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

Gelique D Ayala,Rachel E Linderman,Erica N Woertz,Sergey Tarima,Murray Brilliant,Robert K Valenzuela,Joseph Carroll

doi:10.1016/j.xops.2021.100077

Gelique D Ayala, Rachel E Linderman + Show 5 more

Open Access

https://doi.org/10.1016/j.xops.2021.100077

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Abstract

PurposeTo assess the impact of two TYR hypomorphic alleles (R402Q and S192Y) on foveal pit and foveal avascular zone (FAZ) morphology.DesignProspective, cross-sectional study.ParticipantsA total of 164 participants with normal vision (67 male and 97 female; mean ± standard deviation [SD] age = 30.5 ± 12.8 years) were recruited.MethodsSequencing of more than 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 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 MeasuresFoveal pit depth, diameter, volume, and FAZ area in relation to the presence of hypomorphic alleles R402Q and S192Y on the TYR gene.ResultsHeterozygosity 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).ConclusionsAlthough 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.

Highlights

This study examined the association between TYR R402Q and S192Y hypomorphic alleles and foveal structure
The authors found that the S192Y variant was associated with increased retinal thickness, whereas R402Q was not associated with retinal thickness in their cohort
That study assessed the average retinal nerve fiber layer thickness and GCL-IPL layer thickness across the Macula[6] grid and the total retinal thickness at the fovea, whereas our study assessed the shape of the foveal pit and the foveal avascular zone (FAZ) area

Summary

Introduction

In a study of 110 normal foveae, Tick et al[5] reported large coefficient of variations for both pit depth (16.7%) and foveal inner retinal area (22.1%). Foveal pit morphology was analyzed using a previously published difference of Gaussian algorithm.[3] The retinal pigment epithelium internal limiting membrane thickness data file for each volume was imported into the software and was bilinearly interpolated to 512 Â 512 pixels.

Results

Conclusion