Combined exposure to three heavy metals and the risk of age-related macular degeneration in the Korean population

Abstract

Toxicological and histological evidence suggests that heavy metals accumulate in the retina, implicating their potential role in the development of age-related macular degeneration (AMD). However, most prior epidemiologic studies have focused on individual metal exposures, overlooking possible joint effects. This study assessed the association between co-exposure to lead (Pb), mercury (Hg), and cadmium (Cd) and AMD risk among Korean adults using 2008-2012 Korea National Health and Nutrition Examination Survey data. A total of 4818 participants aged 40 years or older were included. Logistic regression models evaluated single-metal associations, while quantile g-computation and Bayesian kernel machine regression (BKMR) assessed mixture effects. Participants in the third quartile of Pb had significantly higher odds of AMD (adjusted OR: 1.76, 95% CI: 1.07-2.88) than those in the lowest quartile. Quantile g-computation showed that a one-quartile increase in the metal mixture was associated with elevated AMD risk (adjusted OR: 1.20, 95% CI: 1.02-1.41). BKMR confirmed that the heavy metal mixture increased the risk of AMD, with Pb being the primary contributor in smokers and Cd in non-smokers. Our findings indicate that co-exposure to heavy metals elevates AMD risk and that the predominant contributing metal may differ depending on smoking status.

Keywords: Age-related macular degeneration; Cadmium; Heavy metal; Lead; Mercury.

Fig. 1

Quantile g-computation weights (A) and joint effect (B) of heavy metals on AMD among total participants from the KNHANES 2008–2012 (n = 4,818). AMD: age-related macular degeneration, KNHANES: Korea National Health and Nutrition Examination Survey, Pb: lead, Hg: mercury, Cd: cadmium, OR: odds ratio, CI: confidence interval.

Fig. 2

BKMR analysis of the associations between blood heavy metal and AMD among total participants from the KNHANES 2008–2012 (n = 4,818). (A) Univariate exposure-response functions showing the estimated effect of each heavy metal on the risk of AMD. (B) Bivariate exposure-response functions assessing the joint effect of two heavy metals on AMD risk, with the exposure of another metal fixed at the 25th, 50th, and 75th percentiles. (C) Overall effect of the heavy metal mixture on AMD risk, expressed as the change in the estimated effect across exposure quantiles. (D) Estimate effects of a single heavy metal exposure on AMD at different percentiles: comparing 75th vs. 25th percentile exposure. Other metals were set at the 25th, 50th, and 75th percentile. BKMR: Bayesian kernel machine regression, AMD: age-related macular degeneration, KNHANES: Korea National Health and Nutrition Examination Survey Pb: lead, Hg: mercury, Cd: cadmium.