Related Experiment Video
Updated: Aug 24, 2025
Author Spotlight: Advancing Vision Restoration - Stem Cell-Based Therapy for Retinal Diseases
Published on: October 6, 2023
Visual function and retinal changes after voretigene neparvovec treatment in children with biallelic RPE65-related
Francesco Testa1, Paolo Melillo1, Valentina Di Iorio2
1Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Via S. Pansini 5, Building 15, 80131, Naples, Italy.
Insights
Voretigene neparvovec (VN) treatment improved visual acuity in children with RPE65-related dystrophy. Spectral-domain optical coherence tomography showed thickening of the outer nuclear layer (ONL), suggesting partial retinal recovery.
Area of Science:
- Ophthalmology
- Medical Genetics
- Regenerative Medicine
Background:
- RPE65-related inherited retinal dystrophies are severe genetic disorders.
- Voretigene neparvovec (VN) is a gene therapy targeting RPE65 mutations.
- Assessing treatment-induced retinal changes is crucial for understanding efficacy.
Purpose of the Study:
- To quantify retinal structural changes using SD-OCT after voretigene neparvovec (VN) treatment in pediatric patients.
- To correlate these structural changes with visual function outcomes.
Main Methods:
- Retrospective analysis of SD-OCT scans from six pediatric patients with RPE65-related dystrophy treated with VN.
- Quantitative analysis of ETDRS thickness maps for whole retina and outer nuclear layer (ONL).
- Assessment of best-corrected visual acuity (BCVA) and retinal morphology at specified time points.
Main Results:
- Significant improvement in BCVA was observed at 30/45 days and 6 months post-treatment (P < 0.001).
- Outer nuclear layer (ONL) thickness significantly increased in the internal ETDRS ring at both follow-up points (P < 0.001 and P = 0.009).
- Central foveal ONL thickness showed a trend towards increase, though not statistically significant (P = 0.091).
Conclusions:
- Voretigene neparvovec (VN) treatment leads to significant visual function improvement in pediatric RPE65-related dystrophy.
- Observed thickening of the outer nuclear layer (ONL) suggests partial restoration of retinal structure.
- Visual acuity gains may be linked to morphological recovery in the perifoveal region.
Abstract:
To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65-related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extract Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps of the whole retina and the outer nuclear layer (ONL). Changes in visual function were assessed by best-corrected visual acuity (BCVA) and retinal morphology at Days 30/45 and 180. BCVA significantly improved at Day 30/45 and 6 months (both P < 0.001). Central foveal retinal thickness and central foveal ONL thickness tended to increase (6.4 ± 19.2 µm; P = 0.080 and 3.42 ± 7.68 µm; P = 0.091, respectively). ONL thickness of the internal ETDRS-ring significantly increased at day 30/45 (4.7 ± 8.4 µm; P < 0.001) and day 180 (5.0 ± 5.7 µm; P = 0.009). Intra-operative foveal detachment was not associated with a higher function gain in terms of BCVA, but with a mild thinning of foveal ONL after treatment. The improvement of BCVA and thickening of the ONL layer suggest that improvement of visual acuity could be related to partial recovery of retinal morphology in the perifoveal ring.
