Purpose: To evaluate the association between urinary and blood cadmium (Cd) levels with age-related macular degeneration (AMD). Design: Prospective case-control study. Methods: In 53 participants older than 60 years with AMD in both eyes and in 53 age-matched (± 3 years) controls without AMD, Cd levels were measured in blood and urine specimens (with and without creatinine adjustment) by using inductively coupled plasma-mass spectrometry. Data on age, gender, smoking status, and family history were obtained. By using color stereoscopic fundus photographs, the degree of AMD was graded using the Age-Related Eye Disease Study's 4-stage AMD severity scale. The inclusion criterion for AMD cases was a photographic severity level of two to four in both eyes. Median blood and urine Cd and median urine Cd/creatinine concentrations in cases and controls were compared by using the rank-sum test, stratifying for smoking status. Results: Current and former smokers with AMD had median urine Cd/creatinine levels (1.18 μg/g; range, 0.84 to 1.44 μg/g) that were 97% higher than smokers without AMD (0.60 μg/g; range, 0.49 to 0.90 μg/g; P = .02), 111% higher than never smokers with AMD (0.56 μg/g; range, 0.40 to 0.80 μg/g; P < .001) and 107% higher than never smokers without AMD (0.57 μg/g; 0.40 to 0.65 μg/g; P < .001). Blood Cd levels, indicative of short-term exposure levels, were not associated with AMD (P ≥ .06). Conclusions: A higher urinary Cd level, which reflects the total body burden of Cd, was associated with AMD in smokers. Accumulated Cd exposure may be important in the development of smoking-related AMD.
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