OCT and Imaging in Central Nervous System Diseases: The Eye as a Window to the Brain [2nd ed. 2020] 978-3-030-26268-6, 978-3-030-26269-3

Table of contents :
Front Matter ....Pages i-x
Introduction: Retina Imaging—Past and Present (Andrzej Grzybowski, Piero Barboni)....Pages 1-5
OCT Technique: Past, Present and Future (Tigran Kostanyan, Maria de los Angeles Ramos-Cadena, Gadi Wollstein, Joel S. Schuman)....Pages 7-31
The APOSTEL Recommendations (Aykut Aytulun, Andrés Cruz-Herranz, Lisanne Balk, Alexander U. Brandt, Philipp Albrecht)....Pages 33-39
OCT Angiography: Guidelines for Analysis and Interpretation (Enrico Borrelli, Srinivas R. Sadda, Akihito Uji, Giuseppe Querques)....Pages 41-54
Seeing the Brain Through the Eye: What Is Next for Neuroimaging and Neurology Applications (Delia Cabrera DeBuc, Gábor Márk Somfai, Gabriella Szatmáry, Edmund Arthur, Jorge A. Jimenez, Carlos Mendoza-Santiesteban et al.)....Pages 55-82
Advances in Retinal Imaging: Retinal Amyloid Imaging (Maya Koronyo-Hamaoui, Jonah Doustar, Mia Oviatt, Keith L. Black, Yosef Koronyo)....Pages 83-122
Advances in Retinal Imaging: Real-Time Imaging of Single Neuronal Cell Apoptosis (DARC) (Timothy E. Yap, Maja Szymanska, M. Francesca Cordeiro)....Pages 123-138
Retinal Oximetry in Central Nervous System Diseases (Anna Bryndis Einarsdottir, Olof Birna Olafsdottir, Sveinn Hakon Hardarson)....Pages 139-145
Optical Coherence Tomography and Optic Nerve Edema (Laurel N. Vuong, Thomas R. Hedges III)....Pages 147-167
OCT and Compressive Optic Neuropathy (Mário Luiz Ribeiro Monteiro)....Pages 169-194
OCT and Multiple Sclerosis (James V. M. Hanson, Carla A. Wicki, Praveena Manogaran, Axel Petzold, Sven Schippling)....Pages 195-233
OCT in Parkinson’s Disease and Related Disorders (Ivan Bodis-Wollner, Shahnaz Miri, Sofya Glazman, Eric M. Shrier, Reem Deeb)....Pages 235-262
Optical Coherence Tomography in Alzheimer’s Disease (Gianluca Coppola, Vincenzo Parisi, Gianluca Manni, Francesco Pierelli, Alfredo A. Sadun)....Pages 263-288
Friedreich’s Ataxia and More: Optical Coherence Tomography Findings in Rare Neurological Syndromes (Chiara La Morgia, Michele Carbonelli)....Pages 289-316
Other Neurological Disorders: Migraine, Neurosarcoidosis, Schizophrenia, Obstructive Sleep Apnea-Hypopnea Syndrome and Bipolar Disorder (Francisco J. Ascaso, Javier Mateo, Laura Cabezón, Paula Casas, Andrzej Grzybowski)....Pages 317-342
Hereditary Optic Neuropathies (Piero Barboni, Nicole Balducci, Alfredo A. Sadun)....Pages 343-364
Trans Neuronal Retrograde Degeneration to OCT in Central Nervous System Diseases (Bernardo F. Sánchez-Dalmau, Anna Camós-Carreras, Ruben Torres-Torres, Johannes Keller, Laura Sanchez-Vela, Elena H. Martínez-Lapiscina et al.)....Pages 365-374
OCT in Toxic and Nutritional Optic Neuropathies (Andrzej Grzybowski, Iwona Obuchowska, Carl Arndt)....Pages 375-400
Animal Models in Neuro Ophthalmology (Eduardo M. Normando, M. Francesca Cordeiro)....Pages 401-426
OCT in Glaucoma (Harsha Rao, Kaweh Mansouri, Robert Weinreb)....Pages 427-472
OCT in Amblyopia (Paolo Nucci, Andrea Lembo, Stefano Lucentini, Francesco Pichi)....Pages 473-485
Pediatric Neuro-Ophthalmology and OCT (Maja Kostic, Gábor Márk Somfai, Edmund Arthur, Delia Cabrera DeBuc)....Pages 487-505
Machine Learning Approaches in OCT: Application to Neurodegenerative Disorders (Rui Bernardes, Lília Jorge, Ana Nunes, Miguel Castelo-Branco)....Pages 507-521
Optical Coherence Tomography Angiography in Neurology and Neuro-Ophthalmology (Alexander Pinhas, Valerie I. Elmalem, Maria Castanos Toral, Davis B. Zhou, Jorge S. Andrade Romo, Alexander Barash et al.)....Pages 523-544
Conclusion: The Exciting Future of OCT and New Imaging of Retina and Optic Nerve (Piero Barboni, Andrzej Grzybowski)....Pages 545-547
Back Matter ....Pages 549-561

