Atlas of Anterior Segment Optical Coherence Tomography [1st ed.] 9783030533731, 9783030533748

Citation preview

Essentials in Ophthalmology Series Editor: Arun D. Singh

Jorge L. Alió Jorge L. Alió del Barrio   Editors

Atlas of Anterior Segment Optical Coherence Tomography

Essentials in Ophthalmology Series Editor Arun D. Singh

More information about this series at http://www.springer.com/series/5332

Jorge L. Alió  •  Jorge L. Alió del Barrio Editors

Atlas of Anterior Segment Optical Coherence Tomography

Editors Jorge L. Alió Vissum Alicante University Alicante Spain

Jorge L. Alió del Barrio Vissum-Instituto Oftalmologico de Alica Miguel Hernandez University Alicante Spain

ISSN 1612-3212     ISSN 2196-890X (electronic) Essentials in Ophthalmology ISBN 978-3-030-53373-1    ISBN 978-3-030-53374-8 (eBook) https://doi.org/10.1007/978-3-030-53374-8 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Dedicated to our patients, students, colleagues, and especially our families for their supportive love, dedication, and generosity in the development of our medical vocation and in our passion for ophthalmology.

Preface

This book deals with one of the latest and most important developments in diagnostic imaging in ophthalmology  – Optical coherence tomography (OCT) and its applications to the study of the anterior segment of the eye. Since its early development, when this technology was basically applied to study the posterior segment of the eye and particularly the macula, OCT has become an essential tool in the practice of ophthalmology. Nowadays, its application, aided by innovations in implementation, has allowed the study of the cornea, lens, and, in general, the anterior segment, including the ocular surface and glaucoma, and is now an essential element in the diagnosis and treatment guidance of anterior segment diseases. Until recently, we had very few tools for the anterior segment of the eye other than biomicroscopy, gonioscopy, and anterior segment photography. Confocal microscopy was one of the innovations, but it never gained popularity in general clinical application, in spite of its scientific usefulness, owing to the small area from which it offers information (the central cornea, essentially), its relative complexity, the need for a skillful observer, frequently difficult interpretation, and the need for a cooperative patient. Anterior segment OCT (AS-OCT) has, on the contrary, overcome these disadvantages, and any technician or non-expert ophthalmologist can use it easily with basic training. Also, anterior segment OCT requires minimal cooperation from the patient; it is fast, non-invasive, and comfortable for general application in the often busy anterior segment clinic. The sharp imaging that current anterior segment OCT devices provide, has make this technology to become a tool that goes beyond the limits of pure diagnostic imaging and provides in-depth anterior segment diagnosis. This book is aimed at those who are introducing or are already using AS-OCT in their clinical practice. It is to be considered, as a text and atlas, a didactical tool using a systematic approach for the description and resolution of problems similar to Hippocratic teaching. At the time of Hippocrates, when classical medicine was practiced in ancient Greece in the temples devoted to Aesculapius, pupils were guided in their education by the master and lessons were taught by observing and examining patients. This is exactly one of the methods we use here, taking the reader through different cases that show a wide range of examples of the applications of AS-OCT for diagnosis and the keys to its correct use and interpretation as well as therapeutic resolution of difficult, rare, or complex

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cases. In addition, the reader will find chapters that go in depth into the fundamentals and applications of this diagnostic technique. The chapter on future perspectives speculates about the development of this technology in the next 10 to 15 years. I hope the readers will be introduced to and educated in the proper use of AS-OCT. I do think that all practicing clinicians will find the case reports that we have included here very interesting and informative. I also want to thank the authors who have contributed their knowledge and expertise and donated their time to this essay in medical education. Alicante, Spain Jorge L. Alió Jorge L. Alió del Barrio

Preface

Contents

1 Anterior Segment OCT: An Overview ������������������������������������������   1 Shinichi Fukuda, Yoshiaki Yasuno, and Tetsuro Oshika 2 Anterior Segment OCT: Fundamentals and Technological Basis��������������������������������������������������������������������������   5 Gabriele Vestri, Claudio Macaluso, and Francesco Versaci 3 Anterior Segment OCT: How to Choose for Your Practice ��������  21 Miguel J. Maldonado, Melissa G. Paragua Macuri, and Alfredo Holgueras 4 Anterior Segment OCT: Clinical Applications������������������������������  31 Ahmed A. Abdelghany, Jorge L. Alió, Jorge L. Alió del Barrio, Laura Primavera, Francesco D’Oria, Chiara Fariselli, Amar Agarwal, Anthony J. Aldave, Beatriz Castaño Martin, Dan Z. Reinstein, Dhivya Ashok Kumar, Duangratn Niruthisard, Eitan Livny, Francisco Arnalich Montiel, Giovanni Alessio, Irit Bahar, Maria Alejandra Amesty, Miguel A. Teus, Ryan S. Vida, Timothy J. Archer, Uri Elbaz, Yariv Keshet, and Yoav Nahum 5 Anterior Segment OCT: Angiography ������������������������������������������ 159 Marcus Ang, Darren S. J. Ting, Chelvin C. A. Sng, and Leopold Schmetterer 6 Anterior Segment OCT: High-­Resolution Tomography of Corneal and Conjunctival Lesions ������������������������������������������������ 171 Sarah Wall, Despoina Theotoka, Asaf Friehmann, and Carol L. Karp 7 Anterior Segment OCT: Real-Time Intraoperative OCT in Corneal Surgery�������������������������������������������������������������������������� 181 Moushmi Patil, Marcus Ang, and Jodhbir S. Mehta 8 Anterior Segment OCT: Real-Time Intraoperative OCT in Cataract Surgery ������������������������������������������������������������������������ 191 Boris Malyugin and Natalia Anisimova 9 Anterior Segment OCT: Observations in Corneal Stroma Regeneration ���������������������������������������������������������������������� 207 Jorge L. Alió del Barrio, Mona El Zarif, and Jorge L. Alió ix

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10 Anterior Segment OCT: Application in Stromal Lenticule Addition Keratoplasty (SLAK)�������������������������������������� 211 Leonardo Mastropasqua, Mario Nubile, Niccolò Salgari, Jessica Bondì, Emanuele Erroi, and Luca Cerino 11 Anterior Segment OCT: Application to Improve Graft Selection for Corneal Transplantation ������������������������������������������ 223 Berthold Seitz, Fatema Asi, Stephanie Mäurer, Loic Hamon, Adrien Quintin, and Achim Langenbucher 12 Anterior Segment OCT: Polarization-Sensitive OCT������������������ 237 Shinichi Fukuda, Yoshiaki Yasuno, and Tetsuro Oshika Index���������������������������������������������������������������������������������������������������������� 251

Contents

Contributors

Ahmed A. Abdelghany, MD, PhD  Department of Ophthalmology, Faculty of Medicine, Minia University, Minia, Egypt Amar  Agarwal, MBBS, MD, FRCS, FRCOpth Dr. Agarwal’s Eye Hospital and Eye Research Centre, Chennai, Tamilnadu, India Anthony J. Aldave, MD  Ophthalmology, Stein Eye Institute, University of California, Los Angeles, CA, USA Giovanni  Alessio, MD Section of Ophthalmology, Department of Basic Medical Science, Neuroscience and Sense Organs, Policlinico di Bari, Bari, Italy Jorge  L.  Alió  del  Barrio, MD, PhD, FEBOS-CR Vissum-Instituto Oftalmologico de Alica, Miguel Hernandez University, Alicante, Spain Jorge L. Alió, MD, PhD, FEBOphth  Vissum Alicante University, Alicante, Spain Maria Alejandra Amesty, MD, PhD  Department of Oculoplastics, Vissum Instituto Oftalmologico de Alicante, Alicante, Spain Marcus  Ang, MBBS, PhD, FRCS Department of Ophthalmology, Singapore National Eye Centre, Singapore, Singapore Cornea and External Eye Diseases, Department of Ophthalmology, Singapore National Eye Centre, Singapore, Singapore Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore Natalia Anisimova, MD, PhD  Department of Eye Diseases, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia Timothy  J.  Archer, MA(Oxon), DipCompSci(Cantab), PhD London Vision Clinic, London, UK Fatema  Asi, MD Department of Ophthalmology, Saarland University Medical Center UKS, Homburg, Saarland, Germany Irit Bahar, MD  Sackler Faculty of Medicine, Department of Ophthalmology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel

