AIM: To respectively evaluate macular morphological features and functional parameters by using spectral-domain optical coherence tomography (SD-OCT) and macular integrity assessment (MAIA) in patients with diabetic macular edema (DME). METHODS: This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity (BCVA) measurement, MAIA microperimetry, and SD-OCT. DME morphology, including central retinal thickness (CRT) and central retinal volume (CRV); integrity of the external limiting membrane (ELM) and photoreceptor inner segment/outer segment (IS/OS) junction; and the deposition of hard macular exudates were assessed within a 1000-μm central subfield area. MAIA microperimetry parameters evaluated were average threshold (AT)-retinal sensitivity, macular integrity index (MI), fixation points within a circle of radius 1° (P1) and 2° (P2), and bivariate contour ellipse area considering 63% and 95% of the fixation points (A63 and A95, respectively). RESULTS: MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA (logMAR), total AT, AT within 1000-μm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA (logMAR), AT within 1000-μm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION: Functional (BCVA and visual field) and morphological parameters (retinal thickness) were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.