Environmental exposure to per-and polyfluoroalkyl substances and high myopia: a case-control and toxicogenomic study

Emerging evidence has demonstrated the presence of perfluorinated and polyfluoroalkyl substances (PFASs) in contact lenses, which may be a major source of ocular PFAS exposure among myopic individuals. However, whether PFAS influences the development of high myopia (HM) remains unclear.

This case–control study enrolled 99 individuals with HM and 104 age-matched controls at the Eye & ENT Hospital of Fudan University to assess internal PFAS exposure levels. Logistic regression analysis was conducted to evaluate the associations between PFAS exposure and HM. In addition, toxicogenomic analyses were performed to explore potential biological pathways related to PFAS exposure and HM.

Epidemiological analyses indicated that higher levels of perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were associated with HM. Bayesian Kernel Machine Regression suggested complex, non-linear associations between mixed PFAS exposure and HM across different exposure levels. Weighted Quantile Sum analysis further identified PFNA as the largest contributor to the overall mixture effect. Toxicogenomic analysis identified 164 overlapping genes between PFAS exposure and HM, which were enriched in biological processes including xenobiotic response, macrophage-derived foam cell differentiation, IL-1β regulation, and pathways related to endocrine, metabolic, lipid, and immune function. Protein–protein interaction network analysis suggested that inflammatory-related genes, including IL-6, IL-1β, and TNF, may be involved in the observed associations.

Overall, this study suggests an association between PFAS exposure and HM and highlights potential involvement of inflammatory-related biological pathways. Given the case–control design and the timing of exposure assessment, causality cannot be established. These findings provide a basis for further longitudinal and mechanistic investigations.