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Jessica Bondì, MD  Department of Medicine and Aging Sciences, National High-­Tech Eye Center, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy Luca Cerino, MD  Department of Medicine and Aging Sciences, National High-­Tech Eye Center, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy Francesco  D’Oria, MD Cornea, Cataract and Refractive Surgery Unit, Vissum Instituto Oftalmologico de Alicante, Alicante, Spain Uri Elbaz, MD  Sackler Faculty of Medicine, Department of Ophthalmology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel Emanuele  Erroi, MD Department of Medicine and Aging Sciences, National High-Tech Eye Center, University “G. d’Annunzio” of ChietiPescara, Chieti, Italy Chiara Fariselli, MD  Cornea, Cataract and Refractive Surgery Unit, Vissum Instituto Oftalmologico de Alicante, Alicante, Spain Asaf Friehmann, MD  Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Department of Ophthalmology, Sackler Faculty of Medicine, Meir Medical Center, Tel Aviv University, Kefar Sava, Israel Shinichi Fukuda, MD  Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Computational Optics and Ophthalmology Group, University of Tsukuba, Ibaraki, Japan Loic  Hamon, MD Department of Ophthalmology, Saarland University Medical Center UKS, Homburg, Saarland, Germany Alfredo  Holgueras, DOO, MSc  Departments of Surgery and Ophthalmology, Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain Carol  L.  Karp, MD  Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Yariv  Keshet, MD Sackler Faculty of Medicine, Department of Ophthalmology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel Dhivya Ashok Kumar, MBBS, MD, FRCS, FICO, FAICO  Dr. Agarwal’s Eye Hospital and Eye Research Centre, Chennai, Tamilnadu, India Achim  Langenbucher, PhD Institute of Experimental Ophthalmology, Saarland University, Homburg, Saarland, Germany Eitan  Livny, MD  Sackler Faculty of Medicine, Department of Ophthalmology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel

Contributors

Contributors

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Claudio Macaluso, MD  Department of Medicine and Surgery, University of Parma, Parma, Italy Miguel  J.  Maldonado, MD, PhD, FEBO Departments of Surgery and Ophthalmology, Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain Boris  Malyugin, MD, PhD  Department of Cataract and Implant Surgery, S. Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russia Department of Eye Diseases, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia Beatriz Castaño Martin, MD  Department of Ophthalmology, Principe de Asturias University Hospital, University of Alcalá, Madrid, Spain Leonardo Mastropasqua, MD  National High-Tech Eye Center, University of Chieti and Pescara Clinical Hospital, Chieti, Italy Stephanie Mäurer, MS  Institute of Experimental Ophthalmology, Saarland University, Homburg, Saarland, Germany Jodhbir S. Mehta, BSc, PhD, MBBS, FRCS, FAMS, FRCOphth Cornea and External Eye Diseases, Department of Ophthalmology, Singapore National Eye Centre, Singapore, Singapore Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore Francisco  Arnalich  Montiel, MD, PhD, FEBOS-CR Cornea Unit, Opthalmology Department, Hospital Universitario Ramón Y Cajal, Madrid, Spain Vissum Miranza, Madrid, Spain Yoav  Nahum, MD Sackler Faculty of Medicine, Department of Ophthalmology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel Duangratn  Niruthisard, MD Cornea and Refractive Surgery, Stein Eye Institute, University of California, Los Angeles, CA, USA Mario  Nubile, MD  National High-Tech Eye Center, University of Chieti and Pescara Clinical Hospital, Chieti, Italy Tetsuro  Oshika, MD, PhD Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Computational Optics and Ophthalmology Group, University of Tsukuba, Ibaraki, Japan Melissa  G.  Paragua  Macuri, MD, MsC Departments of Surgery and Ophthalmology, Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain

Contributors

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Moushmi Patil, MBBS, DNB, FAEH  Cornea and External Eye Diseases, Department of Ophthalmology, Singapore National Eye Centre, Singapore, Singapore Laura Primavera, MD  Department of Ophthalmology, Istituto Auxologico Italiano, Milan, Italy Adrien  Quintin, MD  Department of Ophthalmology, Saarland University Medical Center UKS, Homburg, Saarland, Germany Dan Z. Reinstein, MDMA(Cantab), FRCSC, DABO, FRCOphth London Vision Clinic, London, UK Niccolò  Salgari, MD  Department Sant’Anna, Ferrara, Italy

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Ophthalmology, Arcispedale

Leopold Schmetterer, PhD, MSC  Singapore Eye Research Institute, Ocular Imaging Research Group, Singapore, Singapore Berthold Seitz, MD, ML, FEBO  Department of Ophthalmology, Saarland University Medical Center UKS, Homburg, Saarland, Germany Chelvin  C.  A.  Sng, MBBChir, MA, MMed, FRCSEdin Department of Ophthalmology, National University Hospital, Singapore, Singapore Miguel  A.  Teus, MD, PhD Department of Ophthalmology, Principe de Asturias University Hospital, University of Alcalá, Madrid, Spain Despoina  Theotoka, MD  Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Darren  S.  J.  Ting, MBChB, PgCertHPE, DRCOphth, FRCOpht  Department of Academic Ophthalmology, Queen’s Medical Centre, Nottingham, UK Francesco Versaci, MSE  CSO Costruzione Strumenti Oftalmici, Florence, Italy Gabriele  Vestri, MSE CSO Costruzione Strumenti Oftalmici, Florence, Italy Ryan S. Vida, OD, FAAO  London Vision Clinic, London, UK Sarah  Wall, BS Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Yoshiaki Yasuno, PhD  Computational Optics and Ophthalmology Group, University of Tsukuba, Ibaraki, Japan Computational Optics Group, University of Tsukuba, Ibaraki, Japan Mona El Zarif, OD  Optica General, Saida, Lebanon

1

Anterior Segment OCT: An Overview Shinichi Fukuda, Yoshiaki Yasuno, and Tetsuro Oshika

Optical coherence tomography (OCT) is a modality using low-coherence interferometry that was initially developed for retinal imaging by Huang et al. in 1991 [1]. It is a noncontact, in vivo imaging technology to produce cross-sectional images of ocular tissues. The first anterior segment OCT (AS-OCT) was proposed in 1994 by Izatt et  al. [2]. AS-OCT imaging allows for visualization and assessment of anterior segment ocular features, including the tear film, cornea, conjunctiva, sclera, rectus muscles, anterior chamber angle, crystalline lens, and anterior hyaloid membrane. Subconjunctival space such as intra-bleb structures after glaucoma filtering surgery can also be depicted noninvasively by AS-OCT.  It is faster, less invasive, more patient friendly, and far less

S. Fukuda · T. Oshika (*) Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Computational Optics and Ophthalmology Group, University of Tsukuba, Ibaraki, Japan e-mail: [email protected] Y. Yasuno Computational Optics and Ophthalmology Group, University of Tsukuba, Ibaraki, Japan Computational Optics Group, University of Tsukuba, Ibaraki, Japan e-mail: [email protected]

cumbersome to perform than other anterior segment imaging devices such as ultrasonic biomicroscopy (UBM). In its development history, the early studies for anterior segment were done with the custom-­ built systems of the commercially available retinal OCT adapted for anterior segment imaging [3]. After a while, a laboratory-based OCT specially designed for anterior investigation appeared [2]. This first generation of AS-OCT was based on a time-domain low-coherence interferometer, which generates depth-resolved interference signal by mechanically scanning one of the mirrors in the interferometer. In 2005, a commercially available time-domain anterior segment OCT system, Visante™ (Carl Zeiss Meditec, CA, USA), was approved by the United States Food and Drug Administration (USFDA). Visante, which was based on time-domain OCT technology, provided two-dimensional cross-sectional images of the anterior segment of the eye with a 1,310-nm wavelength probe beam. Although this wavelength is suboptimal to image the retina due to high absorption by the aqueous and vitreous humor, it deeply penetrates through the conjunctiva and sclera, so it is suitable for anterior segment imaging. In addition, another commercially available anterior OCT, slit-lamp OCT (SL-OCT, Heidelberg Engineering GmbH, Heidelberg, Germany), was approved by USFDA in 2006. Although these systems provide cross-sectional images, three-dimensional OCT investigation

