Eylea reduces chance of vision-threatening complications in Protocol W
Two-year results of an ongoing study show that intravitreal aflibercept injections in eyes with baseline moderate to severe nonproliferative diabetic retinopathy significantly decrease the chance to develop vision-threatening complications.
Those complications include proliferative diabetic retinopathy (PDR) and center-involved diabetic macular edema (CI-DME).
“However, through 2 years, preventive treatment with Eylea (Regeneron) did not confer visual acuity benefit compared with observation plus Eylea PRN if PDR or vision-reducing CI-DME developed,” Adam R. Glassman, MS, one of the study authors, told Healio/OSN.
The 4-year results of the DRCR Retina Network Protocol W will therefore be pivotal in clarifying whether proactive anti-VEGF treatment also has a role in preventing vision loss in the long term, the authors said.
Protocol W recruited patients with both type 1 and type 2 diabetes and moderate to severe NPDR at 64 clinical sites in the U.S. and Canada. Eyes were randomly assigned to receive intravitreal aflibercept injection or sham. Participants with both eyes affected received the treatment in one eye and sham in the other eye. Visits in both groups were planned at 1, 2 and 4 months and every 4 months thereafter, and aflibercept was initiated in the sham group if sight-threatening DME or PDR developed at any time. Two-year data of 399 eyes of 328 patients were analyzed.
Aflibercept showed clear benefits in preventing the disease from progressing to significant complications. The cumulative probability of developing CI-DME with vision loss or PDR within 2 years was 16.3% with aflibercept as compared with 43.5% with sham. Treatment resulted in a threefold reduction in the probability to develop CI-DME with decreased visual acuity and a twofold reduction in the probability to develop PDR. These results were obtained with an average of eight aflibercept injections in the 2 years.
However, over the first 2 years of the study, observation with treatment of complications as they developed showed equally effective as proactive intervention in preserving vision. The median baseline visual acuity in both groups was 20/20 or better, and no statistically significant difference was found between the groups in mean visual acuity at 2 years. Approximately three-quarters of each group had 20/20 visual acuity at 2 years, and less than 10% of each group lost two or more lines.
According to the authors, these data suggest that close monitoring of patients, as done in the study, with prompt treatment of vision-threatening complications as they develop, “may be adequate to recover lost vision or prevent VA loss, on average.” On the other hand, “it is also possible that average VA loss stemming from higher rates of PDR and CI-DME and their complications in the sham group will increase with continued follow-up,” they said.
At this stage, Protocol W results leave a question mark over the benefits of proactive intervention, according to Glassman.
“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 treatment,” he said.
However, the study is ongoing, and 4-year results “will provide additional information to help guide treatment recommendations in these eyes in the future,” he said.
As a side note, the authors drew attention to the 16.3% of eyes in the aflibercept group that developed PDR or CI-DME with vision loss, suggesting that treatment does not completely rule out the risk of vision-threatening complications. Taking this into account, they recommended a regular follow-up with routine examinations in these patients to diagnose and treat PDR and CI-DME, “irrespective of whether intravitreal anti-VEGF therapy is given for prevention of these conditions.”