If Longer Dosing Intervals Are the Goal, These Results Hit the Back of the Net | ASRS 2025

Injections of vascular endothelial growth factor (VEGF) inhibitors have transformed the treatment of retinal diseases such as neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema. But now one of the goals is to space out the time between injections as long as possible to spare patients frequent injections and the risk of side effects without sacrificing treatment effectiveness.

Eric W.Schneider, M.D.

Results presented today at the American Society of Retina Specialists (ASRS) annual meeting suggest that dosing intervals of 20 weeks or more may be possible for Eylea HD (aflibercept 8 milligrams), a VEGF inhibitor, when it is used for treatment for diabetic macular edema, and the question was raised whether patients treated every 24 weeks should continue to be treated.

Eric W. Schneider, M.D., of Tennessee Retina in Middle Tennessee, presented results from the 60-week extension of the 96-week PHOTON trial, which compared 328 patients with diabetic macular edema injected with Eylea HD every 12 weeks with 163 patients injected every 16 weeks. A third group of 167 patients was treated with a 2-milligram dose of aflibercept, which is sold as Eylea, every eight weeks. In the extension trial, the 70 patients in the 2-milligram group were switched over to Eylea HD given every 12 weeks, and 195 in the Eylea HD groups continued with the higher-dose version of the VEGF inhibitor at the last assigned dosing interval. At week 100, dosing intervals were shortened or extended if prespecified criteria were met.

Data shared by Schneider showed that 45% of those originally assigned to the Eylea HD groups had completed dosing intervals of 20 weeks or more. At the end of the 156-week trial, 28% had an assigned dosing interval of 24 weeks and 20% had an assigned dosing interval of 20 weeks to 22 weeks, according to Schneider.

During the question-and-answer period after Schneider and others had presented study results, Schneider was asked whether it makes sense to treat patients who were at a 24-week dosing interval in light of pharmacokinetic modeling and other evidence that suggests that there might be very little anti-VEGF activity from an 8-milligram dose of aflibercept after 20 weeks. Schneider said there may be some added benefits from treating at such intervals, but he added that “it is very reasonable to consider not treating those patients at 24 weeks, for sure.”

In the group that was switched from a 2-milligram dose to Eylea HD, 19% had assigned dosing intervals of 20 weeks or more.

Central retinal thickness is an anatomical measure of the severity of diabetic macular edema and other retinal diseases. Schneider shared results that showed a sharp decrease in central retinal thickness among the patients in the 2-milligram group after they received their first injection of Eylea HD. He also noted central retinal thickness oscillated when patients were treated with the 2-milligram dose and that evened out when they were switched over to Eylea HD.

Schneider told the ASRS audience in Long Beach, California, that there were no new safety signals in the results of the extension trial. There were a total of 37 (52.9%) ocular adverse events among the patients that switched from the 2-milligram dose to the Eylea HD and 108 (55.4%) among those who were assigned Eylea HD from the start. One patient in the group that switched to the higher dose in the extension experienced iridocyclitis, and another experienced uveitis. Among the patients assigned to Eylea HD from the start, two experienced iritis and one, endophthalmitis.

The conclusion of the abstract of results Schneider presented says that the achievement of extended dosing intervals with Eylea HD “in the vast majority of patients,” along with the slower fluid reaccumulation observed among those who switched from the 2-milligram dose to the Eylea HD dose, “supports the longer duration of action of aflibercept 8 mg versus 2 mg.”

The study was supported by Regeneron, the maker of Eylea HD and Eylea.