Optical Coherence Tomography in Glaucoma E-Book

Jullia Rosdahl

• Herausgeber: Thieme Medical Publishers
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2021

Beschreibung

A comprehensive and user-friendly guide on leveraging OCT for the management of glaucoma

Optical coherence tomography (OCT) is a noninvasive diagnostic imaging modality that enables ophthalmologists to visualize different layers of the optic nerve and retinal nerve fiber layer (RNFL) with astounding detail. Today, OCT is an instrumental tool for screening, diagnosing, and tracking the progression of glaucoma in patients. Optical Coherence Tomography in Glaucoma by renowned glaucoma specialist Jullia A. Rosdahl and esteemed contributors is a one-stop, unique resource that summarizes the clinical utility of this imaging technology, from basics to advanced analyses.

The book features 14 chapters, starting with introductory chapters that discuss development of OCT and its applications for visualizing the optic nerve and macula. In chapter 5, case studies illustrate OCT imaging of the optic nerve, RNFL, and macula in all stages of glaucoma, from patients at risk to those with mild, moderate, and severe diseases. The next chapters cover the intrinsic relationship between optic nerve structure and function, the use of structure–function maps, and examples of their relationship, followed by a comparison of commonly used devices and a chapter on artifacts. Anterior segment OCT is covered next, followed by chapters covering special considerations in pediatric glaucomas and in patients with high refractive errors. The final chapters cover innovations in OCT on the horizon including OCT angiography, swept-source OCT, and artificial intelligence.

Key Highlights

• Illustrative case examples provide firsthand clinical insights on how OCT can be leveraged to inform glaucoma treatment.
• In-depth guidance on recognizing and managing artifacts including case examples and key technical steps to help prevent their occurrence.
• Pearls on the use of OCT for less common patient scenarios such as pediatric glaucomas and high refractive errors.
• Future OCT directions including angiography, swept-source, and the use of artificial intelligence.

This practical resource is essential reading for ophthalmology trainees and ophthalmologists new to using OCT for glaucoma. The pearls, examples, and novel topics in this book will also help experienced clinicians deepen their knowledge and increase confidence using OCT in daily practice.

This book includes complimentary access to a digital copy on https://medone.thieme.com.

Leseprobe

Optical Coherence Tomography in Glaucoma

Jullia A. Rosdahl, MD, PhD Associate Professor of Ophthalmology Department of Ophthalmology Duke University School of Medicine Durham, North Carolina, USA

214 illustrations

ThiemeNew York • Stuttgart • Delhi • Rio de Janeiro

Library of Congress Cataloging-in-Publication Data is available from the publisher.

© 2022 Thieme. All rights reserved.

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ISBN: 978-1-68420-247-8

Also available as an e-book: eISBN 978-1-68420-248-5

ePUB ISBN: 978-1-63853-704-5

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This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation without the publisher’s consent is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

To my husband Joe and my children Brian and Katie.

To the medical students, residents, fellows, colleagues, and patients who inspire, delight, and teach me every day.

