Ophthalmic Signs in Practice of Medicine

Foreword
Foreword
Foreword
Preface
Acknowledgements
Contents
Part I: Intraocular Signs
	1: Retinal Capillary Microaneurysms
		1.1	 Introduction
		1.2	 Anatomical Considerations of the Retina
		1.3	 Pathogenesis of Retinal Capillary Microaneurysm Formation in Diabetic Retinopathy
		1.4	 Historical Perspective on the Detection of Retinal Capillary Microaneurysms
		1.5	 Retina Examination to Detect Retinal Capillary Microaneurysms
		1.6	 Differentiating Retinal Capillary Microaneurysms and Dot Haemorrhages
		1.7	 Location of Retinal Microaneurysms
		1.8	 Leakage from the Retinal Capillary Microaneurysms
		1.9	 Life Cycle of Retinal Capillary Microaneurysms
		1.10	 Imaging of Retinal Capillary Microaneurysms
			1.10.1	 Imaging of Retinal Capillary Microaneurysms: Morphology
			1.10.2	 Imaging of Retinal Capillary Microaneurysms: OCT
			1.10.3	 Imaging of Retinal Capillary Microaneurysms: OCTA
		1.11	 Other Causes of Retinal Capillary Microaneurysms
		1.12	 Significance of Retinal Capillary Microaneurysms
		References
	2: Retinal Arteriolar Macroaneurysms (RAM)
		2.1	 Epidemiology
		2.2	 Historical Aspects of Retinal Macroaneurysms
		2.3	 Systemic Associations of RAM
			2.3.1	 Hypertension
			2.3.2	 Diabetes Mellitus
			2.3.3	 Sarcoidosis and Uveitis
				2.3.3.1	 Systemic Arterial Macroaneurysms and Sarcoidosis
			2.3.4	 Polyarteritis Nodosa
			2.3.5	 Leukaemia
			2.3.6	 Cerebral Macroaneurysms
			2.3.7	 Other Systemic Associations
		2.4	 Ocular Associations of RAM
			2.4.1	 Congenital Retinal Arteriolar Anomalies
			2.4.2	 Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis (IRVAN) and RAM
			2.4.3	 Retinal Vein Occlusion
			2.4.4	 Toxoplasma
		2.5	 Clinical Presentations of RAM
			2.5.1	 Fusiform RAM
			2.5.2	 Saccular RAM
			2.5.3	 Retinal Capillary Macroaneurysms
		2.6	 Imaging of RAM
		2.7	 Treatment of RAM
		2.8	 Pathology of RAM
		2.9	 RAM Versus Intracerebral Arterial Microaneurysms
		References
	3: Retinal Cotton Wool Spots
		3.1	 Introduction
		3.2	 Cotton Wool Spots Versus Medullated Nerve Fibres
		3.3	 Causes of Cotton Wool Spots
			3.3.1	 Cotton Wool Spots in Hypertension
			3.3.2	 CWS in Diabetic Retinopathy
			3.3.3	 Cotton Wool Spots and Giant Cell Arteritis
			3.3.4	 CWS in Systemic Lupus Erythematosus (SLE)
			3.3.5	 CWS in HIV
		3.4	 Imaging of the CWS
		3.5	 Paracentral Acute Middle Maculopathy (PAMM)
		References
	Untitled
	4: Retinal Hard Exudates
		4.1	 Introduction
		4.2	 Causes of Retinal Hard Exudates
		4.3	 Differential Diagnosis of Retinal Hard Exudates
			4.3.1	 Hard Exudates Versus Soft Exudates
			4.3.2	 Hard Exudates Versus Drusen
		4.4	 Classification of Retinal Hard Exudates [2]
		4.5	 Significance of Retinal Hard Exudates
		4.6	 Formation of Retinal Hard Exudates
		4.7	 Hyperreflective Foci as Forme Fruste of Retinal Hard Exudates
		4.8	 Histopathology of Hard Exudates
		4.9	 Hard Exudates: A Surrogate for Atherosclerosis
		4.10	 Serum Lipids and Diabetic Retinopathy
			4.10.1	 Hyperlipidaemia and Diabetic Retinopathy
			4.10.2	 Role of Statins in Hard Exudates
		4.11	 Complications of Retinal Hard Exudates
		4.12	 Treatment of Retinal Hard Exudates Associated with Macular Oedema
		4.13	 Other Causes of Retinal Hard Exudates
			4.13.1	 Retinal Hard Exudates in Branch Retinal Vein Occlusion
			4.13.2	 Retinal Hard Exudates in Adult Coats’ Disease
			4.13.3	 Retinal Hard Exudates in Idiopathic Retinal Vasculitis, Aneurysms and Neuroretinitis (IRVAN)
			4.13.4	 Retinal Hard Exudates in Von Hippel–Lindau Disease
				4.13.4.1	 Screening for VHL
		References
	5: Retinal Haemorrhages
		5.1	 Introduction
			5.1.1	 Blood Supply of the Retina and the Ocular Barriers
			5.1.2	 Role of Physicians
		5.2	 Location of Haemorrhages in the Eye
			5.2.1	 Haemorrhage in the Anterior Chamber
			5.2.2	 Vitreous Haemorrhage
			5.2.3	 Subhyaloid and Sub-ILM Haemorrhages
			5.2.4	 Superficial Retinal Haemorrhages
			5.2.5	 Dot and Blot Haemorrhages
			5.2.6	 Petaloid Retinal Haemorrhages (Henle Haemorrhages)
			5.2.7	 Submacular and Sub-RPE Haemorrhage
			5.2.8	 Optic Disc Haemorrhage
