With the advent of fundus fluorescein angiography, the concept of ischemia and the correlation between peripheral nonperfusion and neovascularization has been introduced, which was eventually followed by the advent of new therapeutic strategies, such as peripheral photocoagulation. DR was first considered a pure microvascular disease, due to the evident capillary structural changes (microaneurysms), fluid extravasation, and lipid exudation.
In the last decades, significant changes have been taking place regarding the pathogenesis of diabetic retinopathy (DR) and the complex mechanisms that eventually lead to the various manifestations of the disease, including diabetic macular edema (DME).