© Springer Nature Switzerland AG 2021 J. L. Alió, J. L. Alió del Barrio (eds.), Atlas of Anterior Segment Optical Coherence Tomography, Essentials in Ophthalmology, https://doi.org/10.1007/978-3-030-53374-8_1

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was not available owing to the limitation of measurement speed. The cornea anterior module of RTVue Fourier-­ domain OCT (Optovue, Fremont, CA, USA) enabled three-dimensional investigation of the cornea. RTVue was based on a spectral-domain OCT technology, which is a sub-type of Fourier-­ domain OCT technology, which offers 10 times higher acquisition speed than the time-domain systems. However, the field of view was considerably limited with RTVue. The Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA) had a built-in anterior segment-imaging module, which scanned only a 3 × 1 mm area. Since both systems used a wavelength of 840 nm, the penetration was quite shallower than the system using 1,300-nm wavelength. The three-dimensional AS-OCT (CASIA SS-1000 OCT, Tomey, Nagoya, Japan) using a wavelength of 1,300  nm was developed on the basis of the swept-source OCT technology, which is another sub-type of the Fourier-domain OCT [4]. It enables 16-mm horizontal scan and possesses an axial resolution of 10  μm. With dramatic improvement of measurement speed and resolution, AS-OCT imaging has become an important part of clinical evaluation of the cornea, anterior chamber, and chamber angle. Ultrahigh-resolution OCT is capable of axial resolution of 1 to 4 μm [5] and enables detailed imaging of the corneal and conjunctival layers. In 2015, the deep range AS-OCT (CASIA2, Tomey Corporation, Nagoya, Japan) has improved the scan speed to 50,000 A-scans/s and a scan depth of 13 mm, making it possible to perform imaging from the cornea through the posterior surface of the crystalline lens in a single session [6]. Automated quantitative analysis of the angle parameters was also provided. Tritontm SS-OCT (Topcon, Tokyo, Japan) is another ophthalmic swept-source OCT which uses a 1,050-nm wavelength probe beam and possesses a scan speed of 100,000 A-scans per second and a scan depth of 3 mm. Although this OCT is mainly designed for posterior segment investigation, an external add-on lens enables anterior segment imaging.

S. Fukuda et al.

The MS-39 (Costruzione Strumenti Oftalmici, Florence, Italy) is a stand-alone device that combines spectral-domain OCT and Placido disk corneal topography to obtain measurements of the anterior segment of the eye [7]. After an autocalibration, the scanning process acquires (approximately in 1  s) 1 keratoscopy, 1 iris front image (used for the pupil detection), and a series of 25 OCT radial scans. The device uses a SLED light source at 845 nm and provides an axial resolution of 3.6 μm (in tissue) and transversal resolution of 35  μm (in air). Each section measures 16 × 7.5 mm and includes 1024 A-scans. The ring edges are detected on the keratoscopy so that elevations, slope, and curvature data can be derived by the arc-step with conic curves algorithm. Profiles of the anterior cornea, posterior cornea, anterior lens, and iris are derived from the OCT scans. Data for the anterior surface from the Placido image and OCT scans are merged using a proprietary method. All other measurements for internal structures (posterior cornea, anterior lens, and iris) are derived solely from spectral-­ domain OCT data. Its unique application includes automated measurements of the corneal epithelium, which has been shown to be accurate and useful in clinical situations. OCT angiography (OCT-A) delineates blood vessels by analyzing temporal variation of OCT signal, such as signal decorrelation and signal variance [8]. It emerged as a noninvasive technique for imaging the microvasculature of the retina and the choroid. The main advantages of OCT-A over the conventional angiography include shorter acquisition time and enhanced safety. Injection of fluorescein and indocyanine green dyes is not required, which is associated with the risk of systemic adverse effects and even anaphylactic reactions. Current commercially available OCT-A systems are not specifically designed for the anterior segment, but may be adapted to assess the conjunctival, corneal, iridial, and scleral vessels [9]. Although anterior segment OCT-A has received little attention to date, imaging of corneal neovascularization is among the most obvious applications of this technique. In contrast to evaluation with slit lamp, OCT-A

1  Anterior Segment OCT: An Overview

allows for objective measures of the extent and depth of angiogenesis. The AS-OCT has a potential as research and clinical tools in the field of anterior segment diseases. These include detailed assessment of ocular surface, anterior chamber angle, cornea, sclera, limbus, extraocular muscle, conjunctiva, and subconjunctival space (filtering bleb). AS-OCT is also useful in ocular injuries and trauma. Ultrahigh-resolution OCT can differentiate various corneal and ocular surface pathologies, including ocular surface squamous neoplasia, lymphoma, pterygium, melanosis, and corneal degeneration [10]. In cataract surgery, AS-OCT is utilized in intraocular lens power calculation as well as in preoperative evaluation of crystalline lens, anterior chamber, and angle structures [11]. It is also valuable in corneal transplantation surgery, particularly in lamellar transplantation, and is used for preoperative evaluation of graft donor tissue for thickness and preservation. AS-OCT enables precise monitoring of laser in situ keratomileusis (LASIK) flap [12]. Intraoperative use of AS-OCT has been described for in vivo assessment of clear cornea wound architecture and OCT-guided femtosecond laser-assisted cataract surgery. LenSx (Alcon LenSx Lasers Inc., Aliso Viejo, CA, USA), Catalys (OptiMedica, Sunnyvale, CA, USA), and VICTUS (Technolas Perfect Vision GmbH, Munich, Germany) are commercially available laser cataract surgery systems that equip SD-OCT for three-dimensional and high-resolution reconstruction of the anterior segment structures to improve safety and accuracy. Novel polarization-sensitive OCT (PS-OCT) and OCT elastography will expand functional potentials of AS-OCT [13, 14]. Further advancement of AS-OCT to ultrahigh resolution will sophisticate clinical evaluation of anterior ocular diseases. AS-OCT imaging, including anterior segment OCT-A, is a relatively new field, and there are still many areas that require fine-tuning. These modalities will provide novel insight into the pathophysiology of anterior segment diseases and will therefore remain an active area of research in the coming years.

3 Compliance with Ethical Requirements  Shinichi Fukuda declares that he has no conflict of interest. Yoshiaki Yasuno received research grants from Tomey Corp., Topcon, Yokogawa Electric, Nikon, and Kao. Yoshiaki Yasuno licenses a patent to Tomey Corp. Tetsuro Oshika has received research grants from Tomey Corp. Tetsuro Oshika has received a speaker honorarium from Tomey Corp., Topcon, and Carl Zeiss.

