Association of Ellipsoid Zone Integrity and Treatment Response in Subjects with Non-neovascular AMD Treated with Subcutaneous Elamipretide: Post Hoc Analysis of the Phase 1 ReCLAIM Study

Abstract

Purpose : To assess the association between quantitatively assessed, higher-order optical coherence tomography (OCT) features, such as ellipsoid zone (EZ) integrity and sub-RPE compartment features, evaluated at baseline with visual outcomes in subjects with non-neovascular age-related macular degeneration (AMD) treated with subcutaneous elamipretide.

Methods : ReCLAIM was an open-label, phase 1 clinical trial of daily subcutaneous elamipretide (40 mg) in NNVAMD, stratified into pre-defined nonfoveal geographic atrophy (GA) and high-risk drusen (HRD) subgroups. The primary endpoint was change in low-luminance best corrected visual acuity (LLBCVA). Higher-order OCT features were evaluated via automated machine-learning augmented multilayer retinal segmentation with expert reader manual verification to quantify outer retinal integrity [e.g., EZ-RPE thickness, percent EZ attenuation, outer retinal parameters (i.e., outer nuclear layer (ONL) to RPE thickness)] and sub-RPE anatomical metrics. Post hoc analysis assessed correlation of baseline higher order OCT Features with change in LLBCVA from baseline to end of treatment (week 24).

Results : A total of 40 patients were evaluated (19 in the nonfoveal GA subgroup and 21 in the HRD subgroup). In the nonfoveal GA subgroup, the baseline macular percentage of total EZ attenuation (r=-0.72; p =0.002) and baseline panmacular EZ-RPE volume (r=062; p=0.01) were significantly correlated to change in LLBCVA from baseline to week 24. Eyes gaining 2 lines or more had significantly less macular total EZ attenuation at baseline (9.0% vs 27%; p=0.03) and significantly less percentage area of macular GA (4.7% vs 15.6%; p=0.004).

In the HRD subgroup, mean central macular (e.g., central 2 mm) retinal thickness positively correlated with improvement in LLBCVA (r=0.58; p=0.009). Eyes gaining 2 lines or more had significantly greater baseline preservation of the central macular outer retina (ONL-RPE thickness, 137 mm vs 117 mm, p=0.006) trended towards less baseline macular partial EZ attenuation (1.1% vs 5.0%; p=0.06).

Conclusions : Baseline higher order OCT parameters, such as EZ integrity, were correlated with functional response and improved LLBCVA in eyes treated with subcutaneous elamipretide. Further research is needed to better characterize these potential imaging biomarkers.

This is a 2021 ARVO Annual Meeting abstract.