[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 2,421
Citations 0
Brief Report
December 2016

Anti–Vascular Endothelial Growth Factor Comparative Effectiveness Trial for Diabetic Macular EdemaAdditional Efficacy Post Hoc Analyses of a Randomized Clinical Trial

Author Affiliations
  • 1Feinberg School of Medicine, Northwestern University, Chicago, Illinois
  • 2Jaeb Center for Health Research, Tampa, Florida
  • 3Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 4Editor, JAMA Ophthalmology
  • 5Palmetto Retina Center, West Columbia, South Carolina
JAMA Ophthalmol. 2016;134(12):No Pagination Specified. doi:10.1001/jamaophthalmol.2016.3698
Key Points

Question  Are there additional analyses from the randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema that might aid in the interpretation of the results?

Findings  Mean letter change in visual acuity over 2 years among eyes with initial visual acuity 20/50 or worse was greater in the aflibercept group than in the bevacizumab or ranibizumab groups.

Meaning  Although post hoc analyses should be viewed with caution, in eyes with visual acuity of 20/50 or worse, aflibercept produces the greatest mean improvement over 2 years.


Importance  Post hoc analyses from the Diabetic Retinopathy Clinical Research Network randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) might influence interpretation of study results.

Objective  To provide additional outcomes comparing 3 anti–vascular endothelial growth factor (VEGF) agents for DME.

Design, Setting, and Participants  Post hoc analyses performed from May 3, 2016, to June 21, 2016, of a randomized clinical trial performed from August 22, 2012, to September 23, 2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center-involved DME causing vision impairment.

Exposures  Randomization to intravitreous aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered up to monthly based on a structured retreatment regimen. Focal/grid laser treatment was added after 6 months for the treatment of persistent DME.

Main Outcomes and Measures  Change in visual acuity (VA) area under the curve and change in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study.

Results  Post hoc analyses were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female, 65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean (SD) letter change in VA over 2 years (area under curve) was greater with aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to +7.3; P < .001) or ranibizumab (+13.6 [8.5]; 95% CI, +0.7 to +6.0; P = .009). When VA was 20/50 or worse at baseline, bevacizumab reduced CST less than the other agents at 1 year, but at 2 years the differences had diminished. In subgroups stratified by baseline VA, anti-VEGF agent, and whether focal/grid laser treatment was performed for DME, the only participants to have a substantial reduction in mean CST between 1 and 2 years were those with a baseline VA of 20/50 or worse receiving bevacizumab and laser treatment (mean [SD], −55 [108] µm; 95% CI, −82 to −28 µm; P < .001).

Conclusions and Relevance  Although post hoc analyses should be viewed with caution given the potential for bias, in eyes with a VA of 20/50 or worse, aflibercept has the greatest improvement in VA over 2 years. Focal/grid laser treatment, ceiling and floor effects, or both may account for mean thickness reductions noted only in bevacizumab-treated eyes between 1 and 2 years.

Trial Registration  clinicaltrials.gov Identifier NCT01627249