Abstract
Purpose :
Hyperreflective foci (HRF) are optical coherence tomography (OCT) biomarkers for progression of non-neovascular AMD attributed to anteriorly migrated retinal pigment epithelial cells (RPE). We examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS); we sought a histologic candidate for HRS.
Methods :
AMD severity was determined in patients ≥60 years old via the 9-step Age-Related Eye Disease Study scale for color fundus photography. In OCT scans HRF and HRS were manually counted. Vision tests probed cones (best corrected visual acuity (VA), contrast sensitivity), mixed cones and rods (low luminance VA, low luminance deficit, mesopic light sensitivity), or rods (scotopic light sensitivity, rod-mediated dark adaptation (RMDA)). Normal aged eyes in an online AMD histopathology resource were reviewed.
Results :
In 101 eyes of 101 patients (normal maculas, 34; early AMD, 25; intermediate AMD, 41), HRF and HRS were identified in 25 and 95 eyes, respectively, with good intra- and inter-rater reliability. HRF were present but sparse in normal eyes (number per eye, 0.1±0.2), infrequent in early AMD eyes (0.2±0.5), and frequent but highly variable among intermediate AMD eyes (1.9 ± 3.4). HRS outnumbered HRF in all groups (4.5 ± 3.2; 6.4±5.2; 19.4 ± 22.4). Delayed RMDA was strongly associated with more HRF (p<0.0001) and HRS (p<0.0001). HRF were also associated with worse low luminance VA (p=0.0117). HRS were associated with worse contrast sensitivity (p=0.0278), low luminance VA (p=0.0010), low luminance deficit (p=0.0031), and mesopic (p=0.0018) and scotopic sensitivity (p<0.0001). By histology, cone lipofuscin, a solitary long-lasting inclusion body, was found in inner segments, ONL, and HFL of 25% of normal aged eyes.
Conclusions :
HRF and HRS are markers of cellular activity associated with visual dysfunction, especially delayed RMDA, a risk indicator for AMD onset that assesses efficiency of retinoid transfer and replenishment. HRS may represent lipofuscin granules translocating inwardly within cone photoreceptors. Automated quantification of HRF and HRS may serve as early structural endpoints in clinical trials and inform clinical management of older patients with and without AMD. Confirmation in larger sample is needed.
This is a 2020 ARVO Annual Meeting abstract.