Jullia A. Rosdahl, MD, PhD

Contents

Preface

Acknowledgments

Contributors

1.Introduction: Practical Guide, OCT for Glaucoma

Jullia A. Rosdahl

1.1Introduction

1.2Overview of the Guide

1.2.1Development of OCT

1.2.2OCT of the Optic Nerve

1.2.3OCT of the Macula

1.2.4Illustrative Case Examples

1.2.5Structure–Function Relationship

1.2.6Comparison of Common Devices

1.2.7Artifacts and Masqueraders

1.2.8Anterior Segment OCT in Glaucoma

1.2.9Special Considerations: OCT in Childhood Glaucoma

1.2.10Special Considerations: High

1.2.11Future Directions: OCT Angiography for Glaucoma

1.2.12Future Directions: Swept-Source OCT for Glaucoma

1.2.13Future Directions: Artificial Intelligence Applications

1.3How to Use the Guide

1.4Conclusion

2.Development of Optical Coherence Tomography

Joel S. Schuman and Rachel A. Downes

2.1Introduction

2.2Setting the Stage: Lasers Meet Medicine

2.2.1Light in Flight

2.2.2Interferometry

2.2.3The Pivotal Role of Collaboration

2.3Optical Coherence Tomography: The Debut

2.3.1OCT versus Ultrasound

2.3.2How OCTWorks

2.3.3The First OCT Images

2.3.4Providing Clinical Value

2.4Commercialization

2.4.1From the Bench to the Bedside: The Need for Speed

2.4.2The First Commercial OCT

2.4.3OCT Instrument Design

2.5The Fourier Switch

2.5.1Spectral Domain OCT

2.5.2Swept-Source OCT

2.6OCT-Angiography

2.7Impact

2.7.1Financial

2.7.2Scientific and Clinical

3.Optical Coherence Tomography of the Optic Nerve

Andrew Williams and Jullia A. Rosdahl

3.1Introduction

3.1.1Glaucoma Imaging

3.1.2Optical Coherence Tomography

3.2OCT Output

3.2.1Overview

3.2.2OCT Interpretation

3.3Utility of OCT in Glaucoma Management

3.3.1Reproducibility

3.3.2Reliability

3.3.3Progression Analysis

3.3.4Diagnostic Accuracy

3.3.5Correlation with Patient-Centered Outcomes

3.4Limitations and Pitfalls

3.4.1Common Artifacts

3.4.2Pitfalls

3.4.3Green and Red Disease

3.4.4Limitations

3.5Future Directions

3.6Conclusions

4.Optical Coherence Tomography of the Macula

Divakar Gupta

4.1Retinal Imaging for Glaucoma

4.1.1Glaucoma and Retinal Ganglion Cells

4.1.2RGCs and the Macula

4.2OCT Image of the Macula

4.2.1Devices and Segmentation

4.2.2Correlation between Visual Field and Macular OCT

4.2.3Complementing Peripapillary RNFL Scans with Macular OCT Scans

4.2.4Asymmetry Analysis

4.3Macular OCT and Glaucoma Management

4.3.1 Diagnosis and Progression

4.3.2 Barriers to Proper OCT Interpretation

4.3.3 Practical Uses of Macular OCT

4.4Artifacts

4.4.1Vitreous Traction/Adherence

4.4.2Cystic Changes

4.4.3Epiretinal Membranes

4.4.4Retinal Atrophy

4.4.5Other Macular Pathologies

4.4.6Myopia

4.4.7Active Uveitis

4.4.8Acquisition Artifacts

4.5OCT Angiography

4.6Conclusions

5.Illustrative Case Examples

Jullia A. Rosdahl, Ahmad A. Aref, Lawrence S. Geyman, Teresa C. Chen, Catherine M. Marando, Elli Park, Ki Ho Park, Yong Woo Kim, Hana L. Takusagawa, Atalie Carina Thompson, Andrew Williams, and Ian Conner

5.1Overview

5.2Early (Preperimetric) Glaucoma

5.3Mild-to-Moderate Glaucoma

5.4Severe Glaucoma

5.4.1Severe Stage Glaucoma, due to Significant Visual Field Constriction

5.5Glaucoma that Is Progressing

5.6Conclusions

6.Structure–Function Relationship

Felipe A. Medeiros

6.1Introduction

6.2Mapping Structural to Functional Loss in Glaucoma

6.2.1Does OCT Damage Precede Visual Field Loss in Glaucoma?

6.2.2How Are Structural Changes Linked to Functional Changes in Glaucoma?

7.Comparison of Common Devices

Lawrence S. Geyman and Ahmad A. Aref

7.1Retinal Nerve Fiber Layer Thickness

7.1.1Cirrus 6000 (Carl Zeiss Meditec AG, Jena, Germany)

7.1.2Spectralis (Heidelberg Engineering GmbH, Heidelberg, Germany)

7.1.3Avanti RTVue XR (Optovue, Inc., Fremont, CA, USA)

7.1.43D OCT (Topcon Corporation, Tokyo, Japan)

7.2Optic Nerve Head

7.2.1Cirrus 6000 (Carl Zeiss Meditec AG, Jena, Germany)

7.2.2Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany

7.2.3Avanti RTVue XR (Optovue, Inc., Fremont, CA, USA)

7.2.43D OCT (Topcon Corporation, Tokyo, Japan)

7.3Macula

7.3.1Cirrus 6000 (Carl Zeiss Meditec AG, Jena, Germany)

7.3.2Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany

7.3.3Avanti RTVue XR (Optovue, Inc., Fremont, CA, USA)

7.3.43D OCT (Topcon Corporation, Tokyo, Japan)

7.4Progression Analysi

7.4.1Cirrus 6000 (Carl Zeiss Meditec AG, Jena, Germany)

7.4.2Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany

7.4.3Avanti RTVue XR (Optovue, Inc., Fremont, CA, USA)

7.4.43D-OCT (Topcon Corporation, Tokyo, Japan)

8.Artifacts and Masqueraders

Teresa C. Chen, Catherine M. Marando, and Elli Park

8.1Incidence of Artifacts in OCT Imaging

8.2Etiologies of Peripapillary RNFL OCT Artifacts

8.2.1Artifacts from Errors in Scan Acquisition

8.2.2Artifacts in Boundary Segmentation

8.2.3Artifacts due to Ocular Pathology Unrelated to Glaucoma

8.2.4Artifacts due to Differences in OCT Machines

8.3Etiologies of ONH and Macula Artifacts

8.3.1Bruch’s Membrane Opening– Minimum Rim Width Artifacts

8.3.2Macular Asymmetry Analysis Artifacts

8.4OCT Diseases

8.4.1Red Disease

8.4.2Green Disease

8.5A Relevant Summary of OCT Artifacts for Technicians

8.6Future Directions

8.6.1Three-Dimensional Parameters

8.6.2OCT Angiography

9.Anterior Segment Optical Coherence Tomography in Glaucoma

Ying Han and Julius Oatts

9.1Introduction to Anterior- Segment OCT

9.2Different AS-OCT Modalities and Systems

9.3AS-OCT Identification of Anterior Segment Structures and Parameters

9.4AS-OCT in Different Glaucomatous Conditions

9.4.1Primary Angle Closure Suspect (PACS)

9.4.2Primary Angle Closure Glaucoma (PACG)

9.4.3AS-OCT Following Laser Peripheral Iridotomy (LPI)

9.4.4AS-OCT Following Dilation

9.4.5AS-OCT Following Lens Extraction

9.4.6Other Glaucomatous Conditions

9.5AS-OCT in Postoperative Care

9.6AS-OCT in Additional Glaucoma-Related Situations

9.7Conclusions

10.Special Considerations: OCT in Childhood Glaucoma

Tanya S. Glaser, Michael P. Kelly, Mays A. El-Dairi, and Sharon F. Freedman

10.1Introduction

10.2Handheld and Portable OCT Imaging Modalities

10.3Image Acquisition

10.3.1How OCT Can be Used during Examination Under Anesthesia

10.3.2Tabletop OCT for Children

10.3.3Structural Considerations for Image Acquisition

10.4Interpreting OCT Images in Pediatric Glaucoma

10.4.1Optical and Anatomic Considerations for Image Acquisition and Interpretation

