The aim of this paper was to distinguish the appearance of cysts and non-perfusion areas (NPAs) in diabetic macular edema (DME) using two different Optical Coherence Tomography Angiography (OCTA) devices. In this study, patients underwent OCTA using the AngioVue XR Avanti Spectral Domain (SD) OCTA and the PLEX Elite 9000 Swept-Source (SS) OCTA. Foveal and extrafoveal regions of interest (ROI), defined as any area with an altered flow signal comparing to the surrounding retina, were selected in superficial and deep capillary plexus (SCP and DCP). ROI reflectivity were classified as hypo-reflective or hyper-reflective. Foveal ROI were analyzed to detect suspended scattering particles in motion (SSPiM). Thirty-seven DME eyes were included. A larger number of ROIs were found in SCP (55 vs 39) and DCP (60 vs 49) using PLEX Elite 9000 vs AngioVue. The majority of ROIs were hypo-reflective with both instruments, while slightly more hyper-reflective ROIs (grey) were detected with the PLEX Elite, more likely to be cysts. The hyporeflective ROIs could be NPAs or cysts with both devices. Moreover, PLEX Elite 9000 identified SSPiM in more foveal ROIs than the AngioVue in the SCP (p = 0.005) and in the DCP (p = 0.027). In conclusion, NPAs and cysts may show variable appearances using different OCTA devices. Hyperreflective ROIs generally correspond to cysts, hyporeflective ROIs can be either cysts or NPAs. The SS-OCTA seems to detect SSPiM more frequently than the SD-OCTA.