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

RECOVERY Study Group

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7 Scopus citations


PURPOSE: 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).

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

SUBJECTS: Eyes with PDR and RNP.

METHODS: 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.

MAIN OUTCOME MEASURES: Change in total RNP area (mm 2) 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.

RESULTS: Among all subjects, from baseline to year 2, the mean RNP increased from 235 mm 2 to 402 mm 2 (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 mm 2 at baseline to 386 mm 2 (P < 0.0001) at year 2 in arm 1 and from 207 mm 2 at baseline to 421 mm 2 (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.

CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)557-566
Number of pages10
JournalOphthalmology Retina
Issue number7
StatePublished - Jul 2022


  • Anti-vascular endothelial growth factor
  • Diabetic Retinopathy Severity Scale
  • Ischemic index
  • Proliferative diabetic retinopathy
  • Retinal nonperfusion
  • Receptors, Vascular Endothelial Growth Factor
  • Prospective Studies
  • Intravitreal Injections
  • Tomography, Optical Coherence
  • Humans
  • Visual Acuity
  • Recombinant Fusion Proteins
  • Diabetes Mellitus/drug therapy
  • Diabetic Retinopathy/complications

ASJC Scopus subject areas

  • Ophthalmology


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