**3.5 Macular ischemia**

Retinal ischemia has been recognized as a primary risk factor for developing proliferative diabetic retinopathy (PDR); it sometimes occurs with DME. A paucity of studies describing diabetic macula ischemia (DMI) exists, mainly due to difficulty in its detection using fluorescein angiography and limited treatment options [63]. Clinically, DMI is defined by an enlargement of the foveal avascular zone (FAZ) and paramacular areas of capillary nonperfusion [64]. Two anatomical changes can be characteristically seen in the retina of patients with DMI. First, due to marked cellular and extracellular damage, there is extensive loss of neuro-retinal tissue. Secondly, there is notable occlusion of the vessels supplying the retina [63]. DMI results in the upregulation of growth factors such as VEGF, which contribute to DME development [65], making it difficult to observe and anatomically characterize DMI in isolation. The anatomical and physiological basis of this disease is still very poorly studied [63]. Recently optical coherence tomography angiography (OCTA) offers a better image of macular microvasculature and is superior to conventional FA in assessing DMI. Anatomically the microcirculation supply to the retina is divided mainly into superficial capillary plexus (SCP) and deep capillary plexus (DCP) [66]. Choroidal circulation seems to be the most critical blood supply to the central macula, including the photoreceptor inner segment (IS) band, which appears to be the most critical consumer of oxygen [67]. It is thought that the DCP is responsible for up to 15% of the blood supply to the photoreceptors, especially during dark adaptation [65, 66].
