 The benefit of VEGF antagonists in treating DME validates that the VEGF pathway is a key target. The need for repeated anti-VEGF injections to maintain the benefit of treatment begs the question whether persistent peripheral retinal ischemia may be driving VEGF production in at least a subset of patients with DME. Fluorescein angiographic studies of the mid- and far-periphery of diabetic patients by Shimizu in the 1980s demonstrated areas of peripheral retinal nonperfusion in diabetic patients. These findings have been reproduced and substantiated more recently utilizing a novel, commercially-available imaging system for ultrawide-field angiography UWFA that employs a scanning laser ophthalmoscope and an ellipsoidal mirror. 