A Quick Guide to Pediatric Retina

Preface
Acknowledgments
Contents
Part I: ROP
	1: The Pathophysiology of Retinopathy of Prematurity
		1.1	 Introduction
		1.2	 Pathophysiology Associated with Reduced Vascularity in Phase I and Events Leading into Phase II
			1.2.1	 Postnatal Growth and IGF-1
			1.2.2	 Oxygen
			1.2.3	 Light
			1.2.4	 Erythropoietin and Role of Stress-Induced Factors in Infant
		1.3	 Pathophysiology Related to Phase II
			1.3.1	 Vascular Endothelial Growth Factor Signaling
			1.3.2	 Reactive Oxygen Species
		References
	2: Animal Models of Retinopathy of Prematurity
		2.1	 Introduction
		2.2	 Experimental Models of ROP
			2.2.1	 Early Animal Models of OIR: The Feline and Canine Models
			2.2.2	 The Mouse Model of OIR
				2.2.2.1	 Postnatal Development of Mouse Retinal Vasculature
				2.2.2.2	 The Mouse OIR Model
			2.2.3	 The Rat Model of OIR
			2.2.4	 The Zebrafish Model
			2.2.5	 Hyperglycemia-Associated ROP Models
		2.3	 Summary
		References
	3: Evolution of Major Clinical Trials in ROP
		3.1	 Major Clinical Trials: ROP Treatment (Summary in Table 3.1)
			3.1.1	 The Multicenter Trial of Cryotherapy for ROP (CRYO-ROP) [1–5]
			3.1.2	 Cryotherapy Versus Laser Photocoagulation [6, 7]
			3.1.3	 Early Treatment for Retinopathy of Prematurity Randomized Trial (ETROP) [8, 9]
			3.1.4	 Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity (BEAT-ROP) [10, 11]
		3.2	 Major Clinical Trials: The Role of Oxygen
			3.2.1	 Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) [12]
			3.2.2	 High Oxygen Percentage in Retinopathy of Prematurity Study (HOPE-ROP Study) [13]
			3.2.3	 Target Ranges of Oxygen Saturation in Extremely Preterm Infants (the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) [14]
			3.2.4	 Systematic Review and Meta-analysis
		3.3	 Major Clinical Trial: The Role of Light
			3.3.1	 Lack of Efficacy of Light Reduction in Preventing Retinopathy of Prematurity (LIGHT-ROP) [17]
		3.4	 Major Clinical Trial: The Role of Nutrients
			3.4.1	 Vitamin E Prophylaxis to Reduce Retinopathy of Prematurity: A Reappraisal of Published Trial [18]
		References
	4: Diagnosis and Classification of ROP
		4.1	 Introduction
		4.2	 Diagnosis
		4.3	 Classification
		4.4	 Location of Disease
		4.5	 Clinical Approach to Localization the Zone of ROP
			4.5.1	 Key Points About Zones
		4.6	 Staging of the Disease
			4.6.1	 Key Points About Stages of ROP
		4.7	 Pre-plus and Plus Disease
			4.7.1	 Key Points About Pre-plus and Plus Disease
		4.8	 Aggressive Posterior ROP (AP-ROP)
			4.8.1	 Key Points About AP-ROP
		4.9	 Regression of ROP
		4.10	 Summary
		References
	5: Differential Diagnosis of ROP
		5.1	 Medical History
			5.1.1	 Genetic Background
		5.2	 Clinical Observations
			5.2.1	 Retinal Ischemia
				5.2.1.1	 Familial Exudative Vitreoretinopathy
				5.2.1.2	 Incontinentia Pigmenti
				5.2.1.3	 Shaken Baby Syndrome
			5.2.2	 Subretinal Exudation
			5.2.3	 Retinal Detachment
			5.2.4	 Macular Ectopia
			5.2.5	 Retinal Folds
		References
	6: Aggressive Posterior Retinopathy of Prematurity (APROP)