Citation preview

OCT and Imaging in Central Nervous System Diseases The Eye as a Window to the Brain Andrzej Grzybowski Piero Barboni Editors Second Edition

123

OCT and Imaging in Central Nervous System Diseases

Andrzej Grzybowski  •  Piero Barboni Editors

OCT and Imaging in Central Nervous System Diseases The Eye as a Window to the Brain Second Edition

Editors Andrzej Grzybowski University of Warmia and Mazury Olsztyn Poland

Piero Barboni Studio Oculistico d’Azeglio Bologna Italy

Institute for Research in Ophthalmology Poznań Poland

Scientific Institute San Raffaele Milan Italy

ISBN 978-3-030-26268-6    ISBN 978-3-030-26269-3 (eBook) https://doi.org/10.1007/978-3-030-26269-3 © Springer Nature Switzerland AG 2020 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

Contents

1 Introduction: Retina Imaging—Past and Present�������������������������������������� 1 Andrzej Grzybowski and Piero Barboni 2 OCT Technique: Past, Present and Future�������������������������������������������������� 7 Tigran Kostanyan, Maria de los Angeles Ramos-Cadena, Gadi Wollstein, and Joel S. Schuman 3 The APOSTEL Recommendations������������������������������������������������������������ 33 Aykut Aytulun, Andrés Cruz-Herranz, Lisanne Balk, Alexander U. Brandt, and Philipp Albrecht 4 OCT Angiography: Guidelines for Analysis and Interpretation ������������ 41 Enrico Borrelli, Srinivas R. Sadda, Akihito Uji, and Giuseppe Querques 5 Seeing the Brain Through the Eye: What Is Next for Neuroimaging and Neurology Applications��������������������������������������  55 Delia Cabrera DeBuc, Gábor Márk Somfai, Gabriella Szatmáry, Edmund Arthur, Jorge A. Jimenez, Carlos Mendoza-Santiesteban, and Andrzej Grzybowski 6 Advances in Retinal Imaging: Retinal Amyloid Imaging������������������������ 83 Maya Koronyo-Hamaoui, Jonah Doustar, Mia Oviatt, Keith L. Black, and Yosef Koronyo 7 Advances in Retinal Imaging: Real-Time Imaging of Single Neuronal Cell Apoptosis (DARC) �������������������������������������������� 123 Timothy E. Yap, Maja Szymanska, and M. Francesca Cordeiro 8 Retinal Oximetry in Central Nervous System Diseases�������������������������� 139 Anna Bryndis Einarsdottir, Olof Birna Olafsdottir, and Sveinn Hakon Hardarson 9 Optical Coherence Tomography and Optic Nerve Edema�������������������� 147 Laurel N. Vuong and Thomas R. Hedges III 10 OCT and Compressive Optic Neuropathy���������������������������������������������� 169 Mário Luiz Ribeiro Monteiro v

