Perifoveal Chorioretinal Atrophy following Subretinal Voretigene Neparvovec-rzyl for RPE65-mediated Leber Congenital Amaurosis.

PURPOSE To report an anatomic change observed in a series of patients who underwent subretinal injection of voretigene neparvovec-rzyl (VN) for RPE65-mediated Leber congenital amaurosis. DESIGN Multi-center retrospective chart review. PARTICIPANTS Patients who underwent subretinal VN injection at each of four participating institutions. METHODS Patients were identified as having perifoveal chorioretinal atrophy if: i) the areas of atrophy were not directly related to the touch-down site of the subretinal cannula; and ii) the area of atrophy progressively enlarged over time. Demographic data, visual acuity, refractive error, fundus photos, optical coherence tomography, visual fields, and full-field stimulus threshold (FST) were analyzed. MAIN OUTCOME MEASURES Outcome measures included change in visual acuity, FST, visual fields, and location of atrophy relative to subretinal bleb position. RESULTS 18 eyes of 10 patients who underwent subretinal injection of VN were identified as having developed perifoveal chorioretinal atrophy. 8/10 patients (80%) developed bilateral atrophy. The mean age was 11.6 years (range: 5-20), and 6 patients (60%) were male. Baseline mean logMAR visual acuity and FST were 0.82 (standard deviation (SD): 0.51) and -1.3 log cd.s/m2 (SD: 0.44), respectively. The mean spherical equivalent was -5.7 diopters (range: -11.50 to +1.75). Atrophy was identifiable at an average of 4.7 months (SD: 4.3) following surgery, and progressively enlarged in all cases up to a mean follow-up period of 11.3 months (range: 4-18). Atrophy developed within and outside the area of the subretinal bleb in 10 (55.5%) eyes, exclusively within the area of the bleb in 7 (38.9%) eyes, and exclusively outside the bleb in 1 (5.5%) eye. There was no significant change in visual acuity (p=0.45). There was a consistent improvement in FST with a mean improvement of -3.21 log cd.s/m2 (p<0.0001). Additionally, all 13 eyes with reliable pre- and post-operative Goldmann visual fields demonstrated improvement (expansion and/or gain of isopters) following surgery, but 3 (23.1%) eyes demonstrated paracentral scotomas related to the atrophy. CONCLUSIONS A subset of patients undergoing subretinal VN injection developed progressive perifoveal chorioretinal atrophy following surgery. Further study is necessary to determine what ocular, surgical delivery, and vector-related factors predispose to this complication.