		6.1	 What is APROP?
		6.2	 Importance of APROP Recognition: Poor Response to Treatment
		6.3	 Formal ICROP Definition
		6.4	 Positive Features of APROP
		6.5	 Toward Updating the Definition of APROP
		6.6	 Suspected Pathophysiology
		6.7	 Special Forms of APROP: Oxygen Induced
		6.8	 Special Forms of APROP: Recurrence/Reactivation after anti-VEGF
		6.9	 Present State of APROP Detection and Treatment Options
		6.10	 Treatment of APROP: Laser or Anti-VEGF
		6.11	 Reactivation After Anti-VEGF
		References
	7: Familial Exudative Vitreoretinopathy or Retinopathy of Prematurity
		7.1	 Introduction
		7.2	 Widefield Fluorescein Angiography in ROP, FEVR, and fROP/ROPER
		7.3	 Conclusion
		References
	8: Telemedicine in Retinopathy of Prematurity
		8.1	 Telemedicine in Retinopathy of Prematurity
		8.2	 Challenges in Tele-ROP
		References
	9: Optical Coherence Tomography in Retinopathy of Prematurity
		9.1	 Introduction
		9.2	 SD-OCT
		9.3	 OCT Difference Between Adult, Term and Preterm Infants
		9.4	 OCT in ROP
			9.4.1	 Macular Edema
			9.4.2	 Vitreous Pathology
			9.4.3	 Popcorn Retinopathy/Extraretinal Tissue
			9.4.4	 Plus Disease
			9.4.5	 Foveal Involvement
		9.5	 Conclusion
		References
	10: FA in ROP
	11: Laser Treatment for Retinopathy of Prematurity
		11.1	 Cryotherapy
		11.2	 Laser Photocoagulation
		11.3	 Ongoing Treatments
		11.4	 Conclusions
		References
	12: Anti-VEGF in ROP
		12.1	 Anti-VEGF as a Primary Treatment for ROP
		12.2	 Anti-VEGF for Progressing Cases After They Have Been Previously Treated Either with Laser or with an Anti-VEGF Drug
		12.3	 - Anti-VEGF as an Adjunct in Vitreoretinal Surgery in ROP
		12.4	 Injection Technique
		Reference
	13: Surgical Management of Stage 4 ROP
		13.1	 Epidemiology of Advanced ROP
		13.2	 Pathogenesis
		13.3	 Clinical Course
		13.4	 Management
		13.5	 Lens-Sparing Vitrectomy
		13.6	 Limbal Approach for Lensectomy and Vitrectomy
		13.7	 Minimal Intervention to Achieve Surgical Goals
		References
	14: Surgical Management of Stage 5 Retinopathy of Prematurity
		14.1	 Introduction
		14.2	 Stage 5 ROP
		14.3	 Surgical Technique
		14.4	 Surgical Results
		14.5	 Conclusions
		References
	15: Endoscopic Surgery in ROP
		15.1	 Advent of EAV
		15.2	 Advantages Over Modern-Day Microscope Viewing
		15.3	 ROP Traction Retinal Detachment
		15.4	 Surgical Tips
			15.4.1	 Practical Guide to Setup and How to Perform Surgery
			15.4.2	 Staying Out of Trouble
		15.5	 Case Study Example
			15.5.1	 ROP
		15.6	 Conclusions
		References
	16: Foveal Development in Retinopathy of Prematurity
		16.1	 Normal Foveal Development
			16.1.1	 Early Development
			16.1.2	 20–40 Weeks of Gestation
			16.1.3	 After Birth
			16.1.4	 OCT Imaging of Foveal Development
		16.2	 Effect of Prematurity and Retinopathy of Prematurity on Foveal Development
			16.2.1	 Formation of the Foveal Pit
			16.2.2	 Neurovascular Development in the Fovea
			16.2.3	 Other Foveal Findings Associated with ROP
			16.2.4	 Retinal Schisis and Detachment in ROP
		16.3	 Summary
		References
	17: Neurodevelopmental Outcomes Following Anti-VEGF Treatment for ROP
		References
	18: Artificial Intelligence for Retinopathy of Prematurity Diagnosis
		18.1	 Real-World Problems