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11 OCT and Multiple Sclerosis���������������������������������������������������������������������� 195 James V. M. Hanson, Carla A. Wicki, Praveena Manogaran, Axel Petzold, and Sven Schippling 12 OCT in Parkinson’s Disease and Related Disorders������������������������������ 235 Ivan Bodis-Wollner, Shahnaz Miri, Sofya Glazman, Eric M. Shrier, and Reem Deeb 13 Optical Coherence Tomography in Alzheimer’s Disease������������������������ 263 Gianluca Coppola, Vincenzo Parisi, Gianluca Manni, Francesco Pierelli, and Alfredo A. Sadun 14 Friedreich’s Ataxia and More: Optical Coherence Tomography Findings in Rare Neurological Syndromes ���������������������� 289 Chiara La Morgia and Michele Carbonelli 15 Other Neurological Disorders: Migraine, Neurosarcoidosis, Schizophrenia, Obstructive Sleep Apnea-Hypopnea Syndrome and Bipolar Disorder �������������������������������������������������������������������������������� 317 Francisco J. Ascaso, Javier Mateo, Laura Cabezón, Paula Casas, and Andrzej Grzybowski 16 Hereditary Optic Neuropathies���������������������������������������������������������������� 343 Piero Barboni, Nicole Balducci, and Alfredo A. Sadun 17 Trans Neuronal Retrograde Degeneration to OCT in Central Nervous System Diseases������������������������������������������������������������ 365 Bernardo F. Sánchez-Dalmau, Anna Camós-Carreras, Ruben Torres-Torres, Johannes Keller, Laura Sanchez-Vela, Elena H. Martínez-Lapiscina, and Pablo Villoslada 18 OCT in Toxic and Nutritional Optic Neuropathies�������������������������������� 375 Andrzej Grzybowski, Iwona Obuchowska, and Carl Arndt 19 Animal Models in Neuro Ophthalmology������������������������������������������������ 401 Eduardo M. Normando and M. Francesca Cordeiro 20 OCT in Glaucoma�������������������������������������������������������������������������������������� 427 Harsha Rao, Kaweh Mansouri, and Robert Weinreb 21 OCT in Amblyopia ������������������������������������������������������������������������������������ 473 Paolo Nucci, Andrea Lembo, Stefano Lucentini, and Francesco Pichi 22 Pediatric Neuro-Ophthalmology and OCT �������������������������������������������� 487 Maja Kostic, Gábor Márk Somfai, Edmund Arthur, and Delia Cabrera DeBuc 23 Machine Learning Approaches in OCT: Application to Neurodegenerative Disorders�������������������������������������������������������������������� 507 Rui Bernardes, Lília Jorge, Ana Nunes, and Miguel Castelo-Branco

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24 Optical Coherence Tomography Angiography in Neurology and Neuro-Ophthalmology������������������������������������������������ 523 Alexander Pinhas, Valerie I. Elmalem, Maria Castanos Toral, Davis B. Zhou, Jorge S. Andrade Romo, Alexander Barash, and Richard B. Rosen 25 Conclusion: The Exciting Future of OCT and New Imaging of Retina and Optic Nerve������������������������������������������������������������������������ 545 Piero Barboni and Andrzej Grzybowski Index�������������������������������������������������������������������������������������������������������������������� 549

About the Editors

Andrzej Grzybowski  MD, PhD, MBA, is a Professor of Ophthalmology and Chair of the Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland, and Head of the Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Poznan, Poland. He is active in international scientific societies including EURETINA (Co-opted Board Member 2016– 2018); Retina Society, AAO (International Fellow and Member of the Global ONE Advisory Board and Museum of Vision’s Programme Committee); EVER (Board Member and Chair of Cataract Section); ESCRS (Curator of ESCRS Archive); ISRS (Member of the ISRS International Council); ISBCS, International Council of Ophthalmology (Programme Coordinator for the WCO in 2011–2018); and Cogan Society. He became Lifelong Member (Chair LIV) of the European Academy of Ophthalmology (http://www.eao.eu) and its Treasurer. He has been active contributor to major ophthalmic conferences worldwide, including AAO (Achievement Award 2017, International Scholar Award 2018), APAO (International Coordinator 2017, Achievement Award 2018), WCO (Programme Coordinator 2010–2018), EURETINA, ESCRS, EVER, ISOPT, etc. He has been active Editor, Editor in Chief, and Author of more than 450 peer-­reviewed international publications (total IF higher than 1000) and over 50 book chapters and Reviewer for more than 20 journals. He is a Member of editorial boards of American Journal of Ophthalmology (IF 4.795), Acta Ophthalmologica (IF 3.157), PLOS One (IF 2.806), Graefe’s Archive for Clinical and Experimental Ophthalmology (IF 2.349),

