Abstract:Purpose: To demonstrate that retinal microvasculature per se is a reliable biomarker for Diabetic Retinopathy (DR) and, by extension, cardiovascular diseases. Methods: Deep Learning Convolutional Neural Networks (CNN) applied to color fundus images for semantic segmentation of the blood vessels and severity classification on both vascular and full images. Vessel reconstruction through harmonic descriptors is also used as a smoothing and de-noising tool. The mathematical background of the theory is also outlined. Results: For diabetic patients, at least 93.8% of DR No-Refer vs. Refer classification can be related to vasculature defects. As for the Non-Sight Threatening vs. Sight Threatening case, the ratio is as high as 96.7%. Conclusion: In the case of DR, most of the disease biomarkers are related topologically to the vasculature. Translational Relevance: Experiments conducted on eye blood vasculature reconstruction as a biomarker shows a strong correlation between vasculature shape and later stages of DR.