10.4.2Comparing to a Normative Database

10.4.3OCT Changes in Childhood Glaucoma

10.4.4Postoperative Changes in OCT

10.5Pitfalls and Masqueraders of Pediatric Glaucoma

10.6Imaging Guidelines and Recommended Frequency of Imaging

11.Special Considerations: High Refractive Errors

Ki Ho Park and Yong Woo Kim

11.1Introduction

11.2Technical Issues of OCT that Need to be Considered in High Myopia

11.2.1Scan-Circle Size: Ocular Magnification Error

11.2.2Scan-Circle Size: Pathologies Influencing the Scan Circle

11.2.3Scan-Circle Location: Effect of Major Vessels in Tilted Discs

11.2.4Normative Database

11.2.5Segmentation Errors

11.3Glaucoma Diagnosis in High Myopia

11.3.1Macular Parameters for Glaucoma Diagnosis

11.3.2Neuroretinal Rim Parameters for Glaucoma Diagnosis

11.3.3All at One Glance: 3D Wide-Field Map in SS-OCT

12.Future Directions: Optical Coherence Tomography Angiography for Glaucoma

Darrell WuDunn

12.1Introduction

12.1.1The Role of Ocular Blood Flow in Glaucoma

12.1.2Optical Coherence Tomography Angiography Technology

12.2OCTA of the Optic Nerve Head and Peripapillary Microvasculature

12.2.1OCTA of the Optic Nerve Head Microvasculature in Normal Eyes

12.2.2OCTA of the Optic Nerve and Peripapillary Microvasculature in Glaucoma

12.3OCTA of the Macular Microvasculature

12.3.1OCTA of the Normal Macular Microvasculature

12.3.2OCTA of Macular Microvasculature in Glaucoma

12.4OCTA of the Choroid

12.4.1OCTA of the Normal Choroid

12.4.2OCTA of the Choroid in Glaucoma

12.5OCTA in the Future

13.Future Directions: Swept-Source OCT for Glaucoma

Hana L. Takusagawa and Elizabeth Ann Zane Cretara

13.1Introduction

13.2Imaging of Intraocular Structures Using SS-OCT in Glaucoma

13.2.1Anterior Segment Application of SS-OCT in Glaucoma

13.2.2Analysis of Macular and Peripapillary Retina by SS-OCT

13.2.3Choroidal Application of SS-OCT in Glaucoma

13.2.4Optic Nerve Head Application of SS-OCT in Glaucoma

13.2.5Lamina Cribrosa Application of SS-OCT in Glaucoma

13.3Future Research in SS-OCT for Evaluation of Glaucoma

13.4Conclusions

14.Future Directions: Artificial Intelligence Applications

Atalie Carina Thompson

14.1Introduction

14.2Artificial Intelligence

14.2.1Development of a Deep Learning Algorithm

14.2.2Deep Learning Algorithms to Diagnose Glaucoma on SD-OCT

14.2.3Deep Learning Algorithms Trained to Assess Color Fundus Photos Using SD-OCT

14.2.4Limitations

14.2.5Future Directions

Index

Preface

Every time I look at an optical coherence tomography (OCT) image, I am struck by the detail and I marvel at our ability to see neuronal layers in vivo and in such a way that it can impact people’s vision, and really their lives. What a tool we have, and what a privilege to assemble a book on OCT for glaucoma with experts and leaders in glaucoma care.

I remember the first time I saw an OCT image, as a resident at the Massachusetts Eye and Ear Infirmary in Boston; it was a timedomain image, quite hazy by today’s spectral domain standards, and Dr Simmons Lessellwas sharing his amazement at the technology. Dr Teresa C. Chen, one of the contributors to this book, was doing seminal work on OCT and other computerized imaging modalities; she was my clinical mentor when I was a resident. Boston, Massachusetts, as described by Dr Joel S. Schuman, is really the birthplace of OCT, and I love his chapter describing its inception and history. My personal appreciation for OCT truly developed during my glaucoma fellowship at the Duke Eye Center; the Duke Glaucoma Service is filled to the brim with outstanding teachers, but Dr Sanjay Asrani was and continues to be our OCT champion.

The importance and power of OCT in glaucoma care is really a global endeavor, with almost 10,000 citations on PubMed for “OCT Glaucoma” at the writing of this book. Our goal with this book is to provide a practical guide, especially for trainees and doctors new to glaucoma, but with pearls, examples, and novel topics such that even those who are more experienced would deepen their knowledge. With this in mind, I reached out to colleagues who had the expertise and skill, people I knew personally such as Drs Teresa C. Chen and Felipe A. Medeiros, and people I knewonly by reputation such as Dr Ki Ho Park; thankfully for all of us, all of the contributors kindly agreed. It has been such a privilege and delight to include their work in this book, including the cover image from RyanMcNabb, PhD, and AnthonyKuo, MD, at the Duke Eye Center. I have learned so much by bringing this book toyou, and I hope that you find it most useful in caring for your patients.

Jullia A. Rosdahl, MD, PhD

Acknowledgments

We wish to acknowledge all who have made this book possible, from the editorial team at Thieme, who provided the opportunity to create this book and have so kindly shepherded the process, to those teachers and clinicians and colleagues who have taught us what we know about optical coherence tomography. Most importantly, though, we are grateful to our patients, who allow us into their lives and eyes and who are the reasonwe wrote this book and the reason our readers are reading it, in the hopes of making those lives and eyes better.