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About the Editors

Translational Vision Science & Technology (TVST, IF 2.221), BMC Ophthalmology (IF 1.586), Clinics in Dermatology (IF 2.253), Clinical Medicine (IF 5.8), Frontiers in Neurology (IF 3.5), Journal of NeuroOphthalmology (IF 0.2), Saudi Journal of Ophthalmology, and Asia-Pacific Journal of Ophthalmology and Editor in Chief of Archives of History and Philosophy of Medicine and Historia Ophthalmologica Internationalis (www.histoph.com). Piero  Barboni  received his undergraduate degree from the University of Bologna in 1986 and his medical and surgical training from the University of Bologna, Italy, in 1990. Since then, he has been working in private practice and appointed Professor at the Department of Neurological Science of Bologna University from 2007 to 2011. Currently, he is Consultant Neuroophthalmologist at Scientific Institute San Raffaele, University of Milan, since 2012. He is also devoted to the study of hereditary optic neuropathies, for which he collaborates with several university-based centres (Bologna, London, Los Angeles, Tubingen, São Paulo). This project includes the international research project on Leber’s hereditary optic neuropathy in Brazil. He is also Sub-investigator in many clinical trials. He has authored more than 80 papers on international peerreviewed journals and several books.

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Introduction: Retina Imaging—Past and Present Andrzej Grzybowski and Piero Barboni

The retina is a mysterious structure. The first use of the term comes, as to our present knowledge, from Herophilos (335–280 or 255 BC), Greek anatomist, one of founders of Greek school in Alexandria. He used two different words, arachnoeides and amfiblesteroides, for retina. For many years, both meanings were related to casting net, and retiform, a word which the modern “retina” is derived. However, as it was nicely shown recently, there might be another explanation of these original terms [1]. Amfiblesteroides meant at that time also anything that is thrown around and encircling walls. For many years it was believed, however, that the lens, not retina is the reception organ of the eye responsible for vision and there was even no agreement as to whether the eye emanated light (extramission theory) or received it (intromission theory) [2, 3]. Leonardo da Vinci (1452–1519) and Johannes Kepler (1571–1630) questioned the role of the lens in light reception. Felix Plater (1536–1614), attributed that role to the retina, what was further experimentally supported by Christopher Scheiner (1575–1650) who, by removing part of the sclera and choroids, was able to notice the reversed picture projected onto the bottom of the eye [3–6]. For the next two centuries, it was disputable weather retina or choroid was a precise structure responsible for vision reception [7]. This was finally settled by Herman von Helmholtz (1821–1894), who also constructed and popularized the first ophthalmoscope in 1851 [8]. This revolutionized the development of retinology. A. Grzybowski (*) University of Warmia and Mazury, Olsztyn, Poland Institute for Research in Ophthalmology, Poznań, Poland P. Barboni Studio Oculistico d’Azeglio, Bologna, Italy Scientific Institute San Raffaele, Milan, Italy e-mail: [email protected] © Springer Nature Switzerland AG 2020 A. Grzybowski, P. Barboni (eds.), OCT and Imaging in Central Nervous System Diseases, https://doi.org/10.1007/978-3-030-26269-3_1

