ArticleOphthalmology science2021
An Optimized Treatment Protocol for Subretinal Injections Limits Intravitreal Vector Distribution.
Article in Ophthalmology science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Assessment of the Orbit® subretinal delivery system (Orbit® SDS device) and prototypes in adult and juvenile canine eyes.Drug delivery and translational research · 2026Article
- Subretinal Injection Volume Correlates to Persistent Outer Retinal Thinning in the Pig Eye.Investigative ophthalmology & visual science · 2025Article
- Pars plana vitrectomy followed by subretinal or intravitreal injection with Conbercept and tissue plasminogen activator for clearance of submacular hemorrhage secondary to idiopathic polypoidal choroidal vasculopathy.International ophthalmology · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Techniques for subretinal injections in animals.Veterinary ophthalmology · 2025Review
- Head-mounted surgical robots are an enabling technology for subretinal injections.Science robotics · 2025Article
- Retention Rates of Genetic Therapies Based on AAV Serotypes 2 and 8 Using Different Drug-Delivery Materials.International journal of molecular sciences · 2024Article
- In-depth comparison of Anc80L65 and AAV9 retinal targeting and characterization of cross-reactivity to multiple AAV serotypes in humans.Molecular therapy. Methods & clinical development · 2023Article
- Pars Plana Vitrectomy in Inherited Retinal Diseases: A Comprehensive Review of the Literature.Life (Basel, Switzerland) · 2023Review
- Human Retinal Organoids in Therapeutic Discovery: A Review of Applications.Handbook of experimental pharmacology · 2023Review
- Subretinal Therapy: Technological Solutions to Surgical and Immunological Challenges.Frontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Subretinal injections (SRis) are commonly used in retinal gene therapy procedures to deliver adeno-associated virus (AAV) to photoreceptors and retinal pigment epithelial cells. We present an optimized surgical protocol to minimize off-target application of AAV in the vitreous, which in turn reduces the risk of extensive biodistribution and inflammation, ultimately leading to enhanced safety of the therapy. Design: Experimental animal research study. Participants: Eight cynomolgus monkeys ( Methods: Subretinal injections with an AAV2/8 vector were performed. The animals were allocated to 2 different vector dose groups (1×10 Main Outcome Measures: Intravitreal vector genome copies were analyzed with quantitative polymerase chain reaction and compared between groups. Results: Even uneventful SRi leads to dissemination of millions of AAV particles (0.1-0.7% of viral vector loading dose) into the vitreous cavity. Three minutes of lavage led to a substantial decrease (on average 96%) of intravitreal vector load. Conclusions: Multiple studies have shown that the intravitreal space is not as immune privileged as the subretinal space. Intravitreal AAV particles disseminate into the bloodstream, lead to increased biodistribution into lymphatic tissue, and help to stage an immune response with implications for both safety and efficacy. Therefore, minimizing off-target vector application after reflux of vector from the subretinal space is of significant interest. We show that a simple lavage of intravitreal fluid efficiently decreases the intravitreal vector load. Such a step should be considered when performing subretinal gene therapy.
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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.