of capillary-sized blood vessels with normaI endothelium, vacuolated stromaI cells. and gliosis (1) • RC H: Dlla1ed, th ln-walied blood vessels. with interconnections and an intact endothelium (1) • RRH: Dilated retinal vessels sometimes occupying the entire retinal thidcness causing tyStic degeneration and attelluation of the adjacerrt retinal tissue (1)

DIFFERENTlAL DIAGNOSIS • • • • • •

ChoroidaI melanoma Choroidal granuloma Circumscribed choroidal hemangioma Retinal macroaneurysm Retinoblastoma Coats' disease

fl

COMPLEMENTARY & ALTERNATIVE THERAPIES

REFERENCES

• RHB: Transpuplllary thermotherapy, external or proton beam radiotherapy, and local or systemic anli-VEGFtherapy have been used for RH B, but effKaty is incandusive and role is sliII uncertain (1-3)[C). • RCH: There is no proven treatment (1)[C]. • RRH: There Is no proven treatment (1)[C).

1. Heimann H, Damato B. Congenital vascular malformations of the retina and dloroid. Eye 2010:24:459--467. 2. Singh AD, Shields Cl.., Shields JA. Von HippeiUndau disease. SurvOphtha/mo/2001;46: 117-142. 3. Wong WT, Chew EY. Ocular von Hippei-Undau disease: Clinical update and emerging treatments. Cuff OJin Ophtfla/mo/2008;19:213-2 17. 4. Messmer E, Laqua H, Wessing A. et al. Nine cases of cavernous hemangioma of the retina. Am J Ophtha/mol 1983;95:383-390. 5. Gass JDM. Ci!Vt!l'nous hemangioma of the retina. Aml OphthalmoJ 1971;71:799--314. 6. Schmidt D, Padle M, Schumadler M. The congenital unilateral retinocephalic vascular malformation syndrome (Bonnet...nechaume-Bianc syndrome or Wybum-Mason syndromet. Review a! the literature. Surv O{iltha/mo/2008;53:227-249.

SURGERY/OTHER PROCEDURES o RH B: Resection and Iigature of feeder vessels has been reported but is technically difficult (2)[C) • RCH: No surgical reports • RRH: No surgicaI reports

IN-PATIENT CONSIDERATIONS Outpatient management

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

MEDICATION

• Outpatient care for photocoagulation, photodynamic therapy, or cryotherapy • In-patient or outpatient for plaque radiotherapy, vitrectomy, or enucleation

See • General measures• below.

Petlent Monitoring

ADDITIONAL TREATMENT CienenJI Measures

• 6-m onth foiiDW-ups are recommended for most patients. • Follow more closely when vision is threatened.

TREATMENT

• Retinal hemangioblastoma (RHB): -May be observed if small or jllltapapillary, if it is not visual~ threatening, or if the patient is asymptomatic (2)[C) - Laser pho!DCoagulation or photodynamic therapy preferred for posterior RH Band cryotherapy when more ante~or (2)[C) - Plaque radiotherapy reserved for more advanced RHB (2)[C] • Retinal cavernous hemangioma (RCH): - Most~ nonprogressive and dlo not require treatment (1 ,4, 5)[C) • Retinal racemose hemangioma (RRH): - Mostly nonprogressive and dlo nat require treatment (1 ,6)[C] ISsues for Referral • Treatment should usually be performed by a retina speciaIist or an ocular oncologist. • Patierrts with positive genetic analyses or imaging tests should be pnornpt~ ll!fl!rred to a neurologist, neurosurgeon, or pediatric oncologist.

Arlrlition•l 'nlen~pies • Retinal surgery is required for persistent vitreous hemorrhage or retinal detamment {1)[C]. • Enucleation may be needed for blind and painful eyes with no potential for vision (1)[C). • Assocla1ed hemorrhage, vascular occlusion, or neovasculal1zatlon requl res appropriate treatment with laser. ayopexy, or retinal surgery (1 ,4-6)[C).

DIET No restrictions

PATIENT EDUCATION • Advice regarding Implications of genetic analysis and systemic assodations • Genetic counseling is essential o Use of the Amsler grid for self-monitoring of visual d1anges for early diagnosis and treatment

ADDITIONAL READING • Singh AD, Shields JA, Shields CL Solitary retinal capillary hemangioma. Hereditary (von HippeiLindau disease) or nonhereditary? ArdJ Ophthalmol 2001;119:232-234.

Q

S11 Also (Tapic, Al1arithm, Elactronic

af:3 Madia El1111nt) • • • • • •

www.fighteyecancer.com www.eyecancerinfo.com www.eyecancerbook.corn www.etrf.org www.genetests.org www.ncbi.nlm.nih.gov/omim

PROGNOSIS • Retinal hemangioblastoma (RHB): - 40% of affected eyes have vision 4 mm), juxtapapillary, or multiple. - Enudeatlon may be required In 6% of eyes. • Retinal cavernous hemangioma (RCH}: - Most patients maintain good vision. - Progressive growth is rare. o Retinal racemose hemangioma (RRH): - NLP In 48'!1. If cerebral AVM s are present - VIsion ~ 20/50 In 56% In Isolated cases

COMPUCATlONS Loss of vision or globe, and even death when systemic

assodations are not detected.

.

CODES

ICD9 • 228.03 Hemangioma of retina • 743.58 ViiS(IJiar anomalies, congenital • 757.32 vascular hamartomas

CLINICAL PEARLS • Retinal vascular tumors have associated life-threatening systemic conditions that require proper Imaging tests and genetic analysls. • RH Boften have dila1ed feeding arterioles and draining veins, with remote macular edema. • RC Hare grape-like aneurysms that are often nonprogressive and do not require treatmerrt. • RRH are dilated AVMs of the retina and occasionally involve the orbit and visual pathway.

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RmNAL VASOPROLIFERATIVE TUMOR Emil Anthony T. Say Carol L. Shields

~ BASICS DESCRIPTION • Vasoproliferative tumors of the retina (VPT) are benign vascular lesions located in the sensory retina. • They are nonfamilial. • In a series of 103 patients, Shields and associates reported that the patients were classified as follows (2): - Primary or idiopathic (74%) - Secondary (26%) • In the same series, they may also be subclassified as follows: - Solitary (78%) -Multiple (15%) - Diffuse (7%) • Other synonyms for VPT are as follows: - Presumed acquired retinal hemangioma -Angiomatous mass - Peripheral retinal telangiectasia -Angioma/hemangioma-like mass - Reactionary retinal glioangiosis

ALERT Retinal vasoprol iterative tumor can produce extensive retinal exudation and lead to blindness. EPIDEMIOLOGY • Predominantly affects older patients (mean age = 40 years) • No gender or racial predilection Incidence • Represent 1% of all pseudomelanomas • True incidence is unknown

Prevalence Unknown

RISK FACTORS Unknown

Genetics No definite genetic association

PATHOPHYSIOLOGY • Precise pathogenesis is presently unclear. • Current hypothesis is reactive pigment epithelial and vascular proliferation or reactive gliosis secondary to a variety of underlying disease processes.

614

ETIOLOGY

DIAGNOSTIC TESTS & INTERPRETATION

• Primary cases are idiopathic. • Secondary cases are associated with the following: - Intermediate uveitis (28%) -Retinitis pigmentosa (21 %) -Toxoplasmic retinitis (7%) - Toxocariasis (7%) - Retinochoroidal coloboma (7%) -Traumatic chorioretinopathy (7%)

Lab

COMMONLY ASSOCIATED CONDITIONS • Systemic hypertension (14%) • Hypercholesterolemia (6%) • Neurofibromatosis (2%)

~ DIAGNOSIS HISTORY • Blurred vision and/or floaters are common presenting symptoms. • Photopsias and visual field defects are other possible initial symptoms. • The disease may be asymptomatic (19%).

PHYSICAL EXAM • Visual acuity and laterality: - Better than 20/40 in up to 50% - Most cases are unilateral - Can be bilateral in 40% of secondary cases • Appearance: - Yellowish to yellow-red in color -Mostly solitary and small (BO% - Improved functional outcomes with incomplete palsies and early onset recovery (< 3 weeks) - More complete palsies: Higher likelihood of incomplete recovery and aberrant regeneration - Poorer prognosis: Hyperacusis, decreased tearing, hypertension, age >60 years, diabetes, psychiatric disease. pregnancy o Recovery dependent on site and extent of nerve injury • EMG and nerve conduction studies: Preservation of motor am pi irudes indicates axonal continuity and suggests good prognosis for recovery.

Pediatric Coruiderafions • Neoplastic and congenital etiologies associated with incomplete recovery

COMPLICATIONS • Aberrant regeneration resulting in: Motor Synld nesis or Crocodile Tears • Hemifacial Spasm • Treatment: Chemodenervation with botulinum toxin

4. En!JS!rom M, Berg T, sqernquist-Desatnik A. et al. Prednisolone and valac!clov!r In Bell's palsy: A random ised, double-blind, placebo-controlled, multicentre trial. lancet Neurol 200!1;7:993-1 000. [A] s. Grogan P, Gronseth GS. Practice parameter: Steroids, acyclovir, and surgery for Bell's Palsy {an evidence-based review): Report of the Quality Standards Subcommittee of the AAN. Neurology 2001;56: 83G-a36.

ADDITIONAL READING Wang CH, Chang YC, Shih HM, et al. Fadal palsy !n children: Emergency department management and outcome. Pediiltr Emerg Care 201 0;26: 121-125. • Gilchrist JM. Sewnth a-anial neuropathy. Semin Neurol, 2009;29:5-13. • Hazin R, Azimdeh B, Bhatti, MT. Medical and surgical management of facial nerve palsy. Cu" Op/n O{i!thalmol 2009;20:440-450. • Rahman I, Sadiq SA. Ophthalmic management of facial nerve palsy: A review. Surv Ophtha/mo/ o

2007;52:121-144.

.

CODES

ICD9 • 351.0 Bell's palsy • 351 .8 Other facial nerve disorders • 351 .9 FadaI nerve disorder, unspecified

CLINICAL PEARLS • Differential!! centraI versus periph eraI palsies o Bell's Palsy treatment Oral corticosteroids for 10 days ± amivirals for severe/complete palsies. • CorneaI health and protection must be monitored d054!ly.

REFERENCES 1. L.oclchan P, Daly F, Pltkethly M, et al. Antiviral treatment for Bell's palsy (idiopathic facial paralysis). Cochrane Database S)St Rev 2009; (4): CD001869. [A) 2. Salinas RA. Alvarez G, Daly F, et al. Corticosteroids for Bell's palsy {idiopathic fadal paralysis). Cochrane DatabaseS~ Rev 2010;(3):CD001942. [A)

3. Sullivan FM, Swan IRC, Donnan PT, et al. Early treatment with prednisolone or acydovir in Bell's Palsy. NEng J Med 2007;357:1593-1607. [A]

SURGERY/OTHER PROCEDURES o Facial nerve decompression lacks sufficient evidence (S) • SurgicaI management: Corneal sequela -Gold weigln implant (upper lid) or tarsorrhaphy o For incomplete eyelid closure o Prevents and treats comeal injury

839

I

SJIGREN'S SYNDROME Apurva Patel Frederick B. Vivino Vatinee Y. Bunya

~ BASICS DESCRIPTION • Sjogren's syndrome is a chronic autoimmune disorder in which the body mistakenly attacks its own exocrine tear and salivary glands, leading to dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). • In addition, patients can have systemic features involving multiple systems throughout the body including the skin, lungs. liver, lc.idneys. gastrointestinal tract, vasculature, blood, and nervous system. EPIDEMIOLOGY lnddence Not well-defined. Prevalence • 1.3 million patients with primary Sjiigren's in US (range 0.4-3.1 million) • Prevalence rate 0.43% (0.13-1 %) RISK FACTORS • Females are affected 9 times more frequently than males. • Onset usually fourth to sixth decade of Iife. Genetics Familial predisposition possible, but no single gene has yet been identified. PATHOPHYSIOLOGY Lymphocytic infiltration and destruction of the lacrimal and salivary glands likely triggered by a viral and/or environmental cue in a genetically susceptible individual. ETIOLOGY Exact etiology unknown. Commonly Associated Conditions • Systemic lupus erythematosus, rheumatoid arthritis, mixed oonnective tissue disease, systemic sclerosis, autoimmune thyroid disease, autoimmune liver disease, inflammatory muscle disease, and leulc.ocytoclastic vasculitis. • When sicca symptoms (dry eyes and mouth) develop in patients with established connective tissue disease, the diagnosis is considered seoondary Sjogren's syndrome. • About 5% of patients develop non-Hodglc.in B-cell lymphoma within 10 years of diagnosis.

640

~ DIAGNOSIS HISTORY • Symptoms of dry eye (burning, stinging, gritty feeling, artificial tear use) • Symptoms of dry mouth • History of rheumatic symptoms or severe fatigue PHYSICAL EXAM • Visual acuity • Lid exam looking for ooexisting meibomian gland disease or blepharitis • Tear break-up time, abnormal if< 10 seconds • Staining of conjunctiva and oomea with lissamine green or rose bengal (note rose bengal may cause stinging and is less well-tolerated than lissamine green) • Staining of conjunctiva and cornea with fluorescein • Schirmer's test -Abnormal if unanesthetized and ::55 mm at 5 minutes - Unanesthetized test measures basal and reflex tear secretion -With topical anesthetic. test measures basal tear secretion DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests • Autoantibodies • Anti-Ro/SS-A or Anti-La/SS-B positive in 40--60% of patients with primary Sjogren syndrome • ANA and RF-positivity may be seen in up to 90% Follow-up & special considerations Low complement C4 and cryoglobulins may be markers for lymphomas.

Imaging • No ophthalmic diagnostic imaging indicated. • Nuclear medicine salivary scintigraphy is useful in evaluation of xerostomia

Diagnostic Procedures/Other • American-European Consensus Group Diagnostic Criteria (1 )[C] • 6 criteria: - Symptoms of aqueous tear insufficiency (dry eye for 3 months. foreign body sensation, artificial tear use > 3 x /d) - Oral symptoms (dry mouth for 3 months, swollen salivary glands, need to drink liquids to swallow food)

• • •

•

- Ocular signs (unanesthetized Schirmer's test ::55 mm at 5 minutes, rose bengal staining >4 on van Bijsterveld scale), o Van Bijsterveld scale sums amount of rose bengal staining in: Nasal conjunctiva, Temporal conjunctiva, and cornea. Each area is assigned a staining score of 0-3. Sum of scores equals total score (maximum score of 9). - Oral signs (abnormal salivary scintography, parotid sialography, or unstimulated salivary flow < 1.5 mL in 15 minutes) - Minor salivary gland biopsy showing ~ 1 oon~ lomeration of >50 mononuclear cells in 4 mm of glandular tissue. Autoantibodies: Positive anti-Ro/SS-A or anti-La/SS-B Primary Sjogren's syndrome is diagnosed in previously healthy individuals with sicca symptoms which arise de novo. Diagnosis of primary Sjogren's requires at least 4 positive criteria, one of which has to be histopathology or serum autoantibodies. Diagnosis of secondary Sjogren's requires at least 1 sicca symptom, an established connective tissue disease diagnosis, plus 3 signs of Sjogren's (see criteria 3-5 above).

Pathological Findings • Lacrimal gland biopsy shows focal and/or diffuse lymphocytic infiltration. Advanced disease can show fibrous or fatty replacement of glandular structures. • Labial salivary gland biopsy shows similar changes and is less invasive than lacrimal biopsy.

DIFFERENTIAL DIAGNOSIS • Age-related or medication-induced dry eye and dry mouth. • Thyroid eye disease • Lacrimal infiltrative disease (amyloidosis, sarcoidosis, lymphoma) • Other causes of ocular irritation (blepharitis, eyelid malposition, trichiasis) • Hypovitaminosis A • Other causes of dry mouth (e.g., mouth-breathing, radiation·induced xerostomia)

SJ6GREN'S SYNDROME

.

TREATMENT

MEDICATION RrstLine

•

FOLLOW-UP RECOMMENDATIONS o

• Artificial te.~rs (preservative-free if used more ti1an 4x/d~)

• Topical cyclosporine 0.05-1% 1 drop OU 2xlday (2)[A] • Cyclosporine drops often bum on instillation; this usually Improves with continued use. • 10% N-acetytcysteine 1 drop .Wday for filamentary keratitis.

Second Une • Topical steroids (monitor for intraowlar pressure elevation and cataract formation) • Topical autologous serum drops • Systemic immunomodulatory therapy including oral steroids, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, and IV rituximab are used for systemic disease. Usually managed in consultation with a rheu matologlst. • Muscarinic agonists (pilocarpine PO S mg 3-4x/day or cevimeline 30mg PO 3Jtfday)

ALERT Avoid prescribing medications with anti-cholinergic side effects thi!l can exacerbate sicca symptoms.

ONGOING CARE

o

o

Follow every 4-6 months or more frequently depending on severity of disease. Warn patients of signs and symptoms of microbial keratitis. as there Is a higher r!slc: with corneal epitheliaI bre.~kdown. Contact lenses may be wom wiltl close observillion once corneal epithelium is healed. Newer contact lenses designed for patients with dry eyes should be considered.

DIET Omega-3 fatty acids have been shown to be beneficial in dry eye syndromes in general, and may be helpful in Sjiigren's syndrome. PATIENT EDUCATION o

o

Patients should understand that SjiJgren's syndrome is most often a chronic cond ilion whose symptoms are treatable, but not curable. Dry eye and dry mouth symptoms are usually manageable with medications. Follow-up with a rheumatologist and an ophthalmologist are Important In maintaining systemic he.~lth and eye health. The Sjilgren's Syndrome Foundation m~ be a useful resource for patients. WIIIW.sjogrens.org

PROGNOSIS Slgnlflcant reduction but not always elimination of ocular symptoms wlltl therapy as above. • Systemic manifestations and lymphomas are treatable when diagnosed early. o Mortality increased in lymphoma patients but equivalent ID non-SjOgren's patients wiltl lymphoma. o

ADDITlONAL TREATMENT Gelleral Meuutes • Hurnidified air

• Fish oiI or flaxseed oil supplements • Treat melbomIan gland dlsea.~elf present

• warm compresses ID eyelids twice daily for 5-1 0 minutes. • Clean eyelid margin daily wiltl commercial eyelid .scrub or cotton swab moistened witi1 baby shampoo andWiller.

Issues for Refe~l • An ophltlalmologist should be involved at baseline for evaluation of ocular criteria and then every 4--fi months. or more frequently as needed if dry eye symptoms and signs are uncontrolled wiltl artifidal tears. • Refer patients wltt1 meumatlc symptoms and/or systemic disease to a rtteumatologist. • Refer pregnant patients who are anti-RoiSS-A positive IDa perinatologist for high-risk obstetric care.