References 1. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et  al. Optical coherence tomography. Science (New York, NY). 1991;254(5035):1178–81. 2. Izatt JA, Hee MR, Swanson EA, Lin CP, Huang D, Schuman JS, et al. Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol (Chicago, Ill: 1960). 1994;112(12):1584–9. 3. Feng Y, Varikooty J, Simpson TL.  Diurnal variation of corneal and corneal epithelial thickness measured using optical coherence tomography. Cornea. 2001;20(5):480–3. 4. Fukuda S, Kawana K, Yasuno Y, Oshika T. Anterior ocular biometry using 3-dimensional optical coherence tomography. Ophthalmology. 2009;116(5):882–9. 5. Wang J, Abou Shousha M, Perez VL, Karp CL, Yoo SH, Shen M, et al. Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye. Ophthalmic Surg Lasers Imaging. 2011;42 Suppl:S15–27. 6. Chansangpetch S, Nguyen A, Mora M, Badr M, He M, Porco TC, et  al. Agreement of anterior segment parameters obtained from swept-source Fourier-­ domain and time-domain anterior segment optical coherence tomography. Invest Ophthalmol Vis Sci. 2018;59(3):1554–61. 7. Savini G, Schiano-Lomoriello D, Hoffer KJ.  Repeatability of automatic measurements by a new anterior segment optical coherence tomographer combined with Placido topography and agreement with 2 Scheimpflug cameras. J Cataract Refract Surg. 2018;44(4):471–8. 8. Hong YJ, Makita S, Jaillon F, Ju MJ, Min EJ, Lee BH, et al. High-penetration swept source Doppler optical coherence angiography by fully numerical phase stabilization. Opt Express. 2012;20(3):2740–60. 9. Ang M, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, et  al. Optical coherence tomography angiography for anterior segment vasculature imaging. Ophthalmology. 2015;122(9):1740–7. 10. Shousha MA, Karp CL, Perez VL, Hoffmann R, Ventura R, Chang V, et al. Diagnosis and management of conjunctival and corneal intraepithelial neoplasia using ultra high-resolution optical coherence tomography. Ophthalmology. 2011;118(8):1531–7.

4 11. Nguyen P, Chopra V.  Applications of optical coherence tomography in cataract surgery. Curr Opin Ophthalmol. 2013;24(1):47–52. 1 2. Li Y, Netto MV, Shekhar R, Krueger RR, Huang D.  A longitudinal study of LASIK flap and stromal thickness with high-speed optical coherence tomography. Ophthalmology. 2007;114(6):1124–32.

S. Fukuda et al. 13. Fukuda S, Yamanari M, Lim Y, Hoshi S, Beheregaray S, Oshika T, et  al. Keratoconus diagnosis using anterior segment polarization-sensitive optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54(2):1384–91. 14. Ford MR, Dupps WJ Jr, Rollins AM, Sinha RA, Hu Z. Method for optical coherence elastography of the cornea. J Biomed Opt. 2011;16(1):016005.

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Anterior Segment OCT: Fundamentals and Technological Basis Gabriele Vestri, Claudio Macaluso, and Francesco Versaci

Abbreviations OCT Optical coherence tomography AS-OCT Anterior segment optical coherence tomography TD-OCT Time domain optical coherence tomography FD-OCT Fourier domain optical coherence tomography SD-OCT Spectral domain optical coherence tomography SS-OCT Swept source optical coherence tomography SLD Superluminescent diode

Introduction The last 30 years have seen a progressive evolution of diagnostic devices for the anterior ocular segment, which has accompanied the tremendous improvements in the fields of electronics, optics, and computer science.

G. Vestri (*) · F. Versaci CSO Costruzione Strumenti Oftalmici, Florence, Italy e-mail: [email protected]; [email protected] C. Macaluso Department of Medicine and Surgery, University of Parma, Parma, Italy

The first breakthrough occurred with the invention of corneal topographers [1], based either on the reflection or the projection of a pattern of mires [2]. These devices provided an accurate measurement of a large area of the first corneal surface in one shot. They also provided ophthalmologists with an easy and reliable method to detect irregular astigmatism and keratoconus at mild stages, to measure the contribution of anterior corneal surface to ocular aberrations, and, in general, to better understand the morphology and the optics of the anterior corneal surface. The second important development occurred with the release of optical scanning devices, which could capture the entire anterior segment. In this way, visual and quantitative information were added about posterior corneal surface and anterior chamber (iris, angles, and anterior portion of the crystalline lens). The first of these instruments was the Orbscan (Bausch & Lomb, Rochester, NY) based on a translating illuminating slit. This was followed by a series of machines based on a rotational illuminating scanning slit and on the Scheimpflug principle which allows the device to focus the illuminated section even if it is tilted with respect to the axis of the observation system: Pentacam (Oculus Optikgeräte, Wetzlar, Germany), Galilei (Ziemer, Switzerland), Sirius (CSO, Florence, Italy), and TMS4 (Tomey, Nagoya, Japan). With all these improvements, clinicians were able to get some further important

© Springer Nature Switzerland AG 2021 J. L. Alió, J. L. Alió del Barrio (eds.), Atlas of Anterior Segment Optical Coherence Tomography, Essentials in Ophthalmology, https://doi.org/10.1007/978-3-030-53374-8_2

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information, mainly the elevation map of posterior corneal surface and the corneal thickness map. Consequently, some other achievements were obtained in the early detection of keratoconus and ectasia, in the measurement of posterior and total corneal astigmatism for toric intraocular lens (IOL) planning, and in the calculation of total corneal power for more accurate IOL calculation, particularly after corneal refractive surgery. Nevertheless, Scheimpflug imaging has some major limitations in the low resolution of the scans and the presence of artifacts caused by heavy tissue scattering. The third milestone was the application of optical coherence tomography (OCT) to produce images with higher definition. The first OCT instrument completely dedicated to the anterior segment was Visante (Carl Zeiss Meditec, Dublin, CA). Despite its advanced design, some limitations of Visante soon became clear: • The relative reliability of the measurement made it necessary to combine with the corneal topographer Atlas (Carl Zeiss Meditec, Jena, Germany) for the measurement of the anterior corneal surface. • The relatively slow scanning speed and the consequent low number of scanned sections. • The quality of the image was inferior compared to that of retinal OCTs with a corneal adapter. The next advancements were mainly achieved by retinal OCTs, which were equipped with corneal adapters, but the field of view in depth and/ or width was limited to a few millimeters, and topographic maps were only partially available. Finally, it was the turn of instruments completely dedicated to the anterior segment like Casia SS-1000, followed by Casia 2 (Tomey, Nagoya, Japan), and recently MS-39 (CSO, Florence, Italy) and Anterion (Heidelberg Engineering, Heidelberg, Germany). These devices allow for the acquisition of high-quality angle-to-angle pictures of the anterior segment and a quick scan of a large number of meridians in order to produce accurate, detailed, and extended topographic maps.

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OCT Systems: How Do They Work? Until a few years ago, optical coherence tomography found a very successful application in ophthalmology only for the study of the retina and for the measurement of intraocular distances, firstly the axial length. Only recently have manufacturers turned their attention to topography and tomography of the anterior segment of the eye. The reason behind this delay is due to the complexity of this technology, the reliability, the difficulty of obtaining images that contain the complete anterior segment, and the difficulty in obtaining accurate measurements similar to those of simpler techniques. OCT is an imaging technique based on the interference of two beams of a broadband radiation (typically infrared) from a reference arm and a sample arm [3–6]. In its simplest implementation (Fig.  2.1), it requires a broadband radiation source, an interferometer with at least four arms, a detector for collecting the interference signal, and a processing unit that transforms the interference signal into intelligible data. The four arms of the interferometer are used for the following purposes: 1. One is for the source of the radiation (source arm). 2. One is used for creating a reference in distance and for generating one of the interfering beams (reference arm). 3. One is for imaging the sample, i.e., for generating the interfering beam coming from the object to be imaged (sample arm). 4. One is for collecting the interference from the reference and the sample arm (detection arm). The broadband source  – usually an infrared superluminescent diode (SLD) – emits the radiation into the interferometer, which partially sends it to the reference arm and partially to the sample arm. At the end of the reference arm, a mirror reflects the beam back toward the detection arm where the photodetector collects it. Similarly, the radiation sent to the sample arm is backscattered by the ocular tissues toward the detection arm, where it interferes with the

2  Anterior Segment OCT: Fundamentals and Technological Basis

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Fig. 2.1  Basic OCT schematic Radiation source

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back-reflected beam from the reference arm. If the reference mirror translates axially, thereby altering the length of the reference arm, the interference due to the ocular structures encountered by the incident beam of the sample arm can be sampled at various depths. As a result, the photodiode reveals a peak signal for each backscattering element encountered by the beam incident on the sample at a position corresponding to that of the moving mirror of the reference arm. This design (Fig.  2.2), called time domain OCT (TD-OCT), was the first to be applied in the field of ophthalmology for the measurement of the inter-distances between the various ocular interfaces, in particular the axial length of the eye, the corneal thickness, the anterior chamber depth, and the crystalline lens thickness. The weak point of this technique is the need to move the reference mirror for obtaining a response from the structures at various depths. Thus, it suffers a speed limit when it is necessary to scan hundreds or thousands of contiguous lines (A-scans) to create an image of an ocular section (B-scan). Eye movements during a slow scan lead to artifacts in the scanned image which cannot be corrected.

