Peer Exchange: Advancing care across retinal vascular diseases with next-generation anti-VEGF therapy

In this Ophthalmology Times Peer Exchange, a panel of retina specialists discussed the evolving management of retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy, and retinal vein occlusion (RVO). The panel included Jonathan Jonisch, MD, of Vitreoretinal Consultants of New York, who moderated the discussion; Anton Kolomeyer, MD, PhD, of NJRetina in central New Jersey; David A. Eichenbaum, MD, FASRS, director of research at Retina Vitreous Associates of Florida St Petersburg and Clearwater; and Esther Lee Kim, MD, of Orange County Retina in Orange County, California.

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Opening the discussion, Jonisch said the panel would “review the clinical burden and treatment goals, examine the clinical trial data, [review] recent label updates for next-generation anti-VEGF therapy,” and discuss how these developments influence treatment decisions.

Kolomeyer described the scope of the treatment burden across retinal vascular disease, noting that “the burden is definitely there, the burden is great,” with prevalence varying by practice location but injection volume remaining high across disease states. The panel agreed that patient retention is a persistent challenge, because consistent follow-up correlates closely with long-term visual outcomes. Panelists also pointed to relative undertreatment in real-world practice compared with clinical trials, noting that patients receiving 10 or more injections annually tend to have the best outcomes, whereas real-world cases average closer to 6 injections per year.

On imaging, panelists pointed to increased use of optical coherence tomography (OCT) angiography in place of fluorescein angiography for many applications, along with growing use of widefield and ultrawidefield imaging to detect peripheral pathology, including capillary nonperfusion and neovascularization, that can be missed on routine examination. They also noted that broader adoption of OCT in general ophthalmology and optometry practices has led to earlier referrals for conditions such as cystoid macular edema.

Clinical trial data and treatment strategies

The panel reviewed data from the PULSAR (NCT04423718), PHOTON (NCT04429503), and QUASAR (NCT05850520) trials evaluating aflibercept 8 mg (Eylea HD; Regeneron) against aflibercept 2 mg (Eylea; Regeneron) across wet AMD, DME, and RVO, respectively, noting noninferior efficacy alongside meaningfully fewer injections and faster drying compared with aflibercept 2 mg. Kim discussed real-world IRIS Registry data from more than 10,000 patients, saying treatment-naive patients were largely able to extend to every 12 weeks, whereas previously treated patients gained an average of 2 additional weeks between injections—a change she said represents “a 50% improvement in their treatment interval” for patients previously limited to shorter intervals. Panelists also pointed to recent label updates extending aflibercept 8-mg dosing intervals up to every 20 weeks, as well as the addition of every-4-week dosing for patients who require more frequent treatment.

Eichenbaum discussed faricimab (Vabysmo; Genentech), which combines anti-VEGF with angiopoietin-2 inhibition, describing the current treatment landscape as “the end of the anti-VEGF monotherapy era” as multitargeted agents move through development. He also drew on his experience with the ranibizumab port delivery system (Susvimo; Genentech), noting durability out to 7 years but cautioning that “it does not work without a cost,” citing complications he has managed including exposed implants and endophthalmitis. Panelists noted that with newer, longer-acting intravitreal biologics now available, the calculus around the device’s surgical risk profile has shifted since its original comparison to monthly ranibizumab injections, and that patient selection remains central to its appropriate use.

On managing suboptimal response, panelists described distinguishing between patients who fail to dry and those who cannot be extended to longer intervals, describing approaches including switching therapies, repeat angiographic imaging, photodynamic therapy for focal lesions, and, in select cases, combining intravitreal corticosteroids with anti-VEGF therapy. They also touched on safety considerations specific to higher-volume injections, including use of IOP-lowering drops before treatment and anterior chamber paracentesis in patients with advanced glaucomatous cupping.

Access barriers were another focus of the conversation, including insurance step therapy requirements and funding gaps in patient assistance programs. Panelists noted that bevacizumab remains a viable option for patients without access to other agents, given its relative clinical equivalency to ranibizumab. They also credited manufacturer patient assistance programs with expanding access to newer therapies for uninsured and underinsured patients.

Emerging therapies and looking ahead

Panelists discussed emerging therapies, including tyrosine kinase inhibitors and gene therapy, as likely complementary, rather than replacement, lines of therapy alongside biologics, with tyrosine kinase inhibitors expected to see faster clinical adoption given easier integration into existing treatment workflows.

Closing the discussion, Eichenbaum said, “It’s a great time to be in retina...we have more currently available and more in our pipeline than we’ve ever had for posterior segment common retinal disease.” Kolomeyer encouraged colleagues to “stay excited, stay informed, continue to go to meetings, [and] pay attention to the publications that are coming out.” Kim added, “I would add to stay open-minded,” encouraging colleagues to stay current with emerging data while continuing to offer patients the most effective treatment options available.