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The first visualization of the eye fundus of the living animal, however, was conducted by Jean Mery (1654–1718) in 1704. By plunging the head of a cat in water, Mery was able to observe the retinal vessels, the optic nerve head and the choroid (Fig. 1.1) [9]. This was later confirmed by Adolf Kussmaul in 1845 [10], Johann Nepomuk Czermak in 1851 [11] and Adolf Ernst Coccius in 1852, who introduced a water-box named “orthoscope”, to neutralize the corneal curvature [12, 13]. It was, however, Johannes Purkinje (1787–1869) in 1823 who described the basics of ophthalmoscopy based on his observations living animal and human eye [14]. One of the pioneers in the use of ophthalmoscopy for the diagnosis of central nervous system disorders was Xavier Galezowski (1832–1907), who published one of early textbooks on this subject and coined a term of cerebroscopy for this examination (Fig. 1.2) [15]. The microscopical structure of the retina was described in the nineteenth century, and by the end of the twentieth century it was believed that its histological and functional characteristics was largely recognized. Then, the discovery of intrinsically photosensitive ganglion cells, a novel class of retinal photoreceptors, which express melanopsin, are sensitive to short-wavelength blue light and project throughout the brain, have presented a completely unknown area of retina-brain possible interactions [16, 17]. It is quite clear today that other cellular components of the retina, namely amacrine cells, bipolar cells and microglial cells, although somehow

Fig. 1.1  Extract from the Proceedings of the Royal Academy of Sciences for the year 1709— Session of 20th March 1709. By this diagram, La Hire explains the visualization of the fundus of the submerged cat by the fact that the surface of the water having abolished the corneal dioptric power, the rays coming out of the eye would no longer be parallel, but would diverge and that would make the eye fundus visible to the observer. Source: Heitz RF.  Earliest Visualizations of the Living Eye’s Fundus by Immersion in Water. Archiwum Historii I Filozofii Medycyny 2012; 75: 11–15

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Fig. 1.2  Cover page of the book “Etude ophtalmoscopique sur les altérations du nerf optique et les maladies cérébrales dont elles dépenden” by Xavery Gałęzowski, Paris, 1866

neglected in the past, play important functions both in physiology and pathology of the retina. For example, it was proposed that microglia are involved in the pathogenesis of several degenerative conditions of the retina, including glaucoma, age-related macular degeneration, and inherited photoreceptor degeneration [18]. Moreover, recently the evidence of retinal astrocytopathy in neuromyelitis optica spectrum disorder was provided [19]. One of the major developments in recent years in retinal imaging was the introduction of optical coherence tomography (OCT). OCT was firstly reported by Huang et al. in 1991 [20]. In vivo studies were first reported in 1993 [21, 22], and in 1995 imaging of the normal retina [23] and macular pathology [24] was presented. OCT delivers high-resolution cross-sectional or 3-dimensional images of the retinal and choroid structures, which are generated by an optical beam scanned across the retina (and choroid). OCT testing is quick, easy and noninvasive, and pupil dilation is typically not required. Moreover, OCT yields quantitative anatomical data and is related with low variation for repeated measurements, low intra-individual and inter-individual variation and low variability across different centers using the same device. Retinal ganglion cells axons are nonmyelinated within the retina, thus retinal nerve fiber layer (RNFL) is an optimal structure to visualize the process of neurodegeneration, neuro-protection and neuro-repair [25]. Moreover, OCT enables evaluation of retinal ganglion cells (RGC). For example, it was reported in

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patients with MS a dropout of RGC in 79% of eyes and inner nuclear layer atrophy (including amacrine cells and bipolar cells) in 40% of eyes [26]. It was also argued that OCT might reveal RNFL abnormalities in many patients with no clinical symptoms [27]. Retina and optic nerve originates from diencephalon, thus are a part of central nervous system (CNS). RGC present the typical morphology of CNS neurons. Optic nerve, like all fiber tracts in CNS, is covered with myelin and is unsheathed in all three meningeal layers. Insult to the optic nerve, similar to CNS, lead to retrograde and anterograde degeneration of damaged axons [28]. Because of these many similarities, it has not been very surprising that many CNS diseases can be also detected on the retina level. They include multiple sclerosis, Alzheimer disease, Parkinson disease, and many others. Moreover, it was shown that there are some common degenerative mechanisms between Alzheimer disease and eye diseases, like glaucoma and age-related macular degeneration [29]. Thus, the aim of this book is to review all aspects of OCT retina studies in CNS diseases, and present some other novel and interesting techniques, including retinal amyloid imaging, retinal oximetry, and real-time imaging of single neuronal cell apoptosis.

