Introduction: To characterize the two-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) Phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥ 2 SD over normal values, and Phenotype B, or edema phenotype, identified by increased retinal thickness, i.e. subclinical macular edema, and no significant decrease in VD. Methods: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6-months, one-year and two-year). Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP) and optical coherence tomography (OCT) and OCT Angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-fields CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotype B and C and completed the two-years follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the two-year period (p

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