Abstract
Purpose :
High resolution optical coherence tomography (HR-OCT) provides unprecedentedly detailed views of retina and choroid. Small perturbations of retinal pigment epithelium-basal lamina-Bruch’s membrane band (RPE-BL-BrM) represent earliest stages of AMD. To inform the interpretation of HR-OCT-anchored multimodal imaging, we identified small drusen by histology and fluorescein angiography.
Methods :
We surveyed Project MACULA (https://projectmacula.org/) an online resource of epoxy-resin histology of human donor eyes (N=54, aged-normal; N=24 early-intermediate AMD; N=13 geographic atrophy). Nodular drusen located between RPE- BL and inner collagenous layer of BrM were solid, globular, and homogeneously stained with toluidine blue. They lacked overlying basal laminar deposit (BLamD, between RPE and native BL) and basal mounds (soft drusen material within BLamD). Soft drusen material in any location was granular and light grayish brown. In images acquired with an oil immersion objective, base widths of single (non-confluent) nodular drusen were measured using FIJI. In one eye with non-exudative neovascular AMD, an area of punctate hyperfluorescence in late-phase fluorescein angiography (FA) 11 years before death (PMID 32247535) was mapped in histology.
Results :
In 104 images from 43/92 eyes, small lesions included nodular drusen, 53 images; small soft drusen, 8; BLamD / basal mounds, 33; multilayer BLamD / BLinD-drusen, 10. The Figure shows that the range of nodular drusen (N=128) widths was 2.2 to 110 µm (median, 13.0 µm; interquartile range 7.7, 20.0 µm). In the eye with late phase FA, 91 similar-sized nodular drusen were found in an area with small circles of uniform fluorescence.
Conclusions :
In two samples, 90% and 95% of nodular drusen (92% total) have base width <30 µm, a size just visible in color fundus photography (CFP; PMID 10365048). Results support reports that CFP reveals depigmentation over drusen and underestimates drusen dimensions, relative to histology and OCT (PMID 32568988, 33411474). The FA appearance is consistent with staining of individual drusen. Whether these deposits resemble cuticular drusen with “starry sky” angiograms needs further research (PMID 7525362, 10365048, 20924263, 28964580). Direct visualization of a sequence from numerous small drusen to soft drusen (PMID 17270675, 25905023) may be possible.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.