			5.2.9	 Optic Disc and Peripapillary Haemorrhages in Adolescents
		5.3	 Retinal Haemorrhages in Childhood
			5.3.1	 Birth Trauma and Neonatal Retinal Haemorrhages
			5.3.2	 Battered Child, Abusive Head Trauma (AHT), and the Retinal Haemorrhages
			5.3.3	 Differential Diagnosis of Retinal Haemorrhages in Children
		5.4	 Retinal Haemorrhages in Hematological Disorders
			5.4.1	 Retinal Haemorrhages in Anaemia, Pancytopenia, and Thrombocytopenia
			5.4.2	 Retinal Haemorrhages in Leukaemias
			5.4.3	 Hyperviscosity Syndromes
			5.4.4	 Paroxysmal Nocturnal Haemoglobinuria
			5.4.5	 Retinal Haemorrhages in COVID-19
			5.4.6	 High Altitude Retinal Haemorrhages
		5.5	 Retinal Haemorrhages in Neurological Disorders
			5.5.1	 Subarachnoid Haemorrhage and Preretinal Haemorrhage
			5.5.2	 Idiopathic Intracranial Hypertension (IIH) and Retinal Haemorrhages
			5.5.3	 Wernicke’s Encephalopathy and Retinal Haemorrhages
			5.5.4	 Ocular Ischaemic Syndrome
			5.5.5	 Retinal Haemorrhages in Increased Intracranial Pressure
			5.5.6	 Valsalva Retinopathy
		References
	6: New Vessels on the Optic Disc and Elsewhere in the Retina
		6.1	 Introduction
			6.1.1	 Blood Supply of the Retina
			6.1.2	 Development of Normal Retinal Vessels
		6.2	 Pathophysiology of Diabetic Retinopathy
			6.2.1	 Muller Cells
			6.2.2	 Pericytes-Endothelial Cell Interaction
			6.2.3	 Thickening of Basement Membrane in Diabetes Mellitus
			6.2.4	 Consequences of the Basement Membrane Thickening
			6.2.5	 Formation of Acellular Retinal Capillaries
			6.2.6	 Retinal Capillary Non-Perfusion and Severity of Diabetic Retinopathy
			6.2.7	 Development of Retinal New Vessels
			6.2.8	 Intraretinal Microvascular Abnormalities (IRMA)
			6.2.9	 Retinal Veins Dilatation, Beading, and Risk of Progression
			6.2.10	 New Vessels on the Retina Elsewhere (NVE) and the Optic Disc (NVD)
			6.2.11	 Automated Detection of New Vessels in Diabetic Retinopathy
			6.2.12	 Chronic Kidney Disease and Diabetic Retinopathy
		6.3	 Other Causes of New Vessels on the Retina
			6.3.1	 Retinopathy of Prematurity (ROP)
				6.3.1.1	 Historical Perspective
				6.3.1.2	 Role of Oxygen Supplementation
				6.3.1.3	 Classification of ROP
				6.3.1.4	 Threshold ROP
				6.3.1.5	 Early Treatment of ROP
				6.3.1.6	 Aggressive ROP (A-ROP)
				6.3.1.7	 Cryoablation of ROP
				6.3.1.8	 Laser Photocoagulation for ROP
				6.3.1.9	 Anti-VEGF Therapy for ROP
				6.3.1.10	 Screening Strategies for ROP
			6.3.2	 Familial Exudative Vitreoretinopathy (FEVR)
			6.3.3	 Sickle Cell Retinopathy
				6.3.3.1	 Genetics of Sickle Cell Disease
				6.3.3.2	 Pathophysiology of Sickle Cell Disease
				6.3.3.3	 Clinical Manifestations of Sickle Cell Disease
				6.3.3.4	 Classification of Proliferative Sickle Cell Retinopathy
				6.3.3.5	 Fundus Imaging Studies in Sickle Cell Disease
		References
	7: Subretinal/Submacular Haemorrhage
		7.1	 Introduction
		7.2	 Age-Related Macular Degeneration
		7.3	 Risk Factors for AMD
		7.4	 Pathogenesis of AMD
		7.5	 Clinical Signs of Age-Related Macular Degeneration
		7.6	 Current Nomenclature for AMD Lesions [1]
		7.7	 Imaging Studies in Macular New Vessels (MNV)
		7.8	 Polypoidal Choroidal Vasculopathy
		7.9	 Pathogenesis and Risk Factors for Polypoidal Choroidal Vasculopathy
		7.10	 Treatment of Polypoidal Choroidal Vasculopathy
		7.11	 Treatment of Massive Submacular Haemorrhage
		7.12	 Other Causes of Submacular Haemorrhage
		References
	8: Retinal Arteriolar Changes in Hypertension and Arteriolosclerosis
		8.1	 Structural Considerations of the Blood Vessels
			8.1.1	 Anatomical Considerations of the Central Retinal Artery and the Blood Supply of the Retina
			8.1.2	 Diameter of the Retinal Arterioles and Their Fractal Dimensions
		8.2	 Causes of Hypertension
		8.3	 Measuring Blood Pressure
		8.4	 Arteriosclerosis and Arteriolosclerosis
		8.5	 Fundus Signs of Arteriolosclerosis and Hypertension
			8.5.1	 Enhanced Central Light Reflex
			8.5.2	 Arterial Wall-to-Lumen Ratio
			8.5.3	 Arteriovenous Nicking (AVN)
			8.5.4	 Focal and Diffuse Narrowing of the Retinal Arterioles
			8.5.5	 Retinal Haemorrhages, Cotton Wool Spots, and Microaneurysms
