Purpose
To examine the morphology and distribution of lipid globules (E. Friedman, 1966, PMID 5903818) in age-related macular degeneration (AMD) and non-AMD eyes.
Methods
1) Short post-mortem donor eyes with and without AMD pathology (N=136, ages 59-98 yr) post-fixed in osmium tannic acid paraphenylenediamine were prepared for high-resolution macula-wide sections, stained with toluidine blue, reviewed by light microscopy, and annotated for pathology features (http://projectmacula.cis.uab.edu). 2) A subset of globules were photographed, classified, and measured using ImageJ.
Results
1) Globules, located in the extravascular space in clusters and in isolation, are osmophilic. They stain tan or brown and localize to inner choroid (47 eyes), sclera (5), or both (2). Diagnoses of eyes with globules included neovascular AMD (16/40), geographic atrophy (4/13), early AMD (6/26), 7 eyes with various chorioretinal pathologies (1-2 each), and unremarkable (18/51). Globule distribution did not differ significantly among AMD stages or between AMD and non-AMD eyes. 2) From 29 eyes (mean age = 83 yr; 16F; 13M), 85 globules were categorized by morphology into well-circumscribed (Figure 1A) (16, 18.8%), dissolving (8, 9.4%), disintegrating (4, 4.7%), multilobular (30, 35.5%), crystalline (7, 8.2%), coalescing/dispersing (Figure 1B) (15, 17.6%), and scattered (5, 5.9%). Average area (2140.53 µm2), Feret diameter (58.85 µm), and circularity (0.84) were also calculated.
Conclusions
Friedman lipid globules were found in 34.5% of these donor eyes. As choroidal imaging advances, clinicians will visualize increasingly more histological detail. Lipid globules have diameters comparable to choroidal vessels and may elevate Bruch’s membrane. These novel observations suggest aggregation of smaller lipid globules, breakdown of larger lipid globules, or a combination, constraining future hypotheses about biogenesis. Theories regarding etiology include increased extracellular lipase activity, red blood cell membrane breakdown products, and fat emboli; all will require further investigation.