COMPLEMENTARY • ALTERNATIVE THERAPIES According to some studies. aw pu ndure may provide reliE!f of meumatic and/or sicca symptoms.

COMPUCATIONS Corneal surface breakdown causing corneal ulceration, sea rring. o lnaeiSed prevalence of lymphoma (5%). • 25% of pat!ents have extraglandular Involvement (can be of any organ system). o

Pediatric CotJslderatlons Sjiigren's syndrome may occur in children (about 300 reported cases) and most commonly presents as recurrent parotitis without sicca symptoms.

l'regnancy CQIJsider.tions Mothers who are anti·Ro/Sl"r-A positive may gille birth ID infants with the neonatal lupus syndrome and should be followed by a perina!Diagist.

REFERENCES t . Vitali C, Bombardieri S, Jonsson R, et al. Classlflcatlon cr!terla for Sj6gren's syndrome: A revised version of the European criteria proposed by the American-European Consen~ Group. Ann Rheum Dis 2002;61:551Hi64. 2. Barber LD, Pllugfelder SC, Tauber J, et al. Phase Ill safety evaluation of cyclosporine 0.1% in ophltlalmlc emulsion administered twice dally to dry eye disease patients for up to 3 years.

0/i!thalmo/ogy 2005;112(1 0):1790-1794.

ADDITlONAL READING • Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjogren syndrome.Atdr lntem Med 2004;164:1275-1284. • Foulks GN. Tre.~trnent of dry eye disease by the non-iJ!)hthalmologist. Rheum Dis CHn North Am 2008;34:987-, 000.

.

CODES

ICD9 7t 0.2 Sicca syndrome

CLINICAL PEARLS • There Is a wide spectrum of dry eye disease, Yfhlch can make distinguishing Sj6gren's syndrome patients from other dry eye patients challenging. Consider the diagnosis in any patient wiltl symptoms of dry eye and dry mouth, or with refrac!Diy or severe dry eye disease. Multidisciplinary eYa luatlon Is heIpfulln making the diagnosis af Sjogren's syndrome. • The dry eye symptoms of Sjogren's syndrome dry eye can be well-managed with a regimen ollubricants. anti-inflammatory drops, and pu nctal ocd usion or cautery. Some patients will require systemic medications and close collaboration wltt1 a rtteumatologist to achieve symptom relief. • Dry eye symptoms are a common presenting complaint to the aphthaImologist. Given the rate of undiagnosed Sjiigren's syndrome (estimated at 50%), the ophthalmologist should be mindful of the diagnosis in all dry eye patients and make referrals ID other healthcare providers as appropriate. Note: Grade A recommendation for use in dry eye of any etiology, wiltl a large fraction having Sjiigren's syndrome. Grade B recommendation for use in dry eye due to SJOgren's speclflcally.

SURGERY/OTHER PROCEDURES • Puncta! occlusion or cautery • Lateral tarsonhaphy in severe cases

IN-PATIENT CONSIDERATIONS Initial StabilizetiotJ Inpatient admission usually unnecessary except for severe systemic disease.

641

I

SOlAR RETINOPATHY Gary Shienbaum

~ BASICS DESCRIPTION Phototoxicity of the retinal pigment epithelium (RPE) and photoreceptor layers in the fovea due to exposure to sunlight.

EPIDEMIOLOGY Incidence Uncommon, but clusters of cases appear around eclipses

RISK FACTORS • Eclipse watching, sun gazing, sunbathing • Emmetropia/low hypermetropia, aphakia • Vocation (e.g., aviation, military [e.g., aircraft reconnaissance!. astronomy) • Photosensitizing medications (e.g., tetracyclines), mydriatic;, hallucinogenic drugs (e.g., l5D)

GENERAL PREVENTION Protective shading (e.g., hats, visors, filtering lenses/sunglasses)

PATHOPHYSIOLOGY • Photochemical damage: resulting from the nonthermal effects of visible spectrum short wavelength (i.e., blue) light and ultraviolet radiation to the RPE and photoreceptor layers. • Sun exposure is thought to cause thermal damage. Light absorption by the RPE results in a rise in temperature of the surrounding tissues. The exposure also causes formation of reactive oxygen species.

ETIOLOGY See "Risk. Factors" and "Pathophysiology.·

642

~ DIAGNOSIS HISTORY • Unprotected solar eclipse viewing, sun gazing O.e., related to religious rituals. psychiatric illnesses, hallucinogenic drugs), sunbathing, vocational exposure (e.g., aviation, military service, astronomy) • Decreased visual acuity, central/paracentral scotomata, dyschromatopsia, and metamorphopsia can occur following prolonged sun exposure. • Typically bilateral

PHYSICAL EXAM • Early: - Yellow-white spot in the fovea o Can have surrounding granular gray pigmentation. • Late: -The acute findings resolve in several weeks. In the chronic stage, there is a variable appearance to the fovea (ranging from a normal appearance to a pigmentary disturbance or a pseudolamellar hole appearance). -A red, sharply demarcated, cyst·lilr.e lesion may persist. - Eyes with better initial visual acuities are more lilr.ely to have unremarkable funduscopic examinations at follow-up.

DIAGNOSTIC TESTS & INTERPRETATION Imaging • Fluorescein angiography: -Variable; may be unremarkable; window defects seen later in disease course. • Optical coherence tomography: -Acute findings: o Hyporeflectivity at the level of the RPEfphotoreceptor layer o Associated hyperrefiectivity of the injured neurosensory retina has been described. - Chronic/late findings: o Central defect (hyporeflectivity) at the level of the photoreceptor inner segment-outer segment junction o Foveal atrophy

Pathological Findings • Concentrated in foveal and parafoveal regions - Photoreceptors: swelling of outer segments. fragmentation of lamellae, mitochondrial swelling within the inner segments. nuclear pyknosis. and atrophy have been described. - RPE: irregular pigmentation/depigmentation and atrophy can occur.

DIFFERENTIAL DIAGNOSIS • • • •

Macular hole Idiopathic macular telangiectasia type 2 Cone dystrophy Age-related macular degeneration

SOLAR RETINOPATliY

.

TREATMENT

None

•

ONGOING CARE

FOLlOW-UP RECOMMENDA110NS Monthly for the first few months, then as needed. PA11ENT EDUCATION See • General Prevention." PROGNOSIS • Eyes with better visual acuities on initial l!lilmination tend to I'MlYI!r more vision.

• CentraVparacentraI srotomata can persist, despite improvement in visual acuity. • Long-term slg nlflcant reduction In visual acuity Is rare.

REFERENCES 1. Yannuzzi LA. Fisher YL, Krueger A, et al. Solar retinopathy: A photobiological and geophysical analysis. TnmsAm Ophtha/mol Sac 1987;85: 12D-158. 2. Hope--Ross MW, Mahon GJ, Gardiner TA. et al. Ultrastructural findings In solar retinopathy. Eye 1993;7:29-33. 3. Garg SJ, Martidis A, Nelson MI... et al. Optical roherence tomography of chronic solar retinopathy. Am J Ophthalmo/2004;137:351-354. 4. Wu J, Seregard S, Algvere PV. Photochemical damage of the retina. SutV Ophrha/mol 2006; 51 : 461-481. 5. Jain A, Desai RU, Charalel RA. et al. Solar retinopathy: Comparison of optical coherence tomography (OCT} and fluorescein angiography (FA). RerJna 2009;29:134D-1345.

.

CODES

ICD9 363.31 Solar retinopathy

CLINICAL PEARLS • Solar retinopathy can occur after prolonged sun exposure. and commonly dusters around naturaI phenomenon such as eclipses. • Most patients retain good vision over time.

643

I

STARGARDT DISEASE Christopher J. Brady

~ BASICS DESCRIPTION • The most common form of juvenile macular degeneration • Causes vision loss in the first or second decade of life • "Fundus flavimaculatus· is the descriptive term given to the retinal appearance often found with this condition. The term is usually synonymous with Stargardt disease, although some authors reserve this term for only those patients with the classic retinal appearance or patients with later onset disease. EPIDEMIOLOGY Prevalence 1/8,000-1(1 0,000

RISK FACTORS • Usually autosomal recessive • Classic disease linked to mutations in ABCR (also calledABCA4) on chromosome 1p13-p21. • More than 400 sequence variations have been described. • Mutations in this gene are also linked to autosomal recessive cone-rod dystrophy and retinitis pigmentosa. • Autosomal dominant Stargardt-like diseases caused by mutations on chromosomes 13q, 6q, and 4p. GENERAL PREVENTION Genetic counseling may be of value to some families, but there are no strategies for prevention.

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PATHOPHYSIOLOGY • The ABCR gene codes for an ATP-binding cassette known as Rim protein (RmP) involved in vitamin A metabolism. • Vitamin A is used by rod and cone photoreceptors in the outer retina. • It is thought thatABCR mutations interfere with transport of vitamin A between the photoreceptors and underlying retinal pigment epithelium (RPE). • Leads to a build-up of lipofuscin in RPE cells. • The disease affects the macula and fovea preferentially due to the high concentration of photoreceptors in the area of central fixation.

~ DIAGNOSIS HISTORY Patients describe slowly progressive vision loss. There may be affected siblings, although strong family history is uncommon given autosomal recessive inheritance. PHYSICAL EXAM • The fundus exam may appear completely normal. For this reason, some patients are suspected of malingering. • Typical retinal changes are usually bilateral and include the following: - Nonspecific foveal RPE mottling, which may take on a ·beaten bronze· appearance. - Ill-defined, yellow-white deep retinal "flecks" at the level of the RPE, referred to as "pisciform· for their fish-like shape. - More advanced disease may have an atrophic macula with a • bull's eye• or geographic atrophy appearance.

DIAGNOSTIC TESTS & INTERPRETATION Lab Genetic testing is generally not performed for this condition given the large size of the ABCR gene and the diversity of known mutations.

Diagnostic Procedures/Other • Intravenous fluorescein angiography (IV FA) often reveals a "dark choroid." in which retinal blood vessels are highlighted against a hypofluorescent background due to the accumulation of lipofuscin the RPE cells. This sign is highly specific for this condition, but the absence of this sign does not exclude the diagnosis. • Fundus autofluorescence photography often reveals hypoautofluorescence at the level of fovea corresponding to RPE atrophy. This is usually surrounded by small flecks of hyperautofluorescence, which may outnumber those flecks seen clinically. • IVFA may also reveal hyperfluorescent flecks corresponding to RPE atrophy, which may become confluent in advanced disease. • Full-field ERG (electroretinogram) is usually normal but the photopic (bright-adapted) ERG may be slightly abnormal. Multifocal ERG may show decreased amplitudes corresponding to central vision. • EOG (electrooculogram) may be slightly abnormal in advanced cases.

Pathological Findings • light microscopy reveals a loss of photoreceptors and RPE cells. • RPE cells in the posterior pole are also irregular in size and shape with intracytoplasmic PAS-positive granules of lipofuscin.

STARGARDT DISEASE DIFFERENTlAL DIAGNOSIS • Fundus alblpunctatus: flecks In the mldperlpheral retina, nonprogressive congenital night blindness • Retinitis punctata albescens: similar appearance to fundus albipunctatus with severe, progressive vision loss • Drusen: Small yellow-white spots in macula. Usually develop later in life. Hyperfluorescent on IVFA. • Cone or cone-rod dystrophy: Can present with ·bull's eye· mawlopathy. Significant color vision loss. abnormal ERG. • Chloroqulnelhydroxychloroqulne toxlctty: Can present with "bull's eye• maculopathy • Batten disease and Spielmeyer-Vogt syndrome: Autosomal rece5Sive lysosomaI storage disease. Can produce "bull's ~· maculopathy. • Functional vision loss: Normal exam and testing. Spedal techniques can unmask better vision than claimed.

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TREATMENT

MEDICATION • There are no treatments for thIs disease. Low Ylslon referral may be of great vaIue. uv protection is generally recommended. • As the gf!lletics are further understood, this disease may be amenable to gene therapy.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Ophthalmologic exams • Lowvision • Services for the blind • Fundus autofluorescence photography may be of value In assessing disease activity. PATIENT EDUCATION • http://www.macular.org/stargardts.html • http://www.lowvlslon.org/stargardts.htm PROGNOSIS • Stargardt disease is a chronic disease with poor visuaI prognosis. • Once visual acuity drops below 20/40 it tends to decrease rapidly, then stabilize near 201200. COMPLICATIONS Central vision loss

REFERENCES 1. Boon a, Jeroen Klevering B, Keunen JE, et al.

3. Walia S, Fishman GA. Natural history of phenotypic changes In Stargardt mawlar dystrophy. Ophthalmic Genet 2009;30:63-68. 4. Westerfeld c. Mukai S. Stargardt's disease and the ABCR gene. Semin Ofilthalmoi2008;23:5H5.

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CODES

ICD9 • 362.75 Other dystrophies primarily involving the sensCI)' retina • 362.76 Dystrophies p~marlly lnvoMng the retinal pigment epithelium

CLINICAL PEARLS • • • •

Most common juvenile macular dystrophy Autosomal recessive inheritance Vision usually stabilizes around 20/400 No treatments available, potential gene therapy In the future • Low vision referra I of value

Fundus autofluorescence Imaging of retinal dystrophies. Vision Res 2008;48:2569-2577. 2. Koenekoop RK. The gene for Stargardt disease, ABCA4, Is a major retinal gene: a mini-review. Ophthalmic Genet 2003;24:75-80.

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STEROID-INDUCED GLAUCOMA Robert J. Goulet, Ill

Anand Mantravadi

~ BASICS DESCRIPTION Steroid·induced glaucoma is a secondary open-angle glaucoma that results after the use of local or systemic corticosteroids. Intraocular pressure (lOP) increase results from decreased aqueous humor outflow facility. Glaucomatous optic neuropathy can then develop from this ocular hypertension. EPIDEMIOLOGY lnddence

Genetics

PHYSICAL EXAM

• No clear genetic component • Myocilin may be overexpressed by meshwork cells when exposed to steroids and myocilin gene mutations have been associated with juvenile and adult-onset glaucomas.

• lOP elevated from baseline • If asymmetric optic nerve damage exists, there may be a relative afferent pupillary defect • Slit lamp exam will likely be within normal limits or no change from patient baseline • Gonioscopy will be consistent with patient baseline • Examination of the optic nerve may show evidence of typical glaucomatous damage (diffuse narrowing of the neuroretinal rim, focal notches, disc hemorrhage). Prior glaucomatous damage makes the nerve more susceptible to further damage at lower lOP increases for shorter durations.

GENERAL PREVENTION • Be aware of those populations at risk. • Limit exposure to necessary corticosteroids. • Use formulations less likely to cause lOP rise.

PATHOPHYSIOLOGY

• Incidence of lOP rise varies with route of administration, formulation of medication, and total cumulative dose. • 5% of people treated with topical steroids for 4--6 weeks show an lOP rise of ~ 16 mm Hg, 30% show an lOP rise of6-15 mm Hg • lntravitreal > periocular > topical > systemic • lntravitreal triamcinolone acetonide (4 mg}14.6-44.6% • Prednisolone acetate (1 %}-6.7% • Loteprednol etabonate (0.2 and 0.5%}-1.7% • Case reports with inhaled, intravenous, oral, and topical corticosteroid use

• Decreased aqueous humor outflow facility • Possible architectural changes of the trabecular meshwork (i.e., actin crosslinking) • Possible deposition of material in the trabecular meshwork (i.e., glycosaminoglycans) • Possible decreased phagocytic function of trabecular meshwork cells with decreased ability to remove material accumulated in the meshwork

Prevalence

~ DIAGNOSIS

Unknown

RISK FACTORS • Diagnosis of primary open-angle glaucoma • First-degree relative with primary open-angle glaucoma • High baseline lOP • Traumatic angle recession • High myopia • Connective tissue disease • Type 1 diabetes mellitus • Children • Elderly

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ETIOLOGY Unknown COMMONLY ASSOCIATED CONDITIONS Any requiring use of corticosteroids

HISTORY • Patient being treated with topical or systemic corticosteroids. Do not forget to inquire about depositions (intravitreal, periocular) or inhalational, intranasal, or dermatologic formulations. Attempt to identify those patients that are at higher risk of developing elevated lOP with steroid use. • Presentation may be within 1 week of initiating therapy but may be delayed up to years later. • Typical time to presentation for ophthalmic drop formulations is 3-8 weeks

DIAGNOSTIC TESTS & INTERPRETATION Imaging Optic nerve head imaging (i.e., confocal scanning laser ophthalmoscopy) or retinal nerve fiber layer imaging (optical coherence tomography or scanning laser polarimetry) may be used in conjunction with optic nerve exam to evaluate for glaucomatous damage.

Diagnostic Procedures/Other • Standardized visual fields should be obtained to assess for evidence of glaucomatous functional deficits. • Pachymetry

Pathological Findings None

DIFFERENTIAL DIAGNOSIS • Primary open-angle glaucoma • Uveitic glaucoma

mRDID-INDUCED GLAUCOMA

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TREATMENT

MEDICATION RrstLine • Cessation of steroids if possible. Tapering to a lower dose can ultlmatl!ly resu It In reduction In pressure. • Beta-adrenergic antagonists (topicaO -limolol maleatl! 0.25-{).5'11., one drop daily or b.i.d. - Betaxolol 0.25'11., one drop b.i.d. • Alpha2-adrenergic agonlsts ~oplcal) - Brimonidine tartrate 0.1 5'11., one drop b.i.d. or t.i.d. • Carbonit anhydrase inhibitors (topicaO - Dorzolamide 2.0%, one drop b.i.d. or t.i.d. - Brinzolamide 1'11., one drop b.i.d. ort.i.d. • Prostaglandin analogueslprostamldes (toplcaO - L.atanoprost 0.005%, one drop qHS - Travoprost 0.004%, one drop qHS - Bimatoprnst 0.03%, one drop qHS • Combinations (topical) - Dorzolamldeltlmolol maleatl! 2%/0.5%, one drop b.i.d. - Brimonidine tartrateltimolol maleatl! 2%/0.5%, one drop b.i.d. Second Line • Carbonic anhydrase Inhibitors (systemic) -Acetazolamide 125-250 mg po b.l.d. to q.l.d. -Acetazolamide sequels 500 mg po b.i.d. -Acetazolamide (parenteral) SOD mg IV once daily or 5-1 0 mglkg q6-8h - Methazolamide SD--100 mg po b.i.d. to t.i.d. • Hyperosmotlc agents -Mannitol 20% solution, 0.5-2 mg/kg IV infused over 3D-60 minutes (20% solution has 20 g per 100 ml)

ADDmONAL TREATMENT Addlflonel Therep/H

Selective laser trabecu loplasty (S Ln may be effective In some patients. One must consider the potl!ntial for lOP rise after SIJ and the urgency in which the patient's lOP must be lowered. SURGERY/OTHER PROCEDURES • Trabeculectomy with antlflbrotlc agents (m ltomycln C) • Aqueous drainage device implantation (Baerveldt shunt, Ahmed valve. Molteno implant. ett.)

