Aim: To investigate plasma indices of vascular permeability (vascular endothelial growth factor, VEGF-also an index of angiogenesis, as well as the soluble receptor for VEGF, sFlt-1) and endothelial damage/dysfunction (von Willebrand factor, vWf) in glaucoma. METHODS: Citrated plasma was assayed for VEGF, sFlt-1, and vWf (all ELISA) in a cross sectional study of 50 patients (20 male; mean age 63.9 years, SD 10.5) with glaucoma: 26 had normal tension glaucoma (NTG) and 24 had primary open angle glaucoma (POAG), who were compared with 26 healthy controls (mean age 73.4 years, SD 9.2). RESULTS: Median (interquartile range, IQR) levels of VEGF were significantly elevated in patients with NTG and POAG compared to healthy controls (Kruskal-Wallis test, p<0.001). Similarly, mean (SD) vWF levels were abnormal in NTG and POAG compared to healthy controls (one way ANOVA, p<0.001). Median levels of sFlt-1 were significantly lower in patients with NTG and POAG, when compared to healthy controls (Kruskal-Wallis test, p<0.001; p<0.05 with Tukey's post hoc test for controls v POAG). There were no significant differences in VEGF, sFlt-1 or vWf levels between the NTG and POAG groups (Tukey's test, all p=NS). In both NTG and POAG groups, there was a significant correlation between VEGF and sFlt-1 (Spearman, NTG: r=0.6517, p=0.001; POAG: r=0.6017, p=0.008). There were no significant correlations between VEGF and sFlt-1, or with vWf among the controls. CONCLUSIONS: The pathogenesis of optic nerve damage in both NTG and POAG may be associated with abnormal vascular permeability and endothelial damage/dysfunction, as indicated by abnormal plasma VEGF and vWf levels in these patients.