"Blindness" is not a contraindication for voretigene neparvovec-rzyl treatment: a review of 9 cases.

Abstract

Objective: Biallelic RPE65 pathogenic variants may cause Leber congenital amaurosis (LCA). Voretigene neparvovec-rzyl (VN, Luxturna) is the only approved subretinal gene therapy that demonstrated benefit and safety. The eligibility criteria are vague and variable between centres. This is the first comprehensive outcome report of RPE65-LCA patients with World Health Organization blindness criteria vision treated with VN.

Design: Multicentre retrospective case series.

Participants: Patients meeting the treatment criteria for VN who had best-corrected visual acuity (BCVA) <20/400 or visual field (VF)III4e isopter <10°.

Methods: Patients were followed for a mean of 11.1 ± 4.7 months. Age, sex, BCVA, central retinal thickness (CRT), retinal atrophy, VF, full-field stimulus testing (FST), and subjective impressions were assessed.

Results: Nine patients met the inclusion criteria (mean: BCVA 1.89 LogMAR, range: 1.4 - 2.7 LogMAR, mean age: 28.7-years-old, range: 17-59 years). Though VF area did not improve, FST improved in patients with better baseline FST (-8.83 dB vs -0.56 dB; p = 0.010), and better VFV4e (7245 vs 341^o2; p < 0.001) and III4e (596.1 vs 24.8^o2; p = 0.011) area. VA improved in younger (20 vs 32 years; p = 0.011) patients with thinner CRT^1mm (155 vs 193 µm; p = 0.038). VFV4e loss occurred in older (38 vs 19 years; p = 0.001) patients with worse baseline V4e area (1728 vs 8159^o2; p < 0.001). Subjective improvement in dim light navigation skills occurred in younger patients (20.3 vs 45.3 years; p < 0.001).

Conclusions: Blindness is not a contraindication to VN treatment for RPE65-LCA. Superior results correlated with greater baseline FST but not with CRT^1mm, provided that measurable outer retinal structures persist.