Vision Outcomes in Children Treated With Voretigene Neparvovec for RPE65-Associated Retinopathy

Voretigene neparvovec (VN) marketed as Luxturna (Novartis Europharm Ltd) is the first approved gene therapy for severe RPE65-related retinal dystrophy, showing low-luminance vision improvement in adult trials. Low-luminance tests pose challenges for children, but pattern visual evoked potentials (VEPs) need minimal cooperation and provide objective measures of visual activation of the striate cortex. In this study, VN outcomes in young children were assessed using pattern VEPs in addition to standard measures.

To evaluate vision outcomes and complications after VN treatment in children.

This was a retrospective case series of children receiving VN from February 2020 to December 2023. Children with biallelic pathogenic variants in RPE65 were recruited from Great Ormond Street Hospital, a single-center, UK specialist pediatric hospital.

Treatment with VN, a recombinant adeno-associated virus vector-based gene therapy.

Pretreatment and posttreatment pattern VEPs, visual acuity (VA), full-field stimulus test (FST), optical coherence tomography (OCT) measures, and ocular complications.

A total of 14 pediatric patients (27 eyes) were included in this analysis. Median (IQR) age at treatment of 9 female (64.3%) and 5 male (35.7%) patients was 6.88 (3.27-8.83) years, with a median (IQR) follow-up of 3.42 (2.65-4.08) years. VA improved from logMAR 1.00 to 0.76 (difference, -0.24). When 4 off-chart VA conversions were excluded, the change was less than 1 line, -0.03 (pretreatment, logMAR 0.74 [20/100] to posttreatment, 0.71 [20/100]). Only 3 eyes of 14 children (11%) completed a reliable full-field stimulus test, showing a mean (SD) 20.6 (14.8) dB. All 10 tested patients completed pattern VEPs; 7 showed clinically meaningful improvement, 2 worsened with chorioretinal atrophy, and 1 remained unchanged. Complications included transient inflammation (5 of 14 patients [35.7%]) and localized atrophy (6 of 14 patients [42.9%]).

This case series study reports VN-treated patients as young as 15 months, confirming visual improvements, although not necessarily VA when off-chart VA conversions were excluded, consistent with previously reported outcomes. Pattern VEPs provided an objective measure of retinogeniculostriate recovery, supporting their use as an outcome measure in future trials for young children with inherited retinal diseases.