A more complex implementation is the one which goes under the name of Fourier domain OCT (FD-OCT) [7], which eliminates the need for a moving reference mirror to have a measurement at various depths. This offers the possibility of acquiring axial scans very quickly, thereby reducing artifacts due to eye movements. The FD-OCT, in addition to decreasing the time of acquisition, also presents advantages in terms of signal-to-noise ratio compared to the time domain technique. The basic idea is to measure the spectral interference between the radiation returning from the reference arm and the sample arm in a certain range of wavelengths emitted by the source. This means that, in a single A-scan, for each wavelength, the detection arm collects the interference value of the radiation coming back from both the sample and reference arms. The set of these values at various wavelengths is processed with more or less complex algorithms, basically, containing a Fourier transformation, to obtain the reflectivity profile of the sample along an axis. The FD-OCT devices can be classified into the following two classes depending on how they get the interference values at various ­wavelengths:

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8 Fig. 2.2  Time domain OCT (TD-OCT)

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Fig. 2.3 Spectral domain OCT (SD-OCT) schematic

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spectral domain OCT (SD-OCT in Fig. 2.3) and swept source OCT (SS-OCT in Fig. 2.4). The first class of instruments, SD-OCT, use a broadband source that emits a certain range of wavelengths all at the same time. The detection arm contains a spectrometer to decompose the interference signal deriving from the return radiation of the sample and reference arms into its

components at the various wavelengths. Therefore, in a single shot, the sensor of the spectrometer collects the spectrum necessary to determine the profile of reflectivity along one axis of the sample. The second class of instruments, SS-OCT, use a light source that is a tunable laser, i.e., a laser whose wavelength can be varied very quickly [8].

2  Anterior Segment OCT: Fundamentals and Technological Basis Fig. 2.4  Swept source OCT (SS-OCT) schematic

9 Tunable laser

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The light source is driven to emit the various wavelengths in sequence and synchronizes with a photodiode, which replaces the spectrometer on the detection arm. A processing unit associates the wavelengths emitted by the source with the values measured by the photodiode and reconstructs the interference spectrum between the beams coming back from the reference and sample arms. In order to illustrate the working principle of this technology in detail, let us imagine an object able to backscatter the incident radiation and positioned within the field of view of the instrument. The incident radiation containing all the wavelengths of the source (all together in the SD-OCT case, one at a time as a fast sequence in the SS-OCT case) is partially backscattered toward the instrument and will recombine in the detection arm with the radiation coming from the reference arm which at its turn will contain the same wavelengths. The combination of both the radiations will be collected in the spectrometer if the instrument implements the SD technique and in a photodiode if the instrument adopts the SS technique. In both cases, for each wavelength available in the source, the sensor collects the intensity of a beam generated by the constructive, destructive, or partially constructive interference of two beams coming from the reference and measuring arms.

Let us suppose that the backscattering object is placed in a position, which is very near the one corresponding to the reference mirror, i.e., at the same distance from the origin of the interferometer. In this case, the spectrum measured by the device will be a sequence of peaks and valleys superimposed on the spectrum of the source with a relatively wide period, or in other words a low-­ frequency sinusoid, which modulates in amplitude the source spectrum (Fig. 2.5a). The reconstructed intelligible signal, obtained through a Fourier transform of the measured spectrum, will contain a peak near the zero position (Fig. 2.6a). The peak signal is then converted to gray levels to be associated with the pixels of a column of an image. Let us suppose now that the backscattering object is placed relatively far from the position corresponding to the reference mirror. In this case (Fig.  2.5b), the spectrum measured by the device will be a sequence of peaks and valleys very close to each other superimposed on the spectrum of the source, or in other words a high-­ frequency sinusoid, which modulates in amplitude the source spectrum. The reconstructed intelligible signal, again obtained through a Fourier transform of the spectral intensity, will contain a peak far from the zero position (Fig. 2.6b). The peak signal is newly converted to gray levels to be associated with the pixel of a column of an image.

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Fig. 2.6  Reconstructed signal from the examples of Fig. 2.5 in case of (a) a near object, (b) a far object, (c) both a near and a far object

Fig. 2.7  Example of a 16 mm OCT section in refractive surgery case 2 years after SMILE procedure. All anterior segment as well as corneal details can be visualized. A minor change in stromal reflectivity can be observed despite the absence of increased reflectivity from the interface corresponding to removal of the lenticle. As the section is along the 135° meridian, the site of the external incision can be detected

Let us suppose as a final example that both the previous objects are placed and in front of the instrument at the same time (one is near and the other one is far from the position corresponding to the reference mirror). In this case, the signal measured by the device will be given by the superposition of two sinusoids, a lower-frequency one due to the first object and a higher-frequency one due to the second object (Fig. 2.5c). In this case, the intelligible signal reconstructed by the

Fig. 2.8  A 10  mm enlargement of the same section shown in Fig. 2.7. At higher magnification the epithelium layer can be recognized more easily as well as the mild differences in stromal reflectivity. Even the Bowman’s layer can be detected just below the epithelial layer

Fourier transform will contain two peaks: one of them is near, and the other one is far from the zero position (Fig. 2.6c). This is the explanation about how a single A-scan of an image is obtained. Thanks to the scanning system usually made by two galvanometric mirrors and by one or more lenses, the scanning beam can be moved on the sample according to a certain trajectory. A certain number of A-scans are collected, and the A-scans are juxtaposed to create a B-scan, i.e., an image relative to the scanned section (Figs. 2.7 and 2.8).

2  Anterior Segment OCT: Fundamentals and Technological Basis

The A-scan resolution depends on the width of the spectrum actually collected by the spectrometer or by the photodiode. The wider the spectrum, the better the resolution or, in other words, the smaller the distance between two near objects, which can be discriminated by the device. During the history of OCT technology, the OCT sources passed from the original bandwidth of 25 nm to the current 100  nm and the resolution passed from 20 μm to less than 5 μm. The maximum depth of an A-scan with Fourier domain technique depends on how finely the spectrum collected by the spectrometer or photodiode can be sampled. The smaller the sampling distance between adjacent spectral samples, the greater the maximum depth at which a backscattering object can be acquired. For example, the spectrum of a source at 850 nm with a bandwidth of 100 nm, if sampled with 1024 points, can reach a depth of about 1.8 mm (in air) and if sampled with 4096 points can reach a depth of about 7.4 mm (in air). If we keep the source bandwidth constant and we want to increase the number of samples, we have to use linear sensor with a higher resolution and spectrometers with optical systems able to resolve adequately contiguous wavelengths in the SD-OCT case; in the SS-OCT case, we have to increase the sampling speed of the photodiode. These are some of the technological advances that were made over the past few years by both the companies that manufacture the basic components for this technology and those that incorporate them into their systems. This was also a fundamental improvement over retinal OCT instruments which had a maximum depth of a few millimeters compared to anterior segment OCT devices with maximum depths of 10–40 mm.

SD-AS-OCT VS. SS-AS-OCT, 850 nm VS. 1310 nm Sources The AS-OCT devices, which are currently available on the market, are Casia 2, MS-39, and Anterion. All of them are based on Fourier domain technology, but the first and the third one implement the swept source design, while the second one implements the spectral domain design.

