Voretigene Neparvovec (Luxturna) for Biallelic RPE65-Associated Retinal Dystrophy: Systematic Review.

In 30 seconds

This systematic review synthesized randomized and observational studies of voretigene neparvovec in people with biallelic RPE65-associated inherited retinal disorders. Across 28 studies involving 376 individuals and 673 treated eyes, visual acuity gains were variable and generally modest, while light sensitivity improved consistently and visual-field gains were reported, particularly in the pivotal trial cohort. A random-effects meta-analysis of three studies estimated new or progressive perifoveal atrophy in 75% of treated eyes (95% CI, 57%-89%). Chorioretinal atrophy and intraocular inflammation were the most frequently reported adverse events.

Key findings

• Across three studies, pooled incidence of new or progressive perifoveal atrophy was 75% of treated eyes (95% CI, 57%-89%).
• In the largest cohort, full-field stimulus threshold improved by a mean of -18.24 dB, evident at 1 month and sustained through 6 months.
• The pivotal trial cohort had a 92% mean visual-field increase at 1 year, sustained to 3-4 years.
• BCVA outcomes were variable and generally modest, with somewhat greater gains in pediatric than adult cohorts.

Why it matters

The review highlights that treatment effects differ across visual outcomes: functional gains in light sensitivity and visual field may occur even when BCVA changes are limited. It also identifies perifoveal atrophy as a frequent structural finding, underscoring the importance of considering both functional benefit and retinal changes when counseling about treatment and interpreting follow-up.

What to keep in mind

The review combined randomized and observational studies, and findings were synthesized narratively except where data allowed meta-analysis; results varied across cohorts and outcomes.