Tear levels of apoptotic, matrix-degrading and antioxidant biomarkers in patients with and without keratoconus: A cross sectional study

Purpose: To assess the tear levels of a set of apoptotic, matrix-degrading and antioxidant biomarkers, including Metalloproteinase 9 (MMP9), High Mobility Group Box 1 (HMGB1) and Superoxide Dismutase 3-Extracellular (SOD3). Methods: Sandwich-ELISA commercial kits were used to test the expression of the three tear biomarkers in the lacrimal fluid of eligible participants. Linear logistic regression analysis was performed todetermine whether the set of tear biomarkers could be associated with clinically manifest keratoconus. ROC curve analysis using 10-fold cross-validation was performedto evaluate the prediction accuracy of the model. Results: Eighty-one participants aged 30-48 years old were enrolled in this study; 48 were patients with keratoconus and 33 were age-matched healthy subjects. The linear combination of the three tear biomarkers levels (AUC = 0.811; CI 95 %: 0.712-0.911) accurately indicated the existence of keratoconus; higher levels of MMP9 (Odd Ratio: 1.069; CI 95 %: 1.029-1.130) and HMGB1 (OR: 1.011; CI 95 %: 1.003-1.022) and lower levels of SOD3 (OR: 0.994; CI 95 %: 0.989-0.997) were significantly associated with a higher probability of keratoconus. Conclusion: Multivariable analysis of the set of tear levels of MMP9, HMGB1 and SOD3 biomarkers confirmed a chronic state of inflammation in the ocular surface of patients with keratoconus.