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

Purpose To assess the impact of two TYR hypomorphic alleles (R402Q and S192Y) on foveal pit and FAZ morphology. Design Prospective cross-sectional study Participants One hundred sixty-four participants with normal vision (67 males and 97 females; mean ± SD age = 30.5 ± 12.8 years) were recruited. Methods Sequencing of over 100 pigmentation-related genes was performed, and results were reviewed for the presence or absence of the TYR polymorphisms R402Q (rs1126809) and S192Y (rs1042602). Volumetric scans of the macula were obtained for each participant using optical coherence tomography (OCT) and retinal thickness maps were analyzed using custom software. OCT angiography (OCT-A) was used to image the foveal avascular zone (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 TYR gene. Results Heterozygosity for the TYR R402Q allele was associated with decreased pit diameter (p = 0.0094) and decreased FAZ area (p = 0.025). Homozygosity for the TYR R402Q allele was associated with reduced pit volume (p = 0.0005), decreased pit depth (p = 0.007), reduced pit diameter (p = 0.0052) and reduced FAZ area (p = 0.0012). Homozygosity for TYR S192Y was associated with reduced FAZ area (p = 0.016). Heterozygosity for the TYR S192Y allele was not associated with differences in foveal pit depth, diameter, volume or FAZ area (p > 0.05). Conclusion While the role of the TYR 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.