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Preface
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The human eyes are often called the windows to the body in health and disease. Eyes provide an extraordinary insight into our overall health. The eyes
are the only part of the body where a physician, using non-invasive tools, can
directly visualize pathology as it is evolving, often decades before manifesting as a grave systemic disorder.
Within these small, though intricate organs lies a world of valuable information that can provide vital insights into a person’s well-being. Ophthalmic
signs, the tell-tale indicators in the eyes, are remarkable signatures of underlying systemic diseases. From the subtlest of changes to the most pronounced
abnormalities, these signs can offer a glimpse into the intricate workings of
the human body.
Articial compartmentalization and increasing sub-specialization in every
eld of medicine, beginning in the latter half of the twentieth century, rapidly
created silos of excellence that can deal successfully with the most complicated diseases, often at the cost of missing clues to the earliest onset of the
disease. Unlike when the ophthalmic examination was an integral part of the
patient workup, heavy demand on the trainees’ time in different subspecialties has dramatically reduced the captive time for exposure to ophthalmology
and the ophthalmic signs.
Ophthalmology is a highly visual science wherein such signs can be easily
learnt, objectively documented, and used in clinical practice to improve quality of care, early diagnosis, and appropriate referrals. In medicine, recognizing and interpreting ophthalmic signs has proven to be an invaluable tool.
The eyes are integral to the body’s systems and share structural, physiological, immunological, biochemical, neurological, and biological homology
and pathways. The eyes often reveal the consequences of systemic disorders,
chronic diseases, and genetic disorders. Not only do these signs aid in diagnosing ocular disorders, but they can also serve as early warning signals for a
myriad of systemic diseases.
This book, profusely illustrated, delves into the fascinating realm of ophthalmic signs, exploring their diverse manifestations and signicance in medicine. Through an in-depth exploration of various eye conditions, their
associated signs and pathogenetic mechanisms, we aim to empower clinicians, family physicians, medical students, residents, and fellows in training
with the knowledge and skills necessary to detect, evaluate, and interpret
these invaluable clues.
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Drawing upon the latest research and clinical experiences, this book seeks
to enhance the understanding of ophthalmic signs as a crucial component of
the diagnostic process. By highlighting the interplay between ocular health
and systemic well-being, we hope to foster a holistic approach to patient care
and encourage collaboration between ophthalmologists, general practitioners, internists, endocrinologists, neurologists, and specialists from various
other medical disciplines.
Embark on this enlightening journey through the captivating realm of ophthalmic signs and witness how the eyes are extraordinary indicators of our
overall health.
Chandigarh, India AmodGupta
Chandigarh, India ReemaBansal
Chandigarh, India AmanSharma
Chandigarh, India ArunKapil
Preface
Acknowledgements
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We want to acknowledge several eminent ophthalmologists’ and researchers’
generosity in sharing their precious images with us, without which this book
would have remained incomplete.
Dr Manphool Singhal, Department of Radiodiagnosis and Imaging,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India, for gures 1.13 and 18.7
Dr Alok Sen Sadguru Netra Chikitsalya, Chitrakoot, MP, India, for gures
3.12, 3.18, 10.9B
Dr Simar Rajan Singh, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for gures 6.18 to 6.21
Prof Anjali Agarwal, Head, Department of Anatomy, Postgraduate
Institute of Medical Education and Research, Chandigarh, for gures 8.1,
15.1, 16.2, 20.1
Dr Anuradha V K, Head of Uveitis Services, Aravind Eye Hospital,
Coimbatore, India, for Fig.10.8A
Prof Ramandeep Singh, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for Fig.10.8B
Dr Padmamalini Mahendradas, Uveitis and Ocular Oncology, Narayana
Nethralaya, Bangalore, India, for gures 10.22 to 10.24
Dr Anita Agarwal, West Coast Retina Medical Group, San Francisco, CA
94109, for gures 13.1, 13.7, 13.8, 13.10 to 13.15.
Dr Chirag Ahuja, Department of Radiodiagnosis and Imaging,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India, for the interpretation of Fig.1d.
