Purpose: To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early age-related macular degeneration (eAMD), and intermediate AMD (iAMD).
Design: Prospective cohort study.
Subjects: Participants of the MACUSTAR study.
Methods: MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best corrected visual acuity (BCVA), low-luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12°, contrast sensitivity (CS), mesopic (mesPSD), and scotopic pointwise sensitivity deviation (scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using analysis of variance, linear regression, and Spearman correlation.
Main outcome measures: Presence, burden, and topographic distribution of rpeHRF, as well as association with functional parameters, were determined.
Results: Fifty-six normal aged (33 female, mean age 68.1 ± 6.4 years), 34 eAMD (27 female, 71.7 ± 6.4 years), and 583 iAMD eyes (387 female, 72.0 ± 7.0 years) were included. rpeHRF counts were 0.16 ± 0.85 in normals, 0.33 ± 0.96 in eAMD, and 1.61 ± 2.49 in iAMD (P < .001). BCVA, LLVA, CS (all P < .001), and scPSD (P = .001) differed between disease groups, whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all P < .001), and mesPSD (P = .02). rpeHRF was found to be associated modestly with only CS, scPSD, LLVA, and BCVA.
Conclusions: Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.
Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.