•

PAnENT EDUCATION Patients should be counseled on their risk of I0Prise and the potential of Irreversible vtslon loss via optic nerve damage before Implementation of therapy. PROGNOSIS Prognosis depends on level of lOP rise and amount of optic nerve damage. With regular monitoring and approp~ately aggressive therapy, loss of visual function can frequently be awided. COMPLICA110N5 • VISual f~eld ronstriction • VISion loss

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Patients should be followed closely after the administration of steroids, espedally those receMng intravitreaI, periocular, and topical formulations. • Appropriate follow-up has been suggested to be 2 weeks aftl!r steroids are administl!red. Patients determined to be at higher risk should be examined sooner and more often (after 1, 4, and 8 weeks). • Generally, lowering lOP below 30 mm Hg is a reasonable goal for individuals without optic nerve damage. • Preexisting or newly diagnosed glauromatous damage to the optic nerve warrants more aggressive treatment. In general, lOP should be maintained at or below target lOP as determined in glaucoma patients before starting steroids.

REFERENCES 1. Spaeth GL. de Barros M, Fudem berg 5.Retina 2009;29(8):1OS7-1 061. 2. Jones RIll, Rhee D.CuiT Opn Ophthalmology 2006;17(2):163-167. 3. Stamper R. Lieberman M, Drake M.Berker·Shilffels diagnosis and thera111 of the flauromas. 27D-2 71 .

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CODES

ICD9 365.31 Cortirosteroid·induted glaucoma, glaucoma!Dus stage

Patient Monitoring • Serial examinations in which visual function, lOP, and op'tlc nerve are evaIuated • Repeat visual fieIds as necessary

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I

smtENS-JOHNSON SYNDROME Bhairavi V. Kharod

~ BASICS DESCRIPTION • Stevens-Johnson syndrome (SJS) was first described in 1922. • SJS is a rare life-threatening immune complex-mediated hypersensitivity reaction in which the skin and mucous membranes are severely affected. • SJS is often referred to as erythema multiforme major or bullous erythema multiforme. EPIDEMIOLOGY lnddence • The reported annual incidence of SJS is approximately 3 cases per million persons per year. • In the US, approximately 300 new cases of SJS are reported each year.

Prevalence The prevalence of SJS is reported to be less than 200,000 persons in tile US population.

RISK FACTORS • lmmunocompromised status, including malignancies, chronic viral infections with Epsteirt-Barr virus (EBV) and HIV. systemic lupus erythematosus, and other chronic rheumatologic diseases are considered risk. factors. • Radiation therapy and ultraviolet (UV) light are also considered possible risk factors. • Previous history of SJS is considered a risk factor for further episodes. Genetics Certain HlA subtypes are currently being researched for possible associations with SJS. In some studies, HlA-812 has been shown to increase susceptibility to SJS. GENERAL PREVENTION Early diagnosis, treatment, and supportive therapy are essential to prevent life-threatening complications and permanent damage from SJS. PATHOPHYSIOLOGY • SJS is an immune complex-mediated hypersensitivity reaction. • Cell death causes separation of tile epidermis from the dermis. EnOLOGY • Although the cause of SJS may not be determined in some case, it is most often a response to medication, infection, or illness. • SJS is idiopathic in approximately 50% of the cases. • The leading cause of SJS is the use of antibiotics and sulfa drugs. Some of the common medications that cause SJS include allopurinol, diclofenac, isotretinoin, fluconazole, penicillins, barbiturates, sulfonamides, phenytoin, and azithromycin. • Infectious causes of SJS include herpes simplex virus, EBV. influenza, mumps, histoplasmosis, and cat scratch fever.

648

• Certain lymphomas and carcinomas have also been reported to be tile inciting factors for SJS. • In some studies, herbal supplements containing ginseng have been shown to cause SJS as a rare side effect. Others report cocaine as a possible cause.

• HIV and EBV testing should be done in patients suspected of these diseases. • CBC count and workup of malignancy should be performed. • A tissue biopsy is performed in many cases.

COMMONLY ASSOCIATED CONDITIONS SJS can involve the mucous membrane and skin of multiple organs. Significant involvement of ocular, nasal, oral, vaginal, urethral, gastrointestinal, and respiratory tract mucous membranes can occur over the course of the disease. Necrosis of mucous membranes, especially respiratory and gastrointestinal membranes, may occur over the course of the disease. This can lead to significant morbidity and may lead to death.

Imaging

~ DIAGNOSIS HISTORY • SJS often begins witll flu-like symptoms. Patients may often experience fever, malaise, cough, sore throat, headache, and burning eyes for a few days. Mucocutaneous lesions develop abruptly. • Patients with oral involvement may complain of severe pain that leads to inability to eat or drink. • Patients with genitourinary tract involvement may present with dysuria or inability to void. PHYSICAL EXAM • Ophthalmic findings: - Conjunctivitis of the eyes is reported in approximately 30%. - Conjunctival scarring, including symblepharon formation may occur. - Pseudomembranes may form on palpebral conjunctiva. -Dry eyes and trichiasis are chronic sequelae. - Corneal neovascularization, corneal scarring, anterior uveitis, panuveitis, and severe visual impairment may occur. • Systemic findings: - Patients may often get tongue and facial swelling. - Oral ulcers are common, but ulcers of genital and anal areas may also occur. - Skin involvement may start with hives and pain. A red or purple sk.in nonpruritic rash develops and spreads within hours to days. Papules, vesicles, or bullae may form leading to sloughing of the epidermis. The typical skin lesion of SJS is target shaped. Most commonly affected areas are the palms, soles, dorsum of the hands, and extensor surfaces. - Denuded skin may develop a secondary infection. DIAGNOSTIC TESTS & INTERPRETATION

Lab • Although SJS may often be medication induced, it is important to rule out infectious etiologies and malignancies. • Blood and urine cultures should be done in cases where an infectious cause is suspected. • Sputum cultures should be done in patients with a high index of suspicion for Mycoplasma pneumoniae.

Imaging is rarely required, except in cases where a malignancy is suspected.

Pathological Findings • Biopsy specimens typically show full thickness necrosis of epidermis and minimal dermal inflammatory cell infiltration. The dermal infiltrate is superficial and mostly perivascular. • Histologic clhanges in the epidermal~ermal junction range from vacuolar alteration to subepidermal blisters. • Apoptosis of keratinocytes is also observed.

DIFFERENTIAL DIAGNOSIS • Erythema multiforme minor (involvement of skin only. SJS, or erythema multiforme major, is defined as involvement of both skin and mucous membranes. SJS is often referred to as bullous erythema multiforme.) • Drug rash • Thermal burns • Paraneoplastic pemphigus • Toxic shock syndrome • Ocular cicatricial pemphigoid • Toxic epidermal necrolysis (TEN) (SJS and TEN are considered similar except for their distribution. SJS is defined as < 10% of body surface area involvement. TEN is defined by > 30% of body surface area involvement. Involvement of 15-30% of body surface area is considered SJ5-TEN overlap.)

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TREATMENT

MEDICATION First Line • SJS is a dermatologic emergency that requires hospitalization, often in an intensive care unit or bum unit. • Often the first and most important step in treating SJS is to discontinue any offending medications. • Supportive care is a crucial part of treating SJS. Because skin loss can lead to significant loss of body fluid, fluid replacement is essential. A nasogastric tube may be needed for enteral feedings. • Ophthalmic care should include a thorough eye exam. If a patient has conjunctivitis, pseudomembranes, or other ocular surface disease, topical steroids should be used judiciously. Pseudomembranes should be peeled. Symblepharon should be lysed using a blunt instrument such as a glass rod. A symblepharon ring should be placed to avoid further symblepharon formation. Oral or intravenous corticosteroids should be considered in patients with ocular disease. Patients with uveitis should be treated witll steroids.

STEYENS-JOHNSON SYNDROME SecandUne • Skin lesions should be cleaned thoroughly and protected from serondary infections. • Patients with SJS often have severe pain from mucxutaneous lesions and should be given adequate pain control. • Intravenous steroids are used by many in aOJte SJ S. In cases of recalcitr.mt SJS, intravenous Immunoglobulin has been proposed by some to be beneftcial. • Cydophosphamide may be used in duonic conditions. • Patients on steroids should be placed on gastrointestinal prophylaxis and should be considered at risk for bone mass loss. ADDITIONAL TliEATMENT

GIHNH'al MNsu,.s • Early diagnosis and treatment are crucial to decreasing morbidity and mortality in patients with SJS. • Patients should be monitored closely to avoid sepsis, shade. and organ failure.

Issues for Referral Dermatologists and ophthalmologists are consulted for patients with SJS. Specialists are consulted according to the organs involved.

IN-PAnENT CONSIDERATIONS Initial Stabilization • SJS is a medical emergency that can rapidly evolve into shock and end-organ damageffailure. • Treatment should foOJS on eliminating the under~ing cause, controlling symptllms, and minimizing complications.

Admission Criteria Patients witll SJS can rapidly develop shock and end-organ failure and should be monitored very dosely.

•

ONGOING CARE

FOLLOW-UP RECOMMENDAnONS • Patients have to be monitored very dosely in the InltlaI stages of SJS. • Patients should be monitored closely by an ophthalmologist as symblepharon formation, trlchlasls, corneal neovascularlzat!on, and scarring can develop.

Patlfmt Monitoring • CBC count should be performed wee ldy for the flrst 1-2 months in patients on oral cyclophosphamide to evaIuate for leukopenia. • Urinalysis should be performed periodically to evaluate for hemorrhagic cystitis.

DIET Many patients have difficulty swallowing in tile initial stages of SJSsecondary to Involvement of the gastrointestinal tract. Enteral feeding may be required until the patient can tolerate or.~l feedings. PATIENT EDUCATION • Patients should be advised of the indting factor (medication, infection, etc.) and should be told to avoid the Inciting factor. • Patients should be informed of tile increased risk of SJS witll tile use of certain medications. PROGNOSIS

The mortality in patients with SJS correlates to the body surface area involved. If less than 10% of the body surface Is denuded, tile martalily rate Is approximately 1-5%. If more than 30% of tile body surface is denuded, the mortality rate increases to more than 25%.

REFERENCES 1. Wetter DA, Camilleri MJ. Clinical, etiologic, and histopathologic features of StM!ns-Johnson syndrome during an &-year period at Mayo Clinic. Mayo Clin Proc 201 0;85(2):131-138. 2. Soto.zono c, Ueta M, Kinoshita s. Systemic and local management at the onset of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications. Am J Ophthalmo/2010; 149(2):354. 3. Knowles S, Shear NH. Clinical risk management of Stevens-Johnson syndrome/toxic epidermal necrolysls spectrum. Dermlltol Ther 2009;22(5):441-451. 4. Struck MF, Hilbert P, Mockenhaupt M, et al. Severe rutaneous adverse reactions: emergency approach to non-bum epidermolytic syndromes. Intensive Care Med 2010;36(1):22-32. Epub 2009 Sep 29.

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CODES

ICD9 • 372.30 Can]unctMt!s, unspecified • 372.64 Scarring of conjunctiva • 695.13 Stevens-Johnson syndrome

CLINICAL PEARLS • SJ Sis a mucocutaneous disease that can affect multiple organs. • Drugs, especially sulfa drugs, antleplleptlcs, and antibiotics, are the most common causes. • SJS can CBuse severe momidity and mortality if left untreated.

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I '

mCKLER SYNDROME Scott E. Olitsky Erin D. Stahl

~ BASICS DESCRIPTION Constellation of findings including particular vitreous abnormalities, high myopia, and retinal detachment EPIDEMIOLOGY

Incidence 1 in 7,50o-9,000 newborns

RISK FACTORS Geneffa • Type 1: STL1 (classic, membranous vitreous) 12q 13.11-13.2, COL2A 1 gene, autosomal dominant • Type 2: STLl (+f- ocular, beaded vitreous) 1p21, COL11A1, autosomal dominant • Type 3: STL3 (nonocular) 6p21.3, COL IIA2, autosomal dominant • Autosomal recessive form with ocular involvement. 6q13, COL9A 1 • Mutations in COL 11A2 also cause variants: Weissenbacher-Zweymuller syndrome (neonatal form with distinctive skeletal findings), Marshall syndrome (short stature, hearing loss), MarshallfStickler GENERAL PREVENTION • Genetic counseling andfor prenatal testing (if mutation in family known) • Fetal facial abnormalities may be detected by ultrasound in the second trimester (1). PATHOPHYSIOLOGY Defect in collagen biosynthesis collagen types 2, 9, and 11 expressed in vitreous. COL2A I mutations must involve exon 2 for eye involvement as this exon is not incorporated in nonocular tissues.

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COMMONLY ASSOCIATED CONDITIONS • Ocular - Myopia (90%) (2), with or without pathologic myopia -Vitreous condensation (membranous, beaded, veils) - • Optically empty• vitreous - Retinal detachment (60%) (2) -Glaucoma -Cataract (usually peripheral cortical wedge) - Radial retinal lattice - Rare: retinal degeneration • Nonocular - Hearing loss (70%) (2) - Facial abnormalities (midline defting, Pierre Robin sequence, bifid uvula) (84%) (2) - Mitral valve prolapse -Arthritis, large joints (90%) (2) - Slender extremities. long fingers, and normal/tall height

~ DIAGNOSIS HISTORY Family and patient history of high myopia, retinal detachment. arthritis. deft palate. hearing loss PHYSICAL EXAM • Full ocular examination including attention to vitreous abnormalities at slit lamp (veils [best by indirect ophthalmoscopy]. beading, membranes optical clarity) - Cycloplegic refraction - Peripheral retinal examination looking for perivascular lattice-like degeneration and retinal breaks

- Intraocular pressure (lOP) measurement and optic nerve examination - Physical exam with attention to joint dysfunction, abnormal facial features, hearing, clefting of palatefuvu Ia, and heart murmur

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TREATMENT

MEDICATION • None for the primary disorder but may need treatment for secondary concerns such as glaucoma • Avoid miotics to avoid additional strain on the peripheral vitreoretinal interface. ADDITIONAL TREATMENT

General Measures • Refractive correction, treatment of amblyopia (if present), low vision aids if necessary • Educate patient on warning signs and symptoms of retinal detachment. • Every 6 months to yearly full ocular examination with dilated fundus exam, optic nerve evaluation, refraction, and lOP measurement

SURGERY/OTHER PROCEDURES • Surgical repair of retinal detachment-retinal detachment may reveal multiple severe retinal breaks, prompt referral to retinal specialist is necessary. • Prophylactic retinopexy, if indicated • Cataract extraction-NOTE: elevated risk for postoperative retinal detachment • Medical/surgical treatment of glaucoma

STICKLER SYNDROME

•

ONGOING CARE

FOU.OW-UP RECOMMENDA110NS • Educate patient on the need for routine (every 6 mcnlt1s to yearly) ophtflalmologic examination to detect retinal breaks. • Prompt evaIuatlon should S)Tllptoms of Impending retinal detachment oo:ur (floaters.. photopsia, vision changes) - Genetics ronsult - MaxillofadaI assessment for midline defting if suspected - Rheumatology ronsult If ]oint disease present -Audiology fer hearing testing - Examine parents/siblings (3) PA11ENT EDUCATION • Educate on the signs and svmptoms of retinal detachment and the need for prompt examInation If these oo:ur. • Some ophthalmologists may rerommend avoidance of direct contact sports such as boxing and wrestling to reduce the risk of retinal detachment (no clear data, practice patterns val)'). • Consider recommendation against refractive surgery as tissue response is unknown and may have thinner central romea thickness. • May benefrt from protective eyewear when engaging in other sports • Genetic counseling • Family support networlt http:/IMYw.stldders. org/sip2

PROGNOSIS • Risk for retinal detachment Is grealer than 50%. • Morbidity most common from visual dysfunction, 4% blind (1) • Visual acuity depends on inddence of retinal detachment and success in surgical management. • Decreased visuaI acuity may also occur due to refractive amblyopia If refractive error Is not CDITected.

COMPUCAllONS • Retinal detachment • Glaucoma • Cataract

REFERENCES 1. Palice DW. Stickler syndrome: clinical care and molecular genetics. Am l OfiJthalmo/ 2002; 134(5): 746-748. 2. Stickler GB, Hughes W, Houchin P. Clinical features of hereditary progressive arthro-ophthalmology (Stickler syndrome): a survey. Genetics Med 2001;3(3):192-196. 3. Snead MP, Yates JR. Clinical and molecular genetics of Stickler syndrome. l Mol Genet 1999;36:353-3S9.

ADDITlONAL READING • http://ghr.nlm.nih.gov/condition = stiddersyndrome.

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CODES

ICD9 • 367. 1 Myopia • 379.29 Other disorders ofvitreaus • 759.89 Other specified congenital anomalies

CLINICAL PEARLS • High risk for retinal detachment • Consider genetics consult and counseling. • ExamIne parents/siblings for vltreoretlnal abnormalities. • Educate patient and family on signs and svmptoms of retinal detachment. • Stress importance of regular ocular I!Xllmination.

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I

STURGE-WEBER SYNDROME Jason Hsu

~ BASICS DESCRIPTION • Sturge--Weber syndrome (SWS), also called encephalotrigeminal angiomatosis, is a congenital dermato-oculo-neural syndrome. - Cutaneous nevus flammeus in distribution of trigeminal nerve branches - Ipsilateral glaucoma and diffuse choroidal hemangioma may occur. - Ipsilateral meningeal hemangiomatosis EPIDEMIOLOGY • Frequency is estimated at 1 in 50,000 live births • No apparent gender or racial predilection RISK FACTORS

Genetics • Typically sporadic with no genetic inheritance pattern • Rare familial clusters reported but inheritance pattern unclear

EnOLOGY Embryonal developmental anomaly due to errors in mesodermal and ectodermal development

~ DIAGNOSIS • Ophthalmic features: - Diffuse choroidal hemangioma (50% of patients) ipsilateral to facial nevus flammeus characterized by a much more saturated reddish appearance compared with contralateral eye ("tomato-catsup fundus") - Retinal vascular tortuosity and serous retinal detachment may occur. -Telangiectasia of conjunctival and episcleral vessels

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-Glaucoma (up to 70% of patients) ipsilateral to facial nevus flammeus especially when eyelids are involved may result from elevated episcleral venous pressure, angle malformation, or both. - Buphthalmos may result in cases of congenital glaucoma. -Iris heterochromia -Anisometropic amblyopia • Cutaneous features: -Facial nevus flammeus ("port-wine stain"): unilateral flat to thickened zone of dilated telangiectatic cutaneous capillaries appearing light pink to deep purple in coloration - Involves region innervated by first branch (most common), first and second branches. or all three branches (least common) of trigeminal nerve - Localized hypertrophy of ipsilateral nasal and buccal mucosa may occur. • CNS features: -Ipsilateral leptomeningeal hemangiomatosis - May be associated with cortical atrophy, seizures (80% of patients), recurrent stroke-like episodes, and developmental delay - Recurrent headaches (30-50% of patients), contralateral hemiparesis. hemiplegia, and hemianopsia may also occur.