Prof Daisy Sahni (Ex-Professor) Department of Anatomy, Postgraduate
Institute of Medical Education and Research, Chandigarh, India, for Fig.15.1
Dr SS Pandav, Professor and Head, Advanced Eye Centre, Postgraduate
Institute of Medical Education and Research, Chandigarh, India, for gures
15.3, 15.16
Dr Rithambra Nada, Prof of Pathology,Postgraduate Institute of Medical
Education and Research, Chandigarh, India, for gures 15.20 and 18.8B
Dr Chintan Malhotra, Professor, Cornea, Lens and Refractive Surgery
Services, Advanced Eye Centre, Postgraduate Institute of Medical Education
and Research, Chandigarh, India, for gures 17.3 to 17.13
Dr Anandita Sinha, Department of Radiodiagnosis and Imaging,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India, for gures. 17.14B and 17.17 (d, e)
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Prof Pradeep Bambery, Ex-Professor of Medicine, Postgraduate
Institute of Medical Education and Research, Chandigarh, India, for
Fig.18.16
Dr Amit Gupta, Professor, Cornea, Lens and Refractive Surgery Services,
Advanced Eye Centre, Postgraduate Institute of Medical Education and
Research, Chandigarh, India, for gures 17.14 b–d, 18.6
Dr Kanwar Mohan, Dr Kanwar Mohan’s Squint Centre, Chandigarh,
India, for gures 19.5, 19.7, 19.15, 19.16, 19.18, 19.19, 19.20, 20.1b
Dr Manpreet Singh, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for gures 19.8c,
19.11e, 20.2, 20.6, 20.7
Dr Ali G.Hamedani, Department of Neurology, Hospital of the University
of Pennsylvania, Philadelphia, PA, United States, for gures 19.10 and 19.12
Dr Anja K E Horn, Professor, Ludwig-Maximilian University Munich,
Germany, for Fig.19.21
Prof. Usha Singh, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for gures 20.4, 20.5,
20.8, 20.13, 20.17, 20.18, 20.19
Dr Pankaj Gupta, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for Fig.20.9
Dr Shweta Chaurasia, Advanced Eye Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India, for gures 20.10 to
20.12, 20.14, 20.15
Dr Kasturi Bhattacharjee, Sri Sankaradeva Nethralaya, Guwahati, India,
for gures 20.16, 20.20
Kritika Thakur for graphics—gures 15.2; 16.3 to 16.6; 16.8 to 16.10;
19.1 to 19.4; 19.6; 19.8 a, b; 19.9; 19.11a–d; 19.13; 19.14; 19.22 to 19.26
We want to thank several publishers who allowed us to reuse our images
published over several years in the past.
Publishers of Frontiers of Medicine for reusing Fig.3.11 from our publication Bansal et al. (2021) Frontiers of Medicine 8:681942. doi: 10.3389/
fmed.2021.681942.
Publishers of Neurology for allowing us to reuse Fig.5.15 from our publication Takkar etal. Neurology 2013,81:e40
Springer Singapore for allowing us to reuse Fig.6.5 and Fig.16.1 from our
publication Gupta A (2022). Bench-to-Bedside Research in Ophthalmology.
In: Sobti, R., Ganju, A.K. (eds) Biomedical Translational Research. Springer,
Singapore. https://doi.org/10.1007/978- 981- 16- 8845- 4_5
Elsevier for allowing us to reuse Fig.6.17 published by Chiang et al.
(2021) in Ophthalmology. 2021 Oct;128(10):e51–e68. doi: 10.1016/j.
ophtha.2021.05.031
Publisher for allowing us to reuse gures 10.10C and 10.11B from our
publication, Bansal et al. (2012) Expert Review of Ophthalmology, 7(4),
341–349.doi:10.1586/eop.12.42
Springer Berlin for Fig.10.11C from our publication Gupta A (2016) in
Zierhut etal. (eds) Intraocular Inammation. Springer, Berlin, Heidelberg.
