Diabetic retinopathy (DR) is characterized by retinal microvascular angiopathy and is complicated by retinal neurodegeneration. Recently, the functional and structural concept of neurovascular units has been introduced to better understand the temporal and spatial relationships between vascular and neuronal abnormalities in the pathogenesis of DR. Diabetic macular ischemia (DMI) is one of the vision-threatening conditions associated with neurovascular changes in DR; however, its clinical significance and molecular mechanisms remain poorly understood, making treatment for this complication difficult. There has yet to be agreement on the definition or diagnostic criteria of DMI. Meanwhile, DR severity progression and foveal avascular zone (FAZ) enlargement, both of which are related to visual dysfunction, have been proven to be related to the degree of DMI detected with optical coherence tomography angiography (OCTA). According to clinical and preclinical evidence, this review addresses the impact of DMI on visual function and retinal structure, its treatment concept, the possibility of intervention, and desirable treatment options. DMI is thought to result from irreversible endothelial cell death in most cases, in addition to transient leukocyte embolism in the diabetic retinal vasculature. Currently available drugs against vascular endothelial growth factor (VEGF) have been shown to be ineffective in improving the pathogenesis of DMI. Future treatment strategies are expected to selectively promote retinal revascularization and reperfusion through intraretinal physiological neovascularization for compensating retinal nonperfusion areas while suppressing diabetic macular edema (DME) and intravitreal pathological neovascularization, both of which are secondary to DMI.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 127: 725-740,2023.