Final Outcomes from the Randomized RECOVERY Trial of Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy

Retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy (DR). Data suggest that consistent anti-VEGF pharmacotherapy can slow RNP development. The RECOVERY trial evaluated the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR (PDR).

Prospective, randomized clinical trial with treatment crossover in the second year.

Eyes with PDR and RNP.

At baseline, the subjects were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2 mg aflibercept. At the beginning of year 2, the treatment arms were crossed over so that the monthly-dosed subjects subsequently received quarterly dosing and the quarterly-dosed subjects subsequently received monthly dosing.

Change in total RNP area (mm²) through year 2. Secondary outcomes included Diabetic Retinopathy Severity Scale (DRSS) scores; best-corrected visual acuity; central subfield thickness; additional measures of RNP, including ischemic index (ISI); and adverse event incidence. Means and 95% confidence intervals were calculated.

Among all subjects, from baseline to year 2, the mean RNP increased from 235 mm² to 402 mm² (P < 0.0001), and the ISI increased from 25.8% to 50.4% (P < 0.0001). Increases in the mean RNP (P < 0.0001) and ISI (P < 0.0001) were also observed from year 1 to year 2. The mean total RNP increased from 264 mm² at baseline to 386 mm² (P < 0.0001) at year 2 in arm 1 and from 207 mm² at baseline to 421 mm² (P < 0.0001) at year 2 in arm 2 (P = 0.023, arm 1 vs. arm 2). Increases in the mean RNP for both treatment arms (P < 0.0001) were also specifically observed within year 2 (P = 0.32, arm 1 vs. arm 2). Compared with baseline, the DRSS scores at the end of year 2 improved in 82% (n = 27) of subjects and remained stable in 18% (n = 6), with no subjects experiencing worsening; at 2 years, the DRSS scores had improved by 2 or more steps in 65% (n = 11) and 81% (n = 13) of subjects in arms 1 and 2, respectively.

Through year 2 of the RECOVERY trial, both treatment arms experienced significant increases in RNP. Despite the expansion of the RNP area in nearly all subjects, 82% of subjects demonstrated an improvement in DRSS levels from baseline, with no subjects experiencing worsening in DRSS scores.