The question arises exactly how H pylori infection influences the pathophysiology of glaucoma. The following possible mechanisms are suggested. Helicobacter pylori may promote the formation of L- and P-selectin–dependent platelet-leukocyte aggregates in murine gastric microvessels, and H pylori may also induce platelet activation and aggregation26,27 and atherosclerosis.9 This phenomenon may play a part in the proposed relationship between H pylori and glaucoma, in which platelet activation and aggregation play a relevant pathophysiological role.28,29 Alternatively, release of large amounts of variable proinflammatory and vasoactive substances such as cytokines (interleukin [IL] 1, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α, and interferon γ), eicosanoids (leukotrienes and prostaglandins), and acute-phase proteins (fibrinogen and C-reactive protein) following gastric colonization by H pylori10,30,31 may be involved in a number of vascular disorders thought to be associated with the bacterium. These disorders include Raynaud phenomenon, idiopathic migraine, coronary heart disease,10,30,31 and now possibly glaucoma (a similar cytokine profile seems to be involved in the pathogenesis of glaucoma disease).32,33 Increased endothelin-1 (a potent constrictor of arterioles and venules), nitric oxide, and inducible nitric oxide synthase levels in peptic ulcer disease associated with H pylori infection34 suggest that the resulting microcirculatory disturbance may be a major factor in the pathogenesis of local gastric mucosal ulceration and systemic damage, including glaucoma. Indeed, endothelin-1–induced vasoconstriction of the anterior optic nerve vessel and modulation of vascular tone in the ophthalmic artery by nitric oxide may be involved in the pathogenesis of glaucomatous damage.3,35Helicobacter pylori can coagulate blood by stimulating mononuclear cells. Under bacterial stimulation, mononuclear leukocytes produce a tissue factor–like procoagulant activity that, through the extrinsic pathway of blood coagulation, converts fibrinogen into fibrin. Thus, apart from its effect on fibrinogen level, H pylori has another activity (blood clotting), which might contribute to the pathogenesis of cardiovascular disorders36 or glaucoma. Other factors such as the development of cross mimicry between endothelial and H pylori antigens10 and excessive production of reactive oxygen metabolites and circulating lipid peroxides, which are associated with cardiovascular risk in patients with H pylori infection,7,36 may also be involved indirectly in glaucoma pathophysiology. However, further studies are needed to elucidate these points.