Jullia A. Rosdahl, MD, PhD

Contributors

Ahmad A. Aref, MD, MBA

Associate Professor and Vice-Chair for Clinical Affairs

University of Illinois at Chicago College of Medicine

Illinois Eye & Ear Infirmary

Chicago, Illinois, USA

Ian Conner, MD, PhD

Assistant Professor

Department of Ophthalmology

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, USA

Elizabeth Ann Zane Cretara, MD

Assistant Professor of Ophthalmology

University of New Mexico

Albuquerque, New Mexico, USA

Rachel A. Downes, MD

Department of Ophthalmology

NewYorkUniversity (NYU) Grossman School of Medicine

New York, New York, USA

Mays A. El-Dairi, MD

Associate Professor

Department of Ophthalmology

Duke University School of Medicine

Durham, North Carolina, USA

Sharon F. Freedman, MD

Professor

Departments of Ophthalmology and Pediatrics

Duke University School of Medicine

Durham, North Carolina, USA

Lawrence S. Geyman, MD

University of Illinois at Chicago College of Medicine

Illinois Eye & Ear Infirmary

Chicago, Illinois, USA

Tanya S. Glaser, MD

Assistant Professor

Department of Ophthalmology

Duke University School of Medicine

Durham, North Carolina, USA

Divakar Gupta, MD, MMCi

Assistant Professor

Department of Ophthalmology

Duke University School of Medicine

Durham, North Carolina, USA

Ying Han, MD, PhD

Professor of Ophthalmology

Department of Ophthalmology

University of California at San Francisco

San Francisco, California, USA

Michael P. Kelly, FOPS

Department of Ophthalmology

Duke University School of Medicine

Durham, North Carolina, USA

Yong Woo Kim, MD, PhD

Assistant Professor

Department of Ophthalmology

Seoul National University Hospital (SNUH)

Seoul, South Korea

Catherine M. Marando, MD

Massachusetts Eye and Ear Infirmary

Harvard Medical School

Boston, Massachusetts, USA

Felipe A. Medeiros, MD, PhD

Joseph AC Wadsworth Distinguished Professor of Ophthalmology

Professor of Electrical and Computer Engineering

Duke University School of Medicine

Durham, North Carolina, USA

Julius Oatts, MD, MHS

Assistant Professor

Department of Ophthalmology

University of California at San Francisco

San Francisco, California, USA

Elli Park, MD

Boston University School of Medicine

Boston, Massachusetts, USA

Ki Ho Park, MD, PhD

Professor and Chair

Department of Ophthalmology

Seoul National University Hospital (SNUH)

Seoul, South Korea

Jullia A. Rosdahl, MD, PhD

Associate Professor of Ophthalmology

Department of Ophthalmology

Duke University School of Medicine

Durham, North Carolina, USA

Joel S. Schuman, MD, FACS

Elaine Langone Professor & Vice Chair for Ophthalmology Research

NYU Langone Health, NYU Grossman School of Medicine

New York, New York, USA

Hana L. Takusagawa, MD

Affiliate Associate Professor of Ophthalmology

Oregon Health & Science University, and Eugene VA Health Care Center

Eugene, Oregon, USA

Atalie Carina Thompson, MD, MPH

Assistant Professor

Department of Ophthalmology

Wake Forest School of Medicine

Winston-Salem, North Carolina, USA

Andrew Williams, MD

Assistant Professor

Department of Ophthalmology

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, USA

Darrell WuDunn, MD, PhD

Professor and Chair

Department of Ophthalmology

University of Florida College of Medicine – Jacksonville

Jacksonville, Florida, USA

1 Introduction: Practical Guide, OCT for Glaucoma

Jullia A. Rosdahl

Summary

This is an introduction with a reader’s guide for our book on optical coherence tomography (OCT) for glaucoma. OCT is an invaluable tool for the diagnosis and management of glaucoma. This textbook provides a practical guide for the use of OCT in the clinical care of glaucoma patients: Including background on the development of OCT; in-depth descriptions of OCT of the optic nerve and retina in glaucoma patients, with chapters dedicated to illustrative case examples, artifacts, structure–function correlations, comparison of common devices, and anterior segment OCT; special considerations for OCT for childhood glaucomas and patients with high refractive errors; and future directions, namely, OCT angiography, swept-source OCT, and artificial intelligence. This introductory chapter also includes suggestions on how to use this guide depending on the reader’s background and interests.

Keywords: optical coherence tomography, glaucoma, readers guide, optic nerve, retina, retinal nerve fiber layer

1.1 Introduction

Glaucoma is a group of eye diseases characterized by the loss of neural tissue at the optic nerve head, with “cupping” first visualized in the 1800s with Dr Helmholtz’ ophthalmoscope, and the associated loss of peripheral vision. Over the last several decades, advances in computerized imaging have enabled doctors to visualize and quantify the optic nerve tissue to an astounding degree. In the 2000s, optical coherence tomography (OCT) became an integral part of the care of glaucoma patients, from screening glaucoma suspects, to the diagnosis of glaucoma, and for following patients with glaucoma to assess for progression of the disease.

The purpose of this guide is to serve as both a reference for understanding how OCT is used for the diagnosis and treatment of glaucoma, as well as a practical guide for “everyday” use to help doctors use this technology with greater skill and confidence.

1.2 Overview of the Guide

Summaries of each chapter provide an overview of the guide.

1.2.1 Development of OCT

OCT is a now a fixture in eye clinics around the world but only came to exist less than 30 years ago. Following decades of research on how evolving laser technologies could have clinical applications, in 1991 the first OCT captured an image of the eye. The history of OCT captured an research and development is discussed by summarizing the science, sharing insights on the economic risks and successes, and highlighting clinical impacts.1

1.2.2 OCT of the Optic Nerve

Assessing the optic nerve is critical in the evaluation of glaucoma patients. Computerized imaging technologies such as OCT provide quantitative measurements of optic nerve head parameters, including the retinal nerve fiber layer (RNFL). A systematic approach to OCT interpretation is discussed, including attention to potential limitations and artifacts.2

1.2.3 OCT of the Macula

Retinal imaging of the macula, with attention to the retinal ganglion cell layer, inner plexiform layer, and nerve fiber layer, can supplement the information obtained with the peripapillary RNFL. Applications of macular imaging for glaucoma, advantages and disadvantages, and pitfalls to avoid are discussed.3

1.2.4 Illustrative Case Examples

Case examples illustrate the use of OCT in glaucoma diagnosis and management. Cases spanning the spectrum of glaucoma severity are discussed, from glaucoma suspect, early to advanced glaucoma, as well as examples of glaucomatous progression. Characteristic findings from other chapters (3, 4, 6, and 7 in particular) are reinforced.4