DIAGNOSTIC TESTS & INTERPRETATION

Diagnostic Procedures/Other • MRI (preferred modality) or CT scans of the brain may be used to detect leptomeningeal hemangiomatosis. which is present from birth. -Granular calcification of parenchymal brain tissue adjacent to cortical atrophy can often be seen on CTscan.

• Ultrasonography: 8-scan mode shows generalized choroidal thickening; A-scan demonstrates high internal reflectivity.

Pathological Findings • Facial nevus flammeus: dilated telangiectatic cutaneous capillaries in the dermis lined by single layer of endothelial cells • Diffuse choroidal hemangioma: -Cavernous vascular channels lined by mature endothelial cells and supported by thin intervascular fibrous septa - May contain small, capillary-type vessels -Terminate indistinctly in periphery without sharp margins - Fibrous transformation of retinal pigment epithelium and calcification may occur. - Sensory retina overlying hemangioma often thickened and cystic

DIFFERENTIAL DIAGNOSIS • Klippei-Trenaunay-Weber syndrome: characteristics of SWS plus port-wine stains of extremities and hemihypertrophy of soft and bony tissues • Beckwith-Wiedemann syndrome: facial port-wine stain, macroglossia, omphalocele, visceral hyperplasia with severe hypoglycemia due to pancreatic islet cell hyperplasia

STURGE-WEBER SYNDROME SURGERY/OTHER PROCEDURES

.

TREATMENT

• FadaI news flammeus: derm atologic vascula r-spedfic pulsed-dye laser therapy • Diffuse dloroidal hemangioma: treatment usually considered when assodated with mawlar edema or ser~ retinal detachment - Photodynamic thempy - Low-dose radiation therapy (external beam, proton beam, plaque radiotherapy, gamma knife radiotherapy, stereotactic radiotherapy) • Glaucoma: topical drops -First line: beta-bloder - Second line: carbonic anhydrase inhibitor - 1hird line: prostaglandin analog - If medicaI therapy fails. see • Surgery/Other Procedures• • CNS manifestations: - Seizures treated with anticonvulsants - Aspirin may be benefidaI in patierrts with rea.urem stroke-like episodes o Use with caution in d1 ildren as aspirin use is assodated with Reye ~drome o Va~cella and annual Influenza Immunizations recommended to lower risk of Reye syndrome

ADDITIONAL TREATMENT General AfeasUI'eS • Address refractive error with glasses or contact lens. • Treat amblyopia, which is typically anisometropic due to glaucoma-!nduced myopia.

• Subtotal hemispherectomy has been perfonned for Intractable seizures or progressive mental deterioration. • Trabeculectomy, aqueous tube shunt procedure. goniolllmy, trabeculotomy, laser trabeculoplasty, or cydodestructive procedures may be necessary to rna nage glaucoma If topical therapy !s Inadequate. • Strabismus surge!)' as needed following completion of amblyopia therapy.

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS o Op11thalmologist o Neurologist • Neurosurgeon If Intractable selzu res • Dermatologist

Patient M011ltorlng See • Follow-up•

PATIENT EDUCATION • Sturge-Weber Foundation (hnp:flwww.sturgeweber.org) • Sturge-Weber Syndrome Community (http:/fwww. swscom munity.org) PROGNOSIS Ufe expectancy appears to be significantly reduced especially in patients with profound mental retardation and intractable seizures compared with those with more Iimited disease. COMPUCATIONS • Visual loss due to amblyopia, glaucoma, or serous retinal detachment • Progressive mental deterioration o Seizures

ADDITIONAL READING o

Oakes WJ. The natural history of patients with the Sb.uge-Weber syndrome. Pediatr Neurosurg

1992;18:287-290. • Patrlanakos TD, Nagao K. Walton OS. Surg leal management of glaucoma with the Sturge-Weber ~drome./nt Of/Jtha/mo/ Gin 2008;48:63-78. o Singh AD, Kaiser PK. Sears JE. Choroidal hemangioma. Of/Jtha/mo/ Clin N Am 2005; 18:

151-161 . • SUllivan TJ. Clarke MP, Morin JD.lhe owlar manifestations of lhe Sturge-weber syndrome. J Pediatr Of/Jtha/mo/ Strabismus I992; 29:

349-356.

.

CODES

ICD9 o 228.09 Hemangioma of ather sites • 362. 17 Other lntraret!naI mlcrovascular abnormalities • 759.6 Other congenital hamartoses. not elsewhere classified

CLINICAL PEARLS • SUspect glaucoma v.t.en the port·wine stain involves the eyelids. • Neuroimaging should be performed especially in patients with choroidal hemangiomas since leptomeningeal hemangiomas are almost always present in these cases.

&53

I

SUBCONJUNCTIVAL HEMORRHAGE Steven J. Kanoff

~ BASICS

~ DIAGNOSIS

DESCRIPTION Blood that is under the conjunctiva. This can be spontaneous, associated with incidental trauma or obvious trauma, or recurrent, which may be associated with underlying systemic disease.

HISTORY Patient or bystander usually notes red eye. The patient presents with a painless red eye unless associated with trauma. Question the patient about nose bleeds, spontaneousleasy bruising.

RISK FACTORS

PHYSICAL EXAM Blood under and/or in the conjunctiva. If concerned about associated bleeding problems do a thorough retinal examination.

Antiplatelet therapy, anticoagulant therapy, hypertension, diabetes mellitus, coughing, sneezing, emesis, straining (constipation), bleeding diathesis (thrombocytopenia, impaired clotting. coagulopathy), conjunctivitis (viral).

PATHOPHYSIOLOGY Extravasation of blood from conjunctival blood vessels. EnOLOGY Incidental or obvious trauma, blood dyscrasias, viral infection. COMMONLY ASSOCIATED CONDITIONS Hypertension, diabetes mellitus, blood dyscrasias.

654

DIAGNOSTIC TESTS & INTERPRETATION

Lab If recurrent subconjunctival hemorrhages consider work.up of coagulation system.

Imaging None, unless degree of trauma justifies ttlis Diagnostic Procedures/Other If associated with trauma, a complete eye examination is necessary to rule out ocular patl'lology.

rJ

TREATMENT

MEDICATION None. ADDITIONAL TREATMENT General Measures Reassurance that hemorrhage will clear usually by 2week.s. Issues for Refe"al Bleeding diathesis

SUBCONJUNCTIVAL HEMORRHAGE COMPUCATlONS

Additional Tllfllilplfls If elevated subc011junttival hemorrhage adjacent to

None

.

the limbus. use frequent artlflclal tears every 2 h and lub~catlng ointment at bedtime to try to prevent delle formation.

ADDITIONAL READING

ICD9

•

• American Academy of Ophthalmology Basic and Clinical Science Course. Section 8, 2006-2007,

ONGOING CARE

CODES

372.72 ConjunctivaI hemorrhage

90-91.

FOLLOW-UP RECOM MENDA110NS None unless assodated ocular pathology from trauma or to monitor de lie status

• Mimura T, Usui T, Yamagami 5, et al. Recent causes of subconjunctival hemorrhage. Ophlhalmo/o~ca 2009;224(3):133-137.

PROGNOSIS Excellent

• Ehlers JP. Shah CP, (eds). The WU!s Eye Manual, 5th Ed. Philadelphia: JB LippinCDtt Publishet 2008: 112-113.

I

&55

SUPERIOR LIMBIC KERATOCONJUNCTNITIS [SlX] Nicole R. Fram

~ BASICS DESCRIPTION • Ocular surface disorder is characterized by foreign body sensation, pain out of proportion to exam, and photophobia. The presentation is typically bilateral and frequently asymmetrical. • Classic signs include superior bulbar conjunctival staining and injection, redundant superior bulbar conjunctiva, velvety fine papillary reaction of the superior palpebraVtarsal conjunctiva, superior corneal epithelial keratitis, and/or mucous filaments. EPIDEMIOLOGY Incidence About 50-ii5% of patients with superior limbic keratoconjunctivitis {SLK) have underlying thyroid disease {1,2)

RISK FACTORS • Keratoconjunctivitis sicca {KCS) • Thyroid disease • Cosmetic contact lenses induced (Cl-SLK) • Thimerosal

Genetics No familial association

PATHOPHYSIOLOGY Chronic and recurrent clinical course

656

ETIOLOGY • Unknown: Mechanical versus autoimmune • Possibly related to dry eye, autoimmune disease, or superior conjunctivochalasis • Female: male 3:1 • Mean age 50 years • Increased incidence in thyroid disease, hyperparathyroidism, and KCS {3) COMMONLY ASSOCIATED CONDITIONS • Thyroid disorder • KCS • Filamentary keratitis

~ DIAGNOSIS HISTORY Targeted history onset, duration, location, quality of symptoms, and associated conditions. History of thyroid disease, KCS, and contact lens wear PHYSICAL EXAM • External exam: look for symptoms of thyroid eye disease and inflammatory ptosis • Decreased Schirmer's test, decreased tear lake, increased mucus production in advanced cases • Eyelids: tight upper lids. eversion of upper lid velvety fine papillary reaction of palpebral/tarsal conjunctiva

• Conjunctiva/sclera: sectoral superior bulbar and limbal conjunctival injection, redundant superior conjunctiva, lissamine green/rose bengal staining of superior bulbar conjunctiva (keratinization) • Cornea: superior punctate epithelial keratitis, mucus filaments superiorly • Remainder of anterior and posterior segment exams is typically unremarkable.

DIAGNOSTIC TESTS & INTERPRETATION

Lab • Thyroid function tests • Consider parathyroid function tests

Diagnostic Procedures/Other • lissamine green/rose bengal will stain keratinized or denuded epithelium. • Demonstrate redundant superior conjunctiva by topically anesthetizing the eye, having the patient look down and slide the superior conjunctiva with a cotton tip applicator onto the superior cornea. This should not be feasible in a normal eye.

Pathological Findings • Keratinized conjunctival epithelium with polymorphonuclear leukocytes (PMNs) • Palpebral/tarsal conjunctival cells with lymphocytes and plasma cells on Giemsa scrapings

SUPERIOR LIMBIC KERATOCONJUNCTIYITIS (SUO DIFFERENTlAL DIAGNOSIS • Allergic - Seasonal allergic con]unctlvhls - vemaI keratoconjunctivitis - Atopic kercrtoconjunctivitis -Giant papillary keratoconjunctivitis (GPC) • Contact lens-fl!lall!d ki!rcrtoconjunctivitis

• KCS • Filamentilry keratitis • Murus fishing syndrome • Topical medication toxicity

fl

TREATMENT

MEDICATION FlmLine • Silver nitrate ().5-1 %solution to anesthetized superior palpebral and bulbar conjunctiva. Irrigate ocular surface thoroughly aftl!r 1 minute to neutralize the sliver nltrall! exposure. • Can repeat In 4-6 weel:s If necessary ALERT Do not use sliver nltrate sticks or solid applicators, as this can result in a severe chemical damage to the cornea and sdera.

SecondUne Surgiccll removal of superior conjunctiva and Tenon's capsule from 1() o'dock to 2 o'clock and extending bade. from the limbus 5--8 mm. No need to cover or suture conjunctiva (4).

COMPLEMENTARY & ALTERNATIVE THERAPIES • Filamentary keratitis may respond to N-acelylcystei ne 10% topically or temporary bandage contact lens. • Topical cydosporine A (0.5%) (5} • Topical vitamin A (retinol palmitate) • Topical steroids • Mast cell stabilizing drops • Autologous serum • Punetill ocdusion SURGERY/OTHER PROCEDURES • Thermocauter12atlon • Supratarsal triamdnolone injection (3 mg/0.3 «) with 27 gauge needle (2}

ALERT watch for intraocular pressure (lOP) elevation with supratarsaltriamcinolone injection. Contraindicall!d in patients with gIaucoma.

$

REFERENCES 1. Kadrmas EF, Banley GB. Superior limbic keratoconjunctivitis. A prognostic sign for severe Graves ophthalmopathy. O{iltha/mo/ogy 1995;102:1472-1475. 2. Shen Y-C, wang CY, Tsal HY, e1 aL Supratarsal triamcinolone InJection In the treatment of superior limbic keratoconjunctivitis. Cornea 2007;26(4): 423-426. 3. Theodore FH. Comments on findings a! elevated protein-bound iodine in superior limbic keratoconJunctivitis: I. Arch O{iltha/mol 1968;79:508. 4. Sun YC, Hsiao CH, Chen WL e1 al. Conjunctival resection combined with tenon layer excision and the involvement a! mast cells in superior Iimbic kl!ratocon)unctlvltls. Am 1 Ophtha/mo/2008; 145:445-452. s. Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al. Topical cyclosporine A O.S'llo as a possible new treatment for superior Iimbic keratoconjunctivitis. O{ilthalmology 2003;1t 0: 1578-1 581 .

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

,.,tient Monitoring

ADDI110NAL READING

Q

S11 AIID (Tapic, Al1arithm,

• MoniiDI' lOP if patient is maintilined on topical steroids or has received suprati!rsal triamd nolone injection. • MoniiDI' for chemical injury or stem cell dysfunction aftl!r sliver nitrate treatment.

~ Media Ele11en0

PROGNOSIS Disease is characterized by frequent remission and exacerbations..

.

Electronic

Conjunctivitis

CODES

ICD9 • 370.40 KeratoconjunctMtis, unspedlied • 370.49 Other keratoconjunctivitis. unspecified

CLINICAL PEARLS

• sue. triad: Redundant superior bulbar conjunctiva with sectoral staining, "velvety" flne papillary superior tarsal con)unctllla, superior corneal filaments • Associall! with thyroid disease

657

I

SYMPATHETIC OPHTHALMIA P. KumarRao

~ BASICS DESCRIPTION • Typically it is a bilateral granulomatous panuveitis that occurs following penetrating injury or surgery to one eye. • Although the trauma occurs in only one eye, the uveitis involves both eyes. The traumatized eye is commonly referred to as the "inciting· or "exciting" eye and the oontralateral eye is known as the "sympathizing" eye. EPIDEMIOLOGY

Incidence Incidence of the disorder following trauma or surgery is very rare, occurring in 0.19% of cases following trauma and 0.007% of cases following ocular surgery.

RISK FACTORS Occurs following penetrating injury or surgery to the eye.

Genetics HLA-11, DR4/DRw53, DR4/DRw3, DRB1*04, DQA 1*03, and DQB 1*04 have been identified in some patients.

GENERAL PREVENTION • The avoidance of trauma • Enucleation (removal) of a blind eye within 14 days of the trauma may prevent the development of sympathetic ophthalmia.

658

PATHOPHYSIOLOGY Histological findings are the same in exciting and sympathizing eyes. Findings include a diffuse granulomatous inflammation consisting of lymphocytes (predominantly T-cells) and epithelioid cells within the uveal tract. Epithelioid cells may contain pigment. Multinucleated giant cells may also be present. In addition, dusters of epithelioid cells may accumulate between the retinal pigment epithelium and Bruch's' membrane. These dusters may appear yellow clinically and are len own as Dalen-Fuchs nodules. ETIOLOGY Many studies reveal a role for T-cell mediated inflammation directed against uvea-retina proteins. COMMONLY ASSOCIATED CONDITIONS Trauma

~ DIAGNOSIS HISTORY • A history of trauma or surgery occurring prior to the onset of inflammation is critical to making the diagnosis. • There is no specific laboratory test to confirm the diagnosis. • Patients often complain of pain, redness, photophobia, and blurred vision. PHYSICAL EXAM • Exciting eye • Photophobia, decreased vision, and keratic precipitates on endothelium may be seen. • Sympathizing eye • Symptoms are variable and may be insidious or rapid in onset. Mild anterior or posterior uveitis, ciliary flush, keratic precipitates. pain, photophobia, increased lacrimation, and blurred vision may occur.

• Both eyes • Ciliary injection. partially dilated-poorly responsive pupil, thickened iris, clouding of vitreous. papillitis, generalized retinal edema, Dalen-Fuchs nodules (small, yellow, deposits beneath retinal pigment epithelium), peripheral choroiditis, exudative retinal detachments, and choroidal granulomas have been described.

DIAGNOSTIC TESTS & INTERPRETATION

Imaging Fluorescein angiography reveals multiple hyperfluorescent dots at the level of the RPE that may persist in to the late phase of angiogram. Coalescence of the dye from these foci may occur in areas of exudative retinal detachment. A pattern similar to multiple evanescent white dot syndrome-early hypofluorescence followed by dye leakage in a wreath-like pattern in the venous phase has also been described.

Pathological Findings A diffuse granulomatous inflammation consisting of lymphocytes (predominantly T--cells) and epithelioid cells within the uveal tract. Giant cells may also be present. The choriocapillaris and retina are usually not involved.

DIFFERENTIAL DIAGNOSIS • Sarcoidosis • Tuberculosis • Vogt-Koyanagi--tiarada syndrome

SYMPATHETIC OPHTHAlMIA

.

TREATMENT

MEDICATION FirstUne Oral (1 mg/kgfday) or pulse dose mrtiCDSteroids have a rapid onset of action. However, patients who need more than 10 mg of predn lsone dally to control their inflammation will require steroid-sparing agents as high-dose steroids cannot be used for long periods of time without severe side effects. SecondUne Enudeation of the traumatized eye within 2 weeks of Injury may preven1 development of sympathetic ophthalmia. Re11'10Yi11 of the tra umatiZI!d eye after SO develops is controversia I. ADDITIONAL TREATMENT General Measures Steroid-sparing agents such as mymphenolate mofetil, azathioprine, tytlosporine, tacrolimus, and anti-TNF inhibitors have all been used with some success. lssws for RaffH'I'al A multidisciplinary team may be required to manage the various system lc effects of steroid-sparing therapies (Immunosuppression). SURGERY/OTHER PROCEDURES • Laser photocoaguIation can be used for retinal neovaswlarization and does not produce postoperative inflammation. • Fluoclnolone acetonlde Implantation (Retlsert) may help control inflammation in some patients.

•

ONGOING CARE

3. Rao NA, Robin J, Hartmann D, et al. The role of penetrating wound In the developmen1 of sympathetic ophthalmia: experimentaI observations. Ard! Ophthalmol t 983; 101 : 101-104.

FOLLOW-UP RECOMMENDATIONS Patients wi II need very dose monitoring umil the disease Is brought under control. Patients wlll need continuous follow-up with other specialists as needed.

.

PROGNOSIS A majority of patients treated with corticosteroidsfi mmunosuppression can maintain a vision of 10160 or better.

