Insights into the effects of subretinal voretigene neparvovec-rzyl in RPE65-associated Leber congenital amaurosis: an 18-Month report

Alaa Tayyib; Deepika C Parameswarappa; Peter J Kertes; Rajeev Muni; Anupreet Tumber; Gregory Costain; Alex Schramm; Heather MacDonald; Regan Klatt; Ajoy Vincent; Elise Héon

doi:10.1016/j.jcjo.2024.12.006

Insights into the effects of subretinal voretigene neparvovec-rzyl in RPE65-associated Leber congenital amaurosis: an 18-Month report

Can J Ophthalmol. 2025 Jan 16:S0008-4182(24)00374-0. doi: 10.1016/j.jcjo.2024.12.006. Online ahead of print.

Authors

Affiliations

¹ Department of Ophthalmology and Vision Sciences, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
² Department of Ophthalmology and Vision Sciences, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Department of Ophthalmology, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
³ Department of Ophthalmology and Vision Sciences, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Department of Ophthalmology, St. Michaels Hospital/Unity Health, Toronto, ON, Canada.
⁴ Division of Clinical & Metabolic Genetics, Hospital for Sick Children, Toronto, ON, Canada; Program in Genetics & Genome Biology, SickKids Research Institute, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁵ Department of Ophthalmology and Vision Sciences, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Program in Genetics & Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
⁶ Department of Ophthalmology and Vision Sciences, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Program in Genetics & Genome Biology, SickKids Research Institute, Toronto, ON, Canada. Electronic address: [email protected].

PMID: 39828244
DOI: 10.1016/j.jcjo.2024.12.006

Abstract

Objective: Assess safety and effectiveness of subretinal gene replacement therapy at 18 months post treatment.

Design: Retrospective, longitudinal study conducted at the Hospital for Sick Children in Toronto, Canada.

Participants: Patients with bi-allelic RPE65 variants, early onset retinal degeneration, and residual viable retina who underwent voretigene neparvovec r-zyl gene replacement therapy.

Methods: Data collected included demographic information, molecular genetic results, and comprehensive ocular assessment results from preoperataive and postoperative visits up to 18 months. To assess the treatment's efficacy, postoperative best corrected visual acuity, full-field stimulus test (FST), visual field (VF) area, optical coherence tomography, and global satisfaction were compared to preoperative findings.

Results: The procedures were safe with no complications. There was no significant improvement in visual acuity. Three eyes showed a slight reduction in VF area. All showed a reduction in ellipsoid zone thickness and area, but the outer nuclear layer thickness and area were stable. All had a significant improvement in retinal sensitivity, as per FST, allowing better navigation in a dim environment. All 3 patients reported being "very satisfied".

Conclusion: Following a safe gene replacement therapy, the 3 first Canadian cases had an improvement in retinal sensitivity as per FST, and our patients described their experience as positively life changing.