Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA Normative Aging Study

BACKGROUND: Oxidative stress may play an important role in the etiology of primary open-angle glaucoma (POAG). The association between risk of POAG and lead exposure, which is an environmental source of oxidative stress, has not been fully investigated yet. OBJECTIVE: Our objective was to determine the association between bone lead—a biomarker of cumulative lead dose (tibia lead) or an endogenous source of stored lead (patella lead)—and incident POAG. METHODS: We examined a prospective cohort of 634 POAG-free men [mean baseline [Formula: see text] y of age ([Formula: see text])] from the Normative Aging Study (NAS) who had tibia and patella K X-ray fluorescence lead measurements between 1 January 1991 and 31 December 1999. They also had standard ocular evaluations by NAS optometrists until 31 December 2014. POAG cases were identified by consistent reports of enlarged or asymmetric cup-to-disc ratio together with visual field defect or existence of disc hemorrhage. We used Cox proportional hazards regressions to estimate hazard ratios (HRs) of incident POAG and adjusted survival curves to examine changes in the risk of POAG during follow-up according to bone lead quartiles. RESULTS: We identified 44 incident cases of POAG by the end of follow-up (incidence [Formula: see text] per 10,000 person-years; median [Formula: see text] y). In fully adjusted models, 10-fold increases in patella lead and tibia lead were associated with HRs of 5.06 (95% CI: 1.61, 15.88, [Formula: see text]) and 3.07 (95% CI: 0.94, 10.0, [Formula: see text]), respectively. The HRs comparing participants in the third and fourth quartiles with the lowest quartile were 3.41 (95% CI: 1.34, 8.66) and 3.24 (95% CI: 1.22, 8.62) for patella lead ([Formula: see text]), and 3.84 (95% CI: 1.54, 9.55) and 2.61 (95% CI: 0.95, 7.21) for tibia lead ([Formula: see text]). CONCLUSIONS: Our study provides longitudinal evidence that bone lead may be an important risk factor for POAG in the U.S. population. https://doi.org/10.1289/EHP3442