Purpose: The aim of this study was to examine the relationship between subclinical diabetic macular edema (SCME) and the development of central-involved macular edema (CIME) in patients with diabetes mellitus type-2 and mild nonproliferative diabetic retinopathy (NPDR), from 2 populations of different ethnicities. Methods: Two hundred and five patients with diabetes mellitus type-2 and mild NPDR with no prior laser or intravitreal treatment were followed for 2 years or until the development of CIME. Ophthalmological examinations, including BCVA, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and months 6, 12, and 24. Results: One hundred and fifty eight eyes/patients reached either the study endpoint, CIME (n = 24), or performed the 24-month visit without developing CIME (n = 134). Fifty eyes/patients had SCME at baseline (31.6%). Of these 50 eyes, 16 (32.0%) developed CIME, whereas of the 108 eyes with normal retinal thickness (RT) at baseline, only 8 (7.4%) developed CIME (p < 0.001). Patients with increased RT in the central subfield at baseline showed a 12-fold risk of progression to CIME compared with patients without SCME. Conclusions: In patients with mild NPDR, the presence of SCME is a good predictor of progression to CIME.

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