Added Benefits Seen With Early Initiation of Anti-VEGF Agents for Diabetic Retinopathy

Charles C. Wykoff, MD, PhD


May 26, 2016

In This Article

Ongoing Studies in NPDR Eyes Without DME

Initiation of anti-VEGF intravitreal injections into eyes without clinically significant DME or PDR is not without risks, including endophthalmitis, retinal tear, retinal detachment, cataract, and systemic side effects.[22] Researchers are seeking to better understand the role of intraocular VEGF blockade and more clearly define the risk-to-benefit ratio in NPDR eyes without PDR or significant DME.

Two independent, large, randomized phase 3 trials were recently initiated comparing sham injections with VEGF blockade with aflibercept intravitreal injections.

The first trial is the Diabetic Retinopathy Clinical Research Network protocol W (DRCR-W) ( identifier NCT02634333), a 4-year trial with a projected cohort of 322 eyes with DRSS levels 47 to 53. Eyes are randomly assigned equally to receive sham injections or 2 mg of aflibercept injections given at baseline; months 1, 2, and 4; and then every 4 months until the 2-year primary endpoint. The primary outcome is the cumulative probability of six endpoints indicating the development of either PDR or DME necessitating treatment.

The second trial is PANORAMA ( identifier NCT02718326), a 100-week trial involving a projected 360 eyes with DRSS levels 47 to 53. Eyes are randomly assigned equally into three arms: sham injections and two dosing regimens of 2 mg of aflibercept. The primary outcome measure is the proportion of study eyes that have improved from baseline by two or more DRSS steps.


In the context of diabetes mellitus, by the time an eye has developed DME or PDR, the patient has probably already sustained significant decreases in their visual function-associated HRQOL.

Anti-VEGF pharmacologic agents currently used to manage DME and milder forms of PDR impart additional benefits that appear to substantially alter the natural history of progressive DR worsening over time: blunting progression to more advanced DR stages; improving retinopathy status in many eyes; and slowing the underlying disease process central to DR itself, progressive retinal nonperfusion. Population-based analyses in combination with accumulating clinical trial data indicate that the threshold to initiate ocular-specific anti-VEGF treatments for DR is being lowered to earlier stages of DR.


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