Prospective natural history and clinical biomarkers of EYS-associated retinopathy in the KEYS study

EYS is one of the major causative genes of autosomal recessive retinitis pigmentosa, particularly in Asian, and is expected to be a key target for future therapies. However, reliable biomarkers have not established. This KEYS study aimed to evaluate whether structural and functional parameters could serve as potential biomarkers of disease progression in EYS-associated retinitis pigmentosa (EYS-RP). We prospectively observed 49 patients with EYS-RP at Kobe Eye Hospital over a 2-year period. Visual field testing was performed using the Humphrey Field Analyzer 10- 2 (HFA 10-2). The mean total deviation (TD) was divided into central and surrounding regions for analysis, and the mean deviation (MD) was also evaluated. Horizontal and vertical EZ widths were measured by OCT. Over 2 years, our study showed that visual field progressed in surrounding and central and horizontal EZ width decreased. In subgroup analysis, a decline in horizontal EZ width and correlations between visual field parameters and EZ width were observed only in the higher MD based on the mean baseline HFA-MD value. HFA and horizontal EZ width parameters may serve as useful biomarkers of disease progression in EYS-RP, although their effectiveness varies by disease severity.