Evaluation of Inflammatory Mediators in the Tear Film Before and After Corneal Cross-Linking

Abstract

INTRODUCTION: Keratoconus’ pathogenesis is not completely understood. One suspected contributor is inflammation at the corneal surface, often signaled by elevated levels of pro-inflammatory cytokines in the tear film. Corneal cross-linking is a recognized treatment to slow or halt disease progression. While corneal cross-linking has demonstrated promising results, there is notable variability in outcomes among patients, and the reasons for this remain incompletely understood. Our hypothesis posits that favorable post-operative outcomes may be linked to alterations in the pro-inflammatory cytokine content in a patient’s tear film. This study aims to explore the relationship between tear film pro-inflammatory cytokines and the effectiveness of corneal cross-linking treatment outcomes.
METHODS: Clinical evaluations captured corneal tomographic data, best-corrected distance visual acuity, and past medical history from participants. Two tear film samples were taken from individuals undergoing corneal cross-linking and from age-matched controls. These samples were collected both before the procedure and six months afterward using Schirmer strips. The cytokine analysis in these samples was performed using the commercially available Th1/Th2/Th9/Th17 Cytokine 18-Plex Human ProcartaPlex™ Panel.
RESULTS: We recruited 35 patients for the treatment group (57% females; mean age: 27.61±8.94 years) and 19 for the control group (47% females; mean age: 24.13±7.18 years). After corneal cross-linking, significant enhancements were observed in best-corrected distance visual acuity (p<0.0001) and tomographic indices such as Kmax (p=0.0417). Pre-operative mean total protein content stood at 1.54±0.46 µg/µL10 for the treatment cohort and 1.48±0.27 µg/µL10 for controls. Six months post-procedure, these figures were 1.40±0.428 µg/µL10 and 1.90±0.45 µg/µL10 for the treatment and control groups, respectively. Though there was a discernible trend of elevated pro-inflammatory cytokine levels in the pre-operative treatment group relative to both controls and post-corneal cross-linking results, the mean difference was not statistically significant.
CONCLUSION: Our research indicates that elevated pro-inflammatory cytokine levels are seen in patients with keratoconus. We were unable to confirm our hypothesis that treatment with CXL may reduce PIC levels. Future studies with expanded sample sizes are essential to understand pro-inflammatory cytokines’ influence on both keratoconus pathophysiology and corneal cross-linking outcomes.