Background: A new approach to address focal vitreomacular adhesion in patients with diabetic macular edema may control and stabilize diabetic macular edema with fewer anti-vascular endothelial growth factor injections. Objectives: The aim of this study was to demonstrate that diabetic macular edema can be improved by inducing the release of a vitreomacular adhesion, with less than 2500 μm, with enzymatic vitreolysis. Methods: From a retrospective analysis of clinical records from patients with diabetic retinopathy, patients with diabetic macular edema and vitreomacular adhesion <2500 μm were selected for a single-arm prospective study. The primary endpoint was to control diabetic macular edema with fewer anti-vascular endothelial growth factor injections after an observed vitreomacular adhesion release. A statistical subanalysis was performed for the following two groups: the group with vitreomacular adhesion release (group 1) and the group without vitreomacular adhesion release (group 2). Results: A total of 23 eyes from 19 patients were included. A reduction of the median number of injections was achieved in group 1 ( p = 0.006). Adverse events were mild and transitory. Conclusion: Release of vitreomacular adhesion <2500 μm through enzymatic vitreolysis contributed to the control and stabilization of diabetic macular edema with fewer anti-vascular endothelial growth factor injections, reducing the burden and the risks related to these invasive and frequently chronic treatments.