Deep phenotyping of eyes shut homolog-associated retinopathy based on visual impairment patterns

This study aimed to classify the phenotypes of eyes shut homolog (EYS)-associated retinopathy based on visual impairment patterns and investigate their characteristics.

This retrospective, single-center, cross-sectional study was conducted in 154 patients diagnosed with EYS-related retinopathy who underwent genetic testing between December 2017 and July 2023. Phenotyping was performed only in patients who underwent Goldmann perimetry (GP) and Humphrey visual field (HVF) 10-2 testing. Phenotypes were categorized as early, pericentral, typical, and advanced based on peripheral visual field preservation (GP: V-4e isopter extending beyond a 30-degree radius in ≥2 quadrants), central visual field impairment (HVF10-2: ≤20 points with 26 dB sensitivity), and macular impairment (logMAR ≥ 0.2). Genetic and ophthalmological characteristics were compared between the pericentral and typical types.

A total of 39 eyes from 39 patients with EYS-associated retinopathy (average age: 48.2 ± 11.9 years, 21 women) were analyzed. Ten pathogenic variants were identified, with the three major variants (p.G843E, p.S1653fs, and p.Y2935X) accounting for a combined allele frequency of 83.3%. The phenotypes were classified as early (n=3), pericentral (n=18), typical (n=9), and advanced (n=9). No significant differences were observed between the pericentral and typical types in terms of the presence of major variants or biallelic null variants. Age and age at onset also did not differ significantly. However, macular impairment was significantly more frequent in the pericentral type (61.8%) than in the typical type (11.1%) (P = 0.014).

In EYS-associated retinopathy, the pericentral type is considered a common phenotype, although its correlation with the genotype remains unclear. Despite preserved peripheral vision, careful monitoring is warranted due to the risk of macular impairment.