Purpose: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) are considered the gold standard for diabetic macular edema (DME). Despite adequate anti-VEGF treatments, many patients present persistent DME. The aim of this study is to identify systemic, ocular and anatomical characteristics influencing functional and anatomical outcomes in refractory DME patients treated with IVI of corticosteroid.Materials and Methods: Retrospective multicenter hospital-based cohort study including type 2 diabetic adult patients with refractory DME that switched from intravitreal anti-VEGF to intravitreal corticosteroid between January 2017 and September 2018. Sociodemographic, clinical data, DME and treatment characteristics were collected at baseline (visit before switch), as well as spectral domain OCT features.Results: A total of 101 eyes were included. The median number of anti-VEGF injections before switch was 5.0 (min-max: 4.0-9.0) and the median anti-VEGF treatment duration before switch was 33.2 (min-max: 19.5-50.3) months. More than half of the patients (56; 54.9%) were diagnosed with diffuse DME. At baseline, 80 (88%) patients had cystoid DME, 55 (62.5%) patients had disorganization of retinal inner layers (DRIL) and 16 (17.6%) had subretinal fluid. Dexamethasone was the corticosteroid more commonly used (71.4%), followed by triamcinolone (24.4%) and fluocinolone (4.2%). Regarding best corrected visual acuity (BCVA), post-switch results showed no statistically significant improvement at three-month follow-up (p = .048/0.096), but the mean central macular thickness (CMT) decreased significantly from 486.3 (SD = 159) µm to 369.3 (SD = 129) µm at three-month follow-up (p < .001). DRIL was the tomographic characteristic able to influence significantly both CMT and BCVA final results (p = .02 and 0.012, respectively).Conclusions: Subfoveal DRIL on structural OCT was the DME factor influencing significantly clinical and imaging outcomes in refractory DME patients treated with intravitreal corticosteroid. Portuguese care trend towards DME shows preference for the use of dexamethasone implant after therapeutic failure with ranibizumab or bevacizumab injection.