Efficacy, Safety, and Durability of Gene Therapy for Inherited Retinal Diseases in the Paediatric Population: A Scoping Review.
TL;DR
Paediatric benefit from IRD gene therapy depends on genotype, residual retinal structure, therapeutic platform, dose, surgical strategy, and outcome measure, and the major evidence gaps are long-term paediatric durability and inconsistent age-stratified reporting.
Abstract
Purpose
To map the published interventional gene-based therapies relevant to children with inherited retinal diseases (IRDs), with a focus on efficacy, safety, and durability, including paediatric-versus-adult patterns where available.
Methods
This scoping review followed a prospectively registered protocol specifying the search strategy, eligibility criteria, screening process, data-charting framework, and synthesis plan. PubMed and Embase were searched from January 1, 2008, to April 13, 2026. Retrieved records were independently screened by two reviewers to identify prospective interventional studies of gene-targeted therapies for molecularly confirmed IRDs enrolling participants younger than 18 years; unresolved disagreements were adjudicated by a third reviewer. Overlapping reports were grouped into trial clusters with a primary anchor record. Records with at least three paediatric participants and separately extractable paediatric data were classified as Tier 1 and included in the main synthesis; other eligible records were retained as Tier 2 contextual evidence. Where sufficient individual-level or subgroup-level data were available, review authors extracted descriptive paediatric-versus-adult patterns.
Results
Twenty-four records, grouped into 17 trial clusters across eight genotypes, were included; 14 met Tier 1 criteria. RPE65-associated disease provided the largest paediatric evidence base and the most consistent efficacy and durability signals, although responses varied between trial clusters. AIPL1 gene supplementation showed substantial treated-eye functional gains with relative structural preservation at up to 4 years in four very young children, and high-dose GUCY2D gene supplementation improved retinal sensitivity in three children within a mixed-age cohort. CEP290-targeted splice modulation and gene editing showed early functional signals, but interpretation was limited by dose-related cataract with sepofarsen and few paediatric participants with EDIT-101. Evidence for RPGR, CNGB3, RS1, and MERTK did not support robust paediatric-specific efficacy conclusions. Serious ocular events were predominantly procedure-related, with no reproducible paediatric-specific toxicity signal. Formal age-stratified analyses were uncommon, and several paediatric-versus-adult patterns required review-author extraction.
Conclusions
Paediatric benefit from IRD gene therapy depends on genotype, residual retinal structure, therapeutic platform, dose, surgical strategy, and outcome measure. The major evidence gaps are long-term paediatric durability and inconsistent age-stratified reporting. Future paediatric-inclusive trials should pre-specify subgroup analyses, embed prospective long-term follow-up, use developmentally appropriate endpoints, and report individual-level data sufficient to support paediatric inference.