1.2.5 Structure–Function Relationship

The relationship between structure and function of the optic nerve is the basis of our pathophysiological understanding of glaucoma. This chapter describes structure–function mapping, the temporal relationship between structural damage and functional defects, and how structural changes are linked to functional changes in glaucoma.5

1.2.6 Comparison of Common Devices

OCT devices produced by several manufacturers are available for clinical use. Differences in imaging specifications, analysis techniques, normative databases, and diagnostic capabilities are discussed for the Cirrus 6000 (Carl Zeiss Meditec AG, Jena, Germany), Spectralis (Heidelberg Engineering GmbH, Heidelberg, Germany), Avanti RTVue XR (Optovue, Inc., Fremont, CA, USA), and 3D OCT (Topcon Corporation, Tokyo, Japan).6

1.2.7 Artifacts and Masqueraders

All OCT machines have artifacts. Critical assessment for artifacts and attention to ocular pathology unrelated to glaucoma are discussed, with relevant clinical examples of “red” and “green” “OCT diseases” and future directions.7

1.2.8 Anterior Segment OCT in Glaucoma

OCT of the anterior segment provides noninvasive, high-resolution, cross-sectional images of the anterior segment structures. This technology can provide a useful supplement for the diagnosis and management of glaucomas, particularly primary angle closure disease.8

1.2.9 Special Considerations: OCT in Childhood Glaucoma

OCT is an important tool for the management of childhood glaucoma, especially since children with glaucoma may not be able to perform visual field testing. Special considerations for the use of OCT in children are discussed, including how to acquire OCT images and suggestions for interpreting OCT images from pediatric eyes.9

1.2.10 Special Considerations: High Refractive Errors

Special care should be taken when interpreting OCT scans in eyes with high refractive errors, given the rising prevalence of myopia and that myopia is a risk factor for glaucoma. Causes of OCT scan errors are discussed as well as newer parameters to improve the accuracy of glaucoma diagnosis in myopic eyes.10

1.2.11 Future Directions: OCT Angiography for Glaucoma

OCT angiography is an emerging technology giving detailed images of the microvasculature of the optic nerve and retina. Although its role in the diagnosis and management of glaucoma is still unclear, growing evidence shows good correlation between OCT angiography of the optic nerve and surrounding structures, and tissue loss and visual field loss from glaucoma.11

1.2.12 Future Directions: Swept-source OCT for Glaucoma

Swept-source OCT is an emerging technology using a tunable, longer wave of light than spectral domain OCT, allowing for high resolution with improved range of depth and increased scan speed. How this new technology fits in the framework of clinical glaucoma care is not yet clear, but current research is investigating the role of swept-source OCT in imaging the optic nerve and macula, as well as the anterior segment and choroid, for glaucoma.12

1.2.13 Future Directions: Artificial Intelligence Applications

Artificial intelligence refers to the development of computer programs to automate tasks to mimic human behavior. Deep learning is a type of artificial intelligence and uses a neural network to learn from a training dataset; these algorithms can process complex data such as ophthalmic images. Although research is still needed to study the performance of deep learning algorithms in real-world settings, these algorithms can be trained to distinguish between eyes with glaucoma and control eyes on OCT.13

1.3 How to Use the Guide

Depending on the background of the reader, this book can be approached in a variety of ways. Certainly, it can be read starting from Chapter 2 through Chapter 14, as a comprehensive summary of how OCT can be used for the care of glaucoma patients, which is recommended for trainees and doctors new to OCT. Readers with some general knowledge and experience with OCT may find individual chapters to be more useful; and starting with Chapter 5 to review the Illustrative Cases may help to reveal knowledge gaps to be filled by the reading specific chapters. Readers with an already significant background in OCT will likely find the chapters on Anterior Segment OCT (Chapter 9), special considerations (Chapters 10 and 11), and future directions (Chapters 12, 13, and Chapter 14) most useful. Anyone with an interest in the history of medicine will find Chapter 2 to have unique insights into the development of this technology.

1.4 Conclusion

This book is designed to be a practical guide, summarizing the clinical utility of the OCT technology, covering the basics and more advanced analyses, common clinical scenarios as well as more rare situations such as pediatric cases and high refractive errors, and aspects of OCT that are on the cutting edge such as OCT angiography, swept-source OCT, and artificial intelligence. We hope this guide helps the reader to use OCT with greater skill and confidence to care for their patients with glaucoma.

References

[1]Schuman JS. Spectral domain optical coherence tomography for glaucoma (an AOS thesis). Trans Am Ophthalmol Soc. 2008; 106:426–458

[2]Gracitelli CPB, Abe RY, Tatham AJ, et al. Association between progressive retinal nerve fiber layer loss and longitudinal change in quality of life in glaucoma. JAMA Ophthalmol. 2015; 133(4):384–390

[3]Tan O, Chopra V, Lu AT, et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009; 116(12):2305–14.e1, 2

[4]American Academy of Ophthalmology Preferred Practice Patterns. Primary Open Angle Glaucoma PPP, November 2015. https://www.aao.org/preferred-practice-pattern/primaryopen-angle-glaucoma-ppp-2015

[5]Medeiros FA, Zangwill LM, Bowd C, Mansouri K, Weinreb RN. The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change. Invest Ophthalmol Vis Sci. 2012; 53 (11):6939–6946

[6]Aref AA, Rosdahl JA. Optical coherence tomography in glaucoma diagnosis. 2019 Focal Points Collection. Volume XXXVII, Number 11. American Academy of Ophthalmology; November 2019

[7]Chen TC, Hoguet A, Junk AK, et al. Spectral-domain OCT: helping the clinician diagnose glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology. 2018; 125(11):1817–1827

[8]Leung CK,Weinreb RN. Anterior chamber angle imaging with optical coherence tomography. Eye (Lond). 2011; 25(3):261–267