			8.5.6	 Optic Neuropathy and Choroidopathy in Malignant Hypertension
		References
	9: Retinal Vascular Occlusions
		9.1	 Introduction
		9.2	 Non-arteritic Central and Branch Retinal Artery Occlusion
		9.3	 Branch Retinal Vein Occlusion
			9.3.1	 Epidemiology of Branch Retinal Vein Occlusion (BRVO)
			9.3.2	 Risk Factors for BRVO
			9.3.3	 Pathogenesis of BRVO
			9.3.4	 Clinical Presentations of BRVO
			9.3.5	 Role of Fundus Fluorescein Angiography
			9.3.6	 Consequences and Complications of BRVO
				9.3.6.1	 Macular Oedema in BRVO and Treatment Strategies
				9.3.6.2	 Retinal Neovascularization of Retina and Vitreous Haemorrhage in BRVO
		9.4	 Epidemiology of Central Retinal Vein Occlusion (CRVO)
			9.4.1	 Risk Factors for CRVO
			9.4.2	 Pathogenesis of CRVO
			9.4.3	 Clinical Presentation and Classification of CRVO
				9.4.3.1	 Complications of CRVO: Occlusion of the Cilioretinal Artery (CLRA)
				9.4.3.2	 Complications of CRVO: Paracentral Acute Middle Maculopathy
				9.4.3.3	 Complications of CRVO: Persistent Macular Oedema
				9.4.3.4	 Complications of CRVO: Ocular Neovascularization
		9.5	 Inflammatory Retinal Vein Occlusions
		References
	10: Retinal and Choroidal Infections and Inflammation
		10.1	 Anatomical Considerations
		10.2	 Mediators of Inflammation
		10.3	 Retinal and Choroidal Infections and Inflammations: Definition
		10.4	 Introduction
		10.5	 Differentiating Retinitis from Choroiditis
		10.6	 Infectious Uveitis
			10.6.1	 Toxoplasmic Retinochoroiditis
				10.6.1.1	 Prevalence
				10.6.1.2	 Mechanisms of Toxoplasma gondii Infection
				10.6.1.3	 Clinical Diagnosis of Toxoplasma Retinochoroiditis
				10.6.1.4	 Laboratory Diagnosis of Toxoplasmic Retinochoroiditis
				10.6.1.5	 The Standard of Care for Toxoplasmic Retinochoroiditis
				10.6.1.6	 Mechanism of Latency in Toxoplasma gondii Infection
			10.6.2	 Infectious Herpes Simplex and Varicella Zoster Virus Retinitis
				10.6.2.1	 Clinical Signs
				10.6.2.2	 Recurrences and Latency in HSV and VZV Retinitis
				10.6.2.3	 Treatment of HSV and VZV Retinitis
			10.6.3	 CMV Retinitis
				10.6.3.1	 Risk Factors for CMV Retinitis
				10.6.3.2	 Pathogenesis and Pathology of CMV Retinitis
				10.6.3.3	 Treatment of CMV Retinitis
				10.6.3.4	 Prophylaxis for CMV Retinitis
				10.6.3.5	 Alternate Drugs for the Treatment of CMV-R
				10.6.3.6	 When to Stop the Antiviral Therapy in CMV-R
			10.6.4	 Emerging Viral Infections and Retinitis
				10.6.4.1	 Treatment of Post-Fever Retinitis
			10.6.5	 Bacterial Infectious Uveitis-Spirochetal Infections
				10.6.5.1	 Syphilis
				10.6.5.2	 Lyme borreliosis
				10.6.5.3	 Leptospiral Uveitis
			10.6.6	 Other Bacterial Uveitis: Mycobacterium tuberculosis
				10.6.6.1	 Lessons from the Past-TB or No TB
				10.6.6.2	 Endemicity of TB and Tubercular Uveitis
				10.6.6.3	 Clinical Phenotypes of Tubercular Uveitis
					Serpiginous-like Choroiditis
					Choroidal Granuloma
					Retinal Periphlebitis
				10.6.6.4	 Laboratory Diagnosis of Infectious Uveitis Pathogen-Directed Polymerase Chain Reaction (PCR)
				10.6.6.5	 Next-Generation Sequencing (NGS)
				10.6.6.6	 Metagenomics Deep Sequencing (MDS)
		10.7	 Non-infectious Choroiditis and Retinitis
			10.7.1	 Systemic Immune-Mediated Disorders
				10.7.1.1	 Systemic Lupus Erythematosus (SLE) Retinopathy
				10.7.1.2	 Sarcoidosis
					Diagnostic Criteria for Ocular Sarcoidosis
				10.7.1.3	 Behçet’s Syndrome
					Epidemiology and Genetic Predisposition of Behçet’s Syndrome
					Pathology of Behçet’s Syndrome
					Systemic Signs of Behçet’s Syndrome
					Ocular Signs of Behçet’s Syndrome
					Therapy of Behçet’s Uveitis
					Visual Outcome of Behçet’s Syndrome
			10.7.2	 Organ-Specific (Ocular) Immune-Mediated Panuveitis with Multisystem Involvement
				10.7.2.1	 Vogt-Koyanagi-Harada (VKH) Disease
					Clinical Presentations of VKH Disease
					Prodromal Stage of VKH Disease
					Acute Uveitic Stage of VKH Disease
					Convalescent Stage of VKH Disease
					Chronic Recurrent Stage of VKH Disease
					Complications of Acute Versus Late Presentation of VKH
				10.7.2.2	 Sympathetic Ophthalmia
					Epidemiology of Sympathetic Ophthalmia (SO)