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Both Casia 2 and Anterion use a tunable laser centered at 1310 nm. Their scanned bandwidth is such that their axial resolution is 13  μm in air (about 10 μm in tissue) [9, 10]. MS-39 contains a superluminescent diode emitting a radiation centered around 850  nm. The spectrometer inside MS-39 collects an interval of wavelengths of about 80 nm, thus ensuring an axial resolution of 4.8 μm in air (about 3.5 μm in tissue). Concerning imaging depth, even if the 10 mm depth (in air) provided by the MS-39 is the highest of all the ophthalmic SD-OCT instruments on the market, it is smaller than the imaging depth of SS-OCT instruments, which are able to extend to the posterior surface of the crystalline lens in their axial field of view. The maximum transversal field is similar for the three instruments and is about 16 mm. While SS-OCT technology has some undeniable advantages like high scan rate and imaging depth, SD-OCT technology allows for an axial resolution that is more than double that of the best SS-OCT systems (less than 5  μm in air instead of 13 μm, respectively). To the best of our knowledge, the axial resolution of the MS-39 is the highest of all the OCT instruments currently available on the market including the ones designed for retina. This feature is clinically essential to resolve fine details of anterior segment tissues, like the clear-cut identification of different corneal layers, particularly relevant for obtaining reliable thickness maps of the corneal epithelium. The wavelength adopted by MS-39 (850 nm) is also different from the one used by the other two instruments (1310 nm). The shorter 850 nm wavelength is closer to the spectrum of visible light, hence more adequate to improve the image detail in the corneal layers, but has a worse penetration into tissue as compared to the longer 1310 nm wavelength, which has the advantage of imaging deeper structures such as the scleral spur.

Image Distortion and Measurements on OCT Scans It has always been customary in the medical community to associate the term OCT with high-­ resolution images and accurate measurements.

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This is not directly guaranteed by the acquired raw image, which is actually distorted and does not show the real proportions of the sample. Among the distorting factors, an important effect is caused by refraction, which deviates the scanning beam when it passes from a medium with a certain refractive index to another medium with a different refractive index. To understand this effect, it is necessary to understand what happens to a scanning beam, which enters a sample made of layers with different refractive indices. Let us refer to Fig.  2.9a where a section of a cornea is shown. Let us assume that in this context, two surfaces S1 and S2 delimit three media with different refractive index, respectively, air with n1 = 1, cornea with n2 = 1.376, and aqueous with n3 = 1.336. For the sake of simplicity, let us neglect the presence of several corneal sublayers with different refractive index. The scanning beam travels from medium 1 with refractive index n1 to surface S1 and is refracted according to the law of refraction (Fig. 2.9b). After this it travels along a new direction in medium 2 characterized by refractive index n2 until it hits surface S2, which separates medium 2 from medium 3 with a different refractive index n3 (≠ n2). At surface S2, the ray is again

deflected according to the law of refraction to travel in medium 3 along a new direction, which is very similar to the previous direction because of the small index difference between mediums 2 and 3. The OCT image shows two main interfaces (the two corneal surfaces) at two different distances corresponding to the incidence points of the scanning beam on the anterior and on the posterior corneal surfaces. As can be understood from the previous explanation, the two edges of the corneal surfaces in the same A-scan (in the same column of the image (see Fig. 2.9a)) are not coming from two points both belonging to the initial ray direction. The second edge is generated at a point, which is on a line different from the one of the initial ray. Moreover, the distance between the two points is not directly related to the distance between the two edges in the image, but it has to be divided by the refractive index of medium 2. All this means that getting accurate measurements from an OCT image makes the compensation of refractive effect necessary. Once the measured position is available for points of surface S1, in order to calculate the position of points of surface S2, it is necessary to perform the following steps:

n1 = 1 S1

n2 = 1.376

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Fig. 2.9 (a) Distorted raw image. (b) Reconstruction issue: the points of an A-scan do not actually lie on the same line. Compensation of refraction effect is necessary in order to obtain accurate measurements

2  Anterior Segment OCT: Fundamentals and Technological Basis

1. To apply Snell’s law at the measured points of surface S1 to calculate the trajectory to which the points of surface S2 belong 2. To divide the distance between the first and second corneal edges of the OCT A-scan by the refractive index n2 of the medium 2, in order to get the actual distance at which the measured point of surface S2 relative to the second edge of the A-scan will be placed The same procedure can then be applied several times for all the next interfaces, which the beam can travel across.

I s AS-OCT High Resolution High Enough? Hybrid System and Combination with Placido Disc At first glance, one can imagine that OCT technology is the definitive solution for the demanding accuracy requirements of ophthalmological applications and is superior from every point of view with respect to the former traditional technologies used for topographic purposes. Yet, we can soon reject this assumption if we consider a Fig. 2.10 Sagittal height difference between the height profiles of meridional sections of a 43.25 D and 43 D spheres

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quantitative analysis of the resolution necessary to obtain precise measurements of the anterior corneal curvature. To fully understand the practical relevance of this point, let us compare the height profile of two spheres with curvatures of 43 D (7.85 mm) and 43.25 D (7.80 mm), which differs by only 0.25 D in curvature. The difference between the height profiles of two meridional sections of the two spheres is about 0.1 μm at 0.5 mm from the vertex, 0.38  μm at 1  mm, and 0.85 at 1.5  mm (Fig. 2.10). If we compare these values with the axial resolution of the OCT system in air and consider that one of the primary purposes of the instrument is the accurate measurement of corneal surfaces, we can clearly understand that even the highest axial resolution achievable by means of AS-OCT (dotted lines in Fig. 2.10) is largely under the requirements for detecting the tiny corneal elevation differences of a 0.25 D change in corneal power, hence the utility to add a system with a higher sensitivity for the measurement of corneal curvature like the Placido disc. This is the reason why CSO chose to integrate the OCT with a Placido disc subsystem in the MS-39. The consequent implementation of

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this additional information is such that the MS-39 software, whenever keratoscopy is reliable (i.e., the anterior corneal surface is not too irregular and specular reflection can be processed), is preferred to the measurement coming from the OCT subsystem, as the measurement of the anterior corneal surface coming from the Placido disc subsystem has an inherently higher resolution.

Epithelial Thickness Over the past few years, corneal epithelium assessment has become a hot topic: before the advent of OCT, several technologies, such as confocal microscopy [11] or ultrasound, were used to measure epithelial thickness. In some studies, the latter methods were adopted to measure the average central epithelium thickness. Very-high-frequency ultrasound was also used to map the corneal epithelium and stromal thickness over a wide area: however, this technology is time-consuming, demanding for the operator, and not patient-friendly, as it requires immersion of the eye in a coupling fluid. More recently, OCT technology has been applied to measure the corneal epithelium, as it is a noncontact technique with excellent axial resolution, and its Fourier domain embodiment is fast enough to acquire images of a large number of meridians to create a map of the corneal epithelial thickness [12]. In this application, SD-OCT embodiments seem to have a technological advantage over SS-OCT implementations: in fact, since the epithelium is a relatively thin corneal layer, the more than double axial resolution plays a fundamental role in the edge detection and tracking algorithms. To the best of our knowledge, at the moment of writing this chapter, the MS-39, which is SD-OCT based, is the only commercially available AS-OCT reliably providing maps of corneal epithelium thickness, thanks to its high axial resolution and possibly to its shorter source wavelength (850 nm). Regardless of the technology used, numerous reports have been published describing epithelial

reshaping as a consequence of stromal changes. According to Reinstein et  al. [13], “the corneal epithelium has the ability to alter its thickness profile to re-establish a smooth, symmetrical optical surface and either partially or totally mask the presence of an irregular stromal surface from front surface corneal topography” reason why “based on an understanding of the pattern of the normal epithelial thickness profile, any localized abnormal epithelial changes can be relied upon as a mirror of a relative localized stromal surface irregularity.” Those findings allowed reviewing the regression effects after refractive surgery [14–24], intracorneal ring segment implantation [25], and radial keratotomy [26] as well as explaining refractive changes after orthokeratology contact lens wear [27–31]. In keratoconus, epithelial thickness in the region of the cone has been shown to be thinner than that of normal eyes [13]. It has also been shown that the epithelial thickness profile across the central 8 mm diameter follows a “doughnut pattern” characterized by a thinning region over the cone surrounded by an annulus of thickening [14, 15, 32–34]. It has also been reported that the epithelial changes become more significant as the disease progresses and, certainly, it represents a “smoothing” response of the epithelial layer in its attempt to regularize the curvature. In order to explain the clinical value of those findings, we review some cases acquired with MS-39 and accompanied by their own topographic maps.

