Clinical and genetic characteristics of RPE65-associated inherited retinal degeneration in Koreans

RPE65-associated inherited retinal degeneration (IRD) is a rare autosomal recessive disorder for which a gene therapy (voretigene neparvovec) is available in selected patients with sufficient residual retinal structure. Most clinical and genetic data have been derived from Western cohorts, while information from Asian populations is limited. We conducted a multicenter retrospective study at three tertiary referral centers in Korea, including 11 patients (3 males and 8 females) from 9 unrelated families with biallelic pathogenic or likely pathogenic RPE65 variants. All patients reported symptom onset before 3 years of age. At the initial evaluation (median age, 29 years), best-corrected visual acuity ranged from hand motion to 0.3 decimal (median, 0.1), the mean Goldmann visual field radius on the III4e isopter was 2°, and full-field electroretinography showed extinguished rod and cone responses in every case. Fourteen distinct variants were identified with no novel variants; frameshift variants p.Asn356fs (c.1067dup/c.1067del) were relatively frequent (27.8% of alleles). Ultra-widefield fundus autofluorescence was extinguished and ellipsoid zone disruption was diffuse in all eyes. Most Korean patients presented at an advanced stage of disease, suggesting that the therapeutic window for gene therapy may already be limited and underscoring the importance of early recognition and timely genetic diagnosis.