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In recent years, a decreased intracranial pressure, leading to an abnormally high trans\u2010lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered \u2018glymphatic system\u2019 in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including \u03b2\u2010amyloid, from the brain along paravascular channels. Given that \u03b2\u2010amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open\u2010angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open\u2010angle glaucoma, present supporting preliminary data from our own post\u2010mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and\/or a high trans\u2010lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.<\/jats:p>","DOI":"10.1111\/ceo.12915","type":"journal-article","created":{"date-parts":[[2017,1,28]],"date-time":"2017-01-28T00:33:17Z","timestamp":1485563597000},"page":"539-547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open\u2010angle glaucoma"],"prefix":"10.1111","volume":"45","author":[{"given":"Peter","family":"Wostyn","sequence":"first","affiliation":[{"name":"Department of Psychiatry PC Sint\u2010Amandus  Beernem Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter Esriel","family":"Killer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Kantonsspital Aarau  Aarau Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Paul","family":"De Deyn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior. 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