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April 26, 2026International Journal of Molecular Sciences0 citationsOpen Access

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

TPTiana PetrovicSSSvetlana StanojlovićSPSanja Petrović Pajić

Key Points

  • This study aims to examine tear cytokine and chemokine profiles in keratoconus patients and their association with long-term outcomes after corneal cross-linking.
  • Cross-sectional observational study involving 30 keratoconus eyes and 9 healthy controls.
  • Tear samples analyzed using multiplex bead-based immunoassays for cytokines and chemokines.
  • Follow-up for five years post-corneal cross-linking, assessing corneal flattening.
  • No significant differences in individual cytokine levels between keratoconus and control groups, but KC had higher IL-6 and MCP-1 levels.
  • Pro-/anti-inflammatory cytokine ratios were significantly elevated in keratoconus (p < 0.05), indicating immune imbalance.
  • Lower baseline MCP-1 and IL-8 correlated with greater corneal flattening post-treatment (p < 0.05).

Abstract

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 (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.

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Cite This Study

Petrovic et al. (2026) studied this question.

synapsesocial.com/papers/69edadd94a46254e215b56e2https://doi.org/10.3390/ijms27093768
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