The Impact of Volumetric Intraretinal Fluid Lability in the VISTA Clinical Trial on Functional Outcomes

Abstract

Purpose : To evaluate the impact of intraretinal fluid (IRF) lability in diabetic macular edema (DME) on anatomic and functional outcomes in the Phase III VISTA Clinical Trial in eyes treated with intravitreal aflibercept injection (IAI).

Methods : A post-hoc higher order image analysis was performed on eyes in the Phase III VISTA DME study. Patients were randomized to receive 2mg IAI injection every 4 weeks (2q4), IAI every 8 weeks following 5 initial monthly doses (2q8), or laser photocoagulation. This analysis focused on the 2q8 group for assessment of fluid lability, defined as a 30% increase in IRF central subfield volume (CSV) above the threshold value at week 16 (i.e., last monthly injection administration) at any timepoint between week 20 and week 52. OCT images were evaluated using a machine learning-augmented platform that extracts retinal fluid features, including volumetric characterization and compartmental retinal features, such as ellipsoid zone (EZ) integrity. Groups were compared for baseline variables and final functional outcomes.

Results : For this assessment, 139 of 148 eyes were included from the 2q8 group. There were 71 eyes (51%) that demonstrated IRF volume lability after Week 16, compared to 68 eyes (49%) that did not. Baseline comparative assessment of the 2 groups did not show a significant difference in mean IRF CSV compared to those without lability (0.15 ± 0.10 mm³ vs 0.14 ± 0.12 mm³, respectively; p=0.79) or a difference in BCVA (ETDRS: 58.2 ± 11.2 vs 61.16 ± 10.0, p=0.105). However, eyes with subsequent IRF CSV lability demonstrated greater baseline EZ attenuation [i.e. reduced EZ-RPE central subfield thickness (24.2 ± 16.0 µm vs 30.6 ± 14.8 µm, p=0.017)].
The IRF CSV lability group demonstrated significantly worse mean BCVA at Week 52 (ETDRS: 68.3±13.2 v 73.2±11.09, p=0.027) and Week 100 (68.9±14.1 v 74±11.7, p= 0.035) compared to eyes that had more stable fluid dynamics.

Conclusions : DME eyes with volumetric IRF lability exhibited worse BCVA outcomes compared to those eyes with more stable fluid dynamics. Decreased baseline EZ integrity was more significant in eyes that ultimately developed fluid lability.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.