Impact of Baseline Quantitative Ellipsoid Zone Integrity on Geographic Atrophy Expansion in the ReCLAIM-2 Clinical Trial

Abstract

Purpose : To evaluate the impact of baseline quantitative Ellipsoid Zone (EZ) integrity on geographic atrophy (GA) natural history growth rate in the ReCLAIM-2 clinical trial.

Methods : Re-CLAIM-2 is a randomized, double-masked, placebo-controlled, prospective Phase 2 clinical trial evaluating a mitochondrial protective agent, elamipretide, in advanced AMD with GA. As part of the prespecified planned analysis, the SD-OCT scans were analyzed using a machine learning-enhanced multi-layer retinal segmentation platform to assess both EZ integrity and OCT-based GA measurements. Baseline EZ integrity was measured by evaluating panmacular EZ-RPE thickness. Total EZ attenuation (EZ-RPE thickness = 0μm) and partial EZ attenuation (EZ-RPE thickness ≤ 20μm) were assessed based on the panmacular burden of each parameter, measured as a percentage of the macula. GA was measured based on total loss of the RPE in areas of retinal atrophy in the SD-OCT scan. All B-scans were reviewed for segmentation accuracy and corrected, as needed, by a trained expert reader.
All subjects in the placebo arm were included that had OCT scans of sufficient quality for analysis and completed the week 48 visit. The subset of patients in 25th and 75th percentile groups of the EZ integrity parameters were compared for overall GA growth difference over 48 weeks.

Results : Thirty-eight eyes from the placebo group were included in the analysis. The 25th percentile group had a mean baseline percentage area of partial EZ attenuation of 15.4% and mean baseline percentage area of total EZ attenuation of 9.0%. The 75th percentile group had a mean baseline percentage area of partial EZ attenuation of 33.2% and a mean total EZ attenuation of 23.2%. The 48-week change in GA area was over 3.5-fold higher in the high attenuation groups compared to the low attenuation groups (5.1-5.3% absolute increase in macular GA coverage vs 1.4-1.5%, p < 0.001).

Conclusions : Increased total and partial EZ attenuation were associated with higher rates of GA growth in the placebo group, providing important insights for factors that may impact the natural history growth of GA. EZ loss may be an important biomarker that is associated with GA expansion risk and may serve as an important future clinical trial enrichment biomarker and AMD endpoint.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.