Perspective: recent long-term gene-therapy data spur a 'gene therapy shift' in retinal disease

Modern Retina published a December 8, 2025 perspective by Carl Regillo, Veeral Sheth and Lejla Vajzovic that argued retinal gene therapy is moving from a rare-disease concept toward a possible treatment option in common disorders such as neovascular age-related macular degeneration, diabetic retinopathy and diabetic macular edema. The article centered on a practical problem retina specialists already know well: anti-VEGF drugs work, but many patients need injections every one to two months. The authors wrote that newer gene-therapy programs are being built to cut that treatment burden by turning retinal cells into longer-term producers of anti-VEGF proteins. They did not present the change as an immediate overhaul of practice, but as a development supported by several years of follow-up data and active late-stage programs. ### Which retinal diseases are driving the current gene-therapy discussion? Neovascular age-related macular degeneration, or wet AMD, is the main focus of the current discussion because it is common and usually managed with repeated anti-VEGF injections. Regillo, Sheth and Vajzovic wrote that gene therapy first entered ophthalmology with Spark Therapeutics' Luxturna in 2017 for an inherited retinal disease, and that the field has since expanded toward acquired diseases including wet AMD, diabetic retinopathy and diabetic macular edema. (modernretina.com) AbbVie and REGENXBIO said on January 13, 2025 that their ABBV-RGX-314 program is being developed as a potential one-time treatment for wet AMD and diabetic retinopathy. The companies said pivotal data for subretinal ABBV-RGX-314 in wet AMD are expected in 2026. ### Why are doctors looking beyond standard anti-VEGF injections? (modernretina.com) Anti-VEGF injections have changed retinal care over the past decade, but the burden of frequent office visits and repeat dosing remains central to every discussion of new approaches. Modern Retina's authors wrote that current biologics have improved outcomes "albeit with some limitations," and AbbVie global ophthalmology clinical-development head Michael Robinson said in the January 2025 update that more options are needed to relieve "the current treatment burden of chronic, frequent dosing." (news.abbvie.com) Arshad Khanani said at the American Academy of Ophthalmology meeting in October 2024 that many bilateral wet-AMD patients entering the ABBV-RGX-314 fellow-eye study had been getting injections every one to two months, averaging eight injections before enrollment. He said treating both eyes with a single gene-therapy administration could reduce that burden in routine care. (modernretina.com) ### What kind of data is making this conversation more concrete? 4D Molecular Therapeutics presented 52-week phase 2b PRISM data in February 2025 showing an approximately 83% reduction in injection burden versus projected on-label aflibercept every eight weeks in the overall 3E10 vg/eye population. The same presentation reported about 94% reduction in the recently diagnosed subgroup, with improved visual acuity, sustained anatomical control and no significant intraocular inflammation. (retinalphysician.com) ABBV-RGX-314 has produced longer follow-up in earlier-stage work. Retinal Physician reported in October 2024 that follow-up data extended to four years and that 78% of patients in the fellow-eye study were injection-free at nine months, with a 97% reduction in overall treatment burden, according to Khanani's presentation. (4dmoleculartherapeutics.com) ### Are these programs all using the same approach inside the eye? 4D-150 is being developed as an intravitreal gene therapy, which means it is delivered by injection into the eye in a way retina specialists already use for standard medicines. A February 2025 PRISM presentation described 4D-150 as a proprietary capsid carrying a dual-transgene payload and said the program was designed for routine intravitreal administration with stable aflibercept expression for up to two years in reported samples. (retinalphysician.com) ABBV-RGX-314 is being advanced through both subretinal and suprachoroidal delivery routes. AbbVie and REGENXBIO said the wet-AMD pivotal readout due in 2026 is tied to the subretinal program, while the diabetic-retinopathy phase 3 plan uses Clearside Biomedical's SCS Microinjector for suprachoroidal delivery. (4dmoleculartherapeutics.com) ### What would need to happen before this changes everyday retina practice? Pivotal data are the next hard checkpoint. AbbVie and REGENXBIO said ATMOSPHERE and ASCENT data for subretinal ABBV-RGX-314 in wet AMD are expected in 2026, and those trials are the clearest near-term test of whether durability seen in earlier studies can support broader use. (news.abbvie.com) 4D Molecular Therapeutics is also moving into registration-stage testing. The company said in November 2025 that 4FRONT-1 had randomized more than 200 patients and that 4FRONT-2 enrollment was expected to complete in the second half of 2026. Those milestones, alongside any additional conference updates from PRISM and other wet-AMD programs, are the specific markers to watch over the next several months. (eyewire.news) (news.abbvie.com)