Aflibercept Best for Improving Visual Acuity in Diabetic Macular Edema

By Will Boggs MD

October 11, 2016

NEW YORK (Reuters Health) - Among the available anti-vascular endothelial growth factor (VEGF) therapies, aflibercept appears to offer the greatest improvement in visual acuity in patients with diabetic macular edema (DME) and worse baseline vision, according to post hoc analyses of a randomized controlled trial.

The Diabetic Retinopathy Clinical Research Network Protocol T found similar mean visual acuity (VA) improvements at one and two years for eyes with VAs of 20/32 to 20/40 for patients randomized to aflibercept, bevacizumab, and ranibizumab. For worse baseline VAs, aflibercept appeared to offer greater improvement at one year than the other agents, although differences were small.

Adam R. Glassman from Jaeb Center for Health Research, Tampa, Florida and colleagues examined VA outcomes over time and changes in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study in their post hoc analyses of 660 participants in Protocol T.

For eyes with baseline VA of 20/50 or worse, mean improvements in the VA letter score from baseline through 2 years were significantly higher with aflibercept (17.1 letters) than with bevacizumab (12.1 letters) or ranibizumab (13.6 letters).

The mean percentage of time per eye during the two years that the eye was improved by 15 letters or more from baseline was also greater with aflibercept (58%) than with bevacizumab (43%) or with ranibizumab (46%), according to the October 6th JAMA Ophthalmology online report.

Among these patients, CST decreased from one to two years in eyes in the bevacizumab group that received focal/grid laser treatment during the study.

"Although post hoc analyses should be viewed with caution given the potential for bias, these results, coupled with safety and cost-effectiveness outcomes, provide further information that is potentially helpful when interpreting Protocol T results through two years," the researchers conclude.

Dr. Michael W. Stewart from Mayo Clinic Florida in Jacksonville, who has published numerous reports regarding DME and its treatment, told Reuters Health by email, "This report did not change any of the major findings at one year. An important secondary finding, however, was that bevacizumab eyes also treated with laser experienced improved CST but not VA between years one and two. This suggests that: a. Laser may dry residual edema but not improve VA. b. Waiting 1 year before achieving a dry macular may irreversibly prevent optimal gains in vision."

"Higher binding affinity drugs (aflibercept and ranibizumab) generally work better and should be considered in eyes that respond poorly to bevacizumab," he said. "Though the trial did not investigate switching drugs, physicians should consider switching for early suboptimal results."

"My approach, which I think is consistent with that of many physicians, is to: a. Use bevacizumab for eyes with 20/40 or better because of the low cost. b. Use aflibercept for eyes 20/50 or worse because of efficacy. c. Consider aflibercept for eyes 20/40 or better if the CST is greater than 400 microns," Dr. Stewart said. "I am hesitant to use macular laser because it may compromise VA slightly, so I use corticosteroids as second-line therapy."

Dr. Dimitra Skondra from The University of Chicago, who has studied the role of ocular imaging in the diagnosis and management of macular edema and other retinal diseases, told Reuters Health by email, "I think this study supports previous evidence from one-year data that aflibercept is more effective compared to other anti-VEGF agents for DME patients with worse baseline vision."

"Delay in eliminating retinal edema may affect long-term visual outcome as suggested by the finding that even though patients treated with bevacizumab showed the same final anatomic response on ocular coherence tomography (OCT) at year 2, vision gain was inferior compared to aflibercept," she said.

Glassman did not respond to a request for comments.

Regeneron provided the aflibercept and Genentech provided the ranibizumab for the study. Four of the 5 authors report receiving grants from Regeneron and Genentech/Roche.


JAMA Ophthalmol 2016.