Anti-VEGF for Diabetic Retinopathy: A 'Strong Option'

Despite promising findings with the use of anti-VEGF injections for the treatment of proliferative diabetic retinopathy (PDR) in two recent trials, concerns about these injections limit it's implementation into widespread clinical use, according to an editorial in JAMA Ophthalmology.

Two randomized clinical trials -- the Diabetic Retinopathy Clinical Research Network Protocol S, led by DRCR.net, and the CLARITY study -- reported successful outcomes with the use of anti-VEGF injections compared with panretinal photocoagulation (PRP) treatment, which was considered the "standard treatment" for many years.

Adam R. Glassman, MS, of Jaeb Center for Health Research in Tampa, Fla., argued that while it may not be time for healthcare providers to completely eliminate use of lasers for the treatment of PDR, the recent research has shown anti-VEGF injections to be a strong option for some patients.

"Severe diabetic eye disease (proliferative diabetic retinopathy) continues to be the leading cause of blindness among work age adults in the U.S.," Glassman explained to MedPage Today. "A prior study conducted by the DRCR.net, reported advantages of using anti-VEGF injections into the eye over laser for treatment of proliferative diabetic retinopathy. A second trial performed by the CLARITY study group, recently reported similar results as the Protocol S trial providing confirmatory evidence of the role of anti-VEGF injections in the treatment of proliferative disease."

The 2015 Protocol S trial reported noninferiority with 0.5 mg ranibizumab (Lucentis) treatment versus PRP treatment regarding visual acuity after 2 years. Additionally, the anti-VEGF group reported fewer complications, such as vitrectomies, as well as less visual field loss and superior visual acuity after 2 years.

Published earlier this month in the Lancet, the phase IIb, 52-week CLARITY study, which included 232 participants with PDR with or without diabetic macular edema, built upon the findings of the previous study. The CLARITY trial reported 2.0-mg aflibercept (Eylea) treatment was superior for visual acuity by the end of the trial period, when compared with PRP (mean difference 3.9 letters, 95% CI, 2.3-5.6 letters, P<0.001). Additionally, the authors reported fewer complications among the aflibercept group versus the PRP group.

Despite the promising findings of both randomized clinical trials in favor of anti-VEGF treatment, Glassman added that "barriers for wide-spread use of anti-VEGF agents for this indication persist."

Specifically, Glassman highlighted one major concern that may be a barrier to widespread use of anti-VEGF usage, a lack of adherence regarding follow-up with injections. Although continuity with treatment is "critical to its success," compliance with treatment is a recognized issue with such treatment regarding recurrent neovascularization and hemorrhage, which may lead to vitrectomy possibly resulting in blindness.

Among the Protocol S trial, 12% of participants in the anti-VEGF group failed to complete all visits through 2 years, while 9% of the aflibercept group in the CLARITY trial were also loss to follow-up. Glassman noted that "these rates of losses to follow-up are likely a best-case scenario, because follow-up rates in clinical practice are expected to be lower than retention rates in randomized clinical trials." However, treatment compliance is vital regardless of PDR treatment option, including for PRP treatment.

Additionally, cost is another top barrier to anti-VEGF treatments, which is notably steeper compared to PRP treatment. Although due to the recent FDA approval of ranibizumab in diabetic retinopathy without diabetic macular edema, access to this treatment is widening. Also, Glassman noted that another anti-VEGF, bevacizumab (Avastin), is a cost-effective alternative. However, additional trials comparing outcomes with bevacizumab against ranibizumab or aflibercept treatment is required.

"I believe that identifying approaches that could prevent the development of proliferative diabetic retinopathy would be very useful," Glassman told MedPage Today. "Current randomized trials are underway, including a trial by the DRCR.net, to see if proliferative diabetic retinopathy can be prevented with periodic anti-VEGF injections."

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