Functional outcomes and adverse effects of voretigene neparvovec for biallelic RPE65-mediated inherited retinal dystrophies in a cohort of patients from a single centre

Abstract

Purpose : Voretigene neparvovec (VN) is the first approved gene therapy for biallelic RPE65-mediated inherited retinal dystrophies (IRD). The purpose of this study was to evaluate functional outcomes and adverse effects after VN treatment.

Methods : This retrospective study included 10 eyes (5 patients) treated at the Oxford Eye Hospital. Best corrected visual acuity (BCVA), Goldmann visual field (GVF), and full-field light sensitivity threshold (FST) were assessed at baseline and at the last follow-up. Subjective vision improvement and ocular adverse effects after gene therapy were observed.

Results : The mean age of our patients was 35.6 years (range 19 - 51 years), 4 males and 1 female were treated. All patients reported subjective vision improvement after gene therapy. Mean (±sd) BCVA remained similar after VN treatment [LogMAR at baseline: 1.15 (±0.47) vs. at the last follow-up: 1.17 (±0.38); p=0.93]. Average FST (white) improved from -0.64 (±7.29) db at baseline to -8.97 (±14.12) db at the last follow-up with a trend towards a statistical significance (p=0.09). GVF improved qualitatively in 7 out of 10 eyes. Four eyes developed a transient increase in intraocular pressure (IOP) that was controlled with IOP lowering drops and oral acetazolamide. Two eyes developed subtle intraocular inflammation in the anterior chamber that was controlled with an extended topical steroid regimen. Cataract development after the VN treatment was observed in three eyes and areas of retinal atrophy in eight eyes. In 6 eyes, retinal atrophy was subtle and inside the area of the raised bleb. In a young patient with significant and stable FST improvements, atrophic changes also appear outside the bleb area in both eyes in a symmetric fashion.

Conclusions : Overall safety and effectiveness of VN treatment observed at the Oxford Eye Hospital are consistent with reported outcomes. The atrophic changes previously identified as a new adverse drug reaction have been observed in a majority of treated eyes in our cohort, but were not associated with loss of visual function.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.