The impact of early central macular total retinal fluid index instability on future exudative volatility in neovascular AMD

Abstract

Purpose : To evaluate early total retinal fluid index (TRFI) instability as a potential imaging biomarker for future intolerance of extended anti-VEGF treatment intervals based on recurrence of exudative activity in nAMD.

Methods : This was a post hoc analysis of the phase II OSPREY clinical trial comparing brolucizumab to aflibercept over 56 weeks. Eyes were initially treated with an anti-VEGF agent every 4 weeks for the first 3 months and were then extended to 8-week intervals through week 40 (matched phase). At that time the brolucizumab group was further extended to 12-week intervals. A treatment agnostic approach was used for this analysis. SD-OCT cube scans were imported into a novel machine-learning enabled OCT feature extraction tool, which automatically segmented intraretinal fluid (IRF), subretinal fluid (SRF), and retinal layers including the internal limiting membrane (ILM) and retinal pigment epithelium (RPE). TRFI, defined as the percentage of IRF and SRF between the ILM and RPE, was calculated for the central macula (CM, defined as the central 2-mm zone). Early TRFI instability was defined as an increase in CM-TRFI of ≥0.1% from week 4 to 8. High fluid compartment volatility was defined based on eyes in the 75th percentile for fluid volume fluctuation from week 12 to 56. Optimal anatomic response was defined as achieving a dry retina with minimal or no fluid recurrence.

Results : A total of 81 eyes were included in this analysis. Between week 4 and week 8, 9.8% (8/81) of eyes demonstrated a ≥0.1% increase in CM-TRFI. Among eyes with early CM-TRFI instability, only 25% achieved optimal anatomic response compared to 78% of all other eyes (p<0.01) during the matched phase. Of eyes with early CM-TRFI instability, 88% had high IRF and/or SRF volatility following treatment interval extension compared to 41% of eyes without early CM-TRFI instability (odds ratio: 10.0; p=0.02).

Conclusions : Eyes with early CM-TRFI instability during the anti-VEGF loading phase demonstrated greater risk of treatment extension intolerance and overall poorer anatomic response to anti-VEGF therapy. CM-TRFI changes during early treatment may provide important insights to eyes at high risk for exudative recurrence with treatment extension.

This is a 2021 ARVO Annual Meeting abstract.

 

A representative case of an eye with a ≥0.1% increase in CM-TRFI between weeks 4 and 8.