https://doi.org/10.1007/978- 3- 540- 75387- 2_105
Acknowledgements
Acknowledgements
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Figure 12.7C from Singh et al. (2012) Medicine (Baltimore). 2012
Jul;91(4):179–194. doi: 10.1097/MD.0b013e3182574a0b. PMID: 22732948
Figure 14.12, Gupta A and Gupta V (2009) Paediatric uveitis in Gupta A
et al. (eds) Uveitis: Text and Imaging 1st Edn. Jaypee Brothers Medical
Publishers (P) Ltd., New Delhi. P 518
Fig. 15.15 from Gupta et al. (2012) BMJ Case Rep. 2012 Aug
21;2012:bcr2012006718. doi: 10.1136/bcr-2012-006718. PMID: 22914240
Figure 16.7 with permission from NeurOptics, inc. (Irvine, CA92612,
USA)
Figure 17. 14a, 17.16a, 17.19, 17.20, 18.8, 18.15b, c, d from Bambery
etal. (2009) Systemic examination and imaging in Gupta etal. (eds) Uveitis:
Text and Imaging 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New
Delhi
Figure 17.18 from Gupta etal. (2009) Gupta etal. (eds). Uveitis: Text and
Imaging 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi
Figure 17.24 EyeNet Magazine, Agarwal AK etal., Pigmented Keratic
Precipitates in Herpes Simplex Virus Anterior Uveitis November 2018
Figure 17.27 EyeNet Magazine,Gupta AK, etal. September 2014
Figure 18.1, 18.13 from Sharma et al. In: Sharma A (ed).Textbook of
Systemic Vasculitis, 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd.,
New Delhi
We also thank publishers for allowing us to adapt/reuse material from their
publications to create boxes for various chapters in our book.
Publishers to allow us to reuse/adapt from various publications for
Boxes 10.1 from Holland, 1994
Box 10.2. from Standardization of Uveitis Nomenclature (SUN) Working
Group. Classication Criteria for Acute Retinal Necrosis Syndrome 2021
Box 10.3 from Standardization of Uveitis Nomenclature (SUN) Working
Group. Classication Criteria for Cytomegalovirus Retinitis, 2021
Box 10.4 and 10.5 from Gupta etal. (2015) Classication of intraocular
tuberculosis. Ocul Immunol Inamm. 2015 Feb;23(1):7–13. doi:
10.3109/09273948.2014.967358
Box 10.6 from Fig.2 by Aringer etal. (2019)
Box 10.7 from Korsten etal. (2018)
Box 10.8 from Standardization of Uveitis Nomenclature (SUN) Working
Group
Box 10.9 Classication Criteria for Sarcoidosis-Associated Uveitis, 2021
from Standardization of Uveitis Nomenclature (SUN) Working Group.
Classication Criteria for Behçet Disease Uveitis, 2021
Box 10.9 from Criteria for diagnosis of Behçet’s disease. International
Study Group for Behçet’s Disease, 1990.
Box 10.10 from O'Keefe and Rao from Surv Ophthalmol. 2017 JanFeb;62(1):1–25. doi: 10.1016/j.survophthal.2016.05.002. Epub 2016 May
27. PMID: 27241814
Box 14.1 from Lonser etal. (2003)
Box 14.2 from VHL Alliance, Boston, MA, 02284-4682 and 14.3 from
Ophthalmology. 2006 Dec;113(12):2276–80. doi: 10.1016/j.
ophtha.2006.06.018
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Box 15.1 from Petzold etal. Lancet Neurol. 2022 Dec;21(12):1120–1134.
doi: 10.1016/S1474-4422(22)00200-9
Box 15.2 Reproduced under the Creative Commons Attribution license
(CC BY) from Szekeres and Othman Front Med (Lausanne). 2022 Dec
13;9:1066503. doi: 10.3389/fmed.2022.1066503. PMID: 36582285
Box 19.1 from Jaretzki etal. 2000. Myasthenia gravis: recommendations
for clinical research standards. Task Force of the Medical Scientic Advisory
Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg.
2000 Jul;70(1):327–34. doi: 10.1016/s0003-4975(00)01595-2. PMID:
10921745
Reviewers: We want to thank Dr Anita Agarwal, West Coast Retina
Medical Group, San Francisco, CA, for the review of Chapters 7, 12, and 13
and Dr Aastha Takkar for the review of Chapters 15 and 16. We highly appreciate their valuable comments to improve the quality of our book.