ICD9 • 360.11 Sympathetic uveitis • 360.11 Panuveltls

COMPLICATIONS • Bilateral vision loss due to ocular inflammation • Anterior uveitis can cause cataract formation or glaucoma. Posterior segment inflammation can result in macular and peripheral retina I scaring and choroidal detachment.

REFERENCES

CODES

CLINICAL PEARLS • A history of ocular trauma in a patient with panweltls shoold r.~lse the suspldon for sympathetic ophthalmia. • Aggressive treatment to mntrol the inflammation is aitical to prevent blindness.

1. Galor A, Davis Jl.., Flynn HW Jr, et al. Sympathetic ophthalmia: inddence of ocular mmplications and vision loss In the sympathizing eye. Am J Ophtha/mo/ 2009;148(5):704-71 D. 2. Reynard M, Riffenburg RS, Maes EF. Effects of cortimsteroid treatment and en udeation on the visual prognosis of sympathetic ophthalmia. Am J Ophtha/mo/ 1983;96:19D-294.

659

I

SYSTEMIC LUPUS ERYTHEMATOSUS [SLE] Melissa D. Neuwelt

~ BASICS DESCRIPTION • Multisystem autoimmune disease • Chronic course with relapses and remissions • Organ systems most frequently involved: skin. joints, kidneys. blood, and CNS • Diverse manifestations in eye: - Discoid lesions of eyelids - Keratoconjunctivitis sicca (dry eye) - Episcleritis -Scleritis - Cranial neuropathy - Optic neuropathy - Retinal vasoocclusive disease - Choroidopathy -Antimalarial drug toxicity EPIDEMIOLOGY lnddence • Approximately 250,000 people have systemic lupus erythematosus (SLE) in the US (1)[8] • Up to 1f3 of patients with SLE have ocular manifestations. - Ocular surface disease: up to 30% - Retinal manifestations: 3-30% (depends on systemic disease activity) - Optic nerve involvement: 1%

RISK FACTORS • Gender: female 9: 1 • Age: peak incidence 2nd-4th decade • Race: African-American and Asian descent • Family history • Environmental factors: hormones. sun light • Drug-induced lupus: procainamide, hydralazine, quinidine, chlorpromazine, methyldopa, isoniazid

Geneffa • Twin studies support genetic predisposition. • Linkage studies have identified many candidate genes, particularly on chromosome 1q • Associated with HLA-A 1, HLA-88, and HLA-DR3

PATHOPHYSIOLOGY • Autoimmunity may be triggered by autoantigen exposure during apoptosis. -Autoantibody production - Immune complex deposition • Lupus retinopathy associated with immune complex-mediated arteriolar occlusion and thrombosis COMMONLY ASSOCIATED CONDITIONS • Secondary Sjogren's syndrome • Antiphospholipid antibody (APA) syndrome (found in 77% of SLE patients with retinal or optic nerve disease vs. 29% of other SLE patients) (2)[8]

660

~ DIAGNOSIS SLE is diagnosed by at least 4 of the 11 following American College of Rheumatology (ACR) criteria: • Malar rash • Discoid rash • Oral ulcers • Arthritis • Serositis (pleuritis, pericarditis) • Renal disorder (proteinuria or cellular casts) • CNS disorder (seizures, psychosis) • Hematologic disorder (anemia, leucopenia, thrombocytopenia, lymphopenia) • lm munologic disorder - Antidouble-stranded DNA (anti-dsDNA) -APAs -Anti·Sm - False·positive RPR or VORL • Antinuclear antibody (ANA) positive

HISTORY • Photophobia • Redness • Pain • Diplopia • Floaters • Visual decline PHYSICAL EXAM • Ocular adnexa---i!dema, mass, proptosis • Motility-myositis, cranial neuropathy, intranuclear ophthalmoplegia • Eyelids--discrete, scaly lesions (discoid lupus) • Conjunctiva-inflammation (noninfectious conjunctivitis) • Sclera - Episcleritis (superficial, blanches with topical phenylephrine) - Scleritis (deep, does not blanch with topical phenylephrine. nodular or diffuse. anterior or posterior) • Cornea - Reduced tear film, punctate kl!ratopathy, filaments (dry eye, Sjiigren's syndrome) - Interstitial keratitis (rare) - Peripheral ulcerative keratitis (rare) -Vortex keratopathy (verticillata) o Associated with antimalarial drug use o Rarely visually significant o Reversible with cessation of treatment • Anterior chamber - Cell and flare (iritis) - Hypopyon uveitis (rare)

• Lens (cataract) - Especially posterior subcapsular -Associated with chronic steroid use • Vitreous-inflammation (posterior uveitis) • Retina - Lupus retinopathy o Cottort-Wool spots (nerve fiber layer infarcts) o lntraretinal hemorrhages o Microaneurysms o Exudates o Vascular tortuosity - Vasoocclusive retinopathy (more severe) o Capillary nonperfusion o BRVO, CRVO, BRAD, CRAO o Neovascularization of disc and retina o Vitreous hemorrhage o Traction retinal detachment -Choroid o Uveal effusion o Serous retinal detachment o Choroidal infarction o Choroidal neovascular membrane - Optic nerve o Neuropathy o Neuritis o Papilledema (intracranial hypertension) -CNS o Intranuclear ophthalmoplegia o Retrochiasmal infarcts

DIAGNOSTIC TESTS & INTERPRETATION

Lab Initial lab tests • Anti·dsDNA (highly specific) • ANA (sensitive) • CBC Follow-up 1r special considerations • Other autoantibodies - APA (anticardiolipin and lupus anticoagulant) -Anti-Ro -Anti-La -Anti-c1q -Anti·Sm - Anti·nucleosome - Anti·N·methy1·d·aspartic acid (NMDA) -Anti-alpha actinin

Imaging Initial approach • Fluorescein angiography to assess retinal and choroidal circulation - ICG to assess choroidal circulation - OCT to assess for macular edema or serous retinal detachment - B·scan ultrasonography to assess vitritis and for retinal detachment

SYSTEMIC LUPUS ERYTliEMATDSUS (SLE) Follow-up 1: specl•l cansldel1ltlons

Retinal vascui itis is associated with CNS lupus involvement. Consider CNS imaging with MRVrnagnetic resonance angiography (MRA) to evaluate forth rombotic events.

l'athologiall Findings • Biopsies of eyelid lesions show immunoglobulin deposition at the junction of epidermis and dermis en immunohistochemical staining. • 0 rbita I and adnexal involvement can also be confirmed by biopsy.

DIFFERENTlAL DIAGNOSIS • Discoid lupus on the eyelids should be distinguished from blepharitis. • Optic neuritis in SLE can resemble demyelinating disease but is often more severe. • Lupus retinopathy resembles diabetic and hypertensive retinopathy. • Patients with SLE en immunosuppressive therapy often present with new ocular complaints. It is important to rule out an infectious etiology befure contl nulng or accelerating lmmunosuppresslve therapy. Consider: -Herpetic retinitis (herpes simplex virus [HSV], herpes zoster virus [HZV], cytomegalovirus [CMV]) -Tuberculosis -Toxoplasmosis - [¥me disease

.

TREATMENT

MEDICATION Fii'St Line • Artificial tears for eplsderttls, dry eye • Oral prednisone for more severe ocular manifestations: 1-2 mg/kglday SecondUne • Nonstel'oidal amHnflammatoJY drugs (NSAI Ds) • Antlmala~als: - Chloroqulne - Hydroxydlloroquine • Steroid~ring immunosuppressive agents: - Azathioprine - Cyclosporine - Mycophenolate mofetll -Cyclophosphamide - Methotrexate • Plasmapheresis • Intravenous immunoglobulins • Newer biologic agents: - Rituximab (Rituxan) - Anticytokine agents

ADDmONAL TREATMENT Generalllleesui9S Care should be taken to prevent and manage side effects of immunosuppressive therapy such as gastric prophylaxis, blood sugar and blood pressure monitoring, and purified protein derillative (PPD) tuberculosis saeening. Issues for Refrtrral Systemic treatment of ocular manifestations should be comanaged with the patient's primary doctor and/or rheumatologist Addlflonel Therapies • Antlcoag uladon for vasoocduslve disease or APA syndrome -Aspirin - Walfarin SURGERY/OTHER PROCEDURES • Treat complications of proliferative retinopathy: - Panretlnal ph otocoagulatlon - Vitrectomy IN-PATIENT CONSIDERATIONS Initial Stabilization Consider inpatient admission for pulse IV methylprednisolone: 1g/day

•

ONGOING CARE

FOLLOW·UP RECOMMENDATIONS Patient Monitoring • The antimalarial agents are associated with bull's eye macu lopathy leading to impairment of visual arutty, color vision, and visuaI fleld. • All patients Initiating antimalarial therapy should receive counseling about risk of retinopathy and have baseline eye exam: visual acuity, dilated fundus examination, Amsler, Humphrey 10·2, optional tests (color, fundus photos, fluorescein angiography, muttlfocal electroretlnagram [ERG]) • Risk factor for complications include dose > 6. 5 mglkg hydroxychloroquine, > 3 mglkg dlloroquine, duration >5 years, renal or liver disease, preexisting retinal disease, and age > 60 years. - Low-risk patients do not require additional screening exams. - High-fisk patients should have annual screening exams. • Cessation of treatment may hatt or even reverse sight-threatening complications.

PROGNOSIS • VIsion loss In 55% of patients with severe vasoocdusive retinopathy (4)[B] • Optic neuritis outcomes high~ variable, appear to improve with early initiation of steroid treatment (S)[B]

COMPLICA110NS VIsual loss, ret1 nal detachment, optic neuropathy

REFERENCES 1. Helmick CG, Felson DT, Lawrence RC, et al. Est!mates of the prevalence of arth~tls and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008;58(1): 15-25. 2. Mcntehermoso A, Cervera R, Font J, et al. Association of antiphospholipid anti bodies with retinal vascular disease in systemic lupus erythematosus. Semin Arthritis Rheum 1999;28: 326-332. 3. Marmor MF, Carr RE, Easterbrook M, et al. Recommendations on saeening for dlloroquine and hydroxychloroquine retinopathy. A report by the American Academy of Ophthalmology. Ophthalmology 2002;109: 1377-1382. 4. Jabs DA, Fine SL, Hochberg MC, et al. Severe retinal vaso-occlusive disease in systemic lupus erythematosus. Ardl Ophtha/mo/1986;104:

558-563. 5. Lin YC, Wang AG, Yen MY. Systemic lupus erythematosus-associated optic neuritis: dinical experience and literature review.Adli Ophlhalmol 2009;87(2):204-210.

.

CODES

ICD9 • 370.33 KeratoconjunctMtis sicca, not specilied as sjogren's • 373.34 Discoid lupus erythematosus of eyelid • 7t 0.0 Systemic lupus erythematosus

CLINICAL PEARLS • Episderitis will bland! with topical phenylephrine whereas sderitis will not • Scleritis and vasoocclusive retinopathy require systemic treatment. • At.wys consider infection wl1en evaluating a lupus patient on lmmunosuppresslve ther.~py presenting with a new manifestation or flare.

661

I

TALC ROINOPATHY PaulS. Baker

~ BASICS DESCRIPTION Characteristic retinopathy with small, intraretinal, whitish yellow, refractile deposits in patients who abuse intravenous drugs, especially those made from crushed tablets or powder (1)[8]

• Talc particles embolize to other organs, including the eye. • After many talc particles become lodged in the small arterioles of the retinal vasculature, an ischemic retinopathy develops.

DIAGNOSTIC TESTS & INTERPRETATION Imaging Fluorescein angiography is used to assess capillary nonperfusion and retinal neovascularization.

ETIOLOGY Intravenous drugs that contain talc particles

• Crystalline retinopathy - Cholesterol emboli (Hollenhorst plaque) - Cantllaxanthin ingestion (oral tanning agent) - Tamoxifen (history of breast cancer) - Methoxyflurane anesthesia - Cystinosis - Parafoveal telangiectasia - Calcified drusen - Bietti's crystalline dystrophy -West African crystalline retinopathy -lntraretinallipid exudates

COMMONLY ASSOCIATED CONDITIONS

RISK FACTORS Occurs in patients of any age

Intravenous drug abuse

PATHOPHYSIOLOGY • Drug addicts crush oral medications such as methylphenidate hydrochloride (Ritalin) or methadone hydrochloride and create an aqueous suspension for intravenous injection. • Oral medications contain talc (hydrous magnesium silicate) as an inert filler. • After intravenous administration, talc particles embolize to the pulmonary vasculature. • With chronic intravenous drug abuse, collateral vasculature forms in the lung and allows talc particles to enter tile systemic circulation.

~ DIAGNOSIS HISTORY Chronic intravenous drug abuse, especially with crushed tablets or powder such as methylphenidate (Ritalin) PHYSICAL EXAM • Small. white. glistening crystals concentrated at end arterioles (intravascular space) throughout tile retina, most prominent in the posterior pole. • Ischemic retinopathy with capillary nonperfusion, including microaneurysms, cotton wool spots, and venous loops • Severe cases can have optic disc and peripheral retinal neovascu larization with vitreous hemorrhage (2)]8]. • Inspection of skin may reveal evidence of intravenous drug abuse.

662

DIFFERENTIAL DIAGNOSIS

rJ

TREATMENT

ADDITIONAL TREATMENT General Measures • Patients should stop intravenous drug abuse. • In tile absence of retinal or optic nerve neovascularization, observation is appropriate.

TALC RETINDPATliY SURGERY/OTHER PROCEDURES • In tile presence of perlpl1eral nonperfusion and neovasculal1zatlon, panretlnal photocoagulation should be considered. • Pars plana vitrectomy fur non-dearing vitreous hemorrhage or visually sign meant tradionaI retinal detachment can be benefidaI.

•

ONGOING CARE

FOLLOW-UP RECOM MENDA110N5 Yealiy exam for asymptomatic talc retinopathy, more frequent if there is significant non-perfusion PA11ENT EDUCATION Systemic and 001lar risks of intravenous drug abuse PROGNOSIS • Visual prognosis is variable • VisuaI acuity can be decreased because of macular Ischemia.. vitreous hemorrhage, macular flbrosls, and tractional retinal detachment (3)[8]. • In tile absence of ongoing intravenous drug abuse, talc retinopathy has been shown to be static and nonprogressive (4)[8].

COMPUCAllONS • Ischemic retlnopatily • Retinal and optic nerve neovascularlzatlon • Vitreous hemorrhage • Preretinal fibrosis/tractional retinal detachment

.

CODES

ICD9 362.1 0 Background retinopathy, unspecified

REFERENCES

CLINICAL PEARLS

1. Murphy SB, Jackson WB, Pare JA. Talc retinopathy. CanJ Ophlhalmo/ 1978;13:152-156. 2. Tse DT, Ober RR. Talc retinopathy. Am 1 Ophthalmo/ 1980;90:624-640. 3. Sharma MC, Ho AC. MaaJiar flbrosis associated with talc retinopathy. Am J OfiJthalmo/1999; 128:517-519. 4. Martidis A. Yung CW, Ciulla TA. Talc embolism: a static retinopathy. Am 1 O,A'!thai.M 1997;124: 841-843.

• Wh 1te lntr.uetlnal particles withIn t11e retinal vasculature are characteristic of talc retinopathy.

I

663

TERSON'S SYNDROME Mitchell S. Fineman

~ BASICS DESCRIPTION • Named after the French ophthalmologist Albert Terson who described the condition in 1900 • Originally defined as vitreous hemorrhage in the setting of subarachnoid hemorrhage • Definition has evolved to include any intraocular hemorrhage associated with intracranial hemorrhage and increased intracranial pressure EPIDEMIOLOGY lnddence Approximately 15% of patients with subarachnoid hemorrflage develop intraocular hemorrhage (1)1A].

RISK FACTORS • Patients with higher grade intracranial hemorrhage are more likely to have Terson's syndrome. • The presence of Terson's syndrome is associated with higher mortality and morbidity in patients with intracranial hemorrhage (l)IB].

GENERAL PREVENTION • Modify risk factors associated with intracranial hemorrhage - Smoking cessation -Treatment of hypertension PATHOPHYSIOLOGY • Mechanism is controversial with several competing theories - Original theory suggested that intracerebral blood directly communicated with intraocular space via the optic nerve sheath. - Intracranial bleeding may result in elevated venous pressure that is transmitted to the intraocular vessels. - Elevated intracranial pressure is transmitted along optic nerve sheath resulting in rupture of the peripapillary vessels. EnOLOGY Intracranial hemorrhage combined with intracranial hypertension leading to intraocular hemorrflage

664

~ DIAGNOSIS HISTORY • A history of intracranial hemorrhage and increased intracranial pressure is usually present. • Visual changes are usually present -Decreased vision - Restricted peripheral vision - New-onset floaters • Patients with impaired neurological status may not be able to provide a history. PHYSICAL EXAM • Visual acuity may range from 20/20 to light perception. • Ocular findings are usually bilateral. • Ophthalmic manifestations may include: -Vitreous hemorrhage - Subhyaloid hemorrhage - Sub-internal limiting membrane (ILM) hemorrhage - Retinal hemorrhage - Peripapillary hemorrhage DIAGNOSTIC TESTS & INTERPRETATION Imaging • Neuroimaging studies in consultation with a Neurosurgical specialist - CTscan - MRI scan - Cerebral angiography • B-scan ultrasonography is recommended if the ocular hemorrhage obscures visualization of the retina.

Diagnostic Procedures/Other Cerebrospinal fluid examination may be helpful in equivocal cases.

Pathological Findings • Histology of vitreous samples show red blood cells with few white blood cells. • Epiretinal membranes with glial proliferation may be found.

DIFFERENTIAL DIAGNOSIS • Vitreous hemorrhage due to other causes • Proliferative diabetic retinopathy • Sickle cell retinopathy • Shaken baby syndrome Valsalva retinopathy

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TREATMENT

ADDITIONAL TREATMENT General Measures • Treatment of the intracranial hemorrhage and control of intracranial pressure is managed by a neurosurgical specialist. • Intraocular hemorrhage is managed with: - Observation with elevated head positioning to allow for spontaneous reabsorption -Avoidance of anticoagulant medications when medically possible

Pediatric Considerations • The development of amblyopia in children with unilateral or asymmetric visual loss should be monitored closely. • Early vitrectomy and/or patching of the fellow eye may be necessary to prevent amblyopia.

