Anti-vascular endothelial growth factor (VEGF) therapy may not lead to favorable long-term outcomes in diabetic macular edema (DME) after 2 years, according to study results published in Ophthalmology.

Anti-VEGF therapy is an established first-line treatment for visual impairment in DME. However, limited data exist on long-term outcomes after patients return to receiving standard clinical care. The objective of this study was to assess clinical outcomes at 5 years in participants with DME treated with anti-VEGF therapy and to characterize follow-up treatments.

In this multicenter cohort study, researchers evaluated the effects of three different anti-VEGF therapies, (aflibercept, bevacizumab, and ranibizumab) in patients with a visual impairment from DME. Participants had previously taken part in the Protocol T clinical trial, which ran for 2 years and was conducted by the Diabetic Retinopathy Clinical Research (DRCR) Network. Patients were randomly assigned to 1 of the 3 anti-VEGF therapies, used the therapy for 2 years, then followed up at 5 years. Primary outcome measures included visual acuity and central subfield thickness.

Researchers revealed that, of the 463 patients eligible for this study, 68% (n=317) completed the 5-year follow-up between August 2017 and April 2019. Of those, 317 patients, 36% (n=115) received aflibercept, 30% (n=96) received bevacizumab, and 33% (n=106) received ranibizumab. A total of 217 eyes (68%) received at least 1 anti-VEGF therapy between years 2 and 5, with the median number of treatments being 4 (interquartile range 0-12). 

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The change in visual acuity from baseline to 2 years was similar between participants and nonparticipants (12.1 letters vs 12.5 letters, P =.32), though the mean 2-year visual acuity letter score was higher among participants than nonparticipants (77.7 vs 73.6, P =.03). Among all participants, the mean visual acuity at 5 years improved from baseline by 7.4 letters (95% CI, 5.9-9.0), but decreased by 4.7 letters after 2 years (95% CI, 3.3-6.0). Mean central subfield thickness at 5 years decreased from baseline by 154 μm (95% CI, 142-166), and at 2 years by 1 μm (95% CI, -12 to 9).

Limitations to this study were that results were based on only 68% of the potential cohort and participants who completed the follow-up at 5 years may be different from the full cohort given these patients had better baseline visual acuity than nonparticipants. Additionally, some data may be incomplete given that follow-up and treatment data after 2 years were collected from chart reviews.

The study researchers concluded that mean visual acuity worsened at 2 and 5 years following anti-VEGF therapy and that different treatment strategies and management approaches may be needed to improve long-term outcomes in diabetic macular edema and related visual acuity.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Glassman AR, Wells III JA, Josic K, et al. Five-year outcomes after initial aflibercept, bevacizumab, or ranibizumab treatment for diabetic macular edema (Protocol T extension study) Ophthalmol. [Published online March 29, 2020]. doi: 10.1016/j.ophtha.2020.03.021

This article originally appeared on Ophthalmology Advisor