					Pathogenesis and Pathology of SO
					Pathology of Sympathetic Ophthalmia
					Clinical Picture of Sympathetic Ophthalmia
					Early Symptoms of Sympathetic Ophthalmia
					Similarity of Sympathetic Ophthalmia and the Acute Uveitic Stage of VKH Disease
					Enucleation of the Injured Eye to Prevent Sympathetic Ophthalmia Is a Myth
			10.7.3	 Organ-Specific (Ocular) Immune-Mediated Disorders
		10.8	 Multiple Evanescent White Dot Syndrome (MEWDS)
		10.9	 Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
		10.10	 Punctate Inner Choroidopathy and Idiopathic Multifocal Choroidopathy (PIC and IMFC)
		10.11	 Acute Zonal Occult Outer Retinopathy (AZOOR)
		10.12	 Birdshot Chorioretinopathy (BCR)
		10.13	 Acute Macular Neuroretinitis (AMN)
		References
	11: Macular Oedema
		11.1	 Anatomical Considerations
		11.2	 Homeostasis in the Retinal Microenvironment
		11.3	 Examination of Retina and Documentation of Macular Oedema
			11.3.1	 Clinical Examination of the Macula
			11.3.2	 Documentation of Macular Oedema-Fundus Photography
			11.3.3	 Fundus Fluorescein Angiography
			11.3.4	 Optical Coherence Tomography
			11.3.5	 Measuring the Central Subfield Thickness (CST) with OCT
		11.4	 Causes of Macular Oedema
			11.4.1	 Diabetic Macular Oedema
				11.4.1.1	 Development of Diabetic Macular Oedema-Breakdown in Retinal Homeostasis
				11.4.1.2	 Thickening of Basement Membrane in Diabetes Mellitus
				11.4.1.3	 Consequences of the Basement Membrane Thickening
				11.4.1.4	 Loss of Pericytes and Endothelial Cells and Microaneurysm Formation
				11.4.1.5	 Focal Versus Diffuse Diabetic Macular Oedema and Clinically Significant Macular Oedema
				11.4.1.6	 The New Classification of Diabetic Macular Oedema
				11.4.1.7	 The OCT Biomarkers in DME
				11.4.1.8	 OCT Angiography in Diabetic Macular Oedema
				11.4.1.9	 Role of Vascular Endothelial Growth Factor in DME
				11.4.1.10	 Anti-VEGF Therapy in Diabetic Macular Oedema
				11.4.1.11	 Newer Therapeutic Paradigms for the Treatment of DME
				11.4.1.12	 Is There a Role for Laser Photocoagulation for DME?
				11.4.1.13	 Role of Corticosteroids in Diabetic Macular Oedema
				11.4.1.14	 Control of Diabetes and Other Comorbid Conditions
			11.4.2	 Macular Oedema in Retinal Vein Occlusions
				11.4.2.1	 Macular Oedema in Branch Retinal Vein Occlusions
				11.4.2.2	 Macular Oedema in Central Retinal Vein Occlusion
		11.5	 Macular Oedema in Uveitis
			11.5.1	 Diagnosis of Macular Oedema in Uveitis
			11.5.2	 OCT Biomarkers in Uveitis Macular Oedema
			11.5.3	 Treatment of Uveitis Macular Oedema
			11.5.4	 Sustained-Release Corticosteroid Implants
				11.5.4.1	 Biodegradable Dexamethasone Implant
				11.5.4.2	 Non-biodegradable Implants
			11.5.5	 Suprachoroidal Injection of Triamcinolone Acetonide Suspension
			11.5.6	 Alternative Strategies to Treat UME
		11.6	 Post-surgical Macular Oedema
			11.6.1	 Historical Perspective: Role of Vitreous Traction
			11.6.2	 Clinical Picture and Fluorescein Angiography in CME Following Cataract Surgery
			11.6.3	 Objective Measurement of Pseudophakic Cystoid Macular Oedema (PCME)
			11.6.4	 Incidence and Risk Factor for Post-surgery Macular Oedema
			11.6.5	 Role of Inflammatory Mediators and Prostaglandins in Surgical Trauma
			11.6.6	 Pathogenesis and Prevention of PCME
			11.6.7	 Treatment of PCME
		11.7	 Macular Oedema in Vitreoretinal Traction
		11.8	 Macular Cystic Changes in Inherited Macular Dystrophies
		11.9	 Drug-Induced Macular Oedema
		References
	12: Subretinal Fluid and Retinal Detachment
		12.1	 Developmental, Anatomical, and Physiological Aspects in Brief
		12.2	 The Flow of Aqueous Fluid in the Eye
		12.3	 Factors That Keep the Retina Attached to RPE and the Accumulation of Subretinal Fluid (SRF)
		12.4	 Causes of Subretinal Fluid
			12.4.1	 Central Serous Chorioretinopathy
				12.4.1.1	 Risk Factors for CSC
				12.4.1.2	 OCT in CSC
				12.4.1.3	 Pathogenesis of SRF in CSC
				12.4.1.4	 Formation of Choroidal New Vessels in CSC
				12.4.1.5	 Treatment of CSC
			12.4.2	 Subretinal Fluid in Choroidal Neovascular Membranes
			12.4.3	 Subretinal Fluid in Diabetic Macular Oedema
