Longitudinal Changes in Microaneurysm Count and the Correlation with Leakage Index and Leakage Patterns in Diabetic Retinopathy on Ultra-widefield Fluorescein Angiography Following Intravitreal Aflibercept in the PRIME study

Abstract

Purpose : To quantify longitudinal changes in microaneurysm (MA) count on ultra-widefield fluorescein angiography (UWFA) and their correlation with panretinal leakage index (PLI) in eyes with diabetic retinopathy (DR) being treated with as needed intravitreal aflibercept (IAI) guided by real-time DR severity score (DRSS) and PLI evaluations.

Methods : The PRIME study is a randomized prospective clinical trial comparing real-time DRSS-guided IAI treatment to real-time PLI-guided IAI treatment. 41 eyes with DRSS of 47 to 71 were randomized 1:1 to receive as needed IAI as determined by DRSS (DRSS cohort, n=21) or PLI (PLI cohort, n=20). UWFA and fundus photos were obtained monthly. UWFA images were analyzed in real-time with an automated analysis platform to quantify MA count and PLI with manual validation. Two trained readers evaluated the baseline UWFA images and classified them as having predominantly perivascular leakage or non-perivascular (including focal) leakage.

Results : Mean MA counts and PLI indices did not differ significantly at baseline between the DRSS cohort and the PLI cohort, with 839 ± 307 and 884 ± 331 MAs (P=0.66), respectively. At year 1, the MA count improved significantly to 662±334 (P=0.03) in the DRSS cohort and 744 ± 526 (P=0.05) in the PLI cohort. Total mean MA and PLIs were positively correlated at both month six (r=0.35, P=0.03) and year one (r=0.46, P=0.007).

Eyes with predominant perivascular leakage (n=19) demonstrated a larger but non-significant reduction in mean MA count (-210) compared to eyes with predominant non-perivascular leakage (n=14, -109, P=0.28).

Conclusions : Both DRSS and PLI cohorts demonstrated a significant decrease in MA count after one year of image-guided IAI treatment. Total mean MA count and total mean PLIs were correlated at month six and year one. Eyes with predominant perivascular leakage at baseline had a nonsignificant greater reduction in MA count. Further research in larger datasets is needed to further explore the potential association of MA reduction with underlying leakage patterns and whether this may be indicative of specific active pathways.

This is a 2021 ARVO Annual Meeting abstract.