Eye Discovery · Nov 2026
Natural history of EYS-associated retinitis pigmentosa in a Chinese cohort of 131 patients: A cross-sectional and longitudinal analysis
By Wu J, Teng Z, Zhao Y et al.
Objective To characterize the natural history and genotype-specific phenotypic patterns of eyes shut homolog ( EYS )-associated autosomal recessive retinitis pigmentosa (arRP) in a large Chinese cohort and to distinguish cross-sectional age-related trends from longitudinal within-patient progression. Methods This study involved 131 patients from 124 families with biallelic EYS variants. They were evaluated for best-corrected visual acuity (BCVA), visual field (VF) function (mean deviation [MD] and visual field index [VFI]), and retinal structure via spectral-domain optical coherence tomography (SD-OCT). Cross-sectional age-related trends were modeled through linear regression and locally estimated scatterplot smoothing. In contrast, longitudinal within-patient variations were estimated from individual linear-regression progression rates. Furthermore, genotype-phenotype correlations were assessed across three prespecified groups (Genotypes A, B, and C). Results c.6416G>A (26 patients, 19.8%), c.7492G>C (19 patients, 14.5%), and c.6557G>A (19 patients, 14.5%) were the most frequent variants. The median age at first presentation was 41 years (interquartile range, IQR 33–47) for men and 40.0 years (IQR 29.0–53.0) for women. Cross-sectional analysis showed that BCVA increased by 0.0331 logMAR/year of age (95% confidence interval, CI 0.0217–0.0445), ellipsoid zone width (EZW) decreased by 41.7 μm/year (95% CI 27.3–56.1), and VFI decreased by 0.95 percentage points/year (95% CI 0.44–1.47). Longitudinal data were available for only a few patients (BCVA, 34; EZW, 36; and VFI, 11). The median individual progression rates were computed using per-patient linear regression; the values were +0.012 logMAR/year (IQR −0.061 to +0.159) for BCVA, −109.4 μm/year (IQR −330.2 to +3.2) for EZW, and −1.39 percentage points/year (IQR −3.06 to +1.99) for VFI. Cataract was detected in 61 of 86 patients (70.9%) with an available cataract status. Genotype C was related to better preservation of both VFI (0.60±0.22) and EZW (2156.7±445.2 μm) than Genotype A, which consistently showed worse outcomes. Conclusions This study is one of the largest Chinese cohorts of patients with EYS -associated arRP; it documents slow progression and genotype-related phenotypic differences. The age-related inflection points are exploratory, model-derived observations from cross-sectional data and necessitate independent external validation before their use as clinical cutoffs for therapeutic timing.