The first study to evaluate both eyes treated with a gene therapy targeting neovascular, or wet, age-related macular degeneration (AMD) has found the treatment as safe and effective in the second eye as it was in the first.

The open-label study included 10 patients who had an operation to place the gene therapy, surabgene lomparvovec, also known as sura-vec or ABBV-RGX-314, below the retinal surface in their second, or fellow, eye a year or more after they had the gene therapy placed in the first eye, investigator Dante Pieramici, MD, retina specialist at California Retina Consultants in Santa Barbara, California, reported at the European Society of Retina Specialists (EURETINA) 2025 in Paris, France.

“One of the concerns with viral vectors would be that if you treat one eye you sort of sensitize the system for an inflammatory response and then when you treat the other eye it could be worse,” Pieramici told Medscape Medical News. “Or the patient could also develop neutralizing antibodies to inactivate the vector so it might be less effective, but we didn’t see any of those problems.”

The outcomes in this fellow eye study may be “one of the advantages” of using the subretinal approach to surgically place the vector underneath the retina as opposed to using an intravitreal injection to deliver the vector into the vitreous of the eye, he said.

Sura-vec is an adeno-associated virus-eight gene vector that encodes an antibody fragment that aims to inhibit VEGF, overexpression of which causes the growth of new blood vessels characteristic of exudative retinal disease such as neovascular AMD and diabetic macular edema. All the fellow eyes in the study received the 1.3 × 10¹¹ dose being used in the ongoing phase 3 trial of the treatment.

Vision, Anatomy Remained Stable

“This drug actually maintained or had good efficacy in the fellow eye,” Pieramici told the attendees. “Best-corrected visual acuity remained stable — we don’t expect an improvement — and central subretinal thickness remained stable, and this was true whether patients needed additional treatment with intravitreal injections or remained injection-free.”

In the year after the treatment in the fellow eye, the patients required 92% fewer anti-VEGF injections, on average, in that eye than before the treatment, Pieramici said. The patients averaged 8.8 annual injections before treatment and 0.7 afterward. Overall, 60% of the fellow eyes were injection-free at 1 year, he said.

Among the patients who needed supplemental anti-VEGF treatments, best-corrected visual acuity improved 0.3 Early Treatment Diabetic Retinopathy Study (ETDRS) letters after a year and average central retinal thickness, a biomarker of retinal inflammation, decreased 0.1 µm. In the eyes that remained injection-free, acuity increased by 2.4 letters and retinal thickness decreased 34.8 µm. Snellen visual acuity of 20/20 is the equivalent of 85 ETDRS letters.

None of the patients who had the treatment in the fellow eye experienced a serious adverse event related to the drug treatment, and no cases of chorioretinitis, vasculitis, retinal vein occlusion, or hypotony were reported, Pieramici said. Mild changes in retinal pigmentation were observed in 91% of eyes, and 27.3% had a conjunctival hemorrhage after placement of the gene therapy below the retina, all of which resolved within days to weeks, he added.

“It was very reassuring that the subretinal approach to drug delivery was very well tolerated in the study eye but also in the fellow eye,” Pieramici said.

The 1-year results of the fellow eye study make the case for further investigating bilateral treatment with sura-vec, Dina Zur, MD, president of the Israeli Retina Society and retina specialist at Tel Aviv University, Tel Aviv, Israel, told Medscape Medical News.

“The data are very encouraging, as they demonstrate the safety of fellow eye treatment,” Zur said. “This is an important step since potential systemic immune responses could not have been predicted in advance. Importantly, no new safety signals were observed, and only a minority of patients required rescue therapy.”

Zur added, “The question remains who are the patients who need rescue therapy and how could we identify them in advance?”

AbbVie funded the study. Pieramici reported having financial relationships with RegenxBio/AbbVie, 4D Molecular Therapeutics, Adverum, Genentech, Regeneron, EyePoint, Ocular Therapeutix, RetinAI, Arrowhead, Unity, Apellis, JCyte, EyeBio, Oculus, Boehringer Ingelheim, Janssen, Annexon Biosciences, Novartis, and Avicenna.

Zur reported having financial relationships with Astellas, Roche, Bayer, AbbVie, Espansione, and Johnson & Johnson. 

Richard Mark Kirkner is a medical journalist based in Philadelphia.