Three-Year Follow-up after Unilateral Subretinal Delivery of Adeno-Associated Virus in Patients with Leber Congenital Amaurosis Type 2

Objective: The aim of this study was to show the clinical data of long-term (3-year) follow-up of 5 patients affected by Leber congenital amaurosis type 2 (LCA2) treated with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2. Design: Clinical trial. Participants: Five LCA2 patients with RPE65 gene mutations. Methods: After informed consent and confirmation of trial eligibility criteria, the eye with worse visual function was selected for subretinal delivery of adeno-associated virus (AAV2-hRPE65v2). Subjects were evaluated before and after surgery at designated follow-up visits (1, 2, 3, 14, 30, 60, 90, 180, 270, and 365 days, 1.5 years, and 3 years) by complete ophthalmic examination. Efficacy for each subject was monitored with best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex. Main Outcome Measures: Best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex. Results: The data showed a statistically significant improvement of best-corrected visual acuity between baseline and 3 years after treatment in the treated eye (P < 0.001). In all patients, an enlargement of the area of visual field was observed that remained stable until 3 years after injection (average values: baseline, 1058 deg(2) vs. 3 years after treatment, 4630 deg2) and a reduction of the nystagmus frequency compared with baseline at the 3-year time point. Furthermore, a statistically significant difference was observed in the pupillary constriction of the treated eye (P < 0.05) compared with the untreated eye in 3 patients at 1- and 3-year time points. No patients experienced serious adverse events related to the vector in the 3-year postinjection period. Conclusions: The long-term follow-up data (3 years) on the 5-patient Italian cohort involved in the LCA2 gene therapy clinical trial clearly showed a stability of improvement in visual and retinal function that had been achieved a few months after treatment. Longitudinal data analysis showed that the maximum improvement was achieved within 6 months after treatment, and the visual improvement was stable up to the last observed time point. (C) 2013 by the American Academy of Ophthalmology.