PurposeTo localize early capillary perfusion deficits in patients with diabetes mellitus (DM) without clinical diabetic retinopathy (DR) using averaged optical coherence tomography angiography (OCTA). DesignRetrospective, cross-sectional study. SubjectsPatients with DM without DR and healthy controls. MethodsWe measured perfusion deficits in the full retina, superficial (SCP) and deep capillary plexus (DCP) on averaged 3 x 3 mm OCTA images. Perfusion deficits were defined as the percentage of retinal tissue located further than 30 μm from blood vessels, excluding the foveal avascular zone (FAZ). One eye from each patient was selected based on image quality. We measured deficits in the parafoveal region, the 300 μm surrounding the FAZ, and 300 to 1000 μm surrounding the FAZ. If a capillary layer within one of these regions was significantly different in DM without DR compared to controls, we further characterized the location of perfusion deficit as periarteriolar, perivenular, or the capillaries between these two zones. Main Outcome MeasuresLocation of increased perfusion deficits in patients with DM without DR compared to controls. ResultsSixteen eyes from 16 healthy controls were compared to 16 eyes from 16 patients with DM without DR (age 45.1 ± 10.7 and 47.4 ± 15.2 years respectively, P = 0.64). FAZ area, and perfusion deficits in the entire parafovea and the 300-1000 μm ring around the FAZ were not significantly different between groups (P > 0.05 for all). Perfusion deficits in 300 μm around the FAZ were significantly increased in patients with DM without DR in full retinal thickness, SCP and DCP (P < 0.05 for all). When analyzing the perivenular, periarteriolar and capillary zones, only the perivenular DCP perfusion deficits were significantly increased (5.03 ± 2.92 % in DM without DR and 2.73 ± 1.97 % in controls, P = 0.014). ConclusionsMacular perfusion deficits in patients with DM without DR were significantly increased in the region nearest the FAZ, mainly at the perivenular deep capillaries. Further research on these early changes may improve our understanding of the capillaries most susceptible to vascular injury and disruption during diabetes.