Visual Acuity, Retinal Morphology, and Patients’ Perceptions after Voretigene Neparovec-rzyl Therapy for RPE65-Associated Retinal Disease

Objective: To explore the effect of patients' age, baseline visual acuity (VA), and intraoperative foveal detachment on outcomes of subretinal voretigene neparvovec-rzyl (Luxturna) therapy and to assess patients' perceptions of the treatment effect. Design: Multicenter, retrospective, consecutive case series, and cross-sectional prospective survey. Participants: All 41 consecutive patients treated with voretigene neparvovec-rzyl after Food and Drug Administration approval at 3 institutions between January 2018 and May 2020. Methods: A retrospective chart review of operative reports, clinical notes, ancillary testing, and complications, comparing data at baseline and at 1, 2 to 3, 6 to 9, and 10 to 15 months after subretinal surgery was conducted. A survey was administered to adult patients and parents of pediatric patients. Main Outcome Measures: Changes in best-corrected VA and retinal morphology and in patients' perceptions. Results: Seventy-seven eyes of 41 patients (16 adults and 25 pediatric patients; age range, 2-44 years; mean follow-up, 10 months [range, 1 week to 18.5 months]) were analyzed. There was no statistically significant vision change for the adults, whereas there was a trend of improvement for pediatric patients, which reached statistical significance for some time points. The baseline VA did not affect the posttherapy VA (P = 0.23). The central foveal thickness decreased mildly in both pediatric patients and adults, without significant differences between the populations. The fovea was detached by voretigene neparvovec-rzyl in 62 (81%) eyes. The inner segment-outer segment junction remained unchanged in 91% of 54 eyes with gradable OCT, with or without foveal detachment. Thirty-two (78%) patients were reached for the survey an average of 1.15 +/- 0.50 years (range, 0.31 to 2.31) after the surgery in the first eye. Improvement in night, day, or color vision was reported by 23 (72%), 22 (69%), and 18 (56%) patients, respectively. Conclusions: This study is limited by the large variability in follow-up time. There were no persistent statistically significant vision changes. A decrease in foveal thickness was noted in most eyes, but the long-term significance of this remains to be determined.