The role of low intracranial pressure in the development of glaucoma in patients with Alzheimer's disease

Abstract

October 22, 2013Dear Editor,We read with great interest the paper by Janssen et al. (2013)entitled ‘The vast complexityof primaryopen angle glaucoma: Dis-ease genes, risks, molecular mechanisms and pathobiology.’ Theauthors deserve appreciation for their very informative reviewarticle.However,wewishtomakeacommentconcerningtheirdis-cussion of the potential role of intracranial pressure (ICP) in Alz-heimer’s disease (AD) and glaucoma.In the last section of their paper, Janssen and colleaguesdiscuss the potential relation between primary open angle glau-coma (POAG) and AD. As the authors mention, several studieshave found an increase in the occurrence of glaucoma in AD pa-tients. The authors state: “In our view, POAG damage could becaused by the net pressure over the optic disk, involving boththe aqueous humor pressure of the eye and cerebrospinal fluid(CSF) pressure of the brain, as described above. Also, CSF pressurechanges have been described in AD (Silverberg et al., 2006).Could these pressure changes underlie a relationship betweenPOAG and AD, and at the same time explain the apparently con-flicting association studies?” Further, the authors state: “We hy-pothesize that there is a strong association between normalpressure glaucoma and late AD, since both disease stages,following the ‘net pressure on the optic disk hypothesis’,arecharacterized by one single disease mechanism: an abnormallylow ICP.”Janssen et al. (2013) thus hypothesize that low ICP may play arole in the association between glaucoma and AD. We fully agreewith the authors since our group has previously presented this hy-pothesisforthefirsttime(Wostynetal.,2008,2009a).Intwoofourearlier manuscripts published in 2008 (Wostyn et al., 2008) and2009 (Wostyn et al., 2009a), we proposed low ICP occurring inAD as a factor leading to increased risk of glaucoma. Evidence forthishypothesiswasgainedfromCSFpressuremeasurementstudiesin AD patients and patients with glaucoma. The finding of a highoccurrence of reduced CSF pressure among patients with AD(Silverberg et al., 2006; Wostyn et al., 2009b) could be linked tothe high rate of reported comorbidity between AD and glaucoma(Bayer et al., 2002; Tamura et al., 2006), since it has been shownthat CSF pressure is lower in patients with glaucoma (Berdahlet al., 2008a, 2008b; Ren et al., 2010). This could result in anabnormally high trans-lamina cribrosa pressure difference andlead to glaucomatous damage. Given this previously advanced hy-pothesis, it was a great surprise when Janssen et al. (2013) recentlyhypothesized about the potential role of low ICP in glaucoma andAD without citing our earlier work (Wostyn et al., 2008, 2009a)or making clear the relevant precedents. The authors did cite oneof our papers, one largely focused on the high occurrence rate ofglaucoma among patients with normal pressure hydrocephalus(Wostyn et al., 2010), but this paper has no direct relevance tothe above hypothesis.Sincerely yours,Peter Wostyn, MDVeva De Groot, MD, PhDDebby Van Dam, PhDKurt Audenaert, MD, PhDPeter Paul De Deyn, MD, PhDReferences