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)
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Author(s)
Type
Journal Article
Abstract
Background
To evaluate Detection of Apoptosing Retinal Cells (DARC), Ellipsoid Zone (EZ) loss, EZ–Retinal Pigment Epithelium (RPE) difference, and Hyperreflective Foci (HRF) as predictors of directional macular atrophy (MA) growth in age-related macular degeneration (AMD) using a novel 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, EZ–RPE difference, HRF density, and DARC activity were quantified around the MA center, and angular plots were generated in 1-degree sectors of a full circle centered on the MA lesion. Directional associations with subsequent MA growth were assessed using Spearman’s rank correlation.
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. Angular plot analysis provides a robust approach for evaluating progression and supports DARC as a promising biomarker for identifying patients at high risk of MA expansion.
To evaluate Detection of Apoptosing Retinal Cells (DARC), Ellipsoid Zone (EZ) loss, EZ–Retinal Pigment Epithelium (RPE) difference, and Hyperreflective Foci (HRF) as predictors of directional macular atrophy (MA) growth in age-related macular degeneration (AMD) using a novel 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, EZ–RPE difference, HRF density, and DARC activity were quantified around the MA center, and angular plots were generated in 1-degree sectors of a full circle centered on the MA lesion. Directional associations with subsequent MA growth were assessed using Spearman’s rank correlation.
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. Angular plot analysis provides a robust approach for evaluating progression and supports DARC as a promising biomarker for identifying patients at high risk of MA expansion.
Date Issued
2026-08-01
Date Acceptance
2026-05-21
Citation
Expert Review of Ophthalmology, 2026, 21 (4), pp.369-381
ISSN
1746-9899
Publisher
Informa UK Limited
Start Page
369
End Page
381
Journal / Book Title
Expert Review of Ophthalmology
Volume
21
Issue
4
Copyright Statement
© 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
Publication Status
Published
Date Publish Online
2026-06-18