Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9 +/- 6.62, female 8, male 4) and 11 patients without AMD (age 66.6 +/- 16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 mu mol/L, IQR: 0.40-0.84 vs. 0.06 mu mol/L; IQR: 0.01-.018; p = 0.002), cobalt (median: 3.1 mu mol/L, IQR: 2.62-3.15 vs. 1.17 mu mol/L; IQR: 0.95-1.27; p<0.001), iron (median: 311 mu mol/L, IQR: 289-329 vs. 129 mu mol/L; IQR: 111-145; p<0.001) and zinc (median: 23.1 mu mol/L, IQR: 12.9-32.6 vs. 5.1 mu mol/L; IQR: 4.4-9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 mu mol/L, IQR: 11.4-31.3 vs. 49.9 mu mol/L; IQR: 32.0-. 142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.