Perifoveal Chorioretinal Atrophy after Subretinal Voretigene Neparvovec-rzyl for RPE65-Mediated Leber Congenital Amaurosis

Abstract

Purpose: To report an anatomic change following subretinal injection of voretigene neparvovec-rzyl (VN) for RPE65-mediated Leber congenital amaurosis.

Design: Multicenter, retrospective chart review.

Participants: Patients who underwent subretinal VN injection at each of 4 participating institutions.

Methods: Patients were identified as having perifoveal chorioretinal atrophy if (1) the areas of atrophy were not directly related to the touch-down site of the subretinal cannula; and (2) the area of atrophy progressively enlarged over time. Demographic data, visual acuity, refractive error, fundus photographs, OCT, 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: A total of 18 eyes of 10 patients who underwent subretinal injection of VN were identified as having developed perifoveal chorioretinal atrophy. Eight of 10 patients (80%) developed bilateral atrophy. The mean age was 11.6 years (range, 5-20 years), and 6 patients (60%) were male. Baseline mean logarithm of the minimum angle of resolution 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 (D) (range, -11.50 to +1.75 D). Atrophy was identifiable at an average of 4.7 months (SD, 4.3) after surgery and progressively enlarged in all cases up to a mean follow-up period of 11.3 months (range, 4-18 months). Atrophy developed within and outside the area of the subretinal bleb in 10 eyes (55.5%), exclusively within the area of the bleb in 7 eyes (38.9%), and exclusively outside the bleb in 1 eye (5.5%). 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 Goldmann visual fields demonstrated improvement, but 3 eyes (23.1%) demonstrated paracentral scotomas related to the atrophy.

Conclusions: A subset of patients undergoing subretinal VN injection developed progressive perifoveal chorioretinal atrophy after surgery. Further study is necessary to determine what ocular, surgical delivery, and vector-related factors predispose to this complication.

Keywords: Chorioretinal atrophy; Complications; Gene therapy; Leber congenital amaurosis; Luxturna; Outcomes Research; Subretinal injection; Voretigene neparvovec-rzyl.