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

Abstract

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 age=66.8 y of age (SD=6.7)] 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 rate=74 per 10,000 person-years; median follow-up=10.6 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, p=0.005) and 3.07 (95% CI: 0.94, 10.0, p=0.06), 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 (p-for-trend=0.01), and 3.84 (95% CI: 1.54, 9.55) and 2.61 (95% CI: 0.95, 7.21) for tibia lead (p-for-trend=0.02).

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.

Figure 1.

Diagram illustrating the establishment cohort structure of the study population, from the NAS original recruitment in 1963 to the KXRF measurement in the 1990s, which is the baseline of our study, until the end of the 15-y follow-up. Note: KXRF, K X-ray fluorescence; NAS, Normative Aging Study.

Figure 2.

Adjusted survival curves illustrating changes of survival of different bone lead quartiles during follow-up. x-Axis indicates years since baseline, y-axis indicates the survival calculated by discrete-time hazard models with adjustment for baseline age, body mass index, educational levels, job types, smoking, diabetes mellitus, systemic hypertension, ocular hypertension. (A) Tibia lead; (B) patella lead.