Sir,
We read with great interest the review recently published in Eye by Siaudvytyte et al1 and would like to comment while presenting an additional viewpoint.
Siaudvytyte et al1 mentioned a study by Killer et al2 on normal-tension glaucoma (NTG) patients who showed a decreased cerebrospinal fluid (CSF) flow between the basal cisterns and the subarachnoid space surrounding the optic nerve (ON), and proposed that this could explain why patients with NTG have lower intracranial pressure (ICP). Killer et al2 concluded that the disturbance of CSF dynamics in this specific CSF pathway can be explained by ON compartmentation. It is not fully clear to us how this could explain why NTG patients have lower ICP.
Siaudvytyte et al1 further noted that a higher translaminar pressure difference (TPD), that is, the difference of intraocular pressure (IOP) minus ICP, may lead to abnormal function and ON damage due to deformation of the lamina cribrosa, changes in axonal transport, altered blood flow, or a combination of them all. In view of many arguments against the hypothesis that the translaminar imbalance between the IOP and ICP caused by low ICP could have a role in the pathogenesis of glaucoma through a higher TPD acting across the optic nerve head,3 we present an alternative viewpoint according to which the imbalance between IOP and ICP may reflect the imbalance between production and clearance of neurotoxins in the anterior part of the ON. Indeed, previous findings at least suggest that high IOP may generate inflammatory proteins and neurotoxins, such as amyloid-β (Aβ) that is a hallmark protein in Alzheimer’s disease, that could then be cleared via the CSF.4 Our hypothesis postulates that a higher concentration of neurotoxins may be the physiopathological mechanism causing axonal damage in NTG as well as in high-tension glaucoma. In NTG, diminished clearance of Aβ from the ON may predominate as a result of a general decline in CSF turnover caused by decreased CSF production (and thus lower ICP).5 In high-tension glaucoma, IOP-induced Aβ generation may predominate and even a mild decline in general CSF flow may result in glaucomatous ON damage. From this point of view, the TPD, calculated as the difference of IOP minus ICP, may be considered as an index for neurotoxic burden in the anterior part of the ON.
References
Siaudvytyte L, Januleviciene I, Daveckaite A, Ragauskas A, Bartusis L, Kucinoviene J et al. Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma. Eye 2015; 29 (10): 1242–1250.
Killer HE, Miller NR, Flammer J, Meyer P, Weinreb RN, Remonda L et al. Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma. Br J Ophthalmol 2012; 96 (4): 544–548.
Hayreh SS . Cerebrospinal fluid pressure and glaucomatous optic disc cupping. Graefes Arch Clin Exp Ophthalmol 2009; 247 (6): 721–724.
Wostyn P, De Groot V, Van Dam D, Audenaert K, Killer HE, De Deyn PP . Glaucoma considered as an imbalance between production and clearance of neurotoxins. Invest Ophthalmol Vis Sci 2014; 55 (8): 5351–5352.
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 (1): 5–14.
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Wostyn, P., De Groot, V., Van Dam, D. et al. The translaminar pressure difference as an index for neurotoxic burden in the anterior part of the optic nerve. Eye 30, 1146–1147 (2016). https://doi.org/10.1038/eye.2016.73
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DOI: https://doi.org/10.1038/eye.2016.73
