Four-Year Structural and Functional Outcomes of the First Subretinal Voretigene Neparvovec-rzyl Treatment for RPE65-Associated Inherited Retinal Dystrophy in Korea

Purpose: To describe 4-year functional and structural outcomes of the first bilateral subretinal voretigene neparvovec-rzyl (VN) in Korean patient with molecularly confirmed RPE65-associated inherited retinal dystrophy, with a focus on the relationship between chorioretinal atrophy and visual function. Methods: This was an observational case-based study of a 29-year-old woman with biallelic RPE65 pathogenic variants. Both eyes underwent 25-gauge pars plana vitrectomy and subretinal VN injection 7 days apart. Standardized assessments were performed at baseline and 1 month, 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years. Functional outcomes included best-corrected visual acuity (BCVA, ETDRS letters), kinetic visual fields, full-field stimulus threshold (FST, white light), and multi-luminance mobility test (MLMT). Structural changes were evaluated with spectral-domain optical coherence tomography, ultra-widefield color and autofluorescence imaging, and infrared reflectance. Results: At baseline, BCVA was 9 and 8 ETDRS letters (right/left), with widespread ellipsoid zone loss but relatively preserved retinal pigment epithelium. BCVA improved to 34/33 letters at 1 year and remained higher than baseline in both eyes at 4 years. Goldmann III4e average visual field radius increased from 2.1/0.3° at baseline to 8.8/15.0° at 3 months, followed by partial contraction with paracentral scotomas after 1 year, yet fields remained wider than baseline at 4 years. FST improved from 0.10 log(cd·s/m2) to -1.46 log(cd·s/m2) at 1 month and remained stable at 3 months. MLMT performance improved from 150 lux at baseline to 10 lux binocularly and was maintained at 4 years. Perifoveal, fovea-involving chorioretinal atrophy developed between 3 and 6 months and enlarged mainly during the first year, then progressed slowly thereafter. Conclusions: In this Korean patient, VN provided large and durable functional gains over 4 years despite early, severe chorioretinal atrophy, illustrating structural-functional dissociation and underscoring the need for long-term multimodal monitoring in RPE65-associated disease.