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

Retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy (DR). Data suggests that consistent anti-VEGF pharmacotherapy can slow RNP development. RECOVERY evaluated the impact of aflibercept (Eylea, Regeneron, Tarrytown, NY) on RNP among eyes with proliferative DR (PDR).Prospective, randomized clinical trial with treatment cross-over in 2nd year.Eyes with PDR and RNP.At baseline, 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 while the quarterly dosed subjects subsequently received monthly dosing.Change in total RNP area (mm2) through year 2. Secondary outcomes included DR severity scale (DRSS) scores, best-corrected visual acuity, central subfield thickness, additional measures of RNP including ischemic index (ISI), and adverse events incidence. Means and 95% confidence intervals were calculated.Among all subjects from baseline to year 2, mean RNP increased from 235 mm2 to 402 mm2 (P<0.0001) and ISI increased from 25.8% to 50.4% (P<0.0001). Increases in mean RNP (P<0.0001) and ISI (P<0.0001) were also observed from year 1 to year 2. 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 mean RNP for both treatment arms (P<0.0001) were also observed specifically within year 2 (P=0.32, Arms 1 vs. 2). Compared with baseline, DRSS scores at the end of year 2 improved in 82% (n=27) of subjects and remained stable in 18% (n=6), with no subject experiencing worsening; at 2 years, 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 RECOVERY, both treatment arms experienced significant increases in RNP. Despite expansion of RNP area in nearly all subjects, 82% demonstrated an improvement in DRSS levels from baseline with no subject experiencing worsening in DRSS.