Chronic open-angle glaucoma is the most frequent type of glaucoma and a leading cause for blindness. The role of intraocular pressure (IOP) in the pathogenesis of open-angle glaucoma has been challenged by patients with typical glaucomatous optic disc changes and visual field loss in whom the IOP never exceeded normal values (normal-tension glaucoma), as well as by patients with persistently elevated IOP who do not develop glaucomatous disc or field changes. Recent research has demonstrated that the cerebrospinal fluid (CSF) is not evenly distributed in all CSF spaces and that the subarachnoid space of the optic nerve can turn into a CSF compartment on its own. The biochemical components in this optic nerve compartment can differ markedly from normal CSF and some of its components (such as L-PGDS) may produce a toxic effect on the optic nerve and may therefore play an important role in the pathophysiology of open-angle glaucoma.