Predicting directional macular atrophy progression using angular plot analysis of DARC (apoptosing retinal cells), EZ (ellipsoid zone) loss, EZ–RPE (retinal pigment epithelium) difference, and HRF (hyperreflective foci)

Background Recognizing age-related macular degeneration (AMD) as a leading cause of blindness, this study evaluates Detection of Apoptosing Retinal Cells (DARC), Ellipsoid Zone (EZ) loss, EZ- Retinal Pigment Epithelium (RPE) difference and Hyperreflective Foci (HRF) in predicting directional growth of macular atrophy (MA) in AMD using a novel application of angular plot analysis.Research design and methods Seven eyes with MA from the Phase 2 DARC study (ISRCTN10751859) were identified according to strict criteria. MA growth was measured using sequential follow-up retinal scans. EZ loss was calculated as the distance from the EZ edge to the MA center, RPE loss was calculated as the distance from the edge of RPE to the MA center, HRF was calculated using a density value in a circle of radius of 800um from the MA edge, and DARC activity was quantified using DARC density maps. Angular visualization plots were generated to compare DARC activity, EZ loss, EZ-RPE difference and HRF to MA growth within 1-degree sectors of a full circle centered on the MA lesion. Spearman’s rank correlation was calculated to assess directional associations.Results Over a mean follow-up of 48.4 months, DARC demonstrated a significantly stronger correlation with future MA growth than EZ loss(p = 0.0191), EZ-RPE difference (p = 0.0267) and HRF density (p = 0.0252).Conclusions In this small preliminary study, DARC appears to provide the strongest, most consistent predictor of directional MA growth compared to EZ loss, EZ-RPE difference and HRF. Angular plot analysis offers a robust method for assessing disease progression, supporting DARC as a valuable biomarker for early identification and management of high-risk patients.