This book presents the latest knowledge and expert guidance on all aspects of inherited retinal diseases, including molecular genetics, diagnosis, clinical features, general principles of treatment, novel treatment methods, and genetic counseling. Recent years have witnessed great advances in understanding of the genetic and cytological background of these diseases. Genetic analysis methods such as next generation sequencing have remarkably reduced the cost and time required for massive analysis of patients’ samples. Studies on gene therapy and stem cell therapy have been successfully carried out in animal models, and gene therapy is now available for Leber congenital amaurosis caused by RPE65 mutations. Against this background, Inherited Retinal Disease will be an invaluable up-to-date resource for ophthalmologists, medical students, and researchers in ocular inflammation. In addition to supplying essential information on each individual disorder, it features many interesting cases contributed by global leaders in the field as well as clinical photographs obtained with newer imaging techniques and numerous images of rare but clinically important diseases.
Author(s): Hyeong-Gon Yu
Publisher: Springer
Year: 2022
Language: English
Pages: 245
City: Singapore
Preface
Contents
1: Molecular Genetics of Inherited Retinal Diseases
1.1 Introduction
1.2 Importance of Molecular Genetic Diagnostics in IRD
1.3 Techniques of Genetic Analysis
1.3.1 Linkage Analysis
1.3.2 Sanger Sequencing
1.3.3 Next-Generation Sequencing
1.3.3.1 Targeted Exome Sequencing
1.3.3.2 Whole Exome Sequencing
1.3.3.3 Whole Genome Sequencing
1.4 Molecular Genetics of Inherited Retinal Disease
1.4.1 Genes Affecting Photoreceptor Development
1.4.1.1 CRX
1.4.2 Genes Affecting Intracellular Trafficking and Cilia Function
1.4.2.1 CEP290
1.4.2.2 BBSs
1.4.2.3 RPGR
1.4.2.4 MYO7A
1.4.2.5 USH2A
1.4.2.6 RP1
1.4.3 Genes Affecting Phototransduction and Structure Formation
1.4.3.1 PRPH2
1.4.3.2 RHO
1.4.3.3 PDE6s
1.4.3.4 CNGAs and CNGBs
1.4.4 Genes Affecting Synaptic Transmission
1.4.4.1 CACNA1F
1.4.5 Genes Affecting RPE Integrity or Function
1.4.5.1 RPE65
1.4.5.2 MERTK
1.4.6 Others
1.4.6.1 ABCA4
1.4.6.2 EYS
1.4.6.3 CHM
1.4.6.4 BEST1
1.5 Conclusion
References
2: Approach to Inherited Retinal Diseases
2.1 Introduction
2.2 Examination of Patients with IRDs
2.2.1 Color Fundus Photography and Fundus Autofluorescence Imaging
2.2.2 Optical Coherence Tomography
2.2.3 Visual Field Testing
2.2.4 Electroretinography
2.3 Inherited Retinal Disease Categories
References
3: Stem Cell and Gene Therapy for Inherited Retinal Diseases
3.1 Introduction
3.2 Stem Cell Therapy
3.2.1 Strategies for Stem Cell Therapy for Eyes with Retinal Degeneration
3.2.2 Human Embryonic Stem Cells
3.2.3 Induced Pluripotent Stem Cells
3.2.4 Human Retinal Progenitor Cells
3.2.5 Bone Marrow Stem Cells
3.2.6 Three-Dimensional Retinal Organoid
3.2.7 Safety and Adverse Events with Stem Cell Therapy
3.3 Gene Therapy
3.3.1 Types of Gene Therapy
3.3.2 Vectors
3.3.2.1 Adenovirus
3.3.2.2 Adenovirus-Associated Virus
3.3.2.3 Lentivirus
3.3.2.4 Non-viral Vectors
3.3.3 Gene Editing
3.3.4 Gene Therapy for Inherited Retinal Disease
3.3.5 History of Gene Therapy
3.3.6 Gene Therapy Clinical Trials
3.3.7 Retinitis Pigmentosa
