Over the last 15 to 20 years, monoclonal antibody-based treatments, such as those targeting vascular endothelial growth factor (anti-VEGF), have become the standard of care for major retinal diseases, including wet age-related macular degeneration (wet AMD), diabetic macular edema, and retinal vein occlusion. Similarly, complement inhibitors have become the standard of care for advanced dry age-related macular degeneration (dry AMD). However, the need for recurrent injections remains a significant drawback.
A newer generation of gene-based medicines is now being studied as a way to help the eye produce therapeutic proteins over time. Depending on the product and indication, that approach could reduce treatment burden, extend injection intervals, or potentially provide long-lasting therapeutic effect.
Improving on anti-VEGF antibodies
Anti-VEGF drugs such as Lucentis, Eylea, and Vabysmo can slow disease progression in these retinal conditions, but they typically require repeated intravitreal injections at fixed intervals of four to 16 weeks. That schedule can be burdensome for both patients and providers, and may lead some patients to discontinue treatment despite the risk of vision loss, allowing disease progression to resume.
To address that burden, various drug companies are developing gene therapies intended to support longer-lasting intraocular production of anti-VEGF proteins. Many of these investigational therapies utilize an adeno-associated virus (AAV) to deliver deoxyribonucleic acid (DNA) into the eye so its cells can produce the proteins that function as anti-VEGF antibodies (Figure 1). Depending on the design of the virus, it requires administration into either the vitreous humor or a subretinal bleb. Repeated injections would not be required as long as the eye continues to produce the VEGF-countering proteins. Several of these products are in clinical trials.
Currently leading a crowded field to be first to market is Abbvie/Regenexbio with surabgene lomparvovec (sura-vec, ABBV-RGX-314), which is on track to obtain FDA approval as the first gene therapy for chronic retinal disease. As of this writing in April 2026, enrollment had been completed in pivotal trials evaluating subretinal delivery in wet AMD, with topline data expected in the fourth quarter of 2026.
Figure 1: How ocular gene therapy works
Gene therapy gives cells the ability to produce therapeutic proteins. The gene encoding the therapeutic protein is often delivered by viral vectors, attenuated viruses modified to function as genetic syringes. The gene can also be delivered transiently through lipid nanoparticles, such as those used to deliver mRNA-based COVID-19 vaccines.
Ocular gene therapies can be delivered to specific sites in the eye through various surgical and nonsurgical procedures.
The current state of ocular gene therapy
As of this writing, ClinicalTrials.gov reported 368 studies involving gene therapy for eye diseases. At that time, the FDA had approved two gene-based products for use in the eyes: one AAV-based gene therapy and one gene-modified cellular product.
AAV is considered to be the workhorse for delivering corrective genes in monogenic rare diseases.
Success in Rare Disease
Spark Therapeutics’ Luxturna was the first FDA-approved gene therapy for a genetic disease. The AAV-based gene therapy delivers a functional copy of the RPE65 gene as a single-dose curative treatment for retinitis pigmentosa caused by mutations to the RPE65 gene.
On a related note, Krystal Biotech’s Vyuvek was FDA-approved as a gel for topical application to the skin of patients with epidermolysis bulosa (EB), a condition that causes brittle skin due to mutations to the COL7A1 gene.
The FDA also cleared an investigational new drug (IND) application for compassionate use of a reformulated Vyjuvek as eye drops to treat EB in a pediatric subject, as the disease caused such severe corneal scarring and vision impairment.
The eye drops were applied after surgical removal of the scars. Within three months and 19 doses, the corneal epithelium was fully healed. At eight months, assessments revealed complete epithelial healing, and imaging found no signs of corneal scarring, recurrence, or other abnormalities. The subject demonstrated better visual acuity after Vyjuvek treatment, improving from 20/400 to 20/25 at eight months post-treatment.
Cellular therapies
While most ophthalmology gene therapies studies use genetically engineered viruses, gene-modified cellular therapies are also emerging. In March 2025, the FDA approved the first gene-modified cellular therapy product for ophthalmology: Neurotech Pharmaceuticals’ cell therapy for an eye disease known as macular telangiectasia type 2 (MacTel).
The drug, Encelto, is delivered in a tiny, implanted membrane that encapsulates a type of cell in the retina called a retinal pigment epithelial cell, which has been genetically engineered to express the protein ciliary neurotrophic factor. That protein helps photoreceptors in the eye survive longer, slowing the disease.
Optogenetics
Optogenetics in humans is an emerging technology in early phase clinical trials aimed primarily at restoring vision in people with severe retinal degeneration (e.g., retinitis pigmentosa), in which photoreceptors are lost but inner retinal neurons remain.
This strategy involves delivering light-sensitive proteins (opsins, often derived from algae or bacteria) into surviving retinal cells—typically retinal ganglion cells or bipolar cells—using gene therapy vectors such as AAV. Those modified cells can then respond to light, effectively bypassing damaged photoreceptors.
What do I need for study startup? Streamlining safety reviews.
Diverse technologies are being used under the umbrella of cell and gene therapy, but each carries different risks. Investigators, research staff, participants, and caregivers should be aware that, because cell and gene therapies are intended to be permanent—which is the greatest benefit for those suffering from disease—they also bear a unique risk. Additionally, there are many unique hazards associated with handling, disposal, and cleanup of cell and gene therapeutics that require special care.
For these reasons, the National Institutes of Health (NIH) requires institutional biosafety committee (IBC) reviews for NIH-funded cell and gene therapy trials—and for sites that have received NIH support for research—in addition to FDA-mandated institutional review board (IRB) committee reviews.
An IRB review assesses the ethics of the research, while an IBC review focuses on the safety of site staff, caregivers, and anyone within proximity of the treatment environment. For example, an IBC may recommend protective measures for a child’s caregiver who could come into contact with materials associated with administration of a genetically modified virus via syringe.
IBC and IRB reviews must happen before the first patient is enrolled, which can delay study startup if the reviews are not handled efficiently and effectively. One easy way to streamline these important reviews is to work with a single independent organization experienced in both types of safety reviews. In addition, it is important to vet sites in advance. Sponsors and CROs can streamline IBC reviews by working with research sites that already have experience with cell and gene therapy trials and have IBC registrations with the NIH.
Site readiness also matters. Unfortunately, some eye clinics are not aware of the IBC requirement for gene therapy research, and it can take six to eight weeks to register a site with the NIH before an IBC review can take place. Early planning can help sponsors identify those gaps before activation timelines are affected.
Be sure to do your homework to identify organizations with both IBC review expertise and credentialed reviewers who have specific experience in human gene therapy in ophthalmology on their boards. Universities can be limited to the faculty members who lean more toward general scientific laboratory research rather than deep-domain or clinical specializations.
Finally, keep in mind that IBC and IRB reviews can move faster when handled by experienced review organizations versus locally administered IBC committees.
Want to learn more?
Bear in mind that not every study involving gene modified cellular therapy or gene therapy automatically requires IBC review in every circumstance. Funding source, best practice, and institutional policy still matter. The NIH Guidelines apply based on the nature of the investigational product, NIH support to the research site, and also best practice as noted in NIH OSP’s frequently asked questions:
Want to learn more? Check out this overview of Advarra’s review services or contact us to ask an expert a specific question.
