Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy: Primary Outcomes from the RECOVERY Study

Abstract

Purpose : To evaluate the impact of intravitreal aflibercept on retinal non-perfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR) with no macular edema.

Methods : Forty eyes of 40 subjects with treatment naïve PDR and substantial RNP (defined as > 20 disc areas) but no center-involving diabetic macular edema were enrolled in this IRB approved prospective, randomized, clinical trial (RECOVERY study “NCT02863354”). Subjects were randomized to receive intravitreal 2 mg aflibercept every 4 weeks (Monthly cohort) or every 12 weeks (Quarterly cohort). All subjects underwent complete ophthalmic examination and a panel of diagnostics including ultra-wide field (UWF; Optos) pseudocolor imaging, UWF fluorescence angiography (FA; Optos) and spectral domain optical coherence tomography (Spectralis HRA+OCT). After stereographic projection, RNP area was delineated from the UWF FA images in ImageJ using a standardized grading protocol. Total RNP area (in mm²), ischemic index (ISI) and total area of neovascularization were computed for the entire retina. RNP was not gradable in four cases which were excluded, leaving 36 eyes in the final analysis. Comparative statistics were performed using a student t test with SPSS ver. 18.0 used for all statistical analyses.

Results : The mean age of study subjects was 48 (SD; ± 12) years and 19 were females. For the entire study sample (both cohorts), the mean total RNP area at month 12 (280 ± 143 mm²) was increased but not significantly (p=0.12) when compared with baseline (242 ± 169 mm²). Ischemic index (ISI), however, was significantly (p=0.009) increased at month 12 (34 ± 17) compared with baseline (27 ± 16). For the monthly cohort, ISI increased significantly to 36.3 at month 12 compared with a baseline value of 30 (p=0.23). In the quarterly cohort, ISI was increased significantly (p=0.02) at month 12 (ISI: 31) compared with baseline (ISI: 24). The area of retinal neovascularization (NV) was significantly decreased in both cohorts (by 99% in the monthly, p<0.001 and by 88% in the quarterly, p<0.001) at month 12 following intravitreal aflibercept.

Conclusions : In the RECOVERY study, despite dramatic reductions in the area of NV, there was no significant reduction of RNP area with aflibercept among the enrolled PDR eyes with extensive RNP.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.