Central Visual Function and Genotype-Phenotype Correlations in PDE6A-Associated Retinitis Pigmentosa

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Autosomal recessive retinitis pigmentosa (arRP) is a group of inherited retinal diseases.
• Mutations in the phosphodiesterase 6A (PDE6A) gene are a known cause of arRP.
• Understanding genotype-phenotype correlations is crucial for predicting disease progression.

Purpose of the Study:

• To describe the natural course of disease progression in patients with arRP caused by PDE6A mutations.
• To establish a detailed genotype-phenotype correlation for PDE6A-associated arRP.
• To assess central retinal function, including visual acuity, contrast sensitivity, and color vision.

Main Methods:

• Forty-four patients with genetically confirmed PDE6A-associated arRP were included.
• Comprehensive ophthalmological examinations were performed.
• Standardized charts were used for visual acuity, contrast sensitivity, and color vision testing.

Main Results:

• The most frequent variants identified were c.998+1G>A/p.?, c.304C>A/p.R102S, and c.2053G>A/p.V685M.
• Severity ranking of mutations for central retinal function was established, with c.2053G>A/p.V685M (homozygous) being the most severe and c.304C>A/p.R102S (homozygous) being the mildest.
• Annual decline rates in central retinal function were observed to be small.

Conclusions:

• A clear genotype-phenotype correlation exists for PDE6A-associated arRP regarding central visual function.
• The severity of central retinal dysfunction varies significantly among different PDE6A mutations.
• Small annual decline rates may pose challenges for assessing treatment efficacy in clinical trials.