The “pioneers of angiogenesis,” i.e., Judah Folkman, Harold Dvorak, and Napoleone Ferrara, eventually headed to the discovery of vascular endothelial growth factor (VEGF) a few years later. While in Japan the group of Koichi Shimizu correlated the presence of neovascularization with the extent of peripheral capillary nonperfusion, different scientists started postulating the existence of a neovascular factor responsible for diabetes-related ocular changes. FFA made it possible to visualize, describe, and quantify the microvascular alterations in diabetic eyes and their changes with time the very close relationship between hemorheological alterations, retinal ischemia, and PDR was undoubtedly elucidated. Norton in 1965, and Donald Gass in 1967 made their greatest contribution to the depiction of epiretinal, dye-leaking, convoluted fibrovascular tissue characterizing the most advanced form of DR, namely proliferative DR (PDR). In the future, integration of standard investigations with new diagnostic devices would allow the prompt recognition of DR even before clinical signs of the disease are ophthalmoscopically evident, and the development of personalized treatment for both retinopathy and DME will be available.ĭaniel J.

Nowadays, thanks to more advanced imaging techniques, namely optical coherence tomography (OCT), OCT angiography, and wide-field imaging (imaging up to 200° of the retina in a single shot), it became clear that other elements participate in the occurrence of DR and DME, including inflammation and neurodegeneration. 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).

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