Quantitative Assessment of the Human

36 Purpose: To determine whether morbidity and mortality in patients with cardiovascular 37 comorbidities, but no known ocular disease, is related to demonstrable quantitative changes 38 in the retinal microvasculature. 39 Methods: 11 eyes from 8 donors with cardiovascular comorbidities as a diseased group were 40 compared with 16 eyes from 14 donors free from vascular disease as a control group. All 41 eyes had no known ocular disease. The retina was perfusion-fixed and labelled for endothelial 42 f-actin using micro-cannulation techniques. The retinal microvasculature 3 mm superior to 43 the optic disc was imaged with confocal scanning laser microscopy. Quantitative 44 measurements of capillary diameter and density were obtained using two-dimensional image 45 reconstructions. Pathological vascular changes in other regions of the retinal vasculature 46 found in the diseased group were identified and reconstructed in twoor three-dimensions. 47 Results: Capillary densities were significantly different between each capillary network in 48 the diseased group. There was a significant decrease in density between both the nerve fibre 49 layer and retinal ganglion cell layer of the diseased group when compared to those layers in 50 the control eyes. There were pathological vascular changes including microaneurysms and 51 tortuous, dilated venules identified in the diseased group. 52 Conclusions: Cardiovascular comorbidities may be associated with changes to the capillary 53 density within the human retinal microvasculature, prior to the manifestation of known ocular 54 diseases. These differences in capillary density may have important correlations with 55 neuronal function and facilitates the basis of understanding pathogenic mechanisms in retinal 56 vascular disease. 57