Non-ocular biomarkers for early diagnosis of diabetic retinopathy by non-invasive methods.

Diabetic retinopathy (DR) is the predominant vision-threatening complication in individuals with diabetes mellitus. Timely diagnosis and intervention facilitate the prevention of diabetes-associated visual impairment. Classical imaging methods may prevent the timely detection of DR due to shortages of specialized facilities and retinal specialists, particularly in remote areas. In recent years, research on biomarkers related to DR has rapidly developed, playing an important role in risk assessment and early detection of the disease. Some ocular biomarkers from the vitreous body or aqueous humor were invasive, which hampered their application in clinical practice. Meanwhile, biomarkers based on omics were limited by their uneasily accessible use and complicated variables with a relatively low degree of reproducibility. As modern technology progresses, advanced non-ocular biomarkers of DR have established a comprehensive platform for the prompt identification of DR, independent of ophthalmic professionals or devices and accessible to non-ophthalmologists during community screenings. This review focuses on biomarkers derived from non-ocular sample sources, such as nailfold and skin, accessible through non-invasive methods, to reveal if they can be considered as an effective option for the early identification of DR by non-ophthalmologists in community screening initiatives.