3.3.7.1 Syndromic Retinitis Pigmentosa
3.3.7.2 Non-syndromic Retinitis Pigmentosa
Autosomal Recessive Retinitis Pigmentosa
Autosomal Dominant Retinitis Pigmentosa
X-Linked Retinitis Pigmentosa
3.3.7.3 Leber Congenital Amaurosis
3.3.8 Choroideremia
3.3.9 Achromatopsia
3.3.10 Stargardt Disease
3.3.11 X-Linked Retinoschisis
3.4 Summary
References
4: Retinitis Pigmentosa
4.1 Introduction
4.2 Clinical Findings
4.2.1 Fundus Finding
4.2.2 Prevalence
4.2.3 Inheritance
4.3 Clinical Testing
4.3.1 Electroretinogram
4.3.2 Visual Field
4.3.3 Optical Coherence Tomography
4.3.3.1 Outer Retina
4.3.3.2 Inner Retina
4.3.3.3 Choroid
4.3.3.4 Macular Abnormality
4.3.4 Optical Coherence Tomography Angiography
4.3.5 Fundus Autofluorescence
4.3.6 Fluorescein Angiography
4.3.7 Adaptive Optics
4.4 Genetics of Nonsyndromic RP
4.4.1 Phototransduction Cascade
4.4.2 Visual Cycle
4.4.3 Ciliary Transport
4.4.4 Outer Segment Structure
4.4.5 Interphotoreceptor Matrix
4.5 Management and Treatment of RP
4.5.1 Counseling
4.5.2 Management of Complications
4.5.3 Treatment Based on Specific Genetic Abnormality
4.5.4 Treatment Not Associated with Specific Genetic Abnormality
References
5: Syndromic Retinitis Pigmentosa
5.1 Syndromic Retinitis Pigmentosa
5.2 Usher Syndrome
5.3 Ciliopathy
5.3.1 Bardet-Biedle Syndrome
5.3.2 Senior Loken Syndrome
5.3.3 Joubert Syndrome
5.3.4 Alagille Syndrome
5.4 Retinopathy Associated with Inborn Errors of Metabolism
5.4.1 Neuronal Ceroid Lipofuscinoses
5.4.2 Refsum Disease
5.5 Retinopathy Associated with Mitochondrial Disorders
5.5.1 Kearn-Sayre Syndrome
5.5.2 Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes
References
6: Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy
6.1 Introduction
6.2 Clinical Features
6.2.1 Signs and Symptoms
6.2.2 Fundus Findings
6.3 Retinal Imaging
6.4 Molecular Genetics
6.5 Treatment Principles
6.5.1 Symptomatic Management
6.5.2 Novel Treatment Methods
6.6 Specific Causes of LCA/EOSRD
6.6.1 GUCY2D-LCA/EOSRD
6.6.2 CEP290-LCA/EOSRD
6.6.3 CRB1-LCA/EOSRD
6.6.4 RDH12-LCA/EOSRD
6.6.5 RPE65-LCA/EOSRD
6.6.6 TULP1, AIPL1, and NMNAT1-LCA
6.7 Concluding Remarks and Future Prospects
References
7: Congenital Stationary Night Blindness
7.1 Introduction
7.2 CSNB with Normal Fundus Appearance
7.2.1 Schubert–Bornschein Type CSNB, Complete Form
7.2.1.1 Clinical Presentation
7.2.1.2 Electrophysiology
7.2.1.3 Genetics and Pathogenesis
7.2.2 Schubert–Bornschein Type CSNB, Incomplete Form
7.2.2.1 Clinical Presentation
7.2.2.2 Electrophysiology
7.2.2.3 Genetics and Pathogenesis
7.2.3 Riggs Type CSNB
7.2.3.1 Clinical Presentation
7.2.3.2 Electrophysiology
7.2.3.3 Genetics and Pathogenesis
7.3 CSNB with Abnormal Fundus Appearance
7.3.1 Oguchi Disease
7.3.1.1 Clinical Presentation
7.3.1.2 Electrophysiology
7.3.1.3 Genetics and Pathogenesis
7.3.2 Fundus Albipunctatus
7.3.2.1 Clinical Presentation
7.3.2.2 Electrophysiology
7.3.2.3 Genetics and Pathogenesis
References
8: Vitelliform Macular Dystrophy
8.1 Introduction
8.2 Epidemiology and Asian Perspective
8.3 Molecular Biology
8.4 Clinical Features
8.4.1 BVMD
8.4.2 AVMD
8.5 Genetic Aspects
8.5.1 BVMD
8.5.2 AVMD
8.6 Future Perspectives for Therapy
8.7 Summary
References
9: Stargardt Macular Dystrophy
9.1 Introduction
9.2 Clinical Presentations
9.3 Molecular Genetics
9.4 Disease Mechanism