			12.4.4	 Subretinal Fluid in Retinal Vein Occlusions
			12.4.5	 Subretinal Fluid in Malignant Hypertension
			12.4.6	 Subretinal Fluid in Uveitis
			12.4.7	 Subretinal Fluid in Metastatic Cancer
		12.5	 Consequence of Subretinal Fluid
			12.5.1	 Tractional Retinal Detachment
			12.5.2	 Myopic Tractional Maculopathy
			12.5.3	 Treatment of Tractional Retinal Detachment
			12.5.4	 Rhegmatogenous Retinal Detachment
			12.5.5	 Pathogenesis of Rhegmatogenous Retinal Detachment
			12.5.6	 Risk Factors for Rhegmatogenous Retinal Detachment
			12.5.7	 Clinical Diagnosis of Rhegmatogenous Retinal Detachment
			12.5.8	 Development of Proliferative Vitreoretinopathy in RRD
			12.5.9	 Treatment of RRD
		References
	13: Macular Degeneration, Geographic Atrophy, and Inherited Retinal Disorders
		13.1	 Introduction
		13.2	 Anatomical Considerations
		13.3	 Complement Pathway-Basics
		13.4	 Age-Related Changes in the Retina
		13.5	 Age-Related Macular Degeneration (AMD)
			13.5.1	 Epidemiology
			13.5.2	 Role of Complement Pathways in AMD
			13.5.3	 Risk Factors for AMD and Its Pathogenesis
			13.5.4	 Epigenetic Factors in Dry AMD
			13.5.5	 Clinical Diagnosis of AMD
			13.5.6	 Classification of AMD
				13.5.6.1	 Geographic Atrophy (GA)
				13.5.6.2	 Progression of Dry AMD to GA
				13.5.6.3	 Treatment of GA
					Nutritional Supplement
					Role of AMD Genotyping
					Complement Inhibition in AMD
					RPE Cell Implantation in Dry AMD
		13.6	 Inherited Retinal Disorders
			13.6.1	 Introduction
			13.6.2	 Ancillary Lab Testing in Inherited Retinal Disorders
				13.6.2.1	 Electroretinography [61]
				13.6.2.2	 Fundus Imaging and Fundus Autofluorescence
				13.6.2.3	 Optical Coherence Tomography
				13.6.2.4	 Genetics of Non-syndromic Retinitis Pigmentosa
			13.6.3	 Non-syndromic Retinitis Pigmentosa: Clinical Signs
			13.6.4	 Leber Congenital Amaurosis
			13.6.5	 RPE 65-Associated LCA
			13.6.6	 CEP290-Associated Retinal Dystrophy
			13.6.7	 Primary Ciliopathies and RP
			13.6.8	 Systemic Diseases Associated with Inherited Retinal Degeneration
				13.6.8.1	 Bardet-Biedl Syndrome
				13.6.8.2	 Alström Syndrome
				13.6.8.3	 Differentiating BBS from Alström Syndrome
				13.6.8.4	 Usher Syndrome
				13.6.8.5	 Senior-Loken Syndrome (SLS)
				13.6.8.6	 Joubert Syndrome (JBTS)
				13.6.8.7	 Jeune Syndrome or the Asphyxiating Thoracic Dystrophy (JATD) and Meckel-Gruber Syndrome (MGS)
		13.7	 Inherited Macular Dystrophies
			13.7.1	 Stargardt’s Disease and Fundus Flavimaculatus (ABCA4 Disorders)
				13.7.1.1	 Treatment of STGD
			13.7.2	 Bestrophinopathies
				13.7.2.1	 Best Vitelliform Macular Dystrophy
				13.7.2.2	 Autosomal Recessive Bestrophinopathy
				13.7.2.3	 Adult Onset Vitelliform Dystrophy
		13.8	 Mitochondrial Retinal Dystrophies
		13.9	 Treatment of Inherited Retinal Disorders
			13.9.1	 Gene Supplement Therapy
			13.9.2	 Antisense Oligonucleotide Treatment
			13.9.3	 Optogenetics
		References
	14: Vascular Malformations, Childhood Cancer Predisposition Syndromes and Their Systemic Associations
		14.1	 Introduction
		14.2	 Retinal Capillary Hemangioblastoma
			14.2.1	 Retinal Capillary Hemangioblastoma—Historical Aspects
			14.2.2	 Retinal Capillary Hemangioblastoma—Genetic Aspects
			14.2.3	 Retinal Capillary Hemangioblastoma—Systemic Associations
			14.2.4	 Retinal Capillary Hemangioblastoma (Angiomas)
			14.2.5	 Treatment of von Hippel-Lindau’s Disease
			14.2.6	 Active Surveillance in VHL
		14.3	 Sturge-Weber Syndrome
			14.3.1	 Sturge-Weber Syndrome—Port-Wine Stain
			14.3.2	 Sturge-Weber Syndrome—Diffuse Choroidal Hemangioma
			14.3.3	 Circumscribed Choroidal Hemangiomas Are Not Associated with SWS
			14.3.4	 Sturge-Weber Syndrome—Glaucoma
			14.3.5	 Sturge-Weber Syndrome—Neurological Associations
		14.4	 Arteriovenous Malformation of the Retina (AVM)—Wyburn-Mason Syndrome
		14.5	 Congenital Retinal Macrovessel
			14.5.1	 Retinal Cavernous Hemangioma—Clinical Presentations
			14.5.2	 Retinal Cavernous Hemangioma—Systemic Associations and Genetics
			14.5.3	 Retinal Cavernous Hemangioma—Complications
			14.5.4	 Retinal Cavernous Hemangioma—Treatment