TERSON'S SYNDROME Issues for R.rdarra/ Airy patient who presents with ocular findings consistent with Terson's syndrome should be referred Immediately for urgent neurosurgical consultation

SURGERY/OTHER PROCEDURES • YAG Laser vitreolysis to disrupt the posterior hyaloid

face and promote absorption of the hemorrhage -This may lnaease the risk of eplretlnal membrane formation. • Pars plana vitrectomy surgery is indicated in the following situations: - Nonclearing vitreous hemorrhage - Ret! nal detachment associated w1th vitreous hemorrhage - Thick sulrii.M hemorrhage inY(Jiving the fovea - Monocular patients with deaeased vision - Children at risk for amblyopia

IN-PATIENT CONSIDERATIONS Initial Stabilization Managed by neurosurgical specialist

Admission Ctfterla Determined by neurosurgical specialist

Disdl•rge Criteria Determined by neurosurgical specialist

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS Resolution of the intraocular hemorrhage may take months without surgery Patient NlonitDring Patients should be examIned serially until the lntraorular hemormage has deared completely PATIENT EDUCATION Amsler grid monitoring may help to identify patients with epiretinal membrane development PROGNOSIS • The visual prognosis in adults is excellent with >80% of patients recovering normal or near-normal vision (3)[B]. • Children have a more guarded visual prognosis because of the risk of amblyopia. • Overall prognosis is related to the severity of the intracranial hemorrhage and the subsequent neurological sequelae.

COMPUCATIONS • Risk of am blyopla In children under the age of 9 years • Epiretinal membrane formation occurs as a late finding in a significant proportion ol patients (4). - Subhyaloid or sulrIL.M hemorThage may stimulate gliaI cell proliferation. - May present years following resolution of the hemorrhage - Macular holes may also occur

REFERENCES 1. McCarron MO, Alberts MJ, McCarron P. A systematic review of Terson's syndrome: Frequency and prognosis after subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 2004;75:491-493. 2. Fountas KN, Kapsalaki EZ. Lee GP, et al. Terson hemorrhage in patients suffering aneurysmal subarachnoid hemorrhage: Predisposing factors and prognostic significance. J Neurosurg 2008;109:43s-444. 3. Kuhn F. Morris R. Witherspoon CD, et al. Terson syndrome. Results of vitrectomy and the significance of vitreous hemorrhage in patients with subarachnoid hemorrhage. Ophthalmology 1998;105:472-477. 4. Schultz PN, So.bol WM, Weingeist TA. Long·term visual outcome in Terson syndrome. O{iltha/mology 1991 ;98:t 814-t 819.

.

CODES

ICD9 • 360.43 Hemophthalmos, except OJ rrent InJury • 379.23 VItreous hemorrhage • 432.9 Unspecified intracranial hemorrhage

CLINICAL PEARLS • Terson 's syndrome should be suspected in any patient presenting with neurologicaI findings associated with lntraaanlal hemoohage. • Patients with lntracranlaI hemorrhage should have an ocular examination to saeen for intraocular hemorrhage. • Pediatric patients with Terson's syndrome should be closely monitored for the development of amblyopia.

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I

THYGESON'S SUPERFICIAL PUNCTATE KERATOPATHY PaNeen K. Nagra

~ BASICS DESCRIPTION • Multiple, transient whitish-grey, slightly elevated corneal epithelial opacities • No stromal involvement, corneal edema, or conjunctival hyperemia • Typically bilateral, may be asymmetric (1)[C] EPIDEMIOLOGY • Affects patients of all ages • No sex predilection lnddence/Prevalence Rare RISK FACTORS None identified Genetics Associated with HlA DR3 PATHOPHYSIOLOGY Unknown

~ DIAGNOSIS HISTORY • Patients often present with ocular irritation/foreign body sensation; may have photophobia. • Vision may be slightly blurred or normal. • Usually bilateral but may be asymmetric • May be asymptomatic

PHYSICAL EXAM • Slit-lamp examination - Conjunctival quiet or with minimal inflammation - Small, usually multiple, whitish, coarse corneal epithelial lesions with clear intervening epithelium and stroma - Lesions may have overlying punctate staining -Absence of anterior chamber inflammation

DIAGNOSTIC TESTS & INTERPRETATION

Lab Clinical diagnosis, no additional testing required

Imaging Imaging not required but could consider slit-lamp photographs and/or confocal microscopy (2)[C]

DIFFERENTIAL DIAGNOSIS • Punctate epithelial keratitis • Subepithelial infiltrates • Infectious (bacterial) corneal infiltrate

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TREATMENT

MEDICATION First Line • Mild topical steroid (e.g., fluorometholone 0.1 %, loteprednol 0.2%) with very slow taper over months (1)[CJ • Topical cyclosporine • Asymptomatic patients with few lesions may be observed. • Topical lubrication (artificial tears/gel), usually in conjunction with steroids or alone in asymptomatic patients with few lesions

Second Line • Soft contact lenses reported to provide symptomatic relief • Treatment with idoxuridine contraindicated, (associated with subepithelial infiltrates)

ADDITIONAL TREATMENT General Measures • Topical steroids should be tapered very slowly, with some patients requiring long-term, infrequent use (i.e., weeldy). • Chronic condition marked by exacerbations and flare-ups over years

lliYGESON'S SUPERFICIAL PUNCTATE KERATDPATHY Issues for R.rdarra/

Consider referral to cornea specialist if diagnosis is unclear or patient Is not responding to treatment

Additional Thetilpies Antibiotics ineffective; trifluridine has been shown to be effective in some patients in early reports; idoxuridine is cont!llindicated

SURGERY/OTHER PROCEDURES Has been noted to recur following LASIK. case reportS suggest lower incidence a! recurrence with PRK (3}[C]

REFERENCES 1. Nagra PK. Rapuano CJ, Cohen EJ, et al. lhygeson's superfldaI puncate keratitis: Ten years' eJII)erlence. Ophthalmology 2004;111 :34-37. 2. Cheng Ll.., Young AL, WOng AKK. et al. In vivo confocal microscopy of lhyge!iOn's superficial punctate keratitis. Clin Experiment OphthaJmoJ 2004;32:3 25-3 40. 3. Netto MV, Challta MR, Krueger RR. Thygeson's superfidaI punctate keratitis after laser in situ keratomileusis. Am J O{ilthalmal2004; 138:

507-508.

•

ONGOING CARE

FOU.OW-UP RECOM MENDA110NS Regular follow-up with goal of slow~ tapering steroids over months PROGNOSIS Excellent long-term prognosis COMPLICATIONS • Mild steroid use (andfor cyclosporine} is the mainstay of treatment but may be associated with side effects including elevated intraocular pressure and cataract formation. • Anecdotal evidence suggests t11at steroid use may prolong the course a! the disease.

ADDITIONAL READING

.

CODES

ICD9 371>.21 Punctate keratitis

CLINICAL PEARLS • Thygeson'ssuperfldal punctate keratopathy Is a chronic condition marked by exacerbations and remissions over years. • Mainstay a! treatment is topicaI steroids andfor topicaI cyclosporine. • Clinical diagnosis with excellent long-term visual prognosis

I

• Darrell RW. lhyge!iOn's superficial punctate keratitis: Natural history and assodation with HLA DR3. Trans Am O{iJthalmol Soc 1981;79:486--516. • Tabbara KF, Ostler HB, Dawson C, et al. Thyge!iOn's superficial punctate keratitis. Oph thalmalagy 1981 ;88:75--77. • lhygeson P. Superficial punctate keratitis. .lAMA

1950;144:1544-1 S49.

667

THYROID EYE DISEASE Vladimir Yakopson Jacqueline Carrasco

~ BASICS DESCRIPTION Thyroid eye disease (also referred to as Graves' ophthalmopathy, thyroid-related or associated orbitopathy or ophthalmopathy; TED) is an autoimmune process affecting extraocular muscles and orbital fat and connective tissues. resulting in a spectrum of findings including upper and lower lid retraction, proptosis (exophthalmos). restrictive strabismus. and, in the worst cases, optic neuropathy. EPIDEMIOLOGY Incidence • Age-adjusted incidence of ophthalmopathy is 16/1 00,000 population per year for women and 2.9/100,000 population per year for men. • Majority (up to 70%) of Graves' disease patients demonstrate extraocular muscle (EOM) enlargement on imaging although only ~50% show clinical signs and only 20-30% are clinically relevant manifestations (symptomatic). • 3-5% of cases are severe/sight threatening • Bilateral in 85-95% • Bimodal age distribution - 5th and 7th decades of life • More severe in men and older patients RISK FACTORS • Smoking • Female gender • Uncontrolled thyroid status (hyper- or hypothyroidism) • Radioiodine therapy

Genetics No known genetic predisposition identified at this time

GENERAL PREVENTION • Smoking cessation is the most important modifiable risk factor. • Smoking cessation or avoidance has been shown to reduce - Risk of developing TED - Severity of disease - Rate of recurrence of Graves' disease - Better response to immunosuppressive therapy • 15% of patients treated with radioactive iodine showed progression of ophthalmopathy. This is reduced to 5% with concomitant oral prednisone treatment. PATHOPHYSIOLOGY Enlargement of EOMs and orbital fat leads to proptosis, lid retraction, corneal exposure, diplopia, and optic nerve compression at the orbital apex. EnOLOGY An autoimmune disorder with stimulating autoantibodies binding to thyrotropin receptors in the orbit

COMMONLY ASSOCIATED CONDITIONS • Hyperthyroidism - May occur concurrently, following diagnosis, or preceding diagnosis -TED is the most common extrathyroid sign of hyperthyroidism. • Hypothyroidism • Euthyroid state • Myasthenia gravis

~ DIAGNOSIS • Ophthalmic features in thyroid eye disease include various degrees of: - lid retraction (scleral show) - lid lag (lids do not move down with downgaze) - lagophthalmos (incomplete Iid closure) - Corneal exposure - Superior limbal keratitis (SlK) -lid edema 1 - Redness of eyelids* -Conjunctival injection/redness• -Chemosis* -Inflammation of caruncle and/or plica* - Exophthalmos - Restrictive strabismus - Compressive optic neuropathy • Systemic findings depend on thyroid state. 1

HISTORY • Inquire about -Acuity of onset - Periorbital ache* - Pain with eye movement• - Diplopia (primary gaze or extreme side gaze only?) -Tearing, irritation, and foreign body sensation - Change in vision PHYSICAL EXAM • Visual acuity • Pupillary reaction (check for rAPD) • Color plates • Ocular motility (restriction of movement) • Ocular alignment (measurable tropia) • Presence of external signs (see Diagnosis) • Hertel exophthalmometry (measures proptosis) • Anterior segment exam, with careful attention to corneal surface and presence of su:: • Funduscopy - Examine for evidence of optic nerve swelling or pallor - Presence of macular abnormalities (unrelated to TED but possibly contributing to visual loss, if present) DIAGNOSTIC TESTS & INTERPRETATION

Lab • TSH, T3, and Free T4 • Thyroid stimulating immunoglobulin (absence does not rule out disease. Positive test helps confirm diagnosis in mild disease; may be followed in treatment of Graves' disease) 1

668

Items marked with • cDmprise the Clinical Activity Scm-e. 1 point is assigned tD each. CAS>3 indicates active disease

Imaging • CT of orbits (axial and coronal projections) • Other conditions are ruled out (see Differential Diagnosis) • EOM enlargement is assessed (inferior and medial recti are most commonly involved) • Orbital apex is assessed for evidence of optic nerve compression. • Radiologic proptosis can be measured and correlated with clinical findings. • Quiescent disease often shows fatty infiltration of EOMs (EOMs appear tubular in cross section).

Diagnostic Procedures/Other • Visual field testing (may have various defects in cases of optic neuropathy) • Single binocular Visual Field Test • Hess screen (measures strabismus) • External photography • Color plate deficiencies (decreased color perception may be an indicator of optic neuropathy)

Pathological Findings • Extraocular muscles are separated by granular material consisting of collagen fibrils and glycosaminoglycans. • Focal and diffuse mononuclear cell infiltrates within EOMs and orbital fat in active disease. • Fibrotic changes in inactive disease

DIFFERENTIAL DIAGNOSIS • Idiopathic orbital inflammation • Orbital tumor • Orbital vascular malformation (e.g., varix, lymphocele) • Carotid-3). • Severity is graded mild, moderate-to-severe, and sight-threatening (optic neuropathy or corneal ulceration/breakdown). • May be observed if mild or asymptomatic, otherwise treated based on severity • lubrication with artificial tears for symptoms of corneal exposure (e.g., dry, gritty, foreign body sensation. tearing) • Prisms for mild degrees of diplopia - Fresnel prisms-applied to back. of spectacle lenses (con: decrease visual acuity, may cause glare) -Prisms may be also be ground into glasses (con: expensive. increase weight of lens)

THYROID EYE DISEASE • Madarataly SIVIra Disaast1 - If active: lmmunosuppresslon with pulse 1.v. or p.o. steroids (Level lb evidence for IV pulse) --1 mglkg per day slllrting dllSI! for oral prednisone -Large cumulative doses (8-15 g) of l.v. metnylprednisolone have led to death due to acute liver failure. (Level II~ Total dose -, and eult1yroid sta'leS • Ud retraction is the most common sign. • Number one cause af both unilateral and bilateral proptosis In adults • CorneaI exposure,. optic neuropathy, and side effects of treatment (e.g., steroid-induted calllracts) can lead to lltsualloss..

PROGNOSIS • Most cases are mild and req ulre supportive care and monitoring only. • Smoking cessation is important in mntrol of progresslontseverlty of disease.

COMPLICATIONS • Visual loss • Persistent diplopia • Disftgurement

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I

THYROID OPTIC NEUROPATHY Raed Behbehani

~ BASICS DESCRIPTION Thyroid eye disease (TED) is a chronic orbital inflammatory disease, commonly associated with hyperthyroidism (90%) but occasionally with hypo- or euthyroid status.

EPIDEMIOLOGY Incidence Female: Male ratio of 5: 1(16 women: 3 men per 100,000 population)

Prevalence Occurs in 25-50% of patients with Graves' disease (hyperthyroidism)

RISK FACTORS • Graves' disease • Hashimoto's thyroiditis • Smoking

Genetics Genetic loci implicated include (HLA, 6p21-3), cytotoxic T-Lymphocyte antigen-4 (CTLA-4, 2q33), tumor necrosis factor (TN F), interferon-gamma, intracellular adhesion molecule (ICAM-1 0), and thyroid stimulating hormone receptor (TSH-R).

GENERAL PREVENTION Avoid smoking (odds ratio for smokers vs. nonsmokers is 7.7)

PATHOPHYSIOLOGY • Autoimmunity -Autoantibodies acting specifically on fibroblasts surface TSH-R and insulin-like growth factor-1 receptor (IGF-1 R) (1) -Activated fibroblasts secrete chemok.ines and cytokines promoting lymphocyte migration and B-cell maturation. - Prostaglandin-E2 (PGE2), PGD-2, lnterleukin-6 (IL-6), and IL-8 may stimulate orbital fibroblasts to produce glycosaminoglycans (GAG) and adipose tissue, increasing orbital mass. • Smoking - Cigarette smoking has been found to be a risk factor for the development and severity of TED (2).

ETIOLOGY Autoimmune (see pathophysiology)

COMMONLY ASSOCIATED CONDITIONS • Hyperthyroidism (Graves' disease) in 90% of cases. • Autoimmune conditions (diabetes. myasthenia gravis)

670

~ DIAGNOSIS HISTORY • Known thyroid disease with signs and symptoms (palpitations. weight loss, tremor, proximal muscle weakness) • Proptosis • Eyelid retraction • Diplopia • Ocular pain • Red eye, foreign body sensation • Vision loss • Smoking • Symptoms of associated myasthenia (double vision, ptosis, muscle weakness)

PHYSICAL EXAM • Conjunctival redness over the insertion of the extraocular muscle insertion, exposure k.eratopatl'ly superior limbic conjunctivitis, and dry eye. • Chemosis • Lid edema • Exophthalmos • Strabismus/ophthalmoplegia • Optic neuropatl'ly • High intraocular pressure

DIAGNOSTIC TESTS & INTERPRETATION

Diagnostic Procedures/Other • Complete ophthalmologic evaluation -Slit-lamp examination with fluorescein staining: Rule out exposure keratopathy - Goldman applanation tonometry in primary position and upgaze positions. -Pupillary evaluation: To detect RAPD in compressive optic neuropathy - Hertel exophthalmometry: To measure proptosis - Orthoptic evaluation: For diplopia due to strabismus -Dilated fundus examination: To assess the optic nerve • Visual field assessment is important in case of compressive optic neuropathy.

Pathological Findings The extraocular muscles reveal lymphocyte and plasma cell infiltration along with edema within the endomysium of the extraocular muscles.

DIFFERENTIAL DIAGNOSIS • Orbital inflammatory diseases - Idiopathic orbital inflammatory disease (orbital pseudotumor) - Sarcoidosis -Wegener's granulomatosis - Orbital infiltration (lymphoma, metastatic disease) • Ophthalmoplegia - Ocular myasthenia gravis

Lab lnitialle~b tests • TSH, FT3, FT4, and thyroid stimulating immunoglobulin (TSI). • Acetylcholine receptor antibody testing if ocular myasthenia is suspected Follow-up It special considerations Endocrinologic assessment for monitoring and correction of the thyroid status

Imaging • CT scan of the orbit - Can be ordered (axial and coronal views) as a baseline or in atypical cases and can show enlarged extraocular muscle, orbital fat expansion, straightening of the optic nerve, and muscle crowding at the orbital apex - CT scan should be ordered in all cases of suspected thyroid compressive optic neuropathy to study the apical region of the orbit especially before orbital decompression.

.

TREATMENT

MEDICATION First Line • Local symptomatic management (Mild disease) - Smok.ing cessation -Artificial tears, cold compressors - Patching or prisms for diplopia

Second Line • Moderate--severe disease (severe congestive orbitopathy/exposure keratopathy/optic neuropathy) - Steroids: Oral dose of 6D-1 00 mg can be administered over 2-3 months as a temporizing measure. Intravenous steroids on various pulse regimens for a cumulative dose of 8 g can also be given and appear to be more effective and better tolerated than oral steroids (3).

THYROID OPTlC NEUROPAlHY - Orbillllradiotherapy: This can be given along with steroids for a cumulative dose 20 Gy, but tile data on 1ts efflcacy Is conflict! ng. It Is not effective In treating propillsis but should be mnsidered in patients with active disease with optic neuropathy refractory to maximaI medical therapy and/or surgical demmpression (4). - Orbillll decempression: RemovaI of parts of the orbital bony wa lis (medial, inferiot and lateral) and fat for compressive optic neuropathy or severe proptosis and corneaI exposure -lmmunomodulatary drugs: Rituximab, rapamycin, and etanercept have been recently found benefidaI in TED (5).

ADDITIONAL TREATMENT Genwal Measutes Uncontrolled thyroid function is associated with more severe TED.

lssws for Refwral o The mmplex nalllre of Graves' disease requires multidisdplinary team approach of endocrlnologlsVorbltal surgeon/radiation oncologist. o Corneal exposure and mmpressive optic neuropathy are siglrt-threatening signs and should be managed expeditiously by referral to an orbitallneuroophtha lmology speda list.

Additional TllerapJ.s Botulinum toxin can be give In tile upper lids to relieve lid retraction or into the extraocular muscles as a temporizing measure for diplopia.

