A non-invasive Schirmer strip-based analysis of tear cotinine and MMP-9 levels in chronic smokers

Cont Lens Anterior Eye. 2025 Apr;49(2):102598. doi: 10.1016/j.clae.2025.102598. Epub 2025 Dec 31.

ABSTRACT

PURPOSE: This study aimed to objectively investigate the impact of chronic cigarette smoking on ocular surface inflammation by analyzing the correlation between tear levels of cotinine, a biomarker of active smoke exposure, and matrix metalloproteinase-9 (MMP-9), a key inflammatory mediator.

DESIGN: Prospective, cross-sectional study.

METHODS: In this cross-sectional study, tear fluid samples were collected from 35 chronic smokers and 50 never-smoked controls. Tear concentrations of cotinine and MMP-9 were quantified using enzyme-linked immunosorbent assay (ELISA). All participants underwent comprehensive ophthalmologic examination, including corneal topography with Pentacam HR. Statistical analyses were performed to compare biomarker levels between groups and assess their correlation and diagnostic utility.

RESULTS: Tear cotinine and MMP-9 levels were significantly elevated in smokers compared to controls (p < 0.0001 and p = 0.002, respectively). A strong positive correlation was found between cotinine and MMP-9 levels in the smoking group (Spearman's ρ = 0.786, p < 0.0001). Receiver operating characteristic (ROC) curve analysis indicated that both biomarkers significantly discriminated smokers from non-smokers. No significant differences were found in corneal topography parameters between the groups.

CONCLUSION: Chronic smoking significantly elevates tear MMP-9 levels, indicating subclinical ocular surface inflammation even in the absence of clinical disease. This study is the first to report a strong objective correlation between tear cotinine and MMP-9, establishing tear cotinine as a reliable biomarker for active smoking. Future studies on ocular surface inflammation must account for smoking status as a major confounding variable.

PMID:41477937 | DOI:10.1016/j.clae.2025.102598