ArticleArchives of ophthalmology (Chicago, Ill. : 1960)2012
Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years.
Article in Archives of ophthalmology (Chicago, Ill. : 1960), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 366 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)
Color Vision as an Outcome Measure for Clinical Trials of Inherited Retinal Degenerations
Who cites it
366 citing papers in PubMed, 7 syntheses or guidelines pooled it, 631 citations in OpenAlex.
- Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis.Angiogenesis · 2026Pooled it
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- The Road towards Gene Therapy for X-Linked Juvenile Retinoschisis: A Systematic Review of Preclinical Gene Therapy in Cell-Based and Rodent Models of XLRS.International journal of molecular sciences · 2024Pooled it
- Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.Translational vision science & technology · 2023Pooled it
- A Systematic Review and Meta-Analyses of Interventional Clinical Trial Studies for Gene Therapies for the Inherited Retinal Degenerations (IRDs).Biomolecules · 2021Pooled it
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- The effect of human gene therapy for RPE65-associated Leber's congenital amaurosis on visual function: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2020Pooled it
- Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Parents' perceptions of diagnostic genetic testing for children with inherited retinal disease in China.Molecular genetics & genomic medicine · 2019Trial
- Trial
- Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy.Human gene therapy · 2018Trial
- Gene regulatory behaviors of mutant CRX proteins demonstrated with late-stage human retinal organoids.Human molecular genetics · 2026Article
- Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials.Journal of clinical medicine · 2026Review
- Combination gene therapy with AAV based RPE65 and survivin vectors sustains phenotypic rescue in neural retina of LCA2 mice.Molecular and cellular biochemistry · 2026Article
- Synthesis and characterization of an injectable telechelic material for the epiretinal delivery of retinal gene therapies.Journal of materials chemistry. B · 2026Article
- Test-retest variability of the full-field stimulus test in patients with retinitis pigmentosa: REPEAT Study Report No. 4.Acta ophthalmologica · 2026Article
- Sustained improvement in dark-adapted sensitivity but not BCVA after voretigene neparvovec treatment in a mainland Chinese child with biallelicFrontiers in pharmacology · 2026Article
- Gene Therapy Using Recombinant Adeno-Associated Virus for Leber Congenital Amaurosis Induced by RPE65 Mutation.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Article
- Location and Identity of Photoreceptors Contributing to the Full-Field Stimulus Test (FST).Investigative ophthalmology & visual science · 2025Review
306 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene.
designOpen-label, dose-escalation phase I study of 15 patients (range, 11-30 years of age) evaluated after subretinal injection of the rAAV2- RPE65 vector into the worse-functioning eye. Five cohorts represented 4 dose levels and 2 different injection strategies.
main outcome measuresPrimary outcomes were systemic and ocular safety. Secondary outcomes assayed visual function with dark-adapted full-field sensitivity testing and visual acuity with Early Treatment Diabetic Retinopathy Study charts. Further assays included immune responses to the vector, static visual fields, pupillometry, mobility performance, and optical coherence tomography.
resultsNo systemic toxicity was detected; ocular adverse events were related to surgery. Visual function improved in all patients to different degrees; improvements were localized to treated areas. Cone and rod sensitivities increased significantly in the study eyes but not in the control eyes. Minor acuity improvements were recorded in many study and control eyes. Major acuity improvements occurred in study eyes with the lowest entry acuities and parafoveal fixation loci treated with subretinal injections. Other patients with better foveal structure lost retinal thickness and acuity after subfoveal injections.
conclusionsGene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. There is no benefit and some risk in treating the fovea. No evidence of age-dependent effects was found. Our results point to specific treatment strategies for subsequent phases. APPLICATION TO CLINICAL PRACTICE: Gene therapy for inherited retinal disease has the potential to become a future part of clinical practice.
trial registrationclinicaltrials.gov Identifier: NCT00481546.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.