Metabolomic insights into vitreous humor with therapy outcome in type 2 diabetic retinopathy

The therapeutic outcome for Type 2 Diabetic Retinopathy (T2DR) following vitrectomy has been unsatisfactory, with no definitive biomarker available to predict treatment response. Identifying a biomarker correlated with treatment efficacy is crucial, as the vitreous-situated between the lens and retina-may influence retinal metabolic perturbations.

Vitreous samples were collected during vitrectomy, and their metabolic profiles were analyzed using Ultraperformance Liquid Chromatography coupled with Tandem Mass Spectrometry (UPLC-MS/MS). Statistical analyses were conducted to identify metabolites and metabolic pathways correlated with therapeutic outcomes.

Patients demonstrating poor therapeutic responses exhibited elevated levels of specific metabolites, including Dodecanoylcarnitine, Linoleylcarnitine, Stearylcarnitine, Decanoic acid, and Proline. Perturbed metabolic pathways included Fatty Acid Biosynthesis, Beta Oxidation of Very Long Chain Fatty Acids, and Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids. These metabolites showed strong discriminatory power for predicting positive outcomes, with Area Under the Curve (AUC) values of 0.925, 0.885, 0.864, 0.811, and 0.808, respectively.

This study highlights the potential of Dodecanoylcarnitine, Linoleylcarnitine, Stearylcarnitine, Decanoic acid, and Proline as biomarkers for predicting therapeutic outcomes following vitrectomy for T2DR. These findings provide novel insights into the metabolic factors influencing treatment response variability and suggest pathways for future therapeutic interventions.