Monthly, Quarterly Aflibercept Linked to Increases in Retinal Nonperfusion

New findings from year 2 of the RECOVERY trial suggest treatment with monthly or quarterly intravitreal 2 mg aflibercept in patients with proliferative diabetic retinopathy (PDR) led to significant increases in retinal nonperfusion (RNP)

However, the study reported a majority of subjects demonstrated improvement in Diabetic Retinopathy Severity Scale (DRSS) levels from baseline.

“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,” wrote study author Charles C. Wycoff, MD, PhD, Retina Consultants of Texas.

As an important biomarker for diabetic retinopathy, the development of retinal nonperfusion may be slowed by consistent anti-VEGF pharmacotherapy. THE RECOVERY trial evaluated the impact of aflibercept on RNP among eyes with proliferative diabetic retinopathy (PDR).

The prospectively, randomized clinical trial had treatment crossover in the second year. At baseline, the study individuals were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2 mg aflibercept.

When the second year of study began, the treatment arms were then crossed over. The monthly-dosed subjects then received quarterly dosing and the quarterly-dosed subjects received monthly dosing.

The main outcomes were considered the change in total RNP area (mm2) through year 2. The 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. Investigators calculated means and 95% confidence intervals (CI).

In all study participants from baseline to year 2, investigators found the mean RNP increased from 235 mm2 to 402 mm2 (P <.0001) and the ISI increased from 25.8% to 50.4% (P <.0001).

Moreover, data show increases in the mean RNP (P <.0001) and ISI (P <.0001) were also observed from year 1 to year 2. Additionally, the mean total RNP increased from 264 mm2 at baseline to 386 mm2 (P <.0001) at year 2 in arm 1 and increased from 207 mm2 at baseline to 421 mm2 (P <.0001) at year 2 in arm 2 (P = .023; arm 1 vs arm 2).

Investigators noted the increases in mean RNP for both treatment arms (P <.0001) were specifically observed within year 2 as well (P = .32; arm 1 vs arm 2). In comparison to 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 none experiencing worsening.

At the 2-year mark, the DRSS scores improved by 2 or more steps in 65% (n = 11) and 81% (n = 13) of subjects in arms 1 and 2, respectively.

The study, “Final Outcomes from the Randomized RECOVERY Trial of Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy,” was published in Ophthalmology.