Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy

Purpose This article aims to review the impact of detecting and quantifying intraocular biomarkers (liquid biopsy) in both aqueous and vitreous humor in eyes of people affected by diabetes mellitus. Methods This is a detailed review about aqueous and/or vitreous humor sampling in human diabetic eyes for proteomic and/or metabolomic analysis contributing to the understanding of the pathophysiology and treatment effects of diabetic retinopathy. Results Aqueous and vitreous humor molecular biomarkers proved to be directly correlated to each other and valuable to study retinal conditions. Moreover, proteomic and metabolomic analysis showed that the biomarkers of neuroinflammation, neurodegeneration, and vasculopathy are detectable in intraocular fluids and that their concentration changes in different stages of disease, and in response to treatment of all diabetic retinopathy aspects, mainly diabetic macular edema and proliferative retinopathy. Conclusions Liquid biopsy offers the possibility to improve our knowledge of intraocular eye disease induced by diabetes mellitus. The exact quantification of intraocular biomarkers contributes to the precision medicine approach even in the diabetic retinopathy scenario. The diffusion of this approach should be encouraged to have quantifiable information directly from the human model, which may be coupled with imaging data. Key messages The future perspectives in the management of diabetic retinal involvement are strictly linked to the concept of precision medicine: a tailored approach to patients, according to their phenotypic characteristics is currently desirable. Aqueous and vitreous humor sampling both provide reliable and quantifiable markers of disease, with aqueous biopsy being a safer approach. Liquid biopsy provides a direct aqueous or vitreous sample to study, in vivo, the presence and changes of specific molecules concentration defining phenotypic profiles of diabetic non proliferative and proliferative retinopathy and diabetic macular edema. The correlation between imaging features and biochemical changes provides biochemically-proven structural biomarkers able to define the main pathophysiologic mechanisms of the diabetic retinal manifestations, and prognostic and treatment response perspectives.