References 1. de Jong PT. From where does “rete” in retina originate? Graefes Arch Clin Exp Ophthalmol. 2014;252:1525–7. 2. Magnus H.  Ophthalmology of the ancients, vol. 2 (Waugh RL, Translator). Oostende: Wayenborgh; 1999. p. 461–9. 3. Duke-Elder S, Wybar KC. The history of ophthalmic optics. In: Duke-Elder S, editor. System of ophthalmology, vol. 5. London: Henry Kimpton; 1970. p. 3–23. 4. Mark H. Johanees Kepler on the eye and vision. Am J Ophthalmol. 1971;72:869–78. 5. Daxecker F.  Further studies by Christoph Scheiner concerning the optics of the eye. Doc Ophthalmol. 1994;86:153–61. 6. Daxecker F. Christoph Scheiner’s eye studies. Doc Ophthalmol. 1992;81:27–35. 7. Grzybowski A, Aydin P.  Edme Mariotte (1620-1684): pioneer of neurophysiology. Surv Ophthalmol. 2007;52:443–51. 8. Helmholtz HLFV. Beschreibung eines Augenspiegels zur Untersuchung der Netzhaut im lebenden Auge. Berlin: Forstner; 1851. 9. Heitz RF. Earliest visualizations of the living eye’s fundus by immersion in water. Arch Hist Filoz Med. 2012;75:11–5. 10. Kussmaul A.  Die Farben-Erscheinungen im Grunde des menschlichen Auges. Heidelberg: Groos; 1845. 11. Czermak JN. Ueber eine neue Methode zur genaueren Untersuchung des gesunden und kranken Auges. Vjschr prakt Heilk. 1851;8:154–65. 12. Coccius AE. Ueber die Ernährungsweise der Hornhaut und die Serum führenden Gefässe im menschlichen Körper. Leipzig: Muller; 1852. 13. Coccius AE. Ueber die Anwendung des Augen-Spiegels nebst Angabe eines neuen Instruments. Leipzig: Muller; 1853. 14. Reese PD. The neglect of Purkinje’s technique of ophthalmoscopy prior to Helmholtz’s invention of the ophthalmoscope. Ophthalmology. 1986;93:1457–60. 15. Gałęzowski X.  Etude ophtalmoscopique sur les altérations du nerf optique et les maladies cérébrales dont elles dépendent. Paris: Librairie de L. Leclerc; 1866.

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16. Lucas RJ, Freedman MS, Munoz M, Garcia-Fernandez JM, Foster RG.  Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science. 1999;284:505–7. 17. Schmidt TM, Chen SK, Hattar S. Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci. 2011;34:572–80. 18. Silverman SM, Wong WT. Microglia in the retina: roles in development, maturity, and disease. Annu Rev Vis Sci. 2018;4:45–77. 19. You Y, Zhu L, Zhang T, Shen T, Fontes A, Yiannikas C, Parratt J, Barton J, Schulz A, Gupta V, Barnett MH, Fraser CL, Gillies M, Graham SL, Klistorner A.  Evidence of Müller glial dysfunction in patients with aquaporin-4 immunoglobulin G–positive neuromyelitis optica spectrum disorder. Ophthalmology. 2019; https://doi.org/10.1016/j.ophtha.2019.01.016. 20. Huang D, Swanson EZ, Lin CP, et  al. Optical coherence tomography. Science. 1991;254:1178–81. 21. Swanson EA, Izatt JA, Hee MR, et al. In vivo retinal imaging by optical coherence tomography. Opt Lett. 1993;18:1864–6. 22. Fercher AF, Hitzenberger CK, Drexler W, et al. In vivo optical coherence tomography. Am J Ophthalmol. 1993;116:113–4. 23. Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of the human retina. Arch Ophthalmol. 1995;113:325–32. 24. Puliafito CA, Hee MR, Lin CP, et  al. Imaging of macular diseases with optical coherence tomography. Ophthalmology. 1995;102:217–29. 25. Galetta KM, Calabresi PA, Frohman EM, Balcer LJ.  Optical coherence tomography (OCT): imaging the visual. Pathway as a model for neurodegeneration. Neurotherapeutics. 2011;8:117–32. 26. Green A, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010;133:1591–601. 27. Cettomai D, Hiremath G, Ratchford J, et  al. Associations between retinal nerve fiber layer abnormalities and optic nerve examination. Neurology. 2010;75:1318–25. 28. London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013;9:44–53. 29. Sivak JM. The aging eye: common degenerative mechanisms between the Alzheimer’s brain and retinal disease. Invest Ophthalmol Vis Sci. 2013;54:871–80.

