Hyperreflective Foci Contiguous with the RPE Associate with Visual Function in Aging, Early and Intermediate AMD: MACUSTAR Study Report

Purpose To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early (e) age-related macular degeneration (AMD), and intermediate (i) AMD. 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, and scotopic pointwise sensitivity deviation (mesPSD, scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using ANOVA, linear regression, and Spearman correlation. Main outcome measures Presence, burden, topographic distribution of rpeHRF; association with functional parameters. Results Fifty-six normal aged (33 female (f), mean age 68.1 ± 6.4 years), 34 eAMD (27 f, 71.7 ± 6.4 years), and 583 iAMD eyes (387 f, 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 < 0.001). BCVA, LLVA, CS (all p < 0.001), and scPSD (p = 0.001) differed between disease groups. Whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all p < 0.001), and mesPSD (p = 0.02). rpeHRF cound 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.