Case Presentation 1 A 31-year-old Caucasian patient was referred with recent mild reduction in vision in her right eye and preexisting poor vision in left eye. Clinical history revealed only occasional eye rubbing and apparently no relatives affected by keratoconus. Diagnosis of keratoconus was evident after AS-OCT scans in the left eye (OS, Fig. 2.11), while her right eye (OD Fig. 2.12, top) appeared

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Fig. 2.11  Case presentation 1: summary (top) and keratoconus panel (bottom) for the right eye of the patient

at a first glance to be just a thin cornea. A more detailed analysis by means of the keratoconus screening software revealed (Fig. 2.12, bottom) a localized steepening on the posterior surface, in keeping with initial keratoconus changes such to explain the visual changes reported by the patient. Interestingly, a localized thinning of the epithelium occurred in the same location of the posterior ectasia accompanied by an annulus of augmented epithelial thickness, while the ante-

rior corneal curvature was remarkably regular: the corneal epithelium has a masking effect on the irregularities of the anterior stroma, thereby preventing and/or delaying the diagnosis of ectasia. It is generally believed that such normal-­ appearing eyes in cases with unilateral keratoconus represent a latent form of keratoconus. This case demonstrates how corneal epithelial maps can add valuable information in the clini-

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Fig. 2.12  Case presentation 2: summary (top) and keratoconus panel (bottom) for the left eye of the patient

cal management of early keratoconus and may help our understanding of the early progression of both anterior and posterior stromal surfaces modification. While the importance of epithelial thickness maps in the early diagnosis of ectatic diseases had already been demonstrated, the possibility to obtain reliable maps with the same convenience and rapidity of a simple corneal topography examination may be a useful addition to the clinician’s armamentarium for a thorough characterization of corneal diseases.

Case Presentation 2 A 51-year-old Caucasian patient presented seeking an evaluation for refractive surgery with the aim of reducing dependence on contact lenses. BCVA was 1.25 decimal (−0.1 LogMAR) with −2D/−0.75D ax 180° and 1.25 decimal (−0.1 LogMAR) with −1.75D/−1D ax 160° with his right (OD) and left eye (OS), respectively. MS-39 tomographic summaries are shown in Figs. 2.13 and 2.14. In both eyes, there was a visible steep-

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Fig. 2.13  Case presentation 2: summary (top) and keratoconus panel (bottom) for the right eye of the patient

ening on the anterior corneal surface with an asymmetry typical of a keratoconus pattern. Despite this, looking at the keratoconus screening report revealed that the posterior surface was not showing any sign of ectasia and that the anterior steepening did not correspond to an area of thinner corneal epithelium, but rather the substantial inferior epithelial thickening could explain the abnormal anterior curvature, resulting in a keratoconus-like appearance.

Asymmetrical topographic patterns and focal anterior steepening can sometimes be secondary to corneal warpage: analysis of the epithelial layer with high-resolution AS-OCT allows for direct detection of the abnormality rather than just supposing it. Moreover, this new diagnostic possibility may help the clinician avoiding to consider as keratoconus suspect patients who could actually undergo effective refractive surgery treatment to solve their visual problems.

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Fig. 2.14  Case presentation 2: summary (top) and keratoconus panel (bottom) for the left eye of the patient Compliance with Ethical Requirements  Gabriele Vestri and Francesco Versaci are employees of CSO SRL. Claudio Macaluso declares that he has no conflict of interest. No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

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2. Mejía-Barbosa Y, Malacara-Hernández D.  A review of methods for measuring corneal topography. Optom Vis Sci. 2001;78(4):240–53. 3. Fercher AF, Hitzenberger CK, Drexler W, Kamp G, Sattmann H, Schmetterer LF, et al. In-vivo dual-beam optical coherence tomography. In: Proceedings of SPIE 2083. Microscopy, holography, and interferometry in biomedicine; 1994. 4. Fercher AF, Hitzenberger CK, Kamp G, El-Zaiat SY.  Measurement of intraocular distances by backscattering spectral interferometry. Opt Commun. 1995;117(1):43–8. 5. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991;254(5035):1178–81. 6. Swanson EA, Lzatt JA, Hee MR, Huang D, Lin CP, Schuman JS, et  al. In vivo retinal imaging

2  Anterior Segment OCT: Fundamentals and Technological Basis by optical coherence tomography. Opt Lett. 1993;18:1864–6. 7. Drexler W, Morgner U, Ghanta RK, Kartner FX, Schuman JS, Fujimoto JG. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat Med. 2001;7(4):502–7. 8. Chinn SR, Swanson EA, Fujimoto JG. Optical coherence tomography using a frequency-tunable optical source. Opt Lett. 1997;22(5):340–2. 9. Fourier Domain OCT Casia2, Delight in sight, pamphlet, Tomey, Nagoya. 10. Bille JF, editor. High resolution imaging in microscopy and ophthalmology: new frontiers in biomedical optics. New York: Springer; 2019. p. 278. 11. Petroll WM, Goldberg D, Lindsey SS, Kelley PS, Cavanagh HD, Bowman RW, et al. Confocal assessment of the corneal response to intracorneal lens insertion and laser in situ keratomileusis with flap creation using IntraLase. J Cataract Refract Surg. 2006;32:1119–28. 12. Li Y, Tan O, Brass R, Weiss JL, Huang D.  Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology. 2012;119(12):2425–33. 13. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009;25(7):604–10. 14. Reinstein DZ, Silverman RH, Trokel SL, Coleman DJ. Corneal pachymetric topography. Ophthalmology. 1994;101:432–8. 15. Reinstein DZ, Silverman RH, Sutton HF, Coleman DJ.  Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery: anatomic diagnosis in lamellar surgery. Ophthalmology. 1999;106:474–82. 16. Reinstein DZ, Ameline B, Puech M, Montefiore G, Laroche L. VHF digital ultrasound three-­dimensional scanning in the diagnosis of myopic regression after corneal refractive surgery. J Refract Surg. 2005;21:480–4. 17. Reinstein DZ, Srivannaboon S, Gobbe M, Archer TJ, Silverman RH, Sutton H, Coleman DJ. Epithelial thickness profile changes induced by myopic LASIK as measured by Artemis very high-frequency digital ultrasound. J Refract Surg. 2009;25:444–50. 18. Lohmann CP, Patmore A, Reischl U, Marshall J. The importance of the corneal epithelium in excimer-­ laser photorefractive keratectomy. Ger J Ophthalmol. 1996;5:368–72. 19. Lohmann CP, Güell JL. Regression after LASIK for the treatment of myopia: the role of the corneal epithelium. Semin Ophthalmol. 1998;13:79–82. 20. Lohmann CP, Reischl U, Marshall J. Regression and epithelial hyperplasia after myopic photorefractive

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Anterior Segment OCT: How to Choose for Your Practice Miguel J. Maldonado, Melissa G. Paragua Macuri, and Alfredo Holgueras

Optical coherence tomography (OCT) uses low-­ coherence interferometry [1], which makes it a noncontact noninvasive imaging technology to obtain in  vivo cross-sectional images of ocular structures [2]. The OCT technology in the ophthalmic field was initially devised for imaging the posterior segment of the eye, such as the retina and the optic nerve head [3]. Nevertheless, advancements in the technology made it possible to acquire images of the ocular surface and anterior segment (Fig. 3.1), which has shown to be of significant clinical relevance. Anterior segment OCT (AS-OCT) imaging use was first introduced in 1994, when it proved to yield high-resolution cross-sectional images of structures in the anterior segment of the human eye in  vivo as well as images of dense nuclear cataracts through their full thickness in a cold cataract model in calf eyes in vitro [4]. Thereafter, its first use in a clinical study occurred in 2000 [5], when it was utilized for assessing the anatomic outcome of laser in situ keratomileusis (LASIK) for high myopia with and without astig-

matism. Then, the OCT showed for the first time to be a useful tool for the evaluation of both the qualitative and quantitative anatomic outcomes of LASIK in terms of corneal flap and stromal bed thickness measurements, a concept that has been further refined with more modern technology (Fig. 3.2). From 2001, when AS-OCT entered into commercially circulation [6], it has had a rapid development and impact on clinical practice; it is used throughout the world for the analysis of anterior segment structures. The aim of this chapter is to summarize the AS-OCT technologies available and compare their performance. In order to provide a more schematic approach to our readers, we are classifying the AS-OCT technologies into the two main stem platforms available today: time domain OCT (TD-OCT) and Fourier domain OCT (FD-OCT) [7]. We describe them in detail.

