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Editors Selection IGR 21-4

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Comment by Louis Pasquale on:

20979 Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma, Berdahl JP; Allingham RR; Johnson DH, Ophthalmology, 2008; 115: 763-768

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Berdahl et al. are to be commended for being the first group to examine the hypothesis that CSF pressure may be reduced in glaucoma patients. Using a large patient dataset, they found that the mean CSF pressure in their glaucoma patients was 12.4 cm of water (9.1 mmHg) versus 17.7 cm of water (13.0 mmHg) for the controls. One other study took similar measurements in seven normal-tension glaucoma subjects, but did not report a mean and used no control group but found the range to be within the normal range of 11 to 17 cm of water and concluded that in their cohort the CSF pressure was not significantly reduced.¹

The work by Berdahl used data collected over many years across disciplines at the Mayo Clinic. Patients who had lumbar punctures performed and whose results were stored on the central database were selected and scrutinised for suitability. Suitable patients were either age-matched controls or glaucoma patients with documented ophthalmic assessment close to the time of lumbar puncture with documented glaucoma or documented normality of disc and field. The reasons for lumbar punctures were varied and only subjects with neurological causes presumed not to influence the cerebrospinal fluid pressure were included. Lumbar punctures were performed in the lateral decubitus position using 20 gauge needles. In the few studies where normal subjects have been used, the CSF pressures tended to be lower than reported in this study's control group. For example, Gilland et al.² report a mean CSF pressure of 14.5 cm of water, and May et al.³ report a CSF pressure of 12.8 cm of water with 20 gauge needles. The authors' selection of controls appears to have been entirely appropriate and it would appear that the difference between control group and glaucoma group CSF pressure is likely to be real. A curious question remains as to why the control group CSF pressure is higher than reported normal CSF pressures.

The authors calculate a trans-lamina pressure difference using the intraocular pressure measurement minus CSF pressure measurement taken in the lateral decubitus position. Intraocular pressure is taken sitting with Goldmann applanation tonometry.It is worth bearing in mind that CSF pressure when sitting at eye level ranges from 0 to -14 cms of water (0 to -10 mm/Hg).⁴ There is a strong relationship between the sitting and lateral decubitus CSF pressures,⁵ so the overall calculated trans-lamina pressure difference reported in this paper is likely to be proportional to a true trans-lamina pressure difference with the subjects in the sitting position. This work represents really a first foray into the very important area of trying to estimate trans-lamina pressure differences and also trans-lamina pressure gradients in human subjects. Past measurements have only been performed in animals.⁶ In future it is probably worth bearing in mind postural differences when taking physiological measurements and making mathematical adjustments for them.

Very interesting data is presented showing an association between the calculated trans-lamina pressure difference and the vertical cup:disc ratio. There appears to be a significant association between the two. It is difficult to provide a definite reason for the association as there may be many contributing factors. It is possible that the trans-lamina gradient during early development is a factor which leads to variation in the size and shape of the optic disc. Most of the subjects were elderly and it is plausible that during life with some alteration in intraocular pressure and CSF pressure further effects upon the optic disc occurred. Work with dogs has shown that CSF pressure has as much effect upon optic disc surface morphology as intraocular pressure⁷ and so it is not surprising to see a similar result borne out using these data from humans.

Once again, the authors are to be commended for assembling and analysing the data for us. It really does represent a significant initial exploration of this area. It is unfortunate that there are no accurate non-invasive measurement tests for determining CSF pressure. The only accurate measurement method is with lumbar puncture, which is necessarily invasive and, hence, it is very difficult to justify larger scale studies using glaucoma patients and normals, who are not necessarily going to benefit from having lumbar punctures performed. Various methods for estimating CSF pressure non-invasively are currently under some degree of development including oto-acoustic impedance, neuro-radiological imaging of CSF volume and compliance estimation, and retinal vein pulsation properties.

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