Aflibercept increases retinal nonperfusion in eyes with proliferative diabetic retinopathy: Study

Texas: Aflibercept 2mg, administered intravitreal monthly or quarterly resulted in a significant increase in retinal nonperfusion (RNP) in patients with proliferative diabetic retinopathy (PDR), reports data from year 2 of the RECOVERY trial published in the journal Ophthalmology Retina. 

Diabetic retinopathy is a microvascular complication of diabetes caused by damage to the blood vessels of the retina in the eye. Retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy (DR). Anti-vascular endothelial growth factor therapy, also known as anti-VEGF therapy or anti-VEGF medication, blocks vascular endothelial growth factors. Data suggest that consistent anti-VEGF pharmacotherapy (Aflibercept ) can slow RNP development, reduce the severity of diabetic retinopathy, and is associated with lower rates of proliferative diabetic retinopathy development.

The RECOVERY trial was conducted by Wykoff CC, Houston Methodist Hospital & Weill Cornell Medical College, Texas, and his research team to evaluate the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR (PDR).

Researchers included participants with proliferative diabetic retinopathy and retinal nonperfusion for a prospective, randomized clinical trial with treatment crossover in the second year. At baseline, the subjects were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2 mg aflibercept. At the beginning of the second year, the treatment arms were crossed over so that the monthly-dosed subjects subsequently received quarterly dosing and vice versa. The primary outcome was a 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.

Key findings of the trial:

• From baseline to year 2, the mean RNP increased from 235 mm2 to 402 mm2, and the ISI increased from 25.8% to 50.4%. These increases in RNP and ISI were also observed from year 1 to year 2.

• At year 2, the mean total RNP increased from 264 mm2 at baseline to 386 mm2 in arm 1 and from 207 mm2 at baseline to 421 mm2 at year 2 in arm 2 (arm 1 vs. arm 2).

• Increases in the mean RNP for both treatment arms were also specifically observed within year 2 (arm 1 vs. arm 2).

• Compared with baseline, the DRSS scores at the end of year 2 improved in 82% of subjects and remained stable in 18%, with no subjects experiencing worsening; at 2 years, the DRSS scores had improved by 2 or more steps in 65% and 81% of subjects in arms 1 and 2, respectively.

The authors conclude that both treatment arms, monthly or quarterly intravitreal 2 mg aflibercept, experienced significant increases in retinal nonperfusion through year 2 of the RECOVERY trial. 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.

Reference:

Wykoff CC, Nittala MG, Villanueva Boone C, Yu HJ, Fan W, Velaga SB, Ehlers JP, Ip MS, Sadda SR; RECOVERY Study Group. Final Outcomes from the Randomized RECOVERY Trial of Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy. Ophthalmol Retina. 2022 Jul;6(7):557-566. doi: 10.1016/j.oret.2022.02.013