Current understanding of subclinical diabetic retinopathy informed by histology and high-resolution in vivo imaging

The escalating incidence of diabetes mellitus has amplified the global impact of diabetic retinopathy. There are known structural and functional changes in the diabetic retina that precede the fundus photography abnormalities which currently are used to diagnose clinical diabetic retinopathy. Understanding these subclinical alterations is important for effective disease management. Histology and high-resolution clinical imaging reveal that the entire neurovascular unit, comprised of retinal vasculature, neurons and glial cells, is affected in subclinical disease. Early functional manifestations are seen in the form of blood flow and electroretinography disturbances. Structurally, there are alterations in the cellular components of vasculature, glia and the neuronal network. On clinical imaging, changes to vessel density and thickness of neuronal layers are observed. How these subclinical disturbances interact and ultimately manifest as clinical disease remains elusive. However, this knowledge reveals potential early therapeutic targets and the need for imaging modalities that can detect subclinical changes in a clinical setting.