The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: “disorganization of inner retinal layers (DRIL)”, “diabetic macular edema (DME)” and “biomarkers”. No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.