Christina Y. Weng, MD, MBA, is a professor and the Alice R. McPherson Retina Research Foundation Chair in Ophthalmology at Baylor College of Medicine.

Christina Y. Weng, MD, MBA

Implications of Gene Therapy in Retina, With Christina Y. Weng, MD

In a field marked by rapid innovation, gene therapy is emerging as one of the most promising advances in 

American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting

, Christina Y. Weng, MD, MBA, a professor and the Alice R. McPherson Retina Research Foundation Chair in Ophthalmology at Baylor College of Medicine, offered perspective on the transformative potential of these therapies and what they could mean for both patients and providers.

Weng outlined how these gene therapies have the potential to raise the bar for treatment durability to new levels, highlighting three key benefits these therapies could offer: more consistent dosing, fewer injections, and greater overall efficiency in disease management.

“The first one is that we know that most patients are under-treated with anti-VEGF in the real world, and consequently, they suffer from suboptimal visual outcomes,” Weng told 

. “By providing constant dosing of anti-VEGF, gene therapy might help counteract this challenge.”

Weng also emphasized the value of steady dosing, noting that current treatment methods center on bolus dosing, which often causes recurrent anatomic fluctuations and could negatively impact outcomes. Gene therapy could provide a steadier level of dosing, which could render benefits not yet fully realized, as well as lead to fewer burdensome injections.

“Those injections are not only associated with psychological burden, financial burden, but there's also substantial socioeconomic costs,” Weng told 

. “Many of these patients come in each time, bringing in an accompaniment or arranging transportation, etc. All those things can also be reduced with the reduced treatment burden that gene therapy might bring.”

As several gene therapy programs reach late-stage trials, Weng is closely watching the results to see if efficacy signals seen in earlier trials are replicated with larger cohorts. She cited the importance of safety, with reported issues like intraocular inflammation and pigmentary changes becoming important factors in regulatory and clinical decision-making.

“All of the programs I've mentioned have found their gene therapy candidates to be well tolerated, but many have also been associated with adverse events such as intraocular inflammation, pigmentary changes, and episcleritis,” Weng told 

. “The Phase 3 studies will provide important insights on safety, and they're also going to pressure test some of the prophylactic strategies being evaluated.

Looking ahead, Weng noted gene therapy could drive a paradigm shift in disease management,” particularly when paired with advances like home optical coherence tomography (OCT). However, questions remain about how these new options will fit into treatment algorithms.

“We’ve entered the era of gene therapy, not just for rare diseases, but also for some of our most common,” Weng told 

. “Several programs are in late stages, and those results will be key in providing safety and efficacy data that will determine the viability of these gene therapy candidates. If they do emerge on the market, they have the potential of significantly reducing treatment burden and potentially improving visual outcomes for our patients.”

Weng reports relevant disclosures with Alcon, AbbVie, Apellis, Astellas/Iveric Bio, Genentech, Regeneron, and others.

Weng CY. The Current State of Gene Therapy for Retinal Diseases. Presented at: 2025 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting. April 25-28, 2025. Los Angeles, CA.

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Gene therapy could revolutionize retinal disease treatment, promising consistent dosing, fewer injections, and improved patient outcomes, as highlighted by expert Christina Y. Weng.

Reshaping Retinal Care With Gene Therapy, With Christina Y. Weng, MD

Gene therapy is poised to reshape the treatment landscape in 

—not just for rare inherited retinal disorders, but increasingly for widespread conditions like neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy. At the 2025 

, Christina Y. Weng, MD, MBA, a professor and the Alice R. McPherson Retina Research Foundation Chair in Ophthalmology at Baylor College of Medicine, provided a comprehensive update on the leading gene and cell therapy programs making headway.

The US Food and Drug Administration (FDA) recently approved Neurotech Pharmaceuticals’ Revakinagene taroretcel-lwey (ENCELTO), marking the first and only FDA-approved treatment for Macular Telangiectasia type 2 (MacTel). Designed to deliver continuous therapeutic doses of ciliary neurotrophic factor (CNTF) to the retina using the company’s encapsulated cell therapy (ECT) technology, implantation in two pivotal Phase 3 trials led to a significant halt in the loss of macular photoreceptors across 24 months.