Time Domain OCT (TD-OCT) Anterior Segment TD-OCT

M. J. Maldonado (*) · M. G. Paragua Macuri A. Holgueras Departments of Surgery and Ophthalmology, Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain e-mail: [email protected]; aholguerasl@ ioba.med.uva.es

In TD-OCT, the mirror in the reference arm varies its position at a constant velocity to obtain the cross-sectional images. Different structures within the sample lead to interferences at different positions of the reference mirror [8–9].

© Springer Nature Switzerland AG 2021 J. L. Alió, J. L. Alió del Barrio (eds.), Atlas of Anterior Segment Optical Coherence Tomography, Essentials in Ophthalmology, https://doi.org/10.1007/978-3-030-53374-8_3

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M. J. Maldonado et al.

22 Fig. 3.1 Measurement of anterior segment structures with OCT technology: pachymetry, anterior chamber depth, lens rise, and angle-to-­ angle distance. Acquired with Cirrus HD OCT, Carl Zeiss Meditec, Oberkochen, Germany

a

b

Fig. 3.2 (a) Assessment of the microstructure of the cornea after LASIK with current SA-OCT technology. (b) OCT scan depicting the details of the flap thickness (116 μm), epithelium thickness within the flap (55 μm),

and total corneal thickness 580 μm. As a result, the stromal component of the corneal flap and the residual stromal bed can be quantitated as well. Acquired with Cirrus HD-OCT 5000, Carl Zeiss Meditec, Dublin, CA, USA

The Zeiss Visante OCT™ (Carl Zeiss Meditec, Dublin, CA, USA) and slit-lamp OCT (SL-OCT, Heidelberg Engineering GmbH, Heidelberg, Germany) [10] were the first TD-OCT systems expressly designed for anterior segment imaging. Both were approved by the United States Food and Drug Administration (FDA) in 2005 and 2006, respectively [11]. These systems use a superluminescent diode (SLD) wavelength of 1310  nm; hence, there is reduced scattering, and in opaque media, the signal is lost in small amounts [6, 12]. These characteristics allow a high penetration depth through the sclera and limbus in order to image the scleral spur and iridocorneal angle, with an 18  𝜇m axial  ×  60  𝜇m transversal resolution for Zeiss Visante OCT™ and 25 𝜇m axial × 75 𝜇m transversal resolution for slit-lamp OCT. The Zeiss Visante OCT™ is a stand-alone system, whereas the slit-lamp OCT needs to be conjoined with a commercial Haag Streit slit lamp; in this manner, the Zeiss Visante OCT™ is capable of scanning 4 to 16 meridians simultaneously, with scan speed of 2000 A-scans/second. The slit-lamp OCT only is able to scan one meridian in each exam, with scan speed of 200 A-scans/ second [9, 11, 13] (Table 3.1).

Table 3.1  Comparison of time domain optical coherence tomography systems for anterior segment

Manufacturer

Light source Wavelength Axial resolution Transverse resolution Scan speed (A-scans per second) Scan depth Maximum scan width

Zeiss Visante OCT™ Slit-lamp OCT Heidelberg Carl Zeiss Engineering GmbH, Meditec, Heidelberg, Dublin, CA, Germany USA Superluminescent diode 1310 nm 18 𝜇m 25 𝜇m 60 𝜇m 20–100 𝜇m 2000 (2 kHz)

200 (0.2 kHz)

6 mm 16 mm

7 mm 15 mm

Posterior Segment TD-OCT for Anterior Segment Examination Utilizing a TD-OCT system devised for imaging the posterior segment, the Stratus OCT (Carl Zeiss, Germany), which uses a SLD wavelength of 830  nm, and by modifying its focus as a result of moving the patient’s head backward and, therefore, the anterior segment

3  Anterior Segment OCT: How to Choose for Your Practice

back toward the usual retinal plane [5], it can image the cornea and the anterior chamber angle (ACA) of patients with different angle configurations. It is a helpful tool in the assessment of the ACA [14].

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to 6  mm in many cases (Fig.  3.3), and its scan depth is shorter compared to TD-OCT [20, 21].

 nterior Segment SD-OCT A The device included in this category is the MS39 (Costruzione Strumenti Oftalmici, Firenze, Italy). The MS-39 (software Phoenix v.3.6) is a Fourier Domain OCT (FD-OCT) new stand-alone device that combines SD-OCT and Placido disk corneal topography. Its autoFD-OCT, in contrast with TD-OCT, uses a sta- mated measurements of the corneal epithelium tionary reference mirror [2], and the interference have shown to have good repeatability in normal between the sample and reference is detected as a eyes and eyes following excimer laser surgery. spectrum simultaneously [15, 16]; then, using The device uses a wavelength of 845  nm and Fourier transformation of the spectral interfero- provides an axial resolution of 3.6  𝜇m and a gram, the cross-sectional images are obtained transversal resolution of 35 𝜇m. It includes 1024 [15, 16]. FD-OCT is further subcategorized into A-scans of 16  mm with a maximum depth of spectral domain OCT (SD-OCT) and swept-­ 7.5  mm. The profile of the anterior cornea is source OCT (SS-OCT) [10]. obtained from the Placido image and the SD-OCT scans, which are merged using a proprietary method. Measurements for the internal structures (posterior cornea, anterior lens, and Spectral Domain OCT (SD-OCT) iris) are derived exclusively from the SD-OCT The first category is the SD-OCT, in which the data [22, 23]. reference and sample arms are combined. The spectrum is divided by a diffraction grating and Posterior Segment SD-OCT for Anterior captured by a charge-coupled device (CCD) line Segment Examination camera [17]; consequently, the acquisition speed The devices included into this category are the of spectrometer-based systems is limited by the Topcon 3D OCT (Topcon Corp., Tokyo, Japan), reading rate of the line sensor [18]. In TD-OCT, the RTVue OCT (Optovue, Inc., CA, USA), the the velocity of mechanical movement of the ref- Nidek RS 3000 (Nidek, Gamagori, Japan), the erence mirror limits the speed of image capture. Revo NX (Optopol, Zawiercie, Poland), the The SD-OCT is freed from this limitation [19]; Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, therefore, there is a 10 to 100 times higher speed CA, USA), and the Spectralis OCT (Heidelberg of image acquisition [15]. SD-OCT uses shorter Engineering GmbH, Heidelberg, Germany) wavelengths (820–880 nm); hence, the axial res- [10, 11]. These are primarily posterior segment olution is improved to 4 to 7  𝜇m [17, 18]. SD-OCTs that also display an anterior segment However, its horizontal scan width is limited to 3 module.

a Fig. 3.3  Objective vault (phakic lens  – crystalline lens clearance distance) measurement after implantation of (a) a myopic phakic posterior chamber intraocular lens with central port and (b) a hyperopic phakic posterior chamber

b intraocular lens using anterior segment SD-OCT.  Scan width is