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OCT Technique: Past, Present and Future Tigran Kostanyan, Maria de los Angeles Ramos-Cadena, Gadi Wollstein, and Joel S. Schuman

Abbreviations 2D Two-dimensional 3D Three-dimensional AO Adaptive optics CCD Charge-coupled device EDI Enhanced depth imaging FD Fourier domain GCC Ganglion cell complex ILM Internal limiting membrane IPL Inner plexiform layer IS Inner segment LC Lamina cribrosa OCT Optical coherence tomography OCTA Optical coherence tomography angiography ONH Optic nerve head OS Outer segment PS Polarization sensitive RGC Retinal ganglion cell RNFL Retinal nerve fiber layer RPE Retinal pigment epithelium SD Spectral domain T. Kostanyan Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, Pittsburgh, PA, USA M. de los Angeles Ramos-Cadena · G. Wollstein · J. S. Schuman (*) Department of Ophthalmology, NYU Langone Health, New York, NY, USA e-mail: [email protected] © Springer Nature Switzerland AG 2020 A. Grzybowski, P. Barboni (eds.), OCT and Imaging in Central Nervous System Diseases, https://doi.org/10.1007/978-3-030-26269-3_2

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SS Swept source TD Time-domain Vis-OCT Visible light optical coherence tomography

2.1

Introduction

Optical coherence tomography (OCT), first developed in the 1990s, is a diagnostic imaging technology that has gained a leading position in research and clinical practice due to its ability to obtain noncontact, in vivo, high-resolution, micron-scale images of tissue structures. OCT makes in situ imaging of tissue microstructure possible with a resolution approaching that of histology [1]. The technology uses the principle of low-coherence interferometry, which was originally applied to ophthalmology for in vivo measurements of the axial length of the eye [2]. At the time of introduction, the technology was used to acquire in vivo, cross-­ sectional images of the anterior segment [3], and retinal pathologies. Since then, OCT has evolved significantly, with improvements in both image acquisition methods and image analysis. The evolution of OCT began with the time domain (TD) technique, followed by spectral domain (SD) systems and later, newer iterations with faster acquisition speeds [4, 5] and improved axial resolution [6]. This chapter describes the basic principles of OCT techniques, its history, current status, major ophthalmic applications, and research that will determine the future of the technology.

2.2

Basic Principles

OCT provides cross-sectional and volumetric images of areas of interest by acquiring either the echo time delay or frequency information of back-reflected light. Differences in the optical properties of biological tissues allow the recognition of layered structures. The speed of light makes it impossible to analyze the acquired information directly, since it would be in the order of femtoseconds thus, OCT systems use the optical technique known as interferometry. Low-coherence interferometry enables the analysis of this information and the composition of a depth-resolved reflectivity profile (A-scan) of the scanned tissue by matching the light profiles from the scanning and reference arms. Utilization of light provides OCT technology the ability to obtain images in a non-contact fashion and to achieve resolutions of 1–15 μm, which is 1–2 orders of magnitude finer than other conventional clinical imaging technologies such as ultrasound, computerized tomography, or magnetic resonance. Light is highly absorbed or scattered in most biological tissues, therefore the use of this technology is limited only to locations that are optically accessible or that can be imaged using devices such as endoscopes or catheters. The eye is the most optically accessible organ of

