Efficacy, Safety, and Durability of Gene Therapy for Inherited Retinal Diseases in the Pediatric Population: A...

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 pediatric-vs-adult patterns where available.

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 2 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 3 pediatric participants and separately extractable pediatric 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 pediatric-vs-adult patterns.

Twenty-four records, grouped into 17 trial clusters across 8 genotypes, were included; 14 met Tier 1 criteria. RPE65-associated disease provided the largest pediatric 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 4 very young children, and high-dose GUCY2D gene supplementation improved retinal sensitivity in 3 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 pediatric participants with EDIT-101. Evidence for RPGR, CNGB3, RS1, and MERTK did not support robust pediatric-specific efficacy conclusions. Serious ocular events were predominantly procedure-related, with no reproducible pediatric-specific toxicity signal. Formal age-stratified analyses were uncommon, and several pediatric-vs-adult patterns required review-author extraction.

Pediatric 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 pediatric durability and inconsistent age-stratified reporting. Future pediatric-inclusive trials should prespecify subgroup analyses, embed prospective long-term follow-up, use developmentally appropriate endpoints, and report individual-level data sufficient to support pediatric inference.