Ozone and CO Exposure Are Associated with Tear Film Instability and Corneal Epithelial Damage in Dry Eye Disease: A National Multicenter Study

<title>Abstract</title> <p> Purpose This national multicenter study assessed associations between six ambient air pollutants (PM _2.5 , PM ₁₀ , NO ₂ , SO ₂ , O ₃ , and CO) and dry eye disease (DED) outcomes. Analyses were performed on data collected from 2,143 DED patients residing in 17 Chinese cities, covering non-invasive tear break-up time (NIBUT), Schirmer I test results, tear meniscus height (TMH), corneal fluorescein staining, and Ocular Surface Disease Index (OSDI) scores. Methods Linear mixed models with city-level random intercepts were used for ocular outcomes, and binary logistic regression for corneal staining. Principal component analysis and hierarchical elastic net regression were performed as sensitivity analyses. The Benjamini-Hochberg false discovery rate method was applied to correct for multiple comparisons ( <italic>q</italic>  &lt; 0.05 considered significant). Results Significant associations were observed between O₃ exposure and decreased (NIBUT) ( <italic>β</italic> = − 0.0083, <italic>P</italic>  &lt; 0.001, <italic>q</italic>  = 0.0096). Among all analyzed air pollutants, carbon monoxide (CO) exhibited the strongest correlation with corneal fluorescein staining ( <italic>OR</italic>  = 2.656, <italic>P</italic>  &lt; 0.001, <italic>q</italic>  &lt; 0.001). Similarly, PM _2.5 , PM₁₀, and SO₂ were significantly correlated with corneal staining, with all <italic>q</italic> values below 0.05. Notably, no significant associations were detected between any air pollutant and tear secretion (all <italic>q</italic>  &gt; 0.05). Conclusion This national multicenter study confirms that O₃ exposure is strongly associated with poorer tear film stability, while CO, PM _2.5 , PM₁₀ and SO₂ correlate with higher risks of corneal epithelial lesions. No pollutants showed significant links to aqueous tear secretion. These findings suggest that objective ocular tests should be incorporated into air pollution health evaluations, and highlight the benefits of traffic emission control and eye protection for residents in polluted areas. </p>