Finally, we like to express our gratitude to Prof Jim Rosenbaum MD,
Chair, Emeritus Legacy Devers Eye Institute, Portland, OR, USA, Prof
Athimalaipet V Ramanan, FRCP, Professor of Paediatric Rheumatology,
Bristol Royal Hospital for Children, Bristol, UK, and Prof Philippe Kestelyn,
Emeritus Professor University of Ghent, Belgium, for nding time from their
extremely busy schedule to review our manuscript and write forewords for
this book.
We like to thank Ms Sinchu Mohan, Ms Jagjit Kaur Saini, and Mr Naren
Agarwal of Springer Team India for giving a nal shape to our book
Amod Gupta MBBS; MS, Emeritus Professor, Advanced Eye Centre,
Postgraduate Institute of Medical Education and Research, Chandigarh, India
Reema Bansal MBBS, MS, PhD.Professor of Ophthalmology, Advanced
Eye Centre, Postgraduate Institute of Medical Education and Research,
Chandigarh, India
Aman Sharma MD, FRCP (London). Professor of Medicine, Clinical
Immunology and Rheumatology, Program Director, Centre of Excellence in
HIV/AIDS,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India
Arun Kapil Senior ophthalmic technician, Chief, Digital Retina Imaging
Laboratory, Advanced Eye Centre, Postgraduate Institute of Medical
Education and Research, Chandigarh, India
Chandigarh
Acknowledgements
Contents
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Part I Intraocular Signs
1 Retinal Capillary Microaneurysms . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Anatomical Considerations of the Retina . . . . . . . . . . . . . . . . 5
1.3 Pathogenesis of Retinal Capillary Microaneurysm
Formation in Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . . . 6
1.4 Historical Perspective on the Detection of Retinal
Capillary Microaneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.5 Retina Examination to Detect Retinal Capillary
Microaneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.6 Differentiating Retinal Capillary Microaneurysms
and Dot Haemorrhages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.7 Location of Retinal Microaneurysms . . . . . . . . . . . . . . . . . . . . 9
1.8 Leakage from the Retinal Capillary Microaneurysms . . . . . . . 10
1.9 Life Cycle of Retinal Capillary Microaneurysms . . . . . . . . . . 11
1.10 Imaging of Retinal Capillary Microaneurysms . . . . . . . . . . . . 12
1.10.1 Imaging of Retinal Capillary Microaneurysms:
Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.10.2 Imaging of Retinal Capillary Microaneurysms:
OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.10.3 Imaging of Retinal Capillary Microaneurysms:
OCTA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.11 Other Causes of Retinal Capillary Microaneurysms . . . . . . . . 15
1.12 Signicance of Retinal Capillary Microaneurysms . . . . . . . . . 19
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2 Retinal Arteriolar Macroaneurysms (RAM) . . . . . . . . . . . . . . . . 23
2.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.2 Historical Aspects of Retinal Macroaneurysms . . . . . . . . . . . . 23
2.3 Systemic Associations of RAM . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3.1 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3.2 Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.3.3 Sarcoidosis and Uveitis . . . . . . . . . . . . . . . . . . . . . . . . 27
2.3.4 Polyarteritis Nodosa . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3.5 Leukaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3.6 Cerebral Macroaneurysms . . . . . . . . . . . . . . . . . . . . . . 28
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2.3.7 Other Systemic Associations . . . . . . . . . . . . . . . . . . . . 28
2.4 Ocular Associations of RAM . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.4.1 Congenital Retinal Arteriolar Anomalies . . . . . . . . . . . 28
2.4.2 Idiopathic Retinal Vasculitis, Aneurysms,
and Neuroretinitis (IRVAN) and RAM . . . . . . . . . . . . 28
2.4.3 Retinal Vein Occlusion . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.4.4 Toxoplasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.5 Clinical Presentations of RAM . . . . . . . . . . . . . . . . . . . . . . . . 29
2.5.1 Fusiform RAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.5.2 Saccular RAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.5.3 Retinal Capillary Macroaneurysms . . . . . . . . . . . . . . . 31