[9]Hess DB, Asrani SG, Bhide MG, Enyedi LB, Stinnett SS, Freedman SF. Macular and retinal nerve fiber layer analysis of normal and glaucomatous eyes in children using optical coherence tomography. Am J Ophthalmol. 2005; 139(3):509–517

[10]Kim YW, Park KH. Diagnostic accuracy of three-dimensional neuroretinal rim thickness for differentiation of myopic glaucoma from myopia. Invest Ophthalmol Vis Sci. 2018; 59 (8):3655–3666

[11]Miguel AIM, Silva AB, Azevedo LF. Diagnostic performance of optical coherence tomography angiography in glaucoma: a systematic review and meta-analysis. Br J Ophthalmol. 2019; 103(11):1677–1684

[12]Takusagawa HL, Hoguet A, Junk AK, Nouri-Mahdavi K, Radhakrishnan S, Chen TC. Swept-source OCT for evaluating the lamina cribrosa: a report by the American Academy of Ophthalmology. Ophthalmology. 2019; 126(9):1315–1323

[13]Thompson AC, Jammal AA, Berchuck SI, Mariottoni EB, Medeiros FA. Assessment of a segmentation-free deep learning algorithm for diagnosing glaucoma from optical coherence tomography scans. JAMA Ophthalmol. 2020; 138 (4):333–339

2 Development of Optical Coherence Tomography

Joel S. Schuman and Rachel A. Downes

Summary

Optical coherence tomography (OCT), now a fixture in eye clinics around the world, was developed less 30 years ago. Following decades of research on potential clinical applications for evolving laser technologies, a prototype instrument captured the first OCT images in 1991. A mere 5 years later, a global medical device company launched the first commercial OCT instrument. OCT has since flourished, producing a strong return on investment for the governments and corporations that funded its creation and making an unmeasurable impact on patients’ lives in not only ophthalmology but also in an array of other medical fields. OCT is the product of a resolute group of scientists, engineers, physicians, students, and businesspeople, and its story underscores the importance of persistence and collaboration. This chapter reviews the history of OCT research and development: briefly summarizing the relevant science, providing insight into the economic risks and ultimate successes of key players, and highlighting the profound impact on patient lives.

Keywords: OCT, optical coherence tomography, femtosecond laser, interferometry, Fourier transform, OCT-A, OCT-angiography

2.1 Introduction

Less than three decades have passed since the publication of the first optical coherence tomography (OCT) images of a retina.1 In that time, OCT has evolved from a nascent technology with many skeptics to an integral component of eye care around the world. A 2011 publication estimated the global volume of OCT to be around 30 million ophthalmic images annually.2 This figure was on par with the rate of magnetic resonance imaging (MRI) at the time.2 Given that 9 years have passed since that analysis, and in light of the development of improved OCT technology and broadened applications of OCT in the interim, OCT volume is likely dramatically higher today. This chapter chronicles the development of OCT, providing context for its ascent and highlighting the individuals and ideas that made it possible (Fig. 2‑1).

Fig. 2.1 Presentation of the António Champalimaud Vision Award in 2012 to James Fujimoto, David Huang, Carmen A. Puliafito, Joel S. Schuman, and Eric Swanson. Founded in 2005 in Lisbon, Portugal, the Champalimaud Foundation focuses on biomedical research and discovery with a central mission of improving the health and well-being of mankind. The Vision Award, first given in 2007, highlights contributions to the improvement and preservation of sight for people around the world. The Vision Award recognizes outstanding contributions to vision science in even-numbered years and exceptional work in alleviating visual problems, with a particular focus on developing nations, in odd-numbered years. In 2012, the inventors of optical coherence tomography (OCT) were honored in conjunction with David Williams, who was recognized for applying adaptive optics to the eye.

2.2 Setting the Stage: Lasers Meet Medicine

2.2.1 Light in Flight

In 1971, Michael Duguay, then a researcher at AT&T Bell Laboratories, first proposed that the capture of echoes of light or “light in flight” could yield useful data about the composition of biological tissues.3,4 With the use of a laser-activated Kerr shutter, he proposed a method of freezing the motion of light in order to noninvasively image tissues.3,4 In the same year, Eric Ippen left Bell Labs for Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) where doctoral student James Fujimoto soon joined him.5 The pair and their collaborators began the hard work of developing a practical application for Duguay’s theoretical proposal, and the work that would ultimately culminate in the invention of OCT began.5

By the 1980s, this group had their sights on skin and skin diseases as the first target for applying femtosecond laser technology to clinical medicine.5 The researchers soon found that skin yielded a high degree of optical scattering in response to laser light and thus shifted their focus to the eye.5 With transparent structures throughout its length—from cornea to lens to vitreous to retina—the eye proved to be the optimal test case for developing a practical medical application for capturing “light in flight.”5

Ex vivo bovine and rabbit eyes were the subject of early work in this arena, and experiments on these animal models provided useful insights.5 The earliest experiments utilized laser light with a wavelength of 625 nanometers (nm), resulting in scans with a sensitivity of −70 decibels (dB).5 Later work would find that longer wavelengths were more effective in reducing attenuation from optical scattering, thus improving sensitivity.5 For context, through this change among others, modern OCT machines have achieved three log units better sensitivity than those early scans.5

The original experiments sought to “see inside” of ophthalmic tissues through nonlinear cross-correlation, in which the instrument produced two beams of light: one directed at the tissue and one reference beam with a variable time delay.5,6 By assessing the varying echo profiles and time delays of these beams (e.g., by analyzing and comparing the backscattered and backreflected beams of light), the prototype devices produced inference patterns related to the structure of the tissue, culminating in the generation of an axial scan (A-scan).5,6 As early as this initial work, there was a focus on applying the technology to assess pathological states.5