		14.6	 Retinal Astrocytoma
			14.6.1	 Hamartomas-Tuberous Sclerosis Complex—Introduction
			14.6.2	 Tuberous Sclerosis Complex—Genetics
			14.6.3	 Retinal Astrocytoma—Clinical Signs
			14.6.4	 Retinal Astrocytoma—Treatment
		14.7	 Glioma of the Optic Pathways and Neurofibromatosis
			14.7.1	 Retinoblastoma–Clinical Presentations
			14.7.2	 Retinoblastoma—Genetics in Brief and Implications of Testing
		References
	15: Optic Disc Signs—Cupping, Swelling, Inflammation, and Pallor
		15.1	 Anatomical Considerations
		15.2	 Blood Supply of the Visual Pathways
			15.2.1	 Blood Supply of the Optic Chiasm
			15.2.2	 Blood Supply of the Optic Nerve
			15.2.3	 Blood Supply of the Optic Nerve Head
		15.3	 Evaluation of the Optic Disc
			15.3.1	 Clinical Assessment of the Optic Disc Size
			15.3.2	 Optic Disc Cup (ODC) and Glaucoma
			15.3.3	 Challenges of Evaluation of the Optic Disc Cupping
			15.3.4	 OCT Evaluation of the Glaucomatous Optic Neuropathy (GON)
			15.3.5	 Bruch’s Membrane Opening—Minimum Rim Width in GON
			15.3.6	 Macular OCT in Glaucoma
			15.3.7	 Horizontal Raphe Hemifield Test in Glaucoma
			15.3.8	 OCT Angiography
			15.3.9	 Artificial Intelligence for Automatic Diagnosis of Glaucomatous Optic Neuropathy (GON)
			15.3.10 Myopia and GON
		15.4	 Choosing a Tool for Fundus Examination in Neuro-Ophthalmological Disorders
			15.4.1	 Optic Nerve Head Edema and Papilledema-Clinical Evaluation
			15.4.2	 Ocular Causes of ONH Swelling
			15.4.3	 Signs of Papilledema
				15.4.3.1	 Clinical Grading of Papilledema
			15.4.4	 Role of OCT in Papilledema
			15.4.5	 Psudopapilledema Due to Optic Disc Drusen
			15.4.6	 Papilledema in Idiopathic Intracranial Hypertension
		15.5	 Optic Neuritis—Inflammation of the Optic Nerve
			15.5.1	 Epidemiology of Optic Neuritis
			15.5.2	 Evaluation of Optic Neuritis in the Clinic
				15.5.2.1	 Paraclinical Tests
					Role of Optical Coherence Tomography in Optic Neuritis
					Magnetic Resonance Imaging in Optic Neuritis
			15.5.3	 Diagnosis of Optic Neuritis
			15.5.4	 Multiple Sclerosis-Associated Optic Neuritis (MS-ON)
				15.5.4.1	 Treatment of MS-ON
			15.5.5	 Pathogenic Antibody-Associated Optic Neuritis Syndromes
				15.5.5.1	 Aquaporin-4 Antibody Associated with Neuromyelitis Optica Spectrum Disorder
					Treatment of AQP4-ON and NMOSD
				15.5.5.2	 Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis
					Treatment of MOG-ON
				15.5.5.3	 Collapsin-Response Mediator Protein-5- (CRMP-5) Associated Optic Neuritis
		15.6	 Optic Disc Pallor (Atrophy)
			15.6.1	 Inherited Optic Neuropathies
				15.6.1.1	 Leber’s Hereditary Optic Neuropathy
				15.6.1.2	 Dominant Optic Atrophy
			15.6.2	 Chiasmal Compression Syndrome
				15.6.2.1	 Pituitary Adenomas
				15.6.2.2	 Craniopharyngiomas
				15.6.2.3	 Meningiomas
			15.6.3	 Ischaemic Optic Neuropathies (ION)
				15.6.3.1	 Nonarteritic Anterior Ischaemic Optic Neuropathy
				15.6.3.2	 Risk Factors for NAION
				15.6.3.3	 The Clinical Course of NAION
				15.6.3.4	 Treatment of NAION
			15.6.4	 Posterior Ischaemic Optic Neuropathy (PION)
			15.6.5	 Arteritic Anterior Ischaemic Optic Neuropathy
				15.6.5.1	 Treatment of A-AION
		References
Part II: Extraocular Signs
	16: Pupillary Signs
		16.1	 Anatomical Considerations
			16.1.1	 The Sphincter Pupillae
			16.1.2	 The Dilator Pupillae
			16.1.3	 The Ciliary Ganglion
			16.1.4	 Pupil Size
		16.2	 Pathway for the Pupil Light Reflex
			16.2.1	 Sympathetic Pathway
		16.3	 Testing for Pupillary Reflexes
			16.3.1	 Swinging Flashlight Test
			16.3.2	 Phases of Pupil Light Reflex
			16.3.3	 Causes of RAPD
		16.4	 Pupillary Changes in Lesions of Parasympathetic Pathways
		16.5	 Argyll Robertson Pupil
			16.5.1	 Automated Pupillometry
			16.5.2	 Neurological Pupil Index
		16.6	 Effect of Head Injury on Pupillary Parameters
			16.6.1	 Hutchinson Pupil
			16.6.2	 Parinaud’ Syndrome
			16.6.3	 Horner’s Syndrome
			16.6.4	 Adie’s Tonic Pupil
		16.7	 Limitations of Automated Pupillometry
		16.8	 Effect of Drugs on Pupillary Parameters
		16.9	 Pupillometry in Psychological Evaluation
		References