2.6 Imaging of RAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.7 Treatment of RAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.8 Pathology of RAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.9 RAM Versus Intracerebral Arterial Microaneurysms . . . . . . . 36
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
3 Retinal Cotton Wool Spots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.2 Cotton Wool Spots Versus Medullated Nerve Fibres . . . . . . . . 45
3.3 Causes of Cotton Wool Spots . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.3.1 Cotton Wool Spots in Hypertension . . . . . . . . . . . . . . . 47
3.3.2 CWS in Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . 48
3.3.3 Cotton Wool Spots and Giant Cell Arteritis . . . . . . . . . 51
3.3.4 CWS in Systemic Lupus Erythematosus (SLE). . . . . . 52
3.3.5 CWS in HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
3.4 Imaging of the CWS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.5 Paracentral Acute Middle Maculopathy (PAMM) . . . . . . . . . . 55
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Contents
4 Retinal Hard Exudates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
4.2 Causes of Retinal Hard Exudates . . . . . . . . . . . . . . . . . . . . . . . 60
4.3 Differential Diagnosis of Retinal Hard Exudates . . . . . . . . . . 60
4.3.1 Hard Exudates Versus Soft Exudates . . . . . . . . . . . . . . 60
4.3.2 Hard Exudates Versus Drusen . . . . . . . . . . . . . . . . . . . 60
4.4 Classication of Retinal Hard Exudates [2] . . . . . . . . . . . . . . . 62
4.5 Signicance of Retinal Hard Exudates . . . . . . . . . . . . . . . . . . 62
4.6 Formation of Retinal Hard Exudates . . . . . . . . . . . . . . . . . . . . 63
4.7 Hyperreective Foci as Forme Fruste of Retinal Hard
Exudates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
4.8 Histopathology of Hard Exudates . . . . . . . . . . . . . . . . . . . . . . 66
4.9 Hard Exudates: A Surrogate for Atherosclerosis . . . . . . . . . . . 66
4.10 Serum Lipids and Diabetic Retinopathy . . . . . . . . . . . . . . . . . 66
4.10.1 Hyperlipidaemia and Diabetic Retinopathy . . . . . . . . . 66
4.10.2 Role of Statins in Hard Exudates . . . . . . . . . . . . . . . . . 67
4.11 Complications of Retinal Hard Exudates . . . . . . . . . . . . . . . . . 68
4.12 Treatment of Retinal Hard Exudates Associated with
Macular Oedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
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4.13 Other Causes of Retinal Hard Exudates . . . . . . . . . . . . . . . . . . 70
4.13.1 Retinal Hard Exudates in Branch Retinal Vein
Occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
4.13.2 Retinal Hard Exudates in Adult Coats’ Disease . . . . . 70
4.13.3 Retinal Hard Exudates in Idiopathic Retinal
Vasculitis, Aneurysms and Neuroretinitis (IRVAN) . . 72
4.13.4 Retinal Hard Exudates in Von Hippel–Lindau
Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
5 Retinal Haemorrhages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
5.1.1 Blood Supply of the Retina and the Ocular Barriers . . 81
5.1.2 Role of Physicians . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
5.2 Location of Haemorrhages in the Eye . . . . . . . . . . . . . . . . . . . 82
5.2.1 Haemorrhage in the Anterior Chamber . . . . . . . . . . . . 82
5.2.2 Vitreous Haemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . 82
5.2.3 Subhyaloid and Sub-ILM Haemorrhages . . . . . . . . . . 82
5.2.4 Supercial Retinal Haemorrhages . . . . . . . . . . . . . . . . 85
5.2.5 Dot and Blot Haemorrhages. . . . . . . . . . . . . . . . . . . . . 85
5.2.6 Petaloid Retinal Haemorrhages
(Henle Haemorrhages) . . . . . . . . . . . . . . . . . . . . . . . . . 86
5.2.7 Submacular and Sub-RPE Haemorrhage . . . . . . . . . . . 86
5.2.8 Optic Disc Haemorrhage . . . . . . . . . . . . . . . . . . . . . . . 87
5.2.9 Optic Disc and Peripapillary Haemorrhages in
Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
5.3 Retinal Haemorrhages in Childhood . . . . . . . . . . . . . . . . . . . . 88
5.3.1 Birth Trauma and Neonatal Retinal Haemorrhages . . . 88
5.3.2 Battered Child, Abusive Head Trauma (AHT),
and the Retinal Haemorrhages . . . . . . . . . . . . . . . . . . . 88
