Title: From bench to bedside: Gene therapy for inherited retinal diseases — current evidence, emerging therapies and the global challenge of equitable access
Abstract:
Background: Inherited Retinal Diseases (IRDs) are a clinically and genetically heterogeneous group of conditions causing progressive visual impairment, affecting approximately 5.5 million people worldwide at a prevalence of 1:3, 450. Over 280 causative genes have been identified, and IRDs collectively represent the leading cause of vision loss in the working-age population. Historically, management was limited to supportive care. The 2017 FDA approval of voretigene neparvovec (Luxturna®) — the first in vivo gene therapy for an inherited disease — initiated a paradigm shift. This review evaluates current evidence, emerging pipeline therapies, and barriers to equitable global access.
Methods: A narrative literature review was performed. PubMed, MEDLINE, Cochrane Library and ClinicalTrials.gov were searched (January 2017 – May 2026) using terms including “gene therapy,” “inherited retinal disease,” “AAV vector,” “CRISPR-Cas9,” and “health equity.” Peer-reviewed clinical trial data, regulatory approvals, pipeline therapeutics, and health economics literature were synthesised.
Results: Voretigene neparvovec remains the only FDA/EMA-approved ocular gene therapy. In its pivotal Phase 3 trial (n=31), bilateral subretinal injection produced sustained improvements in multi-luminance mobility and full-field light sensitivity. However, biallelic RPE65 mutations account for only ~2% of IRD cases, and emerging real-world data from the PERCEIVE study (n=323) have identified chorioretinal atrophy in 12.6% of patients. The therapeutic pipeline is expanding rapidly: ATSN-101 (Atsena) for LCA1 produced ~20 dB improvement in full-field stimulus testing (Yang et al., Lancet 2024); EDIT-101 (Editas) became the first in-body CRISPR-Cas9 therapy in humans, with 79% of patients showing measurable vision improvement in the BRILLIANCE trial (Pierce et al., NEJM 2024); MCO-010 (Nanoscope), a mutation-agnostic optogenetic therapy, demonstrated significant visual gains in the Phase 2b/3 RESTORE trial; OCU400 (Ocugen), a modifier gene therapy, achieved stabilisation or improvement in 89% of treated patients at 2 years. However, not all trials succeed — the Phase 3 STAR trial of timrepigene emparvovec for choroideremia failed to meet its primary endpoint (MacLaren et al., Nature Medicine 2023). Despite scientific progress, access remains profoundly inequitable. Voretigene neparvovec is priced at US$850,000 per treatment, with an ICER of £95,072/QALY in the UK. Access is limited to high-income countries — Luxturna remains unavailable in Bulgaria and Romania despite EU approval, while South Korea achieved reimbursement only in February 2024 via outcome-based agreements. Significant racial disparities in IRD genetic diagnosis exist (Abuzaitoun et al., JAMA Ophthalmology 2024), and Asian populations remain underrepresented in genetic databases. Encouragingly, Chinese-developed gene therapy for Bietti Crystalline Dystrophy — a disease prevalent in East Asia — demonstrated 14-letter BCVA improvement in early trials (Wang et al., 2024), and the Asia-Pacific Network for Inherited Eye Diseases now spans 12 countries.
Conclusion: Gene therapy for IRDs has transitioned from concept to clinical reality, with a rapidly expanding pipeline offering hope across a broadening range of conditions. However, transformative potential remains accessible only to a privileged minority. Coordinated action on cost reduction, expanded reimbursement, diverse database representation, and regional clinical networks must accompany scientific innovation to ensure equitable global access.