	17: Red Eyes—Conjunctivitis, Corneal Ulcers, Dry Eye Disease, and Acute Uveitis
		17.1	 Anatomy of the Conjunctiva
			17.1.1	 Blood Supply of the Conjunctiva
			17.1.2	 Nerve Supply of the Conjunctiva
			17.1.3	 Lymphatic Drainage of the Conjunctiva
		17.2	 Brief Anatomy of the Cornea
		17.3	 Red Eyes
			17.3.1	 Allergic Conjunctivitis—Clinical Features and Pathogenetic Mechanisms in Brief
			17.3.2	 Vernal Keratoconjunctivitis
		17.4	 Infectious Conjunctivitis
			17.4.1	 Viral Conjunctivitis
				17.4.1.1	 Epidemic Keratoconjunctivitis
				17.4.1.2	 Herpes Simplex Virus Conjunctivitis
			17.4.2	 Bacterial Conjunctivitis
				17.4.2.1	 Ophthalmia Neonatorum
				17.4.2.2	 Chlamydial Infection of Conjunctiva
					Trachoma
					Inclusion Conjunctivitis
		17.5	 Corneal Ulcers
			17.5.1	 Microbiological Profile of Corneal Ulcers
			17.5.2	 Predisposing Factors for Corneal Ulcers
			17.5.3	 Clinical Features of Corneal Ulcers
				17.5.3.1	 Viral Ulcers
					Herpes Simplex Virus Keratitis
					Herpes Zoster Ophthalmicus
					Differentiating HSV and VZV Keratitis
					Other Clinical Manifestations of HSV and VZV
					Pathogenesis of HSV and VZV Keratitis
					Recurrences of HSV Keratitis
					Diagnosis of HSV and VZV Keratitis
					Treatment of HSV and VZV Keratitis
					Prevention of Recurrences of HSV Keratitis
				17.5.3.2	 Bacterial Corneal Ulcers
				17.5.3.3	 Fungal Corneal Ulcers
				17.5.3.4	 Management of Corneal Ulcers
				17.5.3.5	 Treatment of Bacterial Corneal Ulcers
				17.5.3.6	 Treatment of Filamentous Fungal Keratitis
			17.5.4	 Parasitic Corneal Ulcers
				17.5.4.1	 Diagnosis of Acanthamoeba Keratitis
					Prevention of Acanthamoeba Keratitis
					Treatment of Acanthamoeba Keratitis
				17.5.4.2	 Microsporidial Keratitis
		17.6	 Dry Eye Disorders
			17.6.1	 Physiological Considerations of Tears in Brief
			17.6.2	 Dry Eye Disease
			17.6.3	 Systemic Diseases and Other Factors Associated with DED
			17.6.4	 Pathogenesis of Dry Eye Disorder (DED)
			17.6.5	 Diagnosis of Dry Eye Disease
			17.6.6	 Management of dry eye Disorders
			17.6.7	 Newer Agents in DED
		17.7	 Anterior Uveitis
			17.7.1	 Anatomical, Physiological, and Immunological Considerations of the Anterior Segment
			17.7.2	 Immunology of Uveitis in Brief
			17.7.3	 Mediators of Inflammation
			17.7.4	 Anterior Uveitis-Epidemiology
				17.7.4.1	 Anterior Uveitis (AU)—Clinical Characteristics
					Criteria for SpA
					SpA and Acute Anterior Uveitis
					HLA B 27 and AAU
					Gut-Eye Axis and AAU
					Treatment of AAU
				17.7.4.2	 Anterior Uveitis and Psoriatic Arthritis
				17.7.4.3	 Inflammatory Bowel Disease and Anterior Uveitis
				17.7.4.4	 Reactive Arthritis and Uveitis (Reiter’s Syndrome)
			17.7.5	 Tubulointerstitial Nephritis and Uveitis (TINU)
			17.7.6	 Juvenile Idiopathic Arthritis (JIA) -Associated Uveitis
				17.7.6.1	 Screening, Monitoring, and Treatment for JIA-AU
			17.7.7	 Autoinflammatory Syndromes and Uveitis
				17.7.7.1	 Mechanism of Innate Immunity and its Dysregulation
				17.7.7.2	 Autoinflammatory Disorders and Uveitis
				17.7.7.3	 Blau Syndrome and Sarcoidosis
			17.7.8	 Infective Anterior Uveitis—Viral Uveitis
				17.7.8.1	 Treatment of Viral Anterior Uveitis
		References
	18: Episcleritis, Scleritis, and Peripheral Corneal Ulceration
		18.1	 Sclera and Episclera-Anatomical Considerations
		18.2	 Episcleritis and Scleritis
			18.2.1	 Epidemiology of Episcleritis and Scleritis
			18.2.2	 Etiology of Non-infectious Scleritis
			18.2.3	 Etiology of Infectious Scleritis
			18.2.4	 Clinical Characteristics of Episcleritis
			18.2.5	 Clinical Characteristics of Scleritis
				18.2.5.1	 Classification of Scleritis
				18.2.5.2	 Necrotizing Scleritis
				18.2.5.3	 Posterior Scleritis
				18.2.5.4	 Scleritis in Relapsing Polychondritis
				18.2.5.5	 Scleritis in the Paediatric Age Group
				18.2.5.6	 Severity of Scleritis
			18.2.6	 Surgically Induced Necrotizing Scleritis
			18.2.7	 Complications of Episcleritis and Scleritis
			18.2.8	 Anterior Segment Optical Coherence Tomography to Differentiate Episcleritis from Scleritis
			18.2.9	 Differentiating Infectious from Autoimmune Scleritis