		18.2	 Feature Extraction and Machine Learning
		18.3	 Deep Learning
		18.4	 Translating to Clinical Practice: Development of a Severity Scale for ROP Screening
		18.5	 Disease Monitoring Using an AI-Based Severity Score
		18.6	 Future Applications
		References
	19: E-Education in ROP
		References
	20: Ultra-widefield Imaging in Pediatric Retinal Diseases
		20.1	 Introduction
		20.2	 Imaging Technology
		20.3	 Challenges and New Techniques
			20.3.1	 Patient Cooperation
				20.3.1.1	 Artifacts
				20.3.1.2	 Mercator Projection
			20.3.2	 Oral FFA
		References
Part II: Non-ROP Pediatric Retina
	21: Retinoblastoma
		21.1	 Epidemiology
		21.2	 Genetics
		21.3	 Natural History of Retinoblastoma (Fig. 21.2)
		21.4	 Clinical Presentation
		21.5	 Investigations
		21.6	 Differential Diagnosis
		21.7	 Intraocular Classification (Staging)
		21.8	 Management
		21.9	 General Principles
		21.10	 Treatment Modalities
		References
	22: Paediatric Intra-ocular Tumours (Non-RB)
		22.1	 Retinal Astrocytoma (Astrocytic Hamartoma)
			22.1.1	 History
			22.1.2	 Etiopathogenesis
			22.1.3	 Clinical Features
			22.1.4	 Diagnosis
			22.1.5	 Differential Diagnosis
			22.1.6	 Treatment
			22.1.7	 Outcomes
		22.2	 Combined Hamartoma of Retina and Retinal Pigment Epithelium
			22.2.1	 History
			22.2.2	 Origin
			22.2.3	 Clinical Features
			22.2.4	 Systemic Associations
			22.2.5	 Diagnosis
			22.2.6	 Differential Diagnosis
			22.2.7	 Treatment
			22.2.8	 Prognosis
		22.3	 Medulloepithelioma
			22.3.1	 History
			22.3.2	 Origin
			22.3.3	 Clinical Presentation
			22.3.4	 Diagnosis
			22.3.5	 Histopathology
			22.3.6	 Differential Diagnosis
			22.3.7	 Management
			22.3.8	 Outcomes
		References
	23: Congenital X-Linked Retinoschisis
		23.1	 Introduction
		References
	24: Inherited Retinal Degenerations in the Pediatric Population
		24.1	 Introduction and Short Overview on Inherited Retinal Degenerations (IRDs)
		24.2	 Examination Techniques with Special Focus on the Pediatric Age Group
		24.3	 Selected Examples of IRDs with Identified Genotypes
			24.3.1	 Ocular Development and Metabolic Disease
				24.3.1.1	 PAX6
				24.3.1.2	 Norrie Disease
				24.3.1.3	 Juvenile Ceroid lipofuscinosis (CLN3)
			24.3.2	 Ciliopathies
				24.3.2.1	 CEP290-Associated IRD
				24.3.2.2	 Bardet–Biedl Syndromes
			24.3.3	 Early Onset Severe Retinal Dystrophies (EOSRD, EORD, SECORD)
				24.3.3.1	 Photoreceptor Guanylate Cyclase (GUCY2D) Phenotypes
				24.3.3.2	 AIPL1 (Aryl Hydrocarbon Receptor Interacting Protein-Like 1)
				24.3.3.3	 TULP1 (Tubby-Like Protein 1)
				24.3.3.4	 CRB1 (Crumbs Cell Polarity Complex Component 1)
				24.3.3.5	 MERTK (MER Tyrosine Kinase) Phenotype
				24.3.3.6	 RDH12 (Retinol Dehydrogenase 12) Associated Retinal Degeneration
				24.3.3.7	 RPGRIP (Retinitis Pigmentosa GTPase Interacting Protein 1)
				24.3.3.8	 RPE65 Phenotype (RPE65 Mutation-Associated IRD)
			24.3.4	 Childhood Onset Retinal Dystrophies
				24.3.4.1	 ABCA4 (ATP-Binding Cassette, Subfamily A, Member 4)
				24.3.4.2	 XLRP (RP3)-RPGR (Retinitis Pigmentosa GTPase Regulator)
				24.3.4.3	 Choroideremia
			24.3.5	 Bestrophinopathies
				24.3.5.1	 Vitelliform Macular Dystrophy (Best Disease, VMD2)