9.5 Therapeutic Approaches
9.6 Conclusion
References
10: Cone Dystrophy/Cone-Rod Dystrophy
10.1 Introduction
10.2 Clinical Feature and Diagnosis
10.3 Genetics of Cone/Cone-Rod Dystrophy
10.4 Differential Diagnosis
10.5 Treatment
References
11: X-Linked Retinoschisis
11.1 Introduction
11.2 Genetics
11.3 Clinical Features
11.4 Differential Diagnosis
11.5 Treatment Options
11.6 Visual Prognosis
References
12: Von Hippel Lindau Disease and Retinal Hemangioblastoma
12.1 Introduction
12.2 Genetics
12.3 Clinical Features
12.3.1 Systemic Features
12.3.2 Ocular Features
12.4 Diagnosis of Retinal Hemangioblastoma and von Hippel-Lindau Disease
12.5 Treatment of Ocular von Hippel-Lindau Disease
References
13: Other Macular Dystrophies 1
13.1 Occult Macular Dystrophy
13.2 Butterfly-Shaped Pigment Dystrophy (Pattern Dystrophy)
13.3 Sorsby Fundus Dystrophy
13.4 Bietti’s Crystalline Retinopathy
13.5 Autosomal Dominant Radial Drusen (Doyne Honeycomb Retinal Dystrophy)
13.6 Others
13.6.1 North Carolina Macular Dystrophy
13.6.2 Dominant Cystoid Macular Dystrophy
References
14: Other Macular Dystrophies 2
14.1 Sorsby Fundus Dystrophy
14.1.1 Molecular Genetics
14.1.2 Clinical Manifestation
14.1.3 Differential Diagnosis
14.1.4 Management
14.2 North Carolina Macula Dystrophy
14.3 Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese/Autosomal Dominant Drusen
14.3.1 Molecular Genetics
14.3.2 Clinical Manifestation
14.3.3 Differential Diagnosis
14.3.4 Treatment
14.4 Bietti’s Crystalline Dystrophy
14.4.1 Molecular Genetics
14.4.2 Clinical Manifestation
14.4.3 Differential Diagnosis
14.4.4 Treatment
References
15: Hereditary Vitreoretinal Degenerations
15.1 Chondrodysplasias Associated with Vitreoretinal Degeneration
15.1.1 Stickler Syndrome
15.1.1.1 Molecular Genetics
15.1.1.2 Clinical Phenotypes
Ocular Findings
Extraocular Findings
15.1.1.3 Management
15.1.2 Marshall Syndrome
15.1.3 Knobloch Syndrome
15.1.4 Kniest Dysplasia
15.1.5 Weissenbacher–Zweymüller Syndrome
15.2 Wagner Syndrome
15.2.1 Molecular Genetics
15.2.2 Clinical Phenotypes
15.2.3 Management
15.3 Snowflake Vitreoretinal Degeneration
15.3.1 Molecular Genetics
15.3.2 Clinical Phenotypes
15.3.3 Management
15.4 Retinal Nuclear Receptor (NR2E3)-Related Diseases
15.4.1 Molecular Genetics
15.4.2 Clinical Phenotypes
15.4.3 Electrophysiology
15.4.4 Management
15.5 Autosomal Dominant Vitreoretinochoroidopathy
References
16: Hereditary Choroidal Dystrophy
16.1 Choroideremia
16.1.1 Clinical Features
16.1.2 Molecular Genetics and Pathophysiology
16.1.3 Gene Therapy
16.2 Gyrate Atrophy
16.2.1 Clinical Features
16.2.2 Molecular Genetics and Pathophysiology
16.2.3 Management of Gyrate Atrophy
16.3 Central Areolar Choroidal Dystrophy (CACD)
16.3.1 Genetics
16.3.2 Pathogenesis
16.3.3 Ocular Features
References
17: Retinal Disorders Mimicking Inherited Retinal Diseases
17.1 Introduction
17.2 Phenocopies of Retinitis Pigmentosa
17.2.1 Pigmented Paravenous Chorioretinal Atrophy (PPCRA)
17.2.2 Choroideremia
17.2.3 Gyrate Atrophy of the Choroid and Retina
17.3 Pseudo-inherited Retinal Disease
17.3.1 Traumatic Retinopathy
17.3.2 Autoimmune Retinopathy
17.3.3 Retinal Infections
17.3.4 Chronic Uveitis
17.3.5 Drug Toxicity
17.3.6 Unilateral Pigmentary Retinopathy
17.3.7 Diffuse Unilateral Subacute Neuroretinitis (DUSN)
References