SURGERY/OTliER PROCEDURES o Orbital decompression: A combination of mediaVinferiorllateral bony walls can be decompressed in proptosis. ex-posure keratopatlly, and optic neuropathy. o Strabismus surgery is usually done following orbillll decempression for diplopia. o Lid surgery for lid retraction and dermatochalasis can be done with or following strabismus surgery.

•

ONGOING CARE

FOLLOW-UP RECOMMENDAnONS o

o

o

o

Patient with mild disease and no exposure L:eratopathy or optic neuropathy can be followed q 3-6 months. Patients with adva need exposure keratopalhy and/or compressive optic neuropathy require immediate attention (steroids/radiationforbital deCllmpression). Patients receiving radioactive Iodine ablation therapy for hyperthyroidism should be treated prophylactically with steroids to avoid activation of TED after treatment. Patients fl nishing radioactive ablation therapy should be treated quiddy with thyroid hormone replacement as the sudden change to hypothyroidism can trigger TED activation.

Patient Monitoring o Regular pe~odlc ophthalmic ewluatlon IncIudlng pupilla!'/ assessment, color vision, visual fields o Patients with intermittent diplopia should be assessed for possible associated myasthenia gravis. • IV steroids pulse regimen for active disease have been assodated with hepatic toxidty especially in cumulative doses above 8 g. Liver function testing is recommended during IV steroid pulse therapy. • Oral bisphosphonate should be gi~n to patients requiring steroid treatment to prevent osteoporosis.

PATlENT EDUCATION • Patients are told to watdl for color desatlJration or decreased vision (signs of optic neuropathy) o Emphasize tile importance of smoking cessation • Graves' disease foundation (YoWW. ngdf.org)

PROGNOSIS • Rundle's curve - Acti~ (inflammatory) phase (6 months to 5 years) - lnactiVI! (Fibrotic) phase: Slllble dinicaI signs for at least 6 months suggest that patient has entered the inactive phase. COMPLICAnONS • Corneal exposu rei Cllmeal uIteration • Compressive optic neuropathy • Diplopia o Glaucoma

4. Bradley EA, Gower EW, Bradley DJ, et al. Orbital radiation for Graves ophthalmopathy: Areport by the American Academy of Oplrthalmology. Ophthalmology 2008;1 15:398-409. 5. Khanna D, Chong KK. Afifiyan NF, et al. Rituximab treatment of patients with severe.. corticosteroid-resistant thyroid-associated ophthalmopathy. Ophthalma/ogy 2010;1 17: 133-139.

ADDITIONAL READING o

o

.

CODES

ICD9 o

o

242.00 Toxic diffuse goiter without mention of thyrotoxic crisis or storm 376.21lhyrotoxic exophthalmos

CLINICAL PEARLS o

REFERENCES 1. Lehmann GM, Garcia-Bales TM, Smith TJ, et al. Regulation of lymphocyte function by PPARgamma: Relevance to thyroid eye dlseasH"elated inflammation. PPAR Res 2008;2008:895901. 2. Cawood TJ, Moriarty P, O'Farelly C, et al. Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biologic link. J Clin Endoainol Metab 2007;92(1):59--64. 3. Zoumalan Cl, Cockerham KP, Turbin RE, et al. Efficacy of Cllrtlcosterolds and external beam radiation in the rna nagement of moderate to severe thyroid eye disease. J Neuroophtha/ma/ 2007; 27:205-214.

Perry JD, Feldon SE. Rationale for radiotherapy in thyroid eye disease. Am J Ophthalmo/2009;148: 818-819. Bahn RS. Graves' ophthalmopathy. New Eng J Med 201 0;362:726-738.

o

o

o

o

TED can be assodated with vision-threatening mmplications such as exposure ker.ltopathy and/or Cllm press!~ optic neuropathy. Patients who do not display sevl!re proptosis, espedally older males, are at a higher risk for Cllm pressive optic neuropathy. Patients below the age of 40 years tend to have fat expansion, whereas patients over 60 years tend to have ertraocular muscle swell ing. TED course is divided into an active inflammatory phase and inactive fibrotic phase. Emergent treatment of vision threatening complications with steroids and/or orbltalr.~dlatlon and decompression is important to prevent permanent visual defidt

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TILTED DISC SYNDROME Michael J. Bartiss

~ BASICS DESCRIPTION • E!evated superotemporal optic disc with posteriorly displaced inferonasal disc resulting in an oval appearance ofthe optic nerve head • Long axis of disc obliquely oriented • Situs inversus of retinal vessels, scleral crescent located inferiorly or inferonasally • Thinning of the inferonasal retinal pigment epithelium and choroid is typically present. • Often associated witf1 incomplete bitemporal hemianopia (preferentially involving the superior quadrants) that, unlike chiasmallesions, does not respect the vertical midline • Kinetic perimetry testing demonstrates fairly normal fields with large and small isopters. • Severely constricted medium isopters occur due to marked ectasia of the midperipheral fundus (which often normalizes with appropriate refractive correction). • Typically accompanied by myopic astigmatism refractive error (secondary to fundus ectasia;)

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RISK FACTORS Genetics

DIAGNOSTIC TESTS & INTERPRETATION Imaging

Has been reported in patients with X-linked recessive congenital stationary night blindness (NYX in CSNB 1 and CACNAlF in CSNB2)

Initial approadl Neuro-imaging should be done in any patient with tilted disc syndrome whose visual field defect either respects the vertical midline or fails to preferentially involve the midperipheral kinetic perimetry isopter because suprasellar tumor must be ruled out

PATHOPHYSIOLOGY Staphylomatous defect surrounding the optic disc

ETIOLOGY Cause unknown, but may have pathogenic relationship to retinochoroidal coloboma

~ DIAGNOSIS HISTORY Congenital defect

PHYSICAL EXAM • Full ocular examination including careful evaluation of the optic discs and evaluation for concomitant treatable amblyopia • Careful evaIuation of both eyes

DIFFERENTIAL DIAGNOSIS • Optic nerve dysplasia • Optic nerve hypoplasia • Optic nerve coloboma

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TREATMENT

MEDICATION No medical treatment for the primary disorder

ADDITIONAL TREATMENT General Measures Appropriate refractive error correction as soon as indicated

TILTED DISC SYNDROME Issues for R.rdarra/

Low vision evaluation and support as indicated in cases with significant bilateral Involvement

Patlflnt Monitoring Patient concerns about appearance if significant strabismus Is present

COMPLEMENTARY a ALTERNATIVE THERAPIES None proven or indicated

PATIENT EDUCATION Low vision intervention in patients with significant bilateral involvement

SURGERY/OTHER PROCEDURES Amblyopia therapy and strabismus surgery as indicated

PROGNOSIS Broad range af best conrected vlsuaI acuity

$

ONGOING CARE

FOU.OW-UP RECOM MENDA110NS • Regular follow-ups to monitor for changes In refractive error • As needed for amblyopia and strabismus monitoring and treatment • Low vision care if indicated • Kinetic visual fleld evaIuatlon as soon as patient Is capable of giving rei iable responses

ADDITIONAL READING • Nucci P, Mets MB, Gabianelli EB. Trisomy 4q with moming glory disc anomaly. Oph tha/mic Genetics, 1990;11:143-145. • Brodsky MC, Baker RS, Hamed LM. Pediatric neuro-ophtha/mdogy. New York: Springer,

.

CODES

ICD9 • 368.47 Heteronymous bilateraI field defects

• 743.57 Spedfled congenital anomalies af optic disc

CLINICAL PEARLS • Work to maximize visual potential, espedally in bilateraI cases • Protective eyewear if best corrected visual acuity is subnormal

I

1996;59--61. • Pollack S. The Morning Glory disc anomaly; contractile movement. dassifiCIItion, and embryogenesis. Doc Of/!thalmol 1987;65:

439-460. • Brown G, Tasman W. Congenital anomalies of !he optic disc. New York: New York Grune & Stratton, 1983;171-178.

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TOXIC ANTERIOR SEGMENT SYNDROME [TASS] Richard Tipperman

~ BASICS DESCRIPTION Toxic anterior segment syndrome {TASS) is a sterile postoperative inflammatory reaction which typically occurs 12--48 h following cataract or anterior segment surgery. It is caused by a noninfectious substance and is limited to the anterior segment of the eye. Gram stain and culture samples are negative and the condition is managed with intensive topical steroid treatment. EPIDEMIOLOGY Incidence of TASS is rare but typically occurs in ·outbreaks· at a specific surgical center. RISK FACTORS • Any medication injected in or around the eye or placed topically at the time of surgery can be implicated in TASS. • Preservatives and pH incompatibilities can lead to TASS as can contaminants from sterilization. • Intraocular solutions with inappropriate chemical composition, concentration, pH, or osmolality - Preservatives - Denatured ophthalmic viscosurgical devices - Enzymatic detergents - Bacterial endotoxin - Oxidized metal deposits and residues - Intraocular lens residues

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GENERAL PREVENTION • Following appropriate protocols for instrument sterilization and cleaning • Following appropriate protocols for administration and ordering of intra- and periocular medications

PATHOPHYSIOLOGY The acute inflammatory response induces cellular necrosis and/or apoptosis as well as extracellular damage.

ETIOLOGY See risk factors COMMONLY ASSOCIATED CONDITIONS Occurs at time of anterior segment surgery

~ DIAGNOSIS HISTORY • Inflammatory process which starts within 12-24 h of cataract surgery • Gram stain and cultures are negative. • Improves with topical and/or oral steroids

PHYSICAL EXAM • Severe anterior segment inflammation • Hypopyon is often present. • Limbus to limbus corneal edema is present. • Vitreous cavity is rarely involved. • Gonioscopy can be helpful to look for posterior synechiae.

DIAGNOSTIC TESTS & INTERPRETATION Lab Initial lab tests Gram stain and culture Follow-up ll special considerations Will be negative in TASS but can also be negative in infectious endophthalmitis

Pathological Findings • Hypopyon • limbus to limbus corneal edema

DIFFERENTIAL DIAGNOSIS Infectious endophthalmitis

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TREATMENT

MEDICATION First Line Topical steroids Second Line Oral steroids ADDITIONAL TREATMENT Issues for Refe"al • Permanent corneal edema may require DSEK or PK. • Scarring of trabecular meshworlc may lead to glaucoma.

SURGERY/OTHER PROCEDURES Permanent corneal edema may require surgery as described above

TOXIC ANTERIOR SEGMENT SYNDROME (TASS)

•

ONGOING CARE

PROGNOSIS • Depends on severity of inflammation • Patients can have permanent corneal edema • Patients can have fiXl!d and dilated pupil • Patients can develop glaucoma COMPLICATIONS • Glaucoma • Tonic pupil • Persistent corneal edema

ADDinONAL READING

CLINICAL PEARLS

• Mamalis N, Edelhauser HF, et al. Toxic anterior segment syndrome. J Cataoo Refract SUTg 2006;32:322-323. • Kutty PK. Forster T5, Wood-KDob C, et al. Multislilte outbreak. of toxic anterior segment syndrome, 2005. 1 Cataract Refract Surg 2008;34:585-590.

• As opposed to endophlhalmltls, which typically occurs at 4-7 days postoperatively, TASS is usually seen in the 1st 24 h. • Adnexa llnflammadon, which Is commonly seen with infectious endophtha Imitis. is nat typical with TASS • An inflammatory response in the vitreous cavity is uncommon In TASS and common In Infectious endophthalmitis

.

CODES

ICD9 • 360.19 Other endophthalmitis • 364.05 Hypopyon • 379.8 Other specified disorders of eye and adnexa

I

875

TOXIC KERATOCONJUNCTIVITIS Christine G. Saad

~ BASICS

~ DIAGNOSIS

DESCRIPTION

HISTORY

Toxic keratoconjunctivitis is an inflammation of the bulbar and palpebral conjunctiva with corneal involvement due to exposure to foreign substance(s).

Ocular redness, burning, irritation, and tearing with gradual onset from initial exposure to irritant or use of ophltlalm ic agent

RISK FACTORS

PHYSICAL EXAM

• Use of topical ophthalmic medications, eye cosmetics, and contact lenses. Further, periocular molluscum contagiosum • Exposure to environmental irritants

• Diffuse conjunctival injection associated with a follicular response • Follicles are enlarged and inflamed and mostly noted in the inferior fornix and palpebral conjunctiva • Punctate epithelial staining of the cornea • Chemosis • Mild periocular erythema or edema • Periocular molluscum contagiosum lesions: Elevated, round, white lesions with an umbilicated center

GENERAL PREVENTION Avoidance of known irritants

PATHOPHYSIOLOGY Nonantigenic induction of lymphocytes resulting in mitotic and lymphoblastic transformation

EnOLOGY • Exposure to environmental irritants, topical ophthalmic medications. contact lenses and solutions, and eye cosmetics • Prolonged use of ophthalmic medications including glaucoma medications (e.g., brimonidine, apraclonidine, pilocarpine), antivirals (e.g., trifluridine), antibiotics (e.g., neomycin, gentamicin), and cycloplegics (e.g., atropine, homatropine) • Preservatives in ophthalmic medications and solutions(i.e., benzalkonium chloride) • Preservative-containing soaking solutions and enzymatic cleansers in contact lens wearers • Proteins that spill from molluscum contagiosum lesions

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DIAGNOSTIC TESTS & INTERPRETATION Pathological Findings True ~mphoid follicles that contain genminal centers with ~mphoblasts

DIFFERENTIAL DIAGNOSIS Allergic, bacterial, or viral conjunctivitis. dry eye, blepharitis, and contact lens overwear

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TREATMENT

MEDICATION First Line • Avoid exposure to, or discontinue use of, the offending agent, if possible • Preservative-free artificial tears 4--8 times daily • Artificial tear ointment at bedtime as needed Second Line • Mild topical steroid may be considered in severe cases that are not responsive to first-line therapy -Treatment with topical steroid should be initiated by an eye care provider.

ADDITIONAL TREATMENT General Measures • Identification and removal of offending agent • Contact lens holiday. Use of another contact lens20 mg/dL) or ethylene glycol (> 20 mg/d L) levels - Oxalate crystals in urine with ethylene glycol - Serum bicarbonate -682. • Kerrison JB. Optic neuropathies caused by toxins and advet3e drug reactions. 0/ilthalmo/ Clin North Am 2004;17:481--488. o Kesler A, Pianka P. Toxic optic neuropathy. Curr Neurol Neurosd Rep 2003;3:41 D-414. • Kessler L. L.ucescu c. Plnget M, et al. Taaolimus-assodated optic neuropathy after pancreatic islet transplantation using a sirolimusltaaolimus immunosuppressive regimen. TransplantJtion 2006;81:63H37. • Lloyd MJ, Ftaunfelder FW. Drug-Induced optic neuropathies. Drugs ofToday 2007;43:8217~236. • Purvin V, Kawasaki A. Borruat FX. Optic neuropathy in patients using am iodarone. Aid! 0/ilthalmo/ 2006;124:696-701. • Rucker JC, Hamilton SR, Bardenstein D, et al. Llnezolld-assoclated toxic op11c neuropathy. Neurology 2006;66:595-598.

.

CODES

ICD9 • 377.33 NutritionaI optic neuropathy • 377.34 Toxic optic neuropathy

CLINICAL PEARLS Early recognition and withdrawal of medication can reverse vision loss. • SUspidon and early treatment of methanol or ethylene glycol can be life and vision saving. • Ethambutol patients must be regularly monitored. o

679

T

TOXOCARIASIS Justis P. Ehlers

~ BASICS DESCRIPTION • Ocular toxocariasis is a helminthic disease that is a common cause of posterior LNeitis, particularly in children. • 3 major presentations: - Endophthalmitis - Peripheral granuloma - Posterior granuloma EPIDEMIOLOGY • Varies by region; actual incidence is unknown • Constitutes 1-l% of pediatric uveitis • Average age of onset is 7.5 years • 80% of patients are < 16 years of age

COMMONLY ASSOCIATED CONDITIONS

PHYSICAL EXAM

• Visceral larval migrans -Systemic infection secondary to Toxocara resulting from migration of larvae throughout the body, particularly liver, brain, lung, and eye -Typically in children, 6 months to 3 years of age - History of contact with puppies and/or ingestion of soil - Often asymptomatic, but may have fever, weight loss, and coughing - laboratory resu Its may show leukocytosis with eosinophilia, elevated Toxocara lgG and lgM. - Prognosis usually excellent - Rarely associated with ocular toxocariasis

Ophthalmic Exam

~ DIAGNOSIS

RISK FACTORS • Exposure to soil contaminated with canine feces infected with Toxocara canis eggs • Exposure to infected pets or animals

• Clinical features of ocular toxocariasis include: -Typically, young children but may occur in adults - Usually unilateral

GENERAL PREVENTION • Good hygiene • Reducing exposure to contaminated environment • Periodic treatment of pets

• Exposure to puppies • History of ingestion of soil or other contaminated substances (e.g., grass) • Possible history of systemic infection • Presence or absence of pain. Toxocara, even in the endophthalmitis form, is rarely painful and does not cause significant photophobia.

PATHOPHYSIOLOGY Inflammatory response secondary to parasitic infection resulting in eosinophilic abscess and chronic granulomatous inflammation

ETIOLOGY

Toxocara canis, the dog roundworm, is the primary causative organism. Infectious eggs are ingested and the developing larvae move hematogenously to the eye or other organs.

680

HISTORY

• Variable, multiple presentations - Endophthalmitis o Vitreitis o Granulomatous keratic precipitates o Hypopyon may be present o Possible yellowish-white chorioretinal mass o Retinal detachment may be present o leukocoria may be present - Peripheral granuloma o White elevated mass present in the peripheral retina and/or ciliary body region o Retinal dragging and formation of a falciform fold may occur o Macular heterotopia may be present - Posterior granuloma o Overlying vitreitis and inflammation may be present in the acute stage o White elevated mass typically O.s-4 disc diameters in size o Often diagnosed at older age - Optic papillitis o localized infection of the optic nerve o Disc edema with telangiectatic vessels o Possible subretinal exudate o Variable peripapillary nodule • Other associated ophthalmic findings - Strabismus -Amblyopia - leukocoria

TDXOCARIASIS DIAGNOSnC TESTS & INTERPRETAnON

DMgnostk l'l'ocedures/Other • Thorough slit-lamp and Indirect ophlhalmosmplc exam are aitical tD diagnosis • Ultrasonography is villiI for evaIuating leukocoria to help distinguish between Dltler possible diagnoses (e.g., calcifications for retinoblas!Dma, hyaloid remnants for PH PV). • CBC for eosinophilia is useful for visceral larval migrans. but is not useful for oa.!lar disease. • Serum and vitreous testing for Tcvcocara lgG • VItreous sample with cytopathologic examination for easlnophlls

Pathological Findings In ocular taxocariasis, granulomatous inflammation with eosinophilic abscess is often present Significant quantities of eosinophils may be present in the vitreous and uveal tract. DIFFERENnAL DIAGNOSIS • Retinoblastoma • Coat's disease • Persistent hyperplastic primary vitreous (PHPV) • Retinopathy of prematurity • Familial exudative vltreoretl nopathy • Toxoplasmosis

.

