To evaluate prediagnostic markers of endothelial dysfunction and inflammatory processes in primary open-angle glaucoma (POAG).
Blood samples were collected from 1989 to 1990 in the Nurses' Health Study (women) and from 1993 to 1995 in the Health Professionals Follow-up Study (men), and medical-record confirmed incident POAG cases were identified (women: 229 cases and 455 controls; men: 116 cases and 228 controls). Controls were matched on cohort, age, race, ethnicity, cancer status, and date of blood collection. Plasma concentrations of ICAM-1, E-selectin, and soluble TNF receptor 2 (sTNF-R2), a marker related to TNF-α, were measured with ELISA assays. Cohort-specific multivariable conditional logistic regression model results were meta-analyzed.
We observed no associations with ICAM-1 or E-selectin. For sTNF-R2, the mean (SD) plasma levels (pg/mL) in cases and controls were 2888 (997) and 2993 (913), respectively, in women; and 2622 (664) and 2569 (688), respectively, in men. Pooled multivariable results showed no relation between sTNF-R2 levels and POAG. However, compared with the lowest tertile of sTNF-R2, the highest tertile showed a significant decreased risk of POAG in women (multivariable odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36–0.93; Ptrend = 0.03) but not in men (Ptrend = 0.21; P for heterogeneity by sex = 0.03). Also, among women, the inverse association with sTNF-R2 was stronger with normal-tension glaucoma (NTG; maximum intraocular pressure <21 mm Hg at diagnosis): highest versus lowest tertile comparison OR = 0.29 (95% CI = 0.12–0.71; Ptrend = 0.007).
In women, but not in men, higher sTNF-R2 levels at 6 to 8 years before diagnosis were inversely associated with POAG, but more strongly for NTG.
We evaluated prediagnostic plasma ICAM-1, E-selectin and soluble TNF receptor 2 (sTNF-R2) levels and risk of incident primary open-angle glaucoma (POAG). In women, but not in men, higher sTNF-R2 levels were inversely associated with POAG, particularly normal-tension glaucoma.