Optimizing anti-VEGF in AMD, DME, and RVO: Strategies for durable disease control

Retinal vascular disease presents some of the most demanding management decisions in vitreoretinal practice, particularly when treatment responses plateau and extension proves difficult. Michael Ammar, MD, vitreoretinal surgeon and codirector of clinical research at Retina Consultants San Diego and section chief of ophthalmology at Scripps Memorial Hospital in La Jolla, California, moderated a recent Modern Retina Case-Based Roundtable® focused on optimizing anti-VEGF treatment across age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Three cases from his own practice anchored a discussion on treatment durability, agent selection, and the practical management of patients who are difficult to extend.

Case 1: Central RVO and the challenge of extension

The first case involved a treatment-naive patient with a central RVO who was initially treated with aflibercept 2 mg (Eylea; Regeneron) and did well on a monthly schedule. Upon attempted extension to 6 weeks, however, the patient developed worsening macular edema. Treatment was changed to aflibercept 8 mg (Eylea HD; Regeneron), after which extension to at least 8 weeks was achieved, with active extension continuing at the time of the roundtable.

Ammar described the central teaching point of this case: RVOs produce the highest levels of VEGF among retinal vascular diseases, which can make them particularly difficult to treat and to extend. “RVOs can rapidly develop extremely high VEGF levels, and that can make them difficult to treat, and it can make it difficult to extend those patients at times,” he said.

He noted that next-generation anti-VEGF agents have changed the picture. “With next-generation anti-VEGF agents like aflibercept 8 mg and faricimab (Vabysmo; Genentech), we are seeing better durability than we’ve had in the past, with patients extending further out than they could before. We also see an improved ability to dry out the retina,” Ammar said. “Patients with RVOs are now being able to be extended out longer and require fewer injections than they did in the past.”

Case 2: Wet AMD and the transition from bevacizumab to faricimab

The second case presented a treatment-naive patient with newly diagnosed neovascular AMD who was initially started on bevacizumab (Avastin; Genentech) every 4 weeks. Upon attempted extension to 6 weeks, the patient experienced worsening macular edema and an increase in the size of their choroidal neovascularization (CNV). The patient was then switched to faricimab, with subsequent resolution of fluid and flattening of the CNV, and was able to extend to 13 weeks between injections.

Ammar described the key takeaway from this case as a direct illustration of the relative performance of older and newer agents. He noted that although bevacizumab was a groundbreaking treatment about 20 years ago for retinal vascular disease, compared with second-generation agents such as faricimab and high-dose aflibercept, it appears to be less effective at reducing central subfield thickness and less durable, requiring more frequent injections.

The contrast in this case was notable: The patient could not extend beyond 4 weeks on bevacizumab but reached 13 weeks on faricimab. “I think it just really nicely demonstrated how the newer agents we have really seem to be superior,” Ammar said.

Case 3: DME and the role of adjunctive steroids

The third case involved a treatment-naive patient with DME who was initiated on aflibercept 8 mg. After 3 loading doses, the patient was able to extend, consistent with findings in the phase 3 PHOTON (NCT04429503) clinical trial. The patient did well at 8 weeks but, at the 12-week mark, developed worsening macular edema. An adjunctive subtenon triamcinolone acetonide (Kenalog; Bristol Myers Squibb) injection was added alongside aflibercept 8 mg, and the patient subsequently extended the interval to 16 weeks between injections.

Ammar noted that this case prompted a broader discussion among attendees about the role of adjunctive peri- or intraocular steroids in DME management. “DME can be difficult to treat because while VEGF is the main driver of the disease process, we know that it’s not the only one, and there are others, including inflammatory mediators, that play a role,” he explained. “In this case, steroids were used in conjunction with anti-VEGF to be able to increase the interval between injections and decrease sort of the injection load on the patient. The benefit of using both agents is that you can sort of address the VEGF component, but also those other potential mediators like those inflammatory-driven pathways.”

However, a notable theme emerged from the group discussion: The advent of second-generation anti-VEGF agents has reduced the perceived need for adjunctive steroids in DME. “Collectively, we all felt we were using less adjunctive peri- or intraocular steroids for the treatment of [DME],” Ammar said. “The outcomes from the second-generation anti-VEGF agents alone were so good that there was…less of a need for adjunctive steroids, and we all had felt that independently.”

Emerging discussion: The future pipeline

Beyond the 3 cases, attendees discussed what is coming next in the treatment of retinal vascular disease. Ammar described a palpable sense of anticipation around emerging agents currently in clinical development. “There was some discussion about the future and what might be coming down the pipeline, and there’s a lot of research being done into gene therapy for anti-VEGF and also new agents like tyrosine kinase inhibitors that are all actively in their clinical trials,” he said. “There’s a lot of excitement and anticipation to see what [those] data will be and what those outcomes will show.”

He described the particular value of real-world experience as something that clinical trial data alone cannot capture. “While we all have the same clinical trial data that we process and digest and apply, I think that real-world application and those real-world experiences are also so valuable and are much harder to really capture in a study or a paper,” Ammar said. “So when you bring together all these great minds and you put them at a roundtable discussion, you kind of get all the best parts of everything in one place, and I always find that I come away from these experiences learning something new that I had not known before.”