				24.3.5.2	 Autosomal Recessive Bestrophinopathy
				24.3.5.3	 VRCP (ADVIRC, Vitreoretinochoroidopathy, Autosomal Dominant)
			24.3.6	 The Achromatopsias
				24.3.6.1	 Achromatopsia
				24.3.6.2	 KCNV2 (Potassium Channel, Voltage-Gated, Subfamily V, Member 2)
			24.3.7	 X-Linked Retinoschisis
			24.3.8	 Summary
		References
	25: Familial Exudative Vitreoretinopathy
		25.1	 Introduction and Epidemiology
		25.2	 Pathophysiology
		25.3	 Histopathology
		25.4	 Clinical Presentation
		25.5	 Multimodal Imaging
			25.5.1	 Fluorescein Angiography
			25.5.2	 Optical Coherence Tomography
			25.5.3	 Optical Coherence Tomography Angiography (OCTA)
		25.6	 Differential Diagnosis
		25.7	 Treatment
			25.7.1	 Long-Term Ocular Examinations and Screening
			25.7.2	 Non-surgical Treatment
			25.7.3	 Surgical Treatment
		25.8	 Prognosis
		25.9	 Conclusion
		References
	26: Persistent Fetal Vasculature
		26.1	 Classification of PFV
			26.1.1	 Laterality of PFV
			26.1.2	 Anterior, Posterior, and Combined PFV
		26.2	 Clinical Manifestations of PFV
			26.2.1	 Anterior PFV
			26.2.2	 Posterior PFV
			26.2.3	 Combined PFV
		References
	27: Pediatric Uveitis
		27.1	 Juvenile Idiopathic Arthritis
		27.2	 Tubulointerstitial Nephritis and Uveitis Syndrome
		27.3	 Brau Syndrome
		27.4	 Ocular Toxoplasmosis
		27.5	 Ocular Cat-Scratch Disease
		References
	28: Coats’ Disease
		28.1	 Introduction
		28.2	 Pathogenesis
		28.3	 Epidemiology
		28.4	 Presentation
		28.5	 Clinical Findings at Presentation
		28.6	 Differentiation from Retinoblastoma
		28.7	 Treatment
		28.8	 Prognosis
		References
	29: Stickler Syndrome and Associated Collagenopathies
		29.1	 History
		29.2	 Genetics and Clinical Categories
		29.3	 Diagnosis: Patient Presentation Categories, and Key Clinical Features
		29.4	 Diagnostic Criteria for SS and Clinical Practice Pattern
		29.5	 Management
			29.5.1	 Surveillance
			29.5.2	 Prophylaxis and Degrees of Uncertainty
			29.5.3	 Limiting High-Risk Behaviors
			29.5.4	 Surgical Planning
			29.5.5	 Giant Retinal Tear Surgery
		References
	30: Genetic Testing in Pediatric Retina
		30.1	 Genetic Testing of Pediatric Retina
		30.2	 Genes Causing Retinal Disorders in Children
		30.3	 Strategies for Identifying Causative Mutations
		30.4	 Issues to Be Considered
		References
	31: Pediatric Macular Hole
		References
	32: Non-accidental Trauma
		32.1	 Introduction
		32.2	 Evaluation
		32.3	 Medical Management
		32.4	 Surgical Management
		References
	33: Rhegmatogenous Retinal Detachments in the Pediatric Population and Special Considerations for Pediatric Vitreoretinal Surgery
		33.1	 Introduction
			33.1.1	 Epidemiology and Clinical Presentation
			33.1.2	 RRDs Associated with Congenital Developmental Anomalies
				33.1.2.1	 Stickler Syndrome
				33.1.2.2	 Marfan Syndrome
				33.1.2.3	 Retino-choroidal Coloboma
				33.1.2.4	 Atopic Dermatitis
		33.2	 Special Considerations for Pediatric Vitreoretinal Surgery
			33.2.1	 Anatomical Considerations
			33.2.2	 Surgical Techniques
				33.2.2.1	 Vitrectomy
				33.2.2.2	 Scleral Buckling
				33.2.2.3	 Endoscopic Vitrectomy
				33.2.2.4	 Enzymatic Vitreolysis
			33.2.3	 Vitreous Tamponades
			33.2.4	 Postoperative Care
		33.3	 Conclusion
		References
Index