Histology, Dimensions, and Fluorescein Staining Characteristics of Nodular and Cuticular Drusen in Age-Related Macular Degeneration

Abstract

Purpose: To enable in vivo analysis of drusen composition and lifecycle, we assessed macular nodular and cuticular drusen using histology. Methods: Median and interquartile range (IQR) of base widths of single (non-confluent) nodular drusen in 3 sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography (FA); and two eyes of one patient with bilateral “starry sky” cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy. Results: All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of Bruch’s membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 µm (Source 1, N=128 drusen, IQR 7.7, 20.0 µm), 15.3 µm (Source 2, N=87, IQR 10.6, 20.5 µm), and 7.3 µm (Source 3, N=78, IQR 3.9, 14.1 µm). Conclusions: In three samples, >90% of solitary nodular drusen were <30 µm, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in FA. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include FA.

Age-Related Macular Degeneration, a Mathematically Tractable Disease

“…Soft drusen are distinguishable from histologic nodular and cuticular drusen, which are globular and pan-retinal, by size, ultrastructure, and uptake of in vivo dyes for angiography. 129 Pan-retinal drusen may be associated with complement gene risk variants and confer risk in abundance and over a long time. 130 …”