Abstract
Background/Objectives: Although high myopia primarily affects the eyes, emerging evidence suggests that it is also associated with systemic inflammation and metabolic dysfunction. The liver plays a key role in metabolism and inflammation, and it may share pathological pathways with high myopia. However, no population studies have examined the relationship between high myopia and liver disease progression. This study used UK Biobank data to analyze the relationship between myopia severity and severe liver disease, as well as to determine whether inflammatory markers or metabolites mediate this link. Methods: A prospective cohort of 70,774 UK Biobank participants without severe liver disease at baseline was followed for 14.1 years. Myopia was categorized as emmetropia, low-to-moderate, or high based on refractive error. Cox proportional hazards models, stratified by aspartate aminotransferase (AST) level (≥40 vs. <40 U/L), were used to assess liver disease risk, and mediation analyses were used to evaluate inflammatory markers and metabolites. Results: Among participants with AST levels of at least 40 U/L, high myopia significantly increased liver fibrosis and cirrhosis risk (hazard ratio [HR] = 2.64, 95% confidence interval [CI] = 1.44-4.85, p = 0.002), exhibiting a dose-dependent trend (ptrend = 0.004). No association existed for AST < 40 U/L. C-reactive protein (CRP) partially mediated this link; no metabolites survived correction. Conclusions: High myopia is independently associated with an increased risk of liver fibrosis and cirrhosis in individuals with elevated AST, partially mediated by CRP-related inflammation. Refractive assessment may stratify liver disease risk in subclinical injury, warranting anti-inflammatory intervention research.