Assessing Foveal Structure in Individuals with R402Q and S192Y Hypomorphic Alleles.

Purpose: To assess the impact of two hypomorphic alleles (R402Q and S192Y) on foveal pit and foveal avascular zone (FAZ) morphology.

Design: Prospective, cross-sectional study.

Participants: A total of 164 participants with normal vision (67 male and 97 female; mean ± standard deviation [SD] age = 30.5 ± 12.8 years) were recruited.

Methods: Sequencing of more than 100 pigmentation-related genes was performed, and results were reviewed for the presence or absence of the polymorphisms R402Q (rs1126809) and S192Y (rs1042602). Volumetric scans of the macula were obtained for each participant using OCT, and retinal thickness maps were analyzed using custom software. OCT angiography was used to image the FAZ, which was manually segmented and measured. Linear mixed model analysis was used to assess associations between genotype and foveal pit morphology.

Main Outcome Measures: Foveal pit depth, diameter, volume, and FAZ area in relation to the presence of hypomorphic alleles R402Q and S192Y on the gene.

Results: Heterozygosity for the R402Q allele was associated with decreased pit diameter ( 0.0094) and decreased FAZ area ( 0.025). Homozygosity for the R402Q allele was associated with reduced pit volume ( 0.0005), decreased pit depth ( 0.007), reduced pit diameter ( 0.0052), and reduced FAZ area ( 0.0012). Homozygosity for S192Y was associated with reduced FAZ area ( 0.016). Heterozygosity for the S192Y allele was not associated with differences in foveal pit depth, diameter, volume, or FAZ area ( > 0.05).

Conclusions: Although the role of the R402Q and S192Y hypomorphic alleles in albinism remains controversial, our data suggest that these variants contribute to the extensive inter-individual variability in foveal morphology in the normal population. Our results contribute to the evolving picture of the relationship between ocular pigmentation and foveal morphology.