TREATMENT

MEDICATION • Antl-hel mlnthlc medications are rarely used for ocular disease. • Topical or periocular steroids may be used for control of ocular inflammation. • Topical cycloplegics may be useful in cases with severe anterior segment inflammation. • 0ral steroids may also be employed In cases af severe inflammationo • Amblyopia and strabismus should be addressed, as indicated.

SURGERY/OTHER PROCEDURES • Diagnostic pars plana vltrectomy may be performed In cases with unclear etiology tD obtain vitreous fluid for analysis. • Pars plana vitrectomy may also be utilized to address various complications related to the infection (e.g., retinal detachmen!, severe vitreareti naltraction). • Laser phatamagulatlon af the Toxocara larva has been reported.

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PROGNOSIS • Depends an severity af Inflammation and location af the Infectlon In the eye • Some patients will maintain excellent visual acuity with minimal sequelae and others may have severe complications requiring enucleation. COMPLICAnONS • VIsual lass • Retinal detachment • Phthisis

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Determined based on severity of inflammation and disease • Consultation with vitrearetinal spedalist and/or pediatric aphtha!malaglst may be apprap~ate depending on severity • Monocular precautions (e.g o, eye protection) for all patierrts with severe unilateral vision loss PATIENT EDUCAnON • Centers for Disease Control Pa rasltlc Disease Information: Toxocariasis (http:llwwwocdcogov/ NCIDODIDPD/PARASITE.SitoxocaralfactshUaxocarao htm) • The National Institute for Health and Clinical Excellence Clinical Knowledge Summaries: Taxoca~asls (http://wwwocks.n hs.u ktpatlenL informationJeafletltoxocariasis)

ADDITIONAL READING • Sabrosa NA. Zajdenweber M. Nematode infections of the eye: Taxocariasis, onchocerciasis. diffuse unilateral subacute neuroretinitis, and cysticercosis. Ophfha/mol Clfn NotfhAm 2002;15:351-356. • Shields JA. Ocular tolOCariasis. A review. SuN

Ophlha/mo/1984;28:361-381.

.

CODES

ICD9 • 128o0 Taxocariasis • 360.19 Other endophthalmitis • 363.20 Chorioretinitis, unspecified

CLINICAL PEARLS • Retinoblastoma can closely mimic some presentations of taxoca~asls and must be ruled out

681

I

TOXOPLASMOSIS James H. Whelan

~ BASICS DESCRIPTION • Toxoplasmic chorioretinitis is usually a unifocal, full thickness chorioretinallesion. • Frequently arises from border of preexisting chorioretinal scar • Associated with focal vitreous inflammation directly over the lesion • Anterior segment findings may include mild iritis, large keratic precipitates, raised intraocular pressure. • Signs and symptoms usually limited to the eye, cerebral form seen in HIV EPIDEMIOLOGY Incidence • Majority of cases assumed to be congenital, although recent publications have challenged this • There are documented reports of acquired disease in patients with a previously normal fundus and seronegative antibody titers.

Prevalence • Most common cause of posterior LNeitis • Accounts for 90% of necrotizing retinitis

RISK FACTORS • Ingestion of raw meat • Exposure to cats • HIV GENERAL PREVENTION • Avoid modifiable risk factors • Consider using trimethoprim/sulfamethoxazole in patients with history of toxoplasmosis prior to cataract surgery EnOLOGY • Infestation with an obligate intracellular protozoan, Toxoplasma gondii • Parasite found in cats. Intermediate hosts include rodents and birds. • Infestation is usually congenital (transplacental) and occasionally acquired. • Predilection for the eye and brain. COMMONLY ASSOCIATED CONDITIONS • HIV • lmmunocompromised patients and the elderly

682

~ DIAGNOSIS HISTORY • Young healthy patients with recent onset of blurred vision. - Photophobia -Red eye -Floaters • Ingestion of raw meat that contains tissue cysts. • Exposure to cats • HIVor lmmunocompromise PHYSICAL EXAM Common ophthalmic features of toxoplasmosis chorioretinitis can include: • Decreased vision • Floaters • Conjunctival erythema • Moderate to severe vitreous inflammatory reaction • Focal area of chorioretinal inflammation • Unilateral pale retinal lesion, with adjacent chorioretinal scar • Mild anterior uveitis • Raised intraocular pressure • Optic disc swelling Less common ophthalmic features include: • Pain with severe iridocyclitis • Large keratic precipitates • Neuroretinitis with macular star formation • Retinal artery or vein occlusion • Cystoid macular edema • Retinal vasculitis • Peri-arterial exudation, Kyrieleis arteritis

DIAGNOSTIC TESTS & INTERPRETATION Lab Initial lab tests • Serum lgM and lgG antibodies can be evaluated for presumed acquired infections • lgM found 2 weeks to 6 months after initial infection • High percentages of general population are lgG seropositive • Can compare antibody levels in serum to intraocular fluid (aqueous or vitreous) to confirm intraocular production. • Polymerase chain reaction (PCR) of the aqueous humor may be useful in atypical cases • Chest x-ray, luetic screening, Toxocara serology, and TB testing may be helpful when the diagnosis is uncertain. • HIV testing in atypical cases or patients at risk

DIFFERENTIAL DIAGNOSIS Syphilis Tuberculosis Toxocariasis Sarcoidosis Acute retinal necrosis (ARN) Endophthalmitis - Endogenous -Exogenous

• • • • • •

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TREATMENT

MEDICATION First Line Treatment plan based on location and severity • Small non-sight threatening lesions - Trimethoprim/sulfamethoxazole - Second-generation tetracycline • Sight threatening lesions near disc (2-3 mm) or in macula - Pyrimethamine, PO 200 mg loading dose, then 25 mg PO daily - Sulfadiazine 2 g PO loading dose, then 1 g PO q.i.d - Folinic acid 10 mg PO every second day o Treatment duration is 5~ weeks

TOXOPLASMOSIS • Steroids - Low dose (20-60 mg PO dally 2-3 weeks) - Required to reduce macular or optic nerve inflammation or swelling -Start minimum of 24 hours after initiation of antibiotics o Discootinue 7-1 0 days prior to siDpping antibiotics o Avoid periocular steroids as they may cause scleritis • Topical medications: If anterior segment inflammation ± raised I0 P - Steroids, Prednisolone acetate 1% q.l.d -Cycloplegic agent. Homatropine 2% t.i.d - Antiglaucoma medications, Timolol maleate 0.5% b.l.d

• CNS findings in the newborn - Convulsions - Par.1lysis - Hydrocephalus - lntracranial calcification -Stillbirth - Visceral involvement • Pregnant women seronegative for Toxoplasmosis antlbodles should avoid any contact with cats during preg nanty. • Consult Obstl!trician • Treatment In Pregnancy: - Clindamydn 30Q.-.fi00 mg PO q.i.d - Spiramycin 3 g PO in 3-4 doses - Do not use Pyrlmethamlne

SecondUne

SURGERY/OTHER PROCEDURES Vitrectomy may be required for dense vilreitis or other compl!cat!ons such as retinal detachment

Sulfa allergy: Use Azithromycin, or Atovaquone, or Cllndamycln. ADDITIONAL TREATMENT

Additional Tlleraples • Considerations for lmmunocompromlsed patients. -Frequently subdinical inflammation - May not have preexisting d1 orioretinal scars - Multifocal ± bilateral disease can be seen - Can be relentlessly progressive - Cerebral form more common, patients require CNS imaging studies - Delayed treatment can lead to diffuse spreading form mimicking ARN - Avoid systemic steroid use - May requl re long-term maintenance antibiotic ti1er.lpy

Pregnancy Consldetiltlons • MaternaI feta I transmission can cause more severe otu tar manifestations. • Ophthalmic findings in ti1e newborn - Miaophthalmos -Bilateral matular scars

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Small non-sight threatening lesions require less stringent follow-up care. but should be assessed 1 week after initiating therapy and then every 2 weeks. • Sight ti1reaten ing infections near the optic nerve or macula shoold be assessed at 3 days and then weekly. • Usual course of treatment is 6 weeks. • Avoid delays in treating immunocompromised patients and remember these patients may require long-term antibiotics.

l'ilfiwlt Monitoring • All patients should have a complete dilated ocular exam on each visit. • Resu Its of all blood tests and ancillary testing should be attained as soon as possible. • Patients on Pyrimethamine require weeldy CBC testing. • Fasting blood glucose levels should be determined prior ID starting systemic steroid treatment.

DIET • All patients should be Instructed to avoid eating raw or undercooked meat containing Toxoplasma cysts. • Oti1er dietary risks indude raw milk or unfiltered chlorinated surface water. PATIENT EDUCATION • All patients should be aware that the major routes of transmission are: - Ingestion of contaminated foodstuffs; recommend adequate cooking of meat and care handling raw meat - Contamination of hands from disposing of cat feces or contaminated soiI or sand boxes; recommend gloves or hand washing -Transplacental transmission from infected mother to fetus during gestation; pregnant women shoold avoid any contact with cats PROGNOSIS • 40% of patients may have permanent unilateral 'lisuallossiD 20/1 00 or less • 90% of patients with macular lesions will expe~ence severe v!slon loss • 15% of patients may have mild visual loss (2014D-20/70) • 5 year recurrence rate Is ~80% • Vision loss more associated with duration of active episode than number of rea.nrences mMPUCATIONS • Mild to severe vision loss • Vitreous hemorrhage • Secondary d1oro!dal neovascula~zadon • Epiretinal membrane formation • Chronic and relentless vitreitis • Retinal tear and detad1ment • Cystnid macular edema • Cataract

.

CODES

ICD9 • 130.2 Chorioretinitis due to IDicoplasmosis • 130.9 Toxoplasmosis. unspecified

883

I

TRACHOMA Colleen P. Halfpenny

~ BASICS DESCRIPTION • A blinding infectious condition currently found in mostly undeveloped countries • Consists of an active inflammatory stage in childhood followed by scarring sequelae in adulthood EPIDEMIOLOGY lnddence Incidence varies widely by geographic area

Prevalence • 1.2 billion people live in endemic areas in Africa, Middle East, southern Asia, India, Australia and the Pacific Islands • 48.5% active trachoma concentrated in 5 countries: Ethiopia, India, Nigeria, Sudan, and Guinea. • 50% of the global burden of trichiasis is concentrated in only 3 countries: China, Ethiopia, and Sudan. • Active form affects 40.6 million people • 8.1 million people have trichiasis • Accounts for ~ 3% of world's blindness

RISK FACTORS • Endemic areas • Poverty • Crowded living conditions • Poor water supply • Host immunity • Active stage: Children Ages 2-5 • Late stage: Women • Transmission: - Direct contact (eye-to-eye) - Indirect contact (shared clothes) - Eye seek.ing (synanthropic) muscoid fly -Coughing or sneezing

684

GENERAL PREVENTION • Improved personal hygiene • Improved environmental sanitation

PATHOPHYSIOLOGY • Bacterial cytoplasmic inclusions infect conjunctival epithelial cells. • Chronic conjunctival inflammation causes tarsal scarring, which causes lid deformities and trichiasis. • Recurrent infectious lc.eratitis secondary to exposure and trichiasis • End stage occurs with corneal scarring

ETIOLOGY Recurrent ocular infections with Chlamydia trachoma tis (serotypes A. B, Ba, and C) COMMONLY ASSOCIATED CONDITIONS • Dry eyes • Concurrent infection with Hemophilus influenzae conjunctivitis may cause more severe course.

~ DIAGNOSIS HISTORY • Acute stage: asymptomatic, tearing, discharge, itching, foreign body sensation, and hyperemia • Late stage: foreign body sensation, tearing, photophobia, and decreased vision

PHYSICAL EXAM • Grading system (2): • TF (trachomatous inflammation-follicular): follicles (:::5 of at least 0.5 mm diameter) • Tl (trachomatous inflammation-intense): inflammatory thiclc.ening of the tarsal conjunctiva obscuring half of normal conjunctival vessels

• TS (trachomatous scarring): white lines (Arlt's lines), bands or sheets of scarring of tarsal conjunctiva • TT (trachomatous trichiasis): ::: 1 eyelash(es) rubbing eyeball • CO (corneal opacity): corneal opacity obscuring pupil margin • Corneal vascularization/pannus • Herbert's pits: Shallow limbal depressions, which are old ruptured follicles • Entropion

DIAGNOSTIC TESTS & INTERPRETATION Lab Conjunctival scraping sent for: • Polymerase chain reaction (PCR) • Direct fluorescein-labeled monoclonal antibody (direct fluorescent antibody IDFAI) assay and enzyme immunoassay (EIA) of conjunctival smears • Giemsa cytology

Pathological Findings • • • • •

Chlamydia! inclusions in conjunctival epithelial cells lymphoid follicles loss of goblet cells Squamous cell metaplasia Subepithelial fibrous membrane formation

DIFFERENTIAL DIAGNOSIS • Active phase: -Viral (e.g., adenoviral, HSV, VZII) - Bacterial (Staph aureus, Moraxella) - Medicamentosa/toxicity - Molluscum contagiosum • Late stage: -Viral (e.g., adenoviral, HSV, VZII) -Bacterial (Corynebacterium) - Ocular cicatricial pemphigoid - Stevens-Johnson syndrome - Chemical injury

TRACHOMA

.

TREATMENT

MEDICATION RrstLine • SAFE strategy (3)[A]: - S =Surgery - A = antibiotics - F= fadaI cleanliness - E= environmental improvement • Active, infectious disease (4)[A]: - Azlthromydn: Ch lldren: 20 mglkg oraI single dose; Adults: 1 g oral single dose (l)[A) - Doxycycline: 1DO mg b.i.d for 7 days -Tetracycline: 1.5 mglkglday for 14 days

•

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS • Single, annuaI, high-coverage mass dose of oraI azith romycin can interrupt the tr.~nsmission of trachoma and also reduces childhood mortality in areas where trachoma is moderately prevalent (< 35% In d1lldren; ref. 6, 7) • Repeated biannual treatments in hyperendemic areas (> SO% children) is probably needed for elimination (8). PATIENT EDUCATION • Hyg lene education • Medication compliance education

• Late disease (5)[8): Correction of eyelid deformities (bllamellartarsal rotation procedure) • Corneal opacity: Corneal transplantation (following lid procedure)

PROGNOSIS • Approximately 20-45% of patients with recurrent active trachoma will develop late scarring • Women and lndMduaIs with age >40 more IIkely to have scarring

SecotJd Une Tetracycline ointment b.l.d for 3-6 days every month for 6-month course

COMPUCATIONS Corneal blindness

ADDITIONAL TREATMENT GetJeral Measures • Education on the importance of facia I cleanIiness and hygiene • Improved water supplies {e.g., water provision program, hand-dug wells, rainwater harvesting) • Improved sanitation (e.g., household pit latrines)

REFERENCES

Issues for Referral Referral to health system capable of eyelid repa lrlreconstructlon Is attica!

SURGERY/OTHER PROCEDURES • Eyelid surgery • Corneal transplantation: Poor prognosis if continued lid abnormalities or HcorneaI vascula~zatlon Is present

4. Bailey RJ, Arullendran P, Whittle HC, et al. Randomized controlled trial of slngle-3 is suggestive of B-cell lymphoma.

• Molecular gene analysis: Immunoglobulin heavy chain (lgH) gene rearrangement demonstrated by polymerase chain reaction can be used to establish monoclonality of B-celllymphoma. t (14:18) translocation involving the bcl-2 gene has also been reported. • Cytokine analysis: High levels of interleulcin-1 0 (IL-1 0) are seen in the vitreous of eyes with RV lymphoma, whereas ll-6 (and ll-12) is increased in eyes with inflammatory conditions. ll-1 O:ll-6 ratio > 1.0 is suggestive of B-celllymphoma.

Pathological Findings • Majority of VR lymphomas are B-cell non-Hodgkin lymphomas subtyped as diffuse large B-cell lymphoma, according to the World Health Organization lymphoma classification. • The malignant cells are medium to large pleomorphic cells with high nuclear/cytoplasmic ratios and prominent nucleoli. • Sample for analysis can be obtained from the vitreous (needle biopsy, vitrectomy) or from the sub-RPE infiltrates (needle biopsy, chorioretinal biopsy). -The obtained sample should be handled with care and transferred to the laboratory as quickly as possible to minimize degeneration of fragile lymphoma cells. - Use of cell culture media instead of saline can increase the diagnostic yield. - Prior steroid treatment can induce lysis of lymphoma cells. Discontinuing steroid use before biopsy may increase the diagnostic yield. -The malignant cells are accompanied by large numbers of non-neoplastic cells (small reactive lymphocytes, histiocytes) and necrotic debris making detection of lymphoma cells more challenging. - Multiple tissue biopsies may be required to establish the correct diagnosis.

DIFFERENTIAL DIAGNOSIS • Inflammatory/infectious conditions (Multifocal choroiditis, bird-shot chorioretinitis, acute posterior multifocal placoid pigment epitheliopathy, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada syndrome, toxoplasmosis, sarcoidosis, tuberculosis, syphilis, viral retinitis, etc) - RV lymphoma is the most common cause of masquerade syndrome and should be considered in the differential diagnosis of chronic ocular inflammatory conditions in the elderly. - VR lymphoma can initially and temporarily respond to steroid treatment with decrease in vitreous cells and improvement of symptoms leading to misdiagnosis of inflammatory condition. • Choroidal metastasis: Multifocal choroidal metastasis can simulate the sub-RPE infiltrates of lymphoma but lacks the vitreous cellular infiltration.

VITREDREnNALLYMPHOMA • ChoroidaI lymphoma: Is a distinct entity and although most cases present with diffuse homogenous choroldaI thicken lng, some can manifest yellowish-«ange multifocal dloroidal infiltrates that can be confused with the sub-retinaI infiltrates of VR lymphoma. Features of dloroidal lymphoma that help differentiate it from VR lymphoma lnclude: - Can be associated with anterior epibuIbar (subconjunctival) emnsion of lymphoma manifesting as salmon patches - Does not manifest significant vitreous cellular infiltration - B-scan ultrasound generally shows acoustically hollow diffuse choroidal thickening with occasional posterior epibulbar (extraoallar) extension of tumor. In contrast. eye wall thidcening seen on B-,scan ultrasonography of VR lymphoma is generally focal and less pronou need witl1 no extraocular extension. - In contrast to VR lymphoma, which is highijrade and aggressive, choroidal lymphoma is low-grade and slowly progressivl! with good life prognos~ -Has no association with PCNS lymphoma but