2  OCT Technique: Past, Present and Future

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the human body since the anterior and posterior segments can be visualized and imaged [7]. The key parameters that are typically used to characterize OCT technology are the wavelength of the light source, axial and transverse resolution, scanning speed, and imaging depth. Axial resolution determines the smallest distance along the axial direction where two adjacent points are discernable, and it is inversely related to the bandwidth of the light source. Current commercial OCT devices achieve axial resolutions up to 4  μm, and research systems can achieve up to ~1  μm [8]. The penetration depth (in the axial direction) is approximately 2 mm in the various OCT iterations with the exception of Visible-light OCT that does not penetrate beyond the RPE layer. Transverse resolution is determined by the spot size projected into the eye, which is limited by the optical properties of the eye. As such, the transverse resolution of OCT ranges between 15–20 μm among the different generations of the technology. Improving transverse resolution requires the correction of the optical aberrations of the eye using technologies such as adaptive optics. Scanning speed is dictated by mechanical constrains and the sensitivity of the detector to the back-reflected light. As scanning speed increases, the time the detector remains in the same location is shorter, thus reducing the light that can be detected in each location. Since the power of the projected light is limited in order to be within safety limits, faster scans require a more sensitive detector that can function with a lower level of light. The achievable imaging depth is related to the central wavelength of the light source, with longer wavelengths providing increased imaging depth [9, 10]. However, longer wavelengths are limited by the increased optical absorption of water [11]. Currently available OCT techniques are based on several iterations of the technology: spectral-domain (SD; also known as Fourier or frequency domain), swept-­ source (SS), and visible-light (Vis-OCT). The earliest iteration of the technology, time-domain (TD), is no longer manufactured for ophthalmic use and therefore will not be discussed. SD-OCT uses a broad-bandwidth, low-coherence superluminescent diode laser light that is divided into two arms by a partially reflecting mirror (beam splitter). In the first arm light is projected toward the sampling location, while in the second arm light is projected toward a reference mirror. The backscattered light from both arms travels back to a spectrometer and recombines to form an interference pattern. Light frequency information is analyzed by Fourier transformation to encode distances within tissue microstructure [12]. SD technology allows the acquisition of information from all points along each axial scan (A-scan) simultaneously at a scanning speed of ~25,000–100,000 A-scans/s [13, 14] and up to 20 million A-scans/s in research devices [5]. A cross-sectional image, also known as a B-scan, is generated by performing fast, subsequent A-scans at different transverse positions. Combining rapidly acquired subsequent cross-sectional scans allows the creation of three-­ dimensional (3D) datasets, enabling advanced post-processing analysis. The wide

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bandwidth of the SD-OCT light source also facilitates an axial resolution of 3–6 μm in commercially available systems and up to 1 μm in research systems [15, 16]. SS-OCT uses a tunable laser light source that sweeps through different frequencies in rapid succession to cover the entire broad spectrum. The reflectance of the light from the scanned area is captured by a photodetector, which allows a substantially faster acquisition rate (up to 400,000 A-scans/s) than the spectrometry of SD-OCT [4, 17]. Another important advantage of SS-OCT is an improved signalto-­noise ratio and reduction in the depth dependent signal drop-off observed with SD-OCT technology [18]. Most SS-OCT devices operate with light sources centered at around 1050  nm (compared with 840  nm in the commercially available SD-OCT devices), which reduces the axial resolution to approximately 8 μm but allows for better penetration into the tissue. This combination of improved tissue penetration and reduced signal attenuation allows detailed scanning of structures such as the choroid and the lamina cribrosa (LC) within the ONH. Vis-OCT. Unlike other OCT iterations that use near infrared light sources (~800 and 1000 nm), Vis-OCT utilizes a light source with a shorter center wavelength of ~550  nm resulting in an improved axial resolution of