Central Obesity in Women and High Overall Body Fat in Men are Associated With Higher Odds of Dry Eye Disease

PURPOSE: To compare associations of body mass index, total body fat percentage, and fat distribution with dry eye disease (DED) and assess metabolites mediation. DESIGN: Retrospective cross-sectional study. METHODS: This retrospective cross-sectional study included 483,115 UK Biobank participants (14,570 with DED and 468,545 without DED). Adiposity was assessed by baseline anthropometry and bioelectrical impedance, and DED was identified using primary care. Read codes, self-reports, and medication records. Multivariable logistic regression adjusted for demographic, metabolic, medication, and lifestyle factors. Sex-specific exploratory mediation analyses evaluated baseline NMR metabolites between adiposity and incident DED. RESULTS: In women, after full adjustment including total body fat percentage, each 1% increase in trunk fat percentage was associated with 2.8% higher odds of DED (odds ratio [OR] = 1.028, 95% confidence interval [CI] 1.015-1.040; P < .001), whereas each 1% increase in arm and leg fat percentages was associated with 1.7% (OR = 0.983, 95% CI 0.975-0.990; P < .001) and 2.0% lower odds of DED (OR = 0.980, 95% CI 0.971-0.990; P < .001), respectively. Mediation analyses implicated GlycA-related inflammation, HDL remodeling, and energy metabolism. In men, body mass index ≥40 kg/m² was associated with 46.1% higher odds of DED (OR = 1.461, 95% CI 1.172-1.821; P < .001), and body fat >35% was associated with 22.4% higher odds (OR = 1.224, 95% CI 1.070-1.399; P = .003). Metabolites related to lipid and lipoprotein metabolism were identified as candidate intermediary metabolites in men. CONCLUSIONS: Adiposity showed sex-specific associations with DED, characterized by central obesity in women and higher overall body fat percentage in men. These retrospective cross-sectional findings do not establish causation.