2.2.2 Interferometry

In the late 1980s, superluminescent diode interferometers replaced femtosecond lasers as the primary light source in OCT research.5 Interferometry hastened the development of a feasible clinical product because it enabled the creation of instruments that were less expensive yet offered improved sensitivity.5 Interferometry had its roots in the work of Sir Isaac Newton.5,7 Its first real-world application was in the telecommunications industry, in which this technology improved the transmission of optical data.5,7 Early OCT work used Newton’s classic technique of low-coherence or white-light interferometry.7

Interferometers worked by comparing an optical beam with a reference beam.7 First, a laser source emitted a light, which a partially reflecting mirror called a beamsplitter divided into two perpendicular beams: one beam that would travel into the tissue of interest (e.g., the eye; this was the optical beam), and a reference beam.7 A mirror at a known distance reflected the reference beam such that it traveled back to the beamsplitter at a known time delay (e.g., it served as a time reference).7 At the beamsplitter, this reference beam interfered with the optical beam after it was backreflected and backscattered by the tissue.7 Upon returning from the eye, the optical beam had multiple echoes resulting from the structural variations among the tissues within the eye.7 In other words, intraocular structures had variable microscopic composition and were located at different distances from the light source such that each tissue type reflected and scattered the optical beam differently.7 Thus, the variable echoes of light within the optical beam corresponded to microstructural nuances within the eye.7 Ultimately, a detector compared the reflection and scattering of both beams, measuring the interference or correlation between them.7 This method of time domain detection enabled ultrahigh-resolution time and distance measurements and eventually gave rise to the earliest commercial OCT instruments.5,7

Fercher and his collaborators at Medical University of Vienna (Vienna, Austria) published the first application of interferometry in medicine in 1988, measuring the axial length of in vivo human eyes; their results correlated with the acoustically measured axial lengths within 0.03 mm.8 Despite its advantages in precision and speed, interferometry was not a practical medical tool.5 Researchers and subjects struggled with its sensitivity to movement and vibration and the fact that bulk optics required very precise alignment in order to avoid signal loss.5 In the US, John Apostolopoulous, then an undergraduate student at MIT, pioneered much of the early work in interferometry.5 His experiments proposed a technique similar to nonlinear cross-correlation, but he substituted an inexpensive low-coherence diode laser for the femtosecond lasers used in the latter technique.5 Apostolopoulous’s experiments did not have sufficient sensitivity for generating scans of the eye, but he described a theoretical means for doing so in his unpublished 1989 bachelor’s thesis.5

2.2.3 The Pivotal Role of Collaboration

The developers of OCT worked at an astonishingly fast pace to translate the “light in flight” principle to meaningful clinical impact. The diversity in background and level of training among those involved played a key role in facilitating this expeditious development. The team included a range of scientists from undergraduates like Apostolopoulous to senior principal investigators as well as the full spectrum of medical personnel from preresidency fellows to attending physicians.5 In 1990, Eric Swanson, an engineer at MIT’s Lincoln Laboratories, joined the mix.5 In contrast to many academic enterprises, the emphasis of the work at Lincoln Labs is deeply pragmatic; there is a substantial focus on Department of Defense technology and advanced engineering with an emphasis on feasibility and implementation.5 Swanson worked on intersatellite optical communications and fiber optics networking.5 Compared to the bulk optics previously used in interferometry, fiber optics mitigated alignment issues and enabled use in catheters or endoscopes.5 The latter of these features enabled OCT development work in intravascular applications, including measurement of coronary artery plaques.5 Swanson brought his content expertise and the Lincoln Labs implementation-oriented mindset to the OCT effort.5 With the application of fiber optical elements and other contributions from Swanson, the feasibility of OCT improved dramatically: imaging speed became 100 times faster, the design became more compact (the prototype instrument that initially required a 1-square meter table could then sit on a platform just 19 inches wide), and the patient interface became more flexible.5

2.3 Optical Coherence Tomography: The Debut

2.3.1 OCT versus Ultrasound

Ultrasound (US) existed long before OCT, but both technologies hinged on strikingly similar principles. Whereas ultrasound generated images through the measurement of the time delay and intensity of backreflected and backscattered echoes of soundwaves, OCT sought to achieve the same with echoes of light waves.7 Each technology had a set of advantages and drawbacks that made it most suitable for measurement of different biologic structures.7 US required direct contact of the probe to the tissue it measured as well as the use of gel in order to couple the transmitter–receiver and the tissue, in order to transmit sound waves appropriately; OCT did not require physical coupling or the use of a coupling agent.7 Although these features of US did not inhibit its application in imaging most structures of the body (e.g., intraabdominal organs), they made it less attractive for imaging the fine structures of the eye.7 US waves had a sufficiently low frequency to propagate to the deep structures of the body, but this came with the trade-off of poorer image resolution.7 In contrast, the high frequency light waves emitted in OCT precluded penetration through most opaque biological tissues due to the high degree of scattering and absorption but could achieve much finer resolution.7 This principle limited OCT’s use to structures that were “optically accessible” (i.e., the optically clear components of the eye) and some structures in turbid media that could be accessed via catheters or endoscopes (e.g., coronary plaques).7 Despite these drawbacks compared to US, OCT emerged as a superior technology for imaging of the eye’s intricate microstructure, not only because an instrument that did not require contact with the eye was more tolerable for patients, but also because the use of shorter wavelength light permitted the collection of data that highlighted details as fine as the intricate layers of the retina with a much higher axial resolution than US.7