5.3.3 Differential Diagnosis of Retinal Haemorrhages in
Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
5.4 Retinal Haemorrhages in Hematological Disorders . . . . . . . . 90
5.4.1 Retinal Haemorrhages in Anaemia, Pancytopenia,
and Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . 90
5.4.2 Retinal Haemorrhages in Leukaemias . . . . . . . . . . . . . 91
5.4.3 Hyperviscosity Syndromes . . . . . . . . . . . . . . . . . . . . . 92
5.4.4 Paroxysmal Nocturnal Haemoglobinuria . . . . . . . . . . . 92
5.4.5 Retinal Haemorrhages in COVID-19 . . . . . . . . . . . . . . 93
5.4.6 High Altitude Retinal Haemorrhages . . . . . . . . . . . . . . 93
5.5 Retinal Haemorrhages in Neurological Disorders . . . . . . . . . . 93
5.5.1 Subarachnoid Haemorrhage and Preretinal
Haemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
5.5.2 Idiopathic Intracranial Hypertension (IIH)
and Retinal Haemorrhages . . . . . . . . . . . . . . . . . . . . . . 93
5.5.3 Wernicke’s Encephalopathy and Retinal
Haemorrhages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
5.5.4 Ocular Ischaemic Syndrome . . . . . . . . . . . . . . . . . . . . 95
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5.5.5 Retinal Haemorrhages in Increased Intracranial
Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
5.5.6 Valsalva Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . 95
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6 New Vessels on the Optic Disc and Elsewhere in the Retina . . . . 101
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.1.1 Blood Supply of the Retina . . . . . . . . . . . . . . . . . . . . . 102
6.1.2 Development of Normal Retinal Vessels . . . . . . . . . . . 102
6.2 Pathophysiology of Diabetic Retinopathy . . . . . . . . . . . . . . . . 102
6.2.1 Muller Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
6.2.2 Pericytes-Endothelial Cell Interaction . . . . . . . . . . . . . 103
6.2.3 Thickening of Basement Membrane in Diabetes
Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
6.2.4 Consequences of the Basement Membrane
Thickening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
6.2.5 Formation of Acellular Retinal Capillaries . . . . . . . . . 104
6.2.6 Retinal Capillary Non- Perfusion and Severity
of Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . 106
6.2.7 Development of Retinal New Vessels . . . . . . . . . . . . . 108
6.2.8 Intraretinal Microvascular Abnormalities (IRMA) . . . 109
6.2.9 Retinal Veins Dilatation, Beading, and Risk
of Progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
6.2.10 New Vessels on the Retina Elsewhere (NVE)
and the Optic Disc (NVD) . . . . . . . . . . . . . . . . . . . . . . 112
6.2.11 Automated Detection of New Vessels
in Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . 116
6.2.12 Chronic Kidney Disease and Diabetic Retinopathy . . . 116
6.3 Other Causes of New Vessels on the Retina . . . . . . . . . . . . . . 117
6.3.1 Retinopathy of Prematurity (ROP) . . . . . . . . . . . . . . . 117
6.3.2 Familial Exudative Vitreoretinopathy (FEVR) . . . . . . 124
6.3.3 Sickle Cell Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . 126
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Contents
7 Subretinal/Submacular Haemorrhage . . . . . . . . . . . . . . . . . . . . . 139
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
7.2 Age-Related Macular Degeneration. . . . . . . . . . . . . . . . . . . . . 140
7.3 Risk Factors for AMD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
7.4 Pathogenesis of AMD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
7.5 Clinical Signs of Age-Related Macular Degeneration . . . . . . . 142
7.6 Current Nomenclature for AMD Lesions [1] . . . . . . . . . . . . . . 144
7.7 Imaging Studies in Macular New Vessels (MNV) . . . . . . . . . . 145
7.8 Polypoidal Choroidal Vasculopathy . . . . . . . . . . . . . . . . . . . . . 147
7.9 Pathogenesis and Risk Factors for Polypoidal Choroidal
Vasculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
7.10 Treatment of Polypoidal Choroidal Vasculopathy . . . . . . . . . . 151
7.11 Treatment of Massive Submacular Haemorrhage . . . . . . . . . . 152
7.12 Other Causes of Submacular Haemorrhage . . . . . . . . . . . . . . . 155
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
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