ArticleOphthalmology science
Dose-Dependent Progression of Chorioretinal Atrophy at the Injection Site After Subretinal Injection of rAAV2/8 in Nonhuman Primates.
Article in Ophthalmology science. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Safety and vision outcomes of subretinal gene supplementation therapy inThe British journal of ophthalmology · 2026Trial
- Four-Year Structural and Functional Outcomes of the First Subretinal Voretigene Neparvovec-rzyl Treatment for RPE65-Associated Inherited Retinal Dystrophy in South Korea.Korean journal of ophthalmology : KJO · 2026Article
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Delayed foveal atrophy following early visual improvement after voretigene neparvovec gene therapy in a child.Eye (London, England) · 2026Article
- Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy.Gels (Basel, Switzerland) · 2026Article
- Single-cell and spatial transcriptomic analyses of gene therapy-associated retinal inflammation in non-human primates.Molecular therapy. Advances · 2026Article
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Expert Consensus on Characteristics, Etiology, and Management of Chorioretinal Atrophy in Patients Treated with Voretigene Neparvovec.Ophthalmology science · 2026Article
- Synthesis and characterization of an injectable telechelic material for the epiretinal delivery of retinal gene therapies.Journal of materials chemistry. B · 2026Article
- Pre-existing retinal inflammation exacerbates gene therapy-associated uveitis in more rapidly progressive retinal degeneration.Molecular therapy. Advances · 2026Article
- Investigating the Immunogenic Potential of Variations in Host Cell Protein Levels in Clinical-Grade AAV8 Products.Investigative ophthalmology & visual science · 2025Article
- 12-month outcomes after voretigene neparvovec gene therapy in paediatric patients withThe British journal of ophthalmology · 2025Article
- Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates.Translational vision science & technology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Progressive retinal atrophy has been described after subretinal gene therapy utilizing the adeno-associated virus (AAV) vector platform. To elucidate whether this atrophy is a consequence of inherent properties of AAV, or if it is related to the surgical trauma of subretinal delivery, we analyzed data from an Investigational New Drug-enabling study for PDE6A gene therapy in nonhuman primates. Design: Animal study (nonhuman primates), retrospective data analysis. Subjects: Forty eyes of 30 healthy nonhuman primates (macaca fascicularis) were included in the analysis. Two AAV dose levels (low: 1x10E11, high: 1x10E12) were compared with sham injection (balanced saline solution; BSS). Twenty untreated eyes were not analyzed. Methods: Animals were treated with a sutureless 23G vitrectomy and single subretinal injections of AAV.PDE6A and/or BSS. The follow-up period was 12 weeks. Atrophy development was followed using fundus autofluorescence (AF), OCT, fluorescence angiography, and indocyanine green angiography. Main Outcome Measures: Area [mm Results: Progressive atrophy at the injection site developed in 54% of high-dose-treated, 27% of low-dose-treated, and 0% of sham-treated eyes. At the end of observation, the mean ± SD area of atrophy in AF was 1.19 ± 1.75 mm Conclusion: Subretinal injection of AAV.PDE6A induced dose-dependent, progressive retinal atrophy at the site of injection. Findings from multimodal imaging were in line with focal, transient inflammation within the retina and choroid and secondary atrophy. Atrophic changes after gene therapy with AAV-based vector systems are not primarily due to surgical trauma and increase with the dose given. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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.