2.3.2 How OCT Works (Fig. 2‑2)

Starting from its earliest prototypes, OCT leveraged the intrinsic differences between tissues within the eye to generate detailed images.7 Various tissue-dependent phenomena occurred when the light beam from OCT instruments passed through the structures of the eye. For one, tissues could transmit light; that is, light could continue propagating into deeper tissue layers and structures, much like sound waves in US propagate from superficial skin, subcutaneous tissue, and fascia to the deep viscera.7 Second, tissues could absorb light.7 Tissues that absorbed light, such as those containing melanin or hemoglobin, effectively removed certain wavelengths from the beam.7 This principle explained why the retinal pigment epithelium, a melanin-containing layer, appeared distinctly different in OCT images than microstructures that contained no or different pigments.7 Third, tissues could reflect light back toward the receiver.7 Reflection occurred at the borders of tissues or substances with different indices of refraction, such as at the air-corneal interface or vitreo-retinal interface.7 Finally, tissues could scatter light; scattering occurred due to compositional variations within cells, often due to the presence of major intracellular components including nuclei and other organelles.7 Because of this principle, OCT distinguished the layers of the retina that were composed of organelle-laden cell bodies from those that contained mostly axons; the composition of the latter included primarily cytoplasm and cell membranes with fewer organelles, thus resulting in a lesser degree of scattering when the incident beam met that layer.7 Of note, when tissues scattered light, it propagated in multiple directions; the portion of that scattered light that propagated in the reverse direction of the incident beam was called backscattered light.7 Since OCT instruments only detected light along the same axis as the incident beam, they only detected the backscattered portion of all scattered light.7 Due to these principles, tissues with higher degrees of absorption appeared darker in OCT images, and those with a higher degree of scattering (and thus a more substantial amount of backscattered light) appeared brighter.7

Fig. 2.2 Schematics of optical coherence tomography (OCT). Schematic diagrams are shown of time-domain OCT (TD-OCT), spectral domain OCT (SD-OCT), swept-source OCT (SS-OCT), and the original Michelson interferometer (MI) optical setup upon which OCT is based. A laser source emits a light which is divided into two perpendicular beams by a beamsplitter: one beam that travels into the eye (the optical beam) and the reference beam. A mirror at a known distance reflects the reference beam such that it travels back to the beamsplitter at a known time delay (a time reference). This reference beam interfers with the optical beam after it is backreflected and backscattered by the tissue. The returning optical beam has multiple echoes resulting from the structural variations among the tissues within the eye. The detector compares the reflection and scattering of both beams, measuring the interference or correlation between them. (This figure is taken from an article entitled, “Spectral Domain Optical Coherence Tomography for Glaucoma (An AOS Thesis)” in the Trans Am Ophthalmol Soc 2008;106:426–458 and republished with permission of the American Ophthalmological Society.)

These principles also explained why OCT was not optimal for imaging deep structures of the body.7 Due to the strong absorption and scattering of light incident upon skin, the penetration of the beam was too shallow to reach deeper structures.7 That is, when a tissue absorbed or scattered light too strongly, it effectively cast a shadow over deeper structures and tissues.7 On the other hand, the primarily transparent structures of the eye transmitted most light and demonstrated a very low degree of reflection, absorption, and scattering.7 OCT was developed with sufficient sensitivity to detect the very minor differences among layers that were all weakly absorptive, backreflective, and backscattering.7

Even in its earliest iterations, OCT produced images with microstructural precision on par with histological biopsies. Though the results appeared similar to histologic samples (and the results of early OCT scans were validated through histology), the mechanism of OCT was entirely different.7 Whereas histology relied on external markers of cellular or subcellular components to differentiate structures, OCT leveraged intrinsic features.7

2.3.3 The First OCT Images

In the late 1980s, one of the authors of this chapter (Joel S. Schuman) became involved in the OCT development effort as a fellow at Massachusetts Eye and Ear Infirmary/Harvard Medical School.9 He proposed measurements of the deeper structures of the eye (e.g., the retina and its intricate layers which, though all transparent, were optically distinct) via optical coherence domain reflectometry.9 After the group’s work validated the utility of optical coherence domain reflectometry for measuring structures throughout the eye via individual A-scans, another student working on the project, David Huang, then a Health Sciences Technology Student at Harvard Medical School and Massachusetts Institute of Technology, had the insight that the clear next step was transitioning from multiple A-scans to a two-dimensional B-scan analogous to B-mode ultrasound.9 This transition marked the invention of OCT; the inventors named the technology optical coherence tomography and published the first OCT images in Science.1,9

The 1991 Science paper demonstrated features of postmortem, in vitro human retina with detailed depictions of the optic nerve head and nerve fiber layer.1 The paper also featured images of a fibrocalcific plaque in a postmortem, in vivo human coronary artery specimen.1 To generate the images, multiple A-scans were combined using a logarithmic false color or gray scale.1 Following the generation of these images, the tissues underwent histologic evaluation, which recapitulated the structural findings and validated the technique.1 This publication was not only scientifically interesting but also demonstrated promising clinical applications of OCT in the fields of ophthalmology and cardiology. Of note, a 1994 Japanese patent described a similar concept, though there was no corresponding publication in the literature to catalogue the work of that group.10

At this point, the multidisciplinary team of scientists, engineers, clinicians, and students who contributed to OCT’s development saw the culmination of their efforts in the publication of the first OCT images. The contributions of this team, and Swanson’s engineering expertise, yielded a sound hardware platform for OCT.9 However, the software was not yet adequate for imaging in vivo specimens.9

2.3.4 Providing Clinical Value

The resolution of the first axial images from ophthalmic OCT was approximately 10 to 20 μm, a figure that bested standard B-mode US by 10 to 20 times or more.11 Compared to preceding technologies like US, this impressive resolution was a major component of OCT’s competitive advantage.5 By providing fine detail about the microstructure of a patient’s eye, OCT could inform treatment decisions in diseases where subtle changes were clinically meaningful, such as macular degeneration, glaucoma, and diabetic retinopathy.5 Throughout the mid-1990s, Schuman and Puliafito led a prodigious collection of data at New England Eye Center in order to clinically validate and provide normative data for OCT.5 With the support of NIH funding (Fujimoto and Schuman, PIs), the group collected OCT images for more than 5,000 patients, with a particular focus on glaucoma and diseases of the retina.5 In 1995, Puliafito et al published the first OCT atlas, which provided a framework for clinicians to interpret OCT for an array of retinal pathologies.12