Inherited Retinal Diseases (IRD)

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders characterised by photoreceptor degeneration or dysfunction. These disorders typically present with severe vision loss that can be progressive, with disease onset ranging from congenital to late adulthood.

Classification Approach:

1. Genetic Basis: - Gene Identification: Identification of specific genetic mutations responsible for various IRDs. Over 100 genes have been implicated in these diseases.  Genotype-Phenotype Correlation: Understanding how specific genetic mutations correlate with clinical presentations helps in classifying and managing IRDs.

2. Clinical Presentation: - Phenotypic Variability: IRDs can present with a wide range of symptoms and severities, even among individuals with the same genetic mutation.

Disease Progression: The rate of progression and the specific retinal regions affected can vary, aiding in subclassification.

3. Molecular Diagnostics: - Next-Generation Sequencing (NGS): Utilized to identify mutations in known IRD genes. - Whole Exome/Genome Sequencing: Employed when NGS does not yield a diagnosis, to uncover novel genetic causes.

4. Functional Impact: - Electrophysiological Testing: Techniques like electroretinography (ERG) are used to assess retinal function and help classify the type and extent of retinal dysfunction. - Imaging: Advanced imaging techniques, such as optical coherence tomography (OCT), provide detailed views of retinal structure and are crucial for diagnosis and classification.

Common IRD Categories: 1. Retinitis Pigmentosa (RP): Characterized by progressive peripheral vision loss and night blindness, often due to mutations in genes like RHO, USH2A, and RPGR.

2. Leber Congenital Amaurosis (LCA): Severe vision loss from birth or early infancy, associated with mutations in genes such as RPE65 and CEP290.

3. Stargardt Disease: A form of macular degeneration presenting in childhood or adolescence, commonly linked to mutations in the ABCA4 gene.

4. Cone-Rod Dystrophy: Initial loss of central vision and color perception, progressing to peripheral vision loss, with mutations in genes like CRX and GUCY2D.

5. Choroideremia: X-linked disorder leading to progressive vision loss, caused by mutations in the CHM gene.

Prognosis and Management: - Genetic Counseling: Essential for patients and families to understand the inheritance patterns and risks. - Gene Therapy: Emerging treatments, such as those targeting RPE65 mutations in LCA, offer hope for some IRD patients. - Supportive Care: Includes low vision aids, mobility training, and regular monitoring to manage complications. 

Author

Paddy Kalish OD, JD and B.Arch