© 2014 The Association for Research in Vision and Ophthalmology, Inc. RESULTS. Capillary densities were significantly different between each capillary network in the diseased group. There was a significant decrease in density between both the nerve fiber layer and retinal ganglion cell layer of the diseased group when compared with those layers in the control eyes. There were pathological vascular changes including microaneurysms and tortuous, dilated venules identified in the diseased group. CONCLUSIONS. Cardiovascular comorbidities may be associated with changes to the capillary density within the human retinal microvasculature, before the manifestation of known ocular diseases. These differences in capillary density may have important correlations with neuronal function and facilitates the basis of understanding pathogenic mechanisms in retinal vascular disease. METHODS. Eleven eyes from 8 donors with cardiovascular comorbidities as a diseased group were compared with 16 eyes from 14 donors free from vascular disease as a control group. All eyes had no known ocular disease. The retina was perfusion-fixed and labeled for endothelial f-actin using micro-cannulation techniques. The retinal microvasculature 3 mm superior to the optic disc was imaged with confocal scanning laser microscopy. Quantitative measurements of capillary diameter and density were obtained using two-dimensional image reconstructions. Pathological vascular changes in other regions of the retinal vasculature found in the diseased group were identified and reconstructed in two or three dimensions. PURPOSE. To determine whether morbidity and mortality in patients with cardiovascular comorbidities, but no known ocular disease, is related to demonstrable quantitative changes in the retinal microvasculature.