Regenxbio’s surabgene lomparvovec (sura-vec, ABBV-RGX-314), developed in partnership with AbbVie, is under investigation as a potential one-time alternative for wet AMD, diabetic retinopathy, and other chronic retinal conditions treated with anti-VEGF therapies.

RGX-314’s NAV® AAV8 vector encodes an antibody fragment designed to inhibit expression of VEGF—two separate routes of administration, a standardized subretinal delivery and suprachoroidal space delivery, are under investigation.

In the recent Phase 2 fellow eye sub-study of RGX-314, nine previously treated patients showed a 97% reduction in annualized anti-VEGF treatment burden at nine months post-subretinal administration. Notably, 100% of patients required zero or one supplemental injection, and 78% were completely injection-free.

Ixoberogene soroparvovec (Ixo-vec), formerly known as ADVM-022, is under development by Adverum Biotechnologies as a gene therapy for wet AMD. Using a proprietary vector capsid, AAV.7m8, ixo-vec carries an aflibercept coding sequence under the control of a proprietary expression cassette.

In the OPTIC trial, a single intravitreal injection of Ixo-vec (2E11 vg/eye) led to an 81% reduction in annualized anti-VEGF injection rate overall, and a 94% reduction in patients with baseline NAbs titers <1:125. At three years, aflibercept expression was robust, with maintenance of vision and retinal anatomy—no participants required topical steroids for inflammation.

All treatment-related ocular adverse events were mild (81%) or moderate (19%), suggesting promising safety.

4D-150 is a backbone therapy in development to provide multi-year sustained expression of aflibercept and anti-VEGF-C from the retina with a single intravitreal injection for both wet AMD and DME.

Interim data from the SPECTRA trial found 4D-150 (3E10 vg/eye) well-tolerated in patients with DME, demonstrating strong signs of clinical activity, including improvements in visual acuity and anatomy. The FDA endorsed advancing 4D-150 directly to Phase 3 for DME, with a single pivotal trial of 300–400 patients using BCVA noninferiority to aflibercept and updated, less stringent supplemental injection criteria as the primary endpoint.

After positive data in the PRISM trial, the first patients were enrolled in the Phase 3 4FRONT-1 trial evaluating 4D-150 for wet AMD, with a primary endpoint of non-inferiority in the mean change from baseline in BCVA at 52 weeks. The Phase 3 4FRONT-2 trial, set to begin in Q3 2025, mirrors 4FRONT-1 in design and will assess 4D-150 in both treatment-naïve and recently treated wet AMD patients, with topline data from both studies expected in the second half of 2027.

Watch the full interview with Weng in the above video for more insight into these gene therapy programs.

Iapoce C. FDA approves Revakinagene Taroretcel (ENCELTO) for MacTel. HCP Live. March 6, 2025. Accessed April 22, 2025. 

https://www.hcplive.com/view/fda-approves-revakinagene-taroretcel-encelto-for-mactel

REGENXBIO presents positive data from the phase II study of subretinal ABBV-RGX-314 in patients with bilateral wet AMD at AAO 2024. Regenxbio Inc. Accessed April 22, 2025. 

https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-data-phase-ii-study-subretinal-abbv

Pipeline. Adverum Biotechnologies. January 13, 2025. Accessed April 22, 2025. 

4DMT announces first patients enrolled in 4FRONT-1 phase 3 clinical trial evaluating 4D-150 in wet AMD. 4D Molecular Therapeutics. March 10, 2025. Accessed April 22, 2025. 

https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-first-patients-enrolled-4front-1-phase-3-clinical

4DMT announces positive interim data from 4D-150 spectra clinical trial in DME and alignment with FDA on registrational path. 4D Molecular Therapeutics. January 10, 2025. Accessed April 22, 2025. 

https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-positive-interim-data-4d-150-spectra-clinical

Christina Y. Weng, MD, breaks down emerging gene therapy programs poised to change how retina specialists treat chronic eye disease.

Christina Y. Weng, MD, MBA

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