Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease Following Aflibercept Therapy: The PERMEATE Study

Abstract

To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAI). Prospective open-label study ( clinicaltrials.org identifier, ). Thirty-one treatment-naïve eyes with foveal-involving retinal edema secondary to DME and RVO. Subjects received 2mg IAI q4 weeks for the first 6 months, followed by 2 mg q8 weeks. Ultra-widefield angiograms (UWFA, California Optos) and SD-OCT (Cirrus, Zeiss) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events were also collected. The primary study endpoint was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. Baseline mean age was 67.1 years (range, 46-84). At month 12, visual acuity significantly improved by a mean of 18.4 ± 21.4 letters ( P < 0.0001), and CST also significantly improved with a mean reduction of 301.3 ± 250.3 μm ( P < 0.0001). Mean panretinal leakage index significantly improved, decreasing from 3.4% at baseline to 0.5% at month 6 ( P < 0.0001) and 0.4% at month 12 ( P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 ( P = 0.315) and 8.7% at month 12 ( P = 0.193). Subjects diagnosed with DME showed a decrease in leakage index from 3.5 ± 2.7% at baseline to 1.6 ± 0.8% at month 12 ( P = 0.018) and overall stability in ischemic index from 5.0 ± 4.1% at baseline to 4.7 ± 3.5% at month 12 ( P = 0.689). Subjects with RVO presented a decrease in leakage index from 3.3 ± 1.1% at baseline to 0.02 ± 0.03% at 12 months ( P < 0.0001) and a non-significant increase in ischemic index from 5.9 ± 4.5% at baseline to 12.6 ± 9.8% at month 12 ( P = 0.172). Therapy with IAI resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended towards worsening.