A General Decline in Cerebrospinal Fluid Flow: An Overlooked Risk Factor for Glaucoma?: Response

Letters to the Editor Kurt Audenaert, MD, PhD Department of Psychiatry, Ghent University Hospital, Ghent, Belgium Peter P. De Deyn, MD, PhD Department of Biomedical Sciences, Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Antwerp, Belgium Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands The authors report no conflicts of interest. REFERENCES 1. McCulley TJ, Chang JR, Piluek WJ. Intracranial pressure and glaucoma. J Neuroophthalmol. 2015;35(suppl 1):S38- S44. A General Decline in Cerebrospinal Fluid Flow: An Overlooked Risk Factor for Glaucoma?: Response W e are grateful for the attention received by our recent article (1). Dr Wostyn et al have suggested an additional potential mechanism by which intracranial pressure (ICP) might relate to the development of glaucoma, specifically that alterations in cerebrospinal fluid (CSF) flow may be a contributing factor. This proposal is based on the lack of conclusive evidence that translaminar pressure gradient (TPG) is a glaucoma risk factor. This notion is supported, in part, by referencing Hayreh, who has stated that the alterations in TPG could not result in deformation of the lamina cribrosa (LC) (2). As outlined in detail in our article, there are several recent studies, most using optical coherence tomography, which demonstrated inward and outward bowing of the LC with alterations in IOP and ICP (3-9). There also are numerous examples where alterations in ICP result in other structural changes, such as bone remodeling (10- 12). We agree that TPG-related deformation of the LC remains to be conclusively established to be a glaucoma risk factors, but there is sufficient evidence to warrant further investigation. 228 2. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115:763-768. 3. Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci. 2008;49:5412-5418. 4. Ren R, Jonas JB, Tian G, Zhen Y, Ma K, Li S, Wang H, Li B, Zhang X, Wang N. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117:259-266. 5. Jonas JB, Wang N, Yang D, Ritch R, Panda-Jonas S. Facts and myths of cerebrospinal fluid pressure for the physiology of the eye. Prog Retin Eye Res. 2015;46:67-83. 6. Hayreh SS. Cerebrospinal fluid pressure and glaucomatous optic disc cupping. Graefes Arch Clin Exp Ophthalmol. 2009;247:721-724. 7. Hayreh SS. Cerebrospinal fluid pressure and glaucomatous optic disc cupping (response to Berdahl and colleagues). Graefes Arch Clin Exp Ophthalmol. 2009;247:1291-1294. 8. Wostyn P, De Groot V, Van Dam D, Audenaert K, De Deyn PP. Senescent changes in cerebrospinal fluid circulatory physiology and their role in the pathogenesis of normal-tension glaucoma. Am J Ophthalmol. 2013;156:5-14. 9. Fleischman D, Berdahl JP, Zaydlarova J, Stinnett S, Fautsch MP, Allingham RR. Cerebrospinal fluid pressure decreases with older age. PLoS One. 2012;7:e52664. 10. Jaggi GP, Harlev M, Ziegler U, Dotan S, Miller NR, Killer HE. Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis. Br J Ophthalmol. 2010;94:1088-1093. 11. Zhang Z, Liu D, Jonas JB, Wu S, Kwong JM, Zhang J, Liu Q, Li L, Lu Q, Yang D, Wang J, Wang N. Glaucoma and the role of cerebrospinal fluid dynamics. Invest Ophthalmol Vis Sci. 2015;56:6632. We also agree that other factors may contribute to the glaucoma phenotype. Speculation that "stagnant CSF" may occur with reduced CSF production and result in accumulation of "toxins" is thought provoking. This raises several questions; for example, if toxin accumulation occurs, why should injury seemingly be limited to the optic nerve, sparing other neural structures, which also are bathed in CSF? Why would toxic-induced atrophy not manifest with optic disc pallor, as seen with toxic optic neuropathies, as opposed to cupping? Moreover, pressure is determined by a number of factors, with production rate being only one component. Are we certain that reduced production of CSF and not other factors such as increased resorption is responsible for the lower ICP measured in the various glaucoma subtypes linked to ICP? For example, the findings of Chang and Singh (13) suggest an increased prevalence of glaucoma in patients with normal pressure hydrocephalus (NPH). It has been hypothesized that this could be a consequence of the CSF shunting procedures, commonly used to treat NPH. In such patients, therapeutic lowering of ICP increases the TPG, possibly accounting for the increased frequency of glaucoma. Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Admittedly, a variety of factors may lead to similar glaucoma phenotypes and the hypothesis of Dr Wostyn et al may prove to be one of those factors. Timothy J. McCulley, MD Jessica R. Chang, MD The Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland The authors report no conflicts of interest. REFERENCES 1. McCulley TJ, Chang JR, Piluek WJ. Intracranial pressure and glaucoma. J Neuroophthalmol. 2015;35(suppl 1):S38-S44. 2. Hayreh SS. Cerebrospinal fluid pressure and glaucomatous optic disc cupping. Graefes Arch Clin Exp Ophthalmol. 2009;247:721-724. 3. Sigal IA, Yang H, Roberts MD. IOP-induced lamina cribrosa deformation and scleral canal expansion: independent or related? Invest Ophthalmol Vis Sci. 2011;52:9023-9032. 4. Agoumi Y, Harpe GP, Hutchison DM, Nicolela MT, Artes PH, Chauhan BC. Laminar and prelaminar tissue displacement during intraocular pressure elevation in glaucoma patients and healthy controls. Ophthalmology. 2011;118:52-59. Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 5. Lee EJ, Kim TW, Weinreb RN. Reversal of lamina cribrosa displacement and thickness after trabeculectomy in glaucoma. Ophthalmology. 2012;119:1359-1366. 6. Inoue R, Hangai M, Kotera Y, Nakanishi H, Mori S, Morishita S, Yoshimura N. Three-dimensional high-speed optical coherence tomography imaging of lamina cribrosa in glaucoma. Ophthalmology. 2009;116:214-222. 7. Reis AS, O'Leary N, Stanfield MJ, Shuba LM, Nicolela MT, Chauhan BC. Laminar displacement and prelaminar tissue thickness change after glaucoma surgery imaged with optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53:5817-5826. 8. Park HY, Shin HY, Jung KI, Park CK. Changes in the lamina and prelamina after intraocular pressure reduction in patients with primary open-angle glaucoma and acute primary angle-closure. Invest Ophthalmol Vis Sci. 2014;55:233-239. 9. Perez-Lopez M, Ting DS, Clarke L. Lamina cribrosa displacement after optic nerve sheath fenestration in idiopathic intracranial hypertension: a new tool for monitoring changes in intracranial pressure? Br J Ophthalmol. 2014;98:1603-1604. 10. McCulley TJ, Jordan Piluek W, Chang J. Intracranial pressure and skull remodeling. Saudi J Ophthalmol. 2015;29:57-62. 11. Hwang TN, Rofagha S, McDermott MW, Hoyt WF, Horton JC, McCulley TJ. Sunken eyes, sagging brain syndrome: bilateral enophthalmos from chronic intracranial hypotension. Ophthalmology. 2011;118:2286-2295. 12. McCulley TJ. Sphenoid sinus expansion: a radiographic sign of intracranial hypotension and the sunken eyes, sagging brain syndrome. Trans Am Ophthalmol Soc. 2013;111:145-154. 13. Chang TC, Singh K Glaucomatous disease in patients with normal pressure hydrocephalus. J Glaucoma. 2009;18:243-246. 229 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.