Purpose: The purpose of this study was to investigate retinal layers’ changes in patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response. Methods: Participants in this prospective study were 110 treatment-naïve patients with center involved DME, who were treated with anti-VEGF agents and followed up for at least 12 months. A qualitative and quantitative analysis of retinal layers that can affect visual acuity was performed. Patients with persistent DME were defined, and factors which could affect this outcome were determined. Results: Visual acuity was significantly improved, while there was also a statistically significant reduction in central retinal thickness and in all separate retinal layers’ thickness at month 12 compared to baseline (p < 0.001). Visual acuity was associated with central retinal thickness and outer retinal layers’ thickness;51.8% of the patients presented with persistent DME at month 12, which was found to be significantly associated with baseline visual acuity and HbA1C levels. Conclusions: Anti-VEGF treatment is effective in reducing retinal thickness as a whole and in all separate retinal layers at 12-month follow-up in patients with DME. Changes in central retinal thickness and in outer retinal layers were found to affect visual acuity. HbA1c was the most significant factor to determine persistence of DME at month 12.

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