In diabetic retinopathy, microaneurysms are indicators of microvascular damage (DR). A major pathogenic factor in the development of microvascular disorders was impaired retinal capillary perfusion. However, targeting basic molecular disruptions caused by capillary nonperfusion, such as increased vascular endothelial growth factor expression, does not necessarily restore the anatomic difficulties of DR, suggesting that additional pathogenic pathways other than perfusion are also involved. 

Through three-dimensional analysis of 636 microaneurysms using high-resolution confocal scanning laser microscopy, researchers stratified the effects of capillary nonperfusion, inflammation, and pericyte loss on microaneurysm size and leakage in DR. Nonperfusion of capillaries, pericyte loss, and inflammatory cells were discovered to be independent predictors of microaneurysm size. 

Nonperfusion was not a significant predictor of microaneurysm leakage in the absence of pericyte loss or inflammation. Microaneurysms detected in nonperfused areas were much smaller than those found in perfused areas, and their size was unrelated to pericyte loss or inflammation. Furthermore, in nonperfusion-only locations, the size of the microaneurysm was a significant predictor of leakage. The study improved the understanding of the many pathophysiologic pathways in DR and gave a histologic basis for understanding therapy failure for microvascular problems in DR.