Starting intravitreous aflibercept (Eylea, Regeneron) among patients with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema did not lead to better visual acuity compared with those who received sham treatment but did contribute to significant anatomic improvement, a new 4-year study has found.
Over 4 years, 33.9% of those who were given intravitreous aflibercept injections developed proliferative diabetic retinopathy (PDR) or center-involved diabetic macular edema (CI-DME) with vision loss compared with 56.9% of those who received a sham injection (adjusted hazard ratio, 0.40; P < .001), report Jennifer K. Sun, MD, MPH, an associate professor of ophthalmology at Harvard University in Boston, Massachusetts, and colleagues.
However, other results on visual acuity showed average changes of −2.4 letters with sham and −2.7 letters with aflibercept from baseline to 4 years (adjusted mean difference, −0.5 letters; P = .52), a nonsignificant difference, the researchers found.
The findings were published online in JAMA.
“The major message from this study is that although early treatment of eyes with nonproliferative diabetic retinopathy does improve rates of PDR or CI-DME development, it doesn’t change the long-term visual acuity outcomes,” Sun told Medscape Medical News.
“And therefore, given the small but well-documented potential risks associated with the injections, the treatment burden, including cost and follow-up visits that are necessary for the injections, preventive treatment with anti-VEGF [such as aflibercept] for eyes with NPDR generally is not a strategy that is warranted,” she said.
Results of 4-Year Trial
The existing literature has looked at patients with diabetes who were taking antivascular endothelial growth factor (anti-VEGF) therapy, a class of drugs that includes aflibercept. Trials have shown that anti-VEGF agents are more effective than the previous standard of care, noted Sun.
Other research has also demonstrated that anti-VEGF medications, including aflibercept, are effective for the treatment of peripheral diabetic retinopathy, Sun added.
But they wanted to examine the medication’s effect in patients with moderate to severe nonproliferative diabetic retinopathy compared with sham treatment.
In doing so, the researchers looked specifically at rates of vision-threatening complications and visual acuity.
They earlier reported 2-year outcomes from this trial demonstrating that, compared with sham, aflibercept decreased the occurrence of vision-impairing CI-DME, decreased diabetic retinopathy severity, and lowered progression to proliferative diabetic retinopathy risk, the study authors note.
Here, they provide 4-year results.
The investigators assessed 328 adults across 64 clinical sites in the United States and Canada. Women comprised 42.4% of the cohort, and 45% of the study group was White. They randomized 199 eyes to the sham group and 200 to the 2.0 mg aflibercept group. Mean age was 56 years.
Researchers gave patients eight injections every 2 years and continued this intervention approach each quarter for up to 4 years.
However, they stopped treatment in cases in which the eye developed at least a mild form of nonproliferative diabetic retinopathy. In those cases, both study groups received aflibercept treatment to manage CI-DME with vision loss or high-risk proliferative diabetic retinopathy.
Notably, no subgroup was identified for which there was a clear advantage of early aflibercept intervention on visual acuity when taking into account sex, ethnicity and race, noncentral DME, and Diabetic Retinopathy Severity Scale.
Antiplatelet Trialists’ Collaboration cerebrovascular/cardiovascular event rates were 7.8% in unilateral sham participants, 9.9% in bilateral participants, and 10.9% in unilateral aflibercept participants.
“Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with nonproliferative diabetic retinopathy without CI-DME,” the researchers conclude.
Sun has disclosed relationships with Adaptive Sensory Technologies, American Diabetes Association, Novo Nordisk, Novartis, Roche/Genentech, JDRF, Physical Sciences Inc, KalVista, Janssen, Roche/Genentech, Boehringer Ingelheim, Optovue, Boston Micromachines, American Medical Association, and Merck.
JAMA. 2023;329:376-385. Abstract
Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University’s Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University. Her work has taken her to Honduras, Cambodia, France, and Ghana and has appeared in outlets like The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, TCTMD, Insider, and Tonic (Health by Vice), among other publications.
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