Tear lactate improves the evaluation of proliferative diabetic retinopathy in type-2 diabetes patients

Proliferative diabetic retinopathy (PDR) is the advanced stage of DR and characterized by retinal neovascularization (RNV). The diagnosis of PDR relies primarily on imaging features and blood glucose levels. Whether early biomarkers in other biofluid applied in the evaluation of PDR and RNV remain elusive. In total, 40 Chinese type-2 diabetes with DR and 21 non-diabetic subjects were recruited. Tear glycometabolic profiles and glycometabolite levels were comprehensively analyzed using both untargeted and targeted metabolomics approaches. Additionally, we employed multivariable logistic regression models, Pearson correlation analysis, receiver operating characteristic curve (ROC), retinal non-perfusion area detection and choroid sprouting assay to evaluate and validate the association between tear metabolites and PDR. Our metabolomic analysis revealed significantly elevated levels of metabolites related to the TCA cycle as well as D-glutamine and D-glutamate pathway in PDR subjects compared to non-diabetic controls. Among these metabolites, the fasting tear lactate was the highest in PDR subjects relative to other tear monosaccharides. Notably, tear lactate emerged as an independent risk factor for PDR, achieving an area under the curve (AUC) of 0.896 in predictive modeling. Furthermore, the tear lactate was validated to have effect on RNV. In summary, the study delineated glycometabolic features in tears of type-2 diabetes patients with PDR and identified tear lactate could be a promising novel marker for PDR evaluation.