Anatomic Feature Dynamics and Perfusion Density Following Aflibercept Therapy in Retinal Vascular Disease in the PERMEATE Study

Abstract

Purpose : The specific impact of anti-VEGF therapy on retinal vascular dynamics, outer retinal integrity, and quantitative fluid parameters has not been fully explored. The purpose of this study was to evaluate these features in eyes with diabetic macular edema (DME) or retinal vein occlusion (RVO) undergoing therapy with intravitreal aflibercept injection (IAI) from the PERMEATE study.

Methods : PERMEATE is a prospective open-label study for treatment-naïve eyes with foveal-involving retinal edema secondary to DME or RVO. Subjects received IAI 2 mg monthly for the first 6 months. SD-OCT (Cirrus, Zeiss) scans were analyzed using a novel ellipsoid zone (EZ) and retinal fluid mapping tool. The output of the EZ mapping assessment including quantitative metrics of macular EZ-retinal pigment epithelium (RPE) volume, en face percentage of total EZ attenuation (EZ thickness = 0μm), and en face partial EZ attenuation (EZ thickness <20μm). In addition, volumetric assessment of subretinal fluid and intraretinal fluid metrics. OCT angiography perfusion density analysis (Avanti XR, Optovue) was utilized on the 3mm superficial and deep retinal plexus scans. All imaging was analyzed for baseline and 6-month visits.

Results : Twenty-three eyes had completed the 6-month follow-up with images that were sufficient quality for analysis. At 6-month there was a significant mean gain of 17.3 letters (p<0.001). EZ analysis demonstrated a significant increase in EZ-RPE volume (+10%, p=0.02) and EZ-RPE mean central subfield thickness (CST, +65%, p<0.001). Macular percentage of partial and total EZ attenuation also improved significantly at 6-month (-82% and -85%, respectively, p<0.02). IAI therapy resulted in a 94% reduction of intraretinal fluid volume at 6 months (p<0.001). Retinal perfusion density analysis demonstrated a 9% improvement in the superficial retinal plexus (p=0.01). EZ integrity parameters demonstrated significant correlation with final visual acuity, including percentage partial/total EZ attenuation and EZ-RPE mean CST (all p<0.0001).

Conclusions : Therapy with IAI resulted in significant improvement in multiple outer retinal integrity parameters, quantitative fluid burden, and improvements in superficial retinal perfusion at 6 months. Additional research is ongoing to explore potential imaging biomarkers for therapeutic response and confirming these findings in a larger study cohort.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.