Aflibercept Beats Bevacizumab for Diabetic Macular Edema With Moderate or Worse Vision Loss

Aflibercept improved visual acuity more than bevacizumab in diabetic macular edema, but only in patients with worse vision.

For diabetic macular edema, aflibercept (Eylea, Regeneron) was associated with greater gains in visual acuity, as compared with bevacizumab (Avastin, Genentech) at 2 years, although only among participants with 20/50 vision or worse at baseline, according to data published in Ophthalmology.

Additionally, aflibercept and ranibizumab (Lucentis, Genentech) yielded similar gains in visual acuity after 2 years, which contradict results from a 1-year study demonstrating greater improvement with aflibercept. Moreover, gains in vision were comparable for all 3 drugs among patients with 20/32 or 20/40 vision at baseline.

“This rigorous trial confirms that Eylea, Avastin, and Lucentis are all effective treatments for diabetic macular edema,” Paul A. Sieving, MD, PhD, director of the National Eye Institute of the National Institutes of Health (NIH), said in a press release. “Eye care providers and patients can have confidence in all 3 drugs.”

Two-Year Results

The 2-year trial included 660 participants (mean age, 61 years; mean duration of type 1 or type 2 diabetes, 17 years) with vision impairment related to diabetic macular edema at 89 clinical trial sites in the United States. The researchers randomly assigned participants to aflibercept 2.0 mg, repackaged (compounded) bevacizumab 1.25 mg, or ranibizumab 0.3 mg intravitreous injections.

Monthly evaluations were performed during the first year and every 4 to 16 weeks during the second year.

During the first 6 months, most participants received monthly injections. Participants then received additional injections until diabetic macular edema resolved or stabilized with no further vision impairment. If diabetic macular edema persistent without improvement after 6 months, participants underwent focal/grid laser photocoagulation.

About half of participants had 20/32 to 20/40 vision at enrollment, while the other half had 20/50 or worse vision.

In year 2, median numbers of injections were 5, 6, and 6 for the aflibercept, bevacizumab, and ranibizumab groups, respectively. Over 2 years, median numbers were 15, 16, and 15, respectively (global P=.08).

Overall, mean visual acuity improved by 12.8, 10.0, and 12.3 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, according to the data.

Improvement, however, appeared to vary with baseline vision (P=.02 for interaction), the researchers noted. After 2 years, among participants with worse vision , defined as 20/50 to 20/320, mean visual acuity improved by 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs bevacizumab, P=.02; aflibercept vs ranibizumab, P=.18; ranibizumab vs bevacizumab, P=.18). Among those with better vision, defined as 20/32 to 20/40, mean visual acuity improved by 7.8, 6.8, and 8.6 letters, respectively (P>.10 for pairwise comparisons).

Researchers also noted that 41%, 64%, and 52% of the aflibercept, bevacizumab, and ranibizumab groups received focal/grid laser photocoagulation, respectively (aflibercept vs bevacizumab, P<.001; aflibercept vs ranibizumab, P=.04; bevacizumab vs ranibizumab, P=.01).

“The results of the Diabetic Retinopathy Clinical Research Network’s comparison of Eylea, Avastin, and Lucentis will help doctors and their patients with diabetic macular edema choose the most appropriate therapy,” John A. Wells, MD, the lead author of the study and a retinal specialist at the Palmetto Retina Center in Columbia, South Carolina, said in a press release.

“The study suggests there is little advantage of choosing Eylea or Lucentis over Avastin when a patient’s loss of visual acuity from macular edema is mild, meaning a visual acuity of 20/40 or better. However, patients with 20/50 or worse vision loss may benefit from Eylea, which over the course of the 2-year study outperformed Lucentis and Avastin.”

Potential Cardiovascular Concerns

Risk for heart attack, stroke, or death from a cardiovascular (CV) condition or an unknown cause appeared to be highest in the ranibizumab group compared with the aflibercept and bevacizumab groups (12% vs 5% and 8%; global P=.047; aflibercept vs bevacizumab, P=.34; aflibercept vs ranibizumab, P=.047; ranibizumab vs bevacizumab, P=.20; global P=.09 adjusted for potential confounders).

Because other studies have not denoted this difference in CV events with the treatments, the researchers speculated that it may be due to chance. However, the potential CV risks associated with the drugs warrants future study, they noted.


  1. Wells JA, Glassman AR, Ayala AR, et al; for the Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016. doi:10.1016/j.ophtha.2016.02.022.