Hyperreflective foci (HRF) in intermediate age-related macular degeneration (iAMD): spatial abundance and impact on retinal morphology

Abstract

Purpose : To analyze the topographic distribution of HRF as well as localized retinal layer thicknesses (RLT) in presence or absence of HRF in eyes with large drusen associated with iAMD.

Methods : Sixty-five eyes (59 iAMD patients, (mean age ± SD) 70.9 ± 8.6 years) with large drusen (>125 µm) and 28 control eyes (27 patients; 64.21 ± 9.04 years; unremarkable macula) underwent spectral-domain optical coherence tomography, SD-OCT (volume scan: 30°x25°, 61 B-Scans, spacing 120µm). Within each SD-OCT scan, retinal layers were semi-automatically segmented by a medical reader, HRF manually annotated (at 300% magnification), RLT at each HRF location extracted (using a custom-written ImageJ plugin) and compared to RLT in areas without HRF (HRF area mirrored horizontally at the foveal level) from the same eyes. RLT between positions were compared using the Wilcoxon test, univariate mixed linear models to investigate associations between RLT, HRF presence and HRF size.

Results : In iAMD eyes, 12.8 ± 12.7 HRF per eye were detected with a peak abundance at 0.5 to 1.5 mm eccentricity of the fovea (6.43 ± 8.16 HRF per eye). When HRF are present, outer nuclear layer (ONL) (p=0.0004, average difference -10.06 µm) and retinal pigment epithelium drusen complex (RPEDC) thicknesses (p = 0.0003, average difference +29.54 µm) differed significantly compared to areas with no HRF. In the presence of HRF, ONL thinning was significantly different (p=0.002) even while accounting for RPEDC thickening. Inner and outer photoreceptor segments (IS, OS) and the outer plexiform layer (OPL) thicknesses did not differ significantly. Mixed linear models further revealed a significant association between increasing HRF size and decreasing ONL (association score -0.19, p < 0.0001; 95%CI: -0.24, -0.13) and IS layer thicknesses (-0.09, p = 0.0072: -0.14, -0.04).

Conclusions : In iAMD migrating HRF leave a trail of remodeling that impacts multiple retinal layers. Thickening of the RPEDC with subsequent reduced oxygen and nutrient supply from the underlying choriocapillaris might trigger RPE migration, while the ONL thickness decrease at areas of HRF could result from cell displacement or degradation. Longitudinal studies on the functional impact as well as long-term retinal changes at a cellular and subcellular level are underway to further characterize the importance of HRF as a biomarker for AMD progression.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.