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Are Generalized Reduced Cerebrospinal Fluid Dynamics and Optic Nerve Sheath Compartmentation Sequential Steps in the Pathogenesis of Normal-Tension Glaucoma? [Response to Letter]

Authors Killer HE, Pircher A 

Received 10 May 2021

Accepted for publication 10 May 2021

Published 25 May 2021 Volume 2021:13 Pages 157—158


Hanspeter E Killer,1 Achmed Pircher2,3

1Department of Biomedicine, University Hospital Basel & University Basel, Basel, Switzerland; 2Department of Neuroscience/Ophthalmology, Uppsala University, Uppsala, Sweden; 3Department of Ophthalmology, University Hospital Basel & University Basel, Basel, Switzerland

Correspondence: Achmed Pircher
Department of Neuroscience/Ophthalmology, Uppsala University, Uppsala, Sweden
Tel +46 0 76 496 37 51
Email [email protected]

View the original paper by Dr Pircher and colleagues

This is in response to the Letter to the Editor

Dear editor

We appreciate the thoughtful considerations of Peter Wostyn concerning our paper Lipocalin-type prostaglandin D synthase concentration gradients in the cerebrospinal fluid in normal-tension glaucoma patients with optic nerve sheath compartmentation.1 We are aware of his many creative contributions to the field of glaucoma and neurodegeneration.

We fully agree that impaired cerebrospinal fluid (CSF) dynamics may play a crucial role in normal-tension glaucoma2 as well as in the pathophysiology of other neurodegenerative diseases, such as Alzheimer´s3 and Parkinson´s disease.4 Elevated Lipocalin-type prostaglandin D-synthase (L-PGDS) levels in the lumbar CSF in our cohort of normal-tension glaucoma patients compared to the concentration measured in healthy controls in other studies might indeed indicate generalized dysfunctional CSF dynamics in patients with normal-tension glaucoma.

CSF and its content are distributed between the extracranial and the intercranial CSF spaces, eg, subarachnoid spaces, cisterns and ventricles. In order for CSF to perform its multiple functions, it also needs to be distributed within the parenchyma of the brain and the optic nerve itself. It therefore would be of great interest to know more about the concentration of proteins, such as L-PGDS, alpha synuclein and abetalipoprotein not only in the CSF surrounding the brain, but in the brain parenchyma (interstitial fluid) as well. The mechanism by which it is transported within parenchyma is still shrouded in mystery5 and should be subject of future studies.


The authors report no conflicts of interest in this communication.


1. Pircher A, Neutzner A, Montali M, et al. Lipocalin-type prostaglandin D synthase concentration gradients in the cerebrospinal fluid in normal-tension glaucoma patients with optic nerve sheath compartmentation. Eye Brain. 2021;13:89–97. doi:10.2147/EB.S297274

2. Wostyn P, De Groot V, Van Dam D, Audenaert K, De Deyn PP. Senescent changes in 94 cerebrospinal fluid circulatory physiology and their role in the pathogenesis of 95 normal-tension glaucoma. Am J Ophthalmol. 2013;156(1):5–14. doi:10.1016/j.ajo.2013.03.003

3. Lahiri DK, Ray B. Abnormal cerebrospinal fluid (CSF) dynamics in Alzheimer’s disease and normal pressure hydrocephalus: CSF-amyloid β precursor protein metabolites as possible biomarkers. Eur J Neurol. 2013;20(2):211–213. doi:10.1111/j.1468-1331.2012.03832.x

4. Murakami H, Tokuda T, El-Agnaf OMA, et al. Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson’s disease. BMC Neurol. 2019;19(1):113. doi:10.1186/s12883-019-1346-y

5. Abbott NJ, Pizzo ME, Preston JE, Janigro D, Thorne RG. The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Acta Neuropathol. 2018;135(3):387–407. doi:10.1007/s00401-018-1812-4

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