Intravitreal injections with aflibercept (Eylea) don’t improve the visual acuity of people with nonproliferative diabetic retinopathy (NPDR), researchers say.
The treatments do reduce the risk for center-involved diabetic macular edema and proliferative diabetic retinopathy, however, said Adam R. Glassman, MS, principal investigator of the DRCR Retina Network Coordinating Center, Tampa, Florida.
“Some clinicians may decide to initiate preventative Eylea treatment for eyes with severe NPDR based on the reduction in anatomic complications, but some clinicians may choose to wait until disease worsens before initiating anti-VEGF [vascular endothelial growth factor] treatment,” Glassman told Medscape Medical News in an email.
The DRCR Retina Network Protocol W trial was published online March 30 in JAMA Ophthalmology.
Previously large randomized clinical trials showed that treatments with anti-VEGF intravitreal injections are effective in protecting and restoring vision for patients with diabetic macular edema and proliferative diabetic retinopathy.
But it was uncertain whether these treatments would benefit patients in whose diabetic retinopathy had not led to such complications.
To address that question, Glassman and colleagues recruited adults with diabetes and moderate to severe NPDR. They randomly assigned 200 of them to receive intravitreal aflibercept 2 mg and 199 to receive sham injections at baseline and at 1, 2, and 4 months, and then every 4 months for 2 years.
The patients in both groups also received aflibercept injections if they developed center-involved diabetic macular edema with vision loss or high-risk proliferative diabetic retinopathy.
After 2 years, the mean number of aflibercept injections in the aflibercept group was 8.0; 7.7 of those were given for prevention alone. In the sham group, the mean number of aflibercept injections was 1.1, and the mean number of sham injections was 7.4.
After 2 years, significantly more patients in the sham group than in the aflibercept group developed sight-threatening complications. The difference in the change in visual acuity was not significant between the two groups.
Table. Complications and Visual Acuity
|Outcome||Aflibercept group||Sham group||P value|
|Center-involved diabetic macular, % edema||4.1||14.8||.002|
|Proliferative diabetic retinopathy, %||13.5||33.2||.001|
|One or both of these complications, %||16.3||43.5||.001|
|Mean change in visual acuity, ETDRS letters||–.09||–2.0||.47|
There were three cases of endophthalmitis in the aflibercept group and none in the sham group. There was no difference between the groups in cardiovascular or cerebrovascular adverse events.
On the basis of these results, Jayanth Sridhar, MD, associate professor of clinical ophthalmology at the Bascom Palmer Eye Institute in Miami, Florida, said he doesn’t see a need to administer anti-VEGF treatments as prophylaxis for his patients with NPDR.
The burden of frequent intravitreal injections outweighs the benefit of preventing complications, he said. That could change if longer-term treatments, such as drug-eluting implants or gene therapy, become available, he said.
For now, Sridhar closely monitors his patients with NPDR for complications, he told Medscape Medical News. “If they do develop a complication, treat them early with anti-VEGF, and you will not lose any sort of visual acuity benefit by waiting to treat them.”
Protocol W is continuing for 2 more years, and it is possible that a difference in visual acuity will emerge between the two groups over that time because it can take that long for diabetic macular edema and proliferative diabetic retinopathy to affect vision, Glassman said.
But Sridhar doesn’t expect that to happen because the design of the trial calls for the treatment of complications, and it appears possible to restore visual acuity once complications develop.
“It’s reassuring, and it really gives providers a lot of options to kind of tailor treatment depending on the patient,” Sridhar said.
The findings of Protocol W confirm those of the PANORAMA trial, which had a similar design but was sponsored by Regeneron, the maker of Eylea, said Sridhar. “It’s great to see the pharmaceutical-sponsored study sort of matched by the nonaffiliated study,” he said.
While completing the 4-year results of Protocol W, the DRCR Retina Network is also studying the cholesterol-lowering drug fenofibrate to see whether it can slow the progression of diabetic retinopathy, said Glassman.
JAMA Ophthalmol. Published online March 30, 2021. Full text
Sridhar is a consultant for Regeneron. Glassman reported grants from Regeneron and Genentech.
Laird Harrison writes about science, health and culture. His work has appeared in magazines, newspapers , and online publications. He is at work on a novel about alternate realities in physics. Harrison has taught writing at San Francisco State University, UC Berkeley Extension and the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter: @LairdH.