The Pro- and Anti-Inflammatory Cytokine Profile in Keratoconus as a Predictor of Five-Year Corneal Cross-Linking...

The aim of this study was to evaluate tear cytokine and chemokine profiles in keratoconus (KC) and to assess their association with long-term tomographic outcomes after corneal collagen cross-linking (CXL). In this cross-sectional observational study, 30 KC eyes and nine healthy controls were enrolled. KC severity was graded using the modified Amsler-Krumeich classification. Tear samples were collected and analyzed using multiplex bead-based immunoassays (LEGENDplex™) for cytokines, chemokines, and TGF-β1. Patients were followed for five years after CXL. Treatment response was categorized according to corneal flattening (<1 D, 1-3 D, >3 D). Individual cytokine levels showed no major differences between the KC and controls, although IL-6 and MCP-1 tended to be higher in the KC group. However, IP 10 and IL-17 were higher in controls (p < 0.05). In contrast, multiple pro-/anti-inflammatory ratios (TNF/TGF-β1, IL-17/IL-10, MCP-1/IL-10, IL-6/IL-10, IL-8/TGF-β1, MCP-1/TGF-β1, IL-6/TGF-β1, and IL-8/IL-10) were significantly elevated in the KC group (p < 0.05), indicating immune imbalance. After five years, all treated eyes remained stable or flattened. Lower baseline MCP-1 and IL-8 levels correlated with greater postoperative corneal flattening (p < 0.05). Keratoconus is characterized by disturbed tear immune homeostasis rather than isolated cytokine elevation. Lower preoperative inflammatory activity may predict a more favorable biomechanical response to CXL, supporting the potential role of tear cytokine profiling in patient stratification and prognostication.