Association of Thyroid Autoimmunity With Age-Related Macular Degeneration in U.S. Adults

Purpose: To investigate the associations of thyroid autoimmunity, assessed by thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), with prevalent age-related macular degeneration (AMD) in U.S. adults, and to explore whether genetic liabilities to Hashimoto thyroiditis (HT) and Graves' disease (GD) were associated with AMD risk using two-sample Mendelian randomization (MR). Methods: This cross-sectional study included 2967 adults aged 40 years or older from the 2007-2008 National Health and Nutrition Examination Survey. Survey-weighted logistic regression models included TPOAb and TgAb positivity simultaneously. Two-sample MR analyses were exploratory. Results: Among 2967 participants, 234 had AMD, corresponding to a weighted prevalence of 6.6% (95% confidence interval [CI], 5.6%-7.9%). In the mutually adjusted observational model, TgAb positivity was associated with higher odds of prevalent AMD (odds ratio [OR], 2.02; 95% CI, 1.13-3.61; P = 0.022), whereas TPOAb positivity was not associated with AMD (OR, 0.93; 95% CI, 0.63-1.37; P = 0.676). Exploratory MR analyses suggested a possible association between genetic liability to HT and AMD (OR, 1.14; 95% CI, 1.01-1.29; P = 0.033), whereas evidence for GD was less consistent. Conclusions: TgAb positivity was associated with prevalent AMD. The cross-sectional design and the nonidentical exposures assessed in the observational and MR analyses preclude causal inference. Translational Relevance: Thyroglobulin antibody positivity was associated with prevalent AMD and may reflect a systemic immune phenotype warranting prospective investigation.