			18.2.10 Pathogenesis of Scleritis
			18.2.11 Pathology of Scleritis
			18.2.12 Treatment of Episcleritis and Scleritis
		18.3	 Cornea-Anatomical Considerations
			18.3.1	 Epidemiology and Etiology of Peripheral Ulcerative Keratitis
			18.3.2	 Systemic Associations of Peripheral Ulcerative Keratitis
			18.3.3	 Peripheral Stromal Keratitis and Peripheral Ulcerative Keratitis
			18.3.4	 Para Central Corneal Melt-Pathogenesis
			18.3.5	 Mooren’s Ulcer
			18.3.6	 Pathology of PUK
			18.3.7	 Systemic Implications for PUK in Systemic Collagen Vascular Diseases
			18.3.8	 Pathogenetic Mechanism for Peripheral Ulcerative Keratitis
			18.3.9	 Treatment of PUK
			18.3.10 Adjunctive Local Treatment to Restore the Integrity of the Globe
		References
	19: Lid Signs, Paralytic Squint, and Ocular Movement Disorders
		19.1	 Lids: Anatomical Considerations
		19.2	 Anthropometry of Lids
		19.3	 Lid Signs
			19.3.1	 Ptosis
				19.3.1.1	 Mechanical Ptosis
				19.3.1.2	 Congenital Ptosis
				19.3.1.3	 Neurogenic Ptosis
				19.3.1.4	 Horner’s Syndrome
			19.3.2	 Lid Retraction of the Upper Eyelid
				19.3.2.1	 Differential Diagnosis of Upper Lid Retraction
			19.3.3	 Lid Lag
				19.3.3.1	 Differential Diagnosis of Lid Lag
			19.3.4	 Spontaneous Blinking
				19.3.4.1	 Apraxia of Eyelid Opening
			19.3.5	 Blepharospasm
		19.4	 Extraocular Muscles- Anatomical Considerations
		19.5	 Cranial Nerve Palsies
			19.5.1	 Oculomotor Nerve Paresis
			19.5.2	 Recurrent Painful Ophthalmoplegic Neuropathy (Previously Labelled) Ophthalmoplegic Migraine)
			19.5.3	 Tolosa-Hunt Syndrome
			19.5.4	 Generalized Myasthenia Gravis
			19.5.5	 Ocular Myasthenia Gravis
		19.6	 Paralytic Squint (Tropia)
			19.6.1	 Testing for the Paretic Muscle
			19.6.2	 Parks-Bielschowsky 3-Step Test-Diagnosing Paresis of a Cyclovertical Muscle
			19.6.3	 Diplopia
			19.6.4	 Hess/Lees Screen/KM Digital Screen
		19.7	 Brief Physiological Considerations of Eye Movements
			19.7.1	 Movements of the Eye-Ductions
			19.7.2	 Conjugate Movements-Versions
			19.7.3	 Vergence
		19.8	 Supranuclear Control of Conjugate Ocular Movements (Gaze)
			19.8.1	 Saccades
			19.8.2	 Smooth Pursuit Movements
			19.8.3	 Vestibulo-Ocular Reflexes
			19.8.4	 Optokinetic Movement Reflex
		19.9	 Nystagmus
		19.10	 Disorders of the Ocular Movements
			19.10.1 Internuclear Ophthalmoplegia
		References
	20: Orbital Signs
		20.1	 Anatomical Considerations
			20.1.1	 Superior Orbital Fissure
			20.1.2	 Inferior Orbital Fissure
			20.1.3	 Contents of the Orbit
			20.1.4	 Spaces of the Orbit
			20.1.5	 Spaces of the Orbit and Orbital Pathologies
		20.2	 Measurement of the Proptosis
		20.3	 Orbital Signs
		20.4	 Thyroid Eye Disease
			20.4.1	 Pathogenesis of Thyroid-Associated Orbitopathy
			20.4.2	 Ophthalmic Signs of Thyroid Eye Disease
				20.4.2.1	 Lid Retraction of the Upper Eyelid
				20.4.2.2	 Lid Lag
				20.4.2.3	 Orbital Signs of Thyroid-Associated Orbitopathy (Ophthalmopathy)
			20.4.3	 Evaluation of the Patient with Thyroid Orbitopathy
				20.4.3.1	 NOSPECS Classification
				20.4.3.2	 Classification of the Severity of Thyroid-Associated Orbitopathy
			20.4.4	 Laboratory Evaluation of Thyroid-Associated Orbitopathy
			20.4.5	 Prevention of Thyroid-Associated Orbitopathy
			20.4.6	 Treatment of Thyroid-Associated Orbitopathy
				20.4.6.1	 Mild TAO
				20.4.6.2	 Moderate to Severe Thyroid Associated Orbitopathy
				20.4.6.3	 Sight Threatening Thyroid-Associated Orbitopathy
		20.5	 Infiltrative Lesions of Extraocular Muscles
		20.6	 Causes of Extraocular Muscles Enlargement
			20.6.1	 Orbital Myositis
				20.6.1.1	 Measuring the Diameter of the Extraocular Muscles
			20.6.2	 IgG4-Related Ophthalmic Disease (IgG4-ROD)
		20.7	 Orbital Lymphoma
		20.8	 Orbital Metastasis
		20.9	 Lacrimal Gland Granulomas and Tumours
		20.10	 Orbital Granulomas
		20.11	 Tuberculosis of the Orbit
		20.12	 Orbital Granulomatosis with Polyangiitis
		20.13	 Vascular Malformations of the Orbit
			20.13.1 Carotid-Cavernous Fistula
			20.13.2 Other Orbital Malformations: (Figs. 20.18, 20.19, and 20.20)
				20.13.2.1	 Orbital Varices
				20.13.2.2	 Arteriovenous Malformations
		References