Aflibercept may reduce risk of PDR and DME in patients with severe NPDR

Aflibercept may reduce risk of PDR and DME in patients with severe NPDR


Investigators evaluated the efficacy of intravitreous aflibercept injections in mitigating complications in eyes with moderate to severe nonproliferative diabetic retinopathy (NPDR).

Study design

The DRCR Retina Network Protocol W included adults with type 1 or 2 diabetes and moderate to severe NPDR. Researchers randomized 399 eyes to receive 2 mg of intravitreal aflibercept or sham injections at baseline and at each study visit through 2 years (1, 2, and 4 months, and then every 4 months). The primary outcome was development of center-involved diabetic macular edema (DME) with vision loss or proliferative diabetic retinopathy (PDR).


Compared with the sham group, the aflibercept group had a lower 2-year cumulative probability of developing PDR (14.5% vs. 33.2%) and DME (4.1% vs. 14.8%). The cumulative probability of developing high-risk PDR any time within 2 years was 2.4% with aflibercept and 8.9% with sham. During the study period, the average change in visual acuity was -0.9 letters with aflibercept and -2 letters with sham.


Retention was 80% to 84% during the study period; data missing due to loss to follow-up may have affected the final results. While the 2-year findings are informative, vision-threatening complications may take longer to develop. The 4-year results will be helpful in deciding whether to implement prophylactic anti-VEGF therapy.

Clinical significance

Among eyes with moderate to severe NPDR, aflibercept conferred a more than 3-fold reduction in the incidence of center-involved DME and a more than 2-fold reduction in PDR. However, through 2 years, preventive treatment did not provide improved visual acuity compared with observation plus aflibercept if complications developed.