FLUID PRESSURE

Evidence is accumulating that, rather than the intraocular pressure (IOP) itself, it is the impact of a pressure imbalance between IOP and cerebrospinal fluid pressure on the lamina cribrosa, in favour of IOP, that makes the optic nerve more vulnerable to damage in eyes with open-angle glaucoma, said Jost B Jonas MD, University Eye Clinic, Mannheim, Germany. “The ocular cerebrospinal pressure is the real anatomical and physiological counter-pressure against the IOP across the lamina cribrosa. The trans-lamina cribrosa pressure is physiologically the critical factor, not the transcorneal pressure that we typically call IOP,” Dr Jonas said at a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam, The Netherlands.

He emphasised that IOP must be understood in the context of its place in the eye’s fluid dynamics, which involves a complex interplay between IOP, systemic arterial blood pressure and cerebrospinal fluid (CSF) pressure. The correlation between elevated IOP and glaucomatous damage is well established, yet eyes with normal pressure glaucoma have a very similar pattern of damage to the optic nerve head to that of eyes with highpressure glaucoma.

The defining morphological characteristics of glaucoma are loss of the neuroretinal rim and the deepening of the cup; second a development of beta zone of peripapillary atrophy and also the development of glaucomatous disk haemorrhages. Another characteristic finding in eyes with glaucoma is a thinning of the retinal arteries, leading some to suggest that glaucoma is a vascular disease. However, vascular optic neuropathies have a different pattern of nerve damage than glaucoma, and have neither disc-cupping nor the development of an area of peripapillary atrophy.

Evidence for the cerebrospinal fluid pressure theory

Meanwhile, there is an increasing body of evidence supporting a central role for low CSF pressure in the aetiology of open-angle glaucoma. Moreover, a reduced CSF pressure could explain the optic nerve’s reduced degree of tolerance to even normal IOP levels in eyes with normal pressure glaucoma, Dr Jonas said. He noted that in a prospective study carried out in Beijing, lumbar CSF pressure was significantly lower in normal-pressure glaucoma patients (9.5 mmHg) than in glaucoma patients with elevated IOP (11.7 mmHg) and those without glaucoma (12.9 mmHg).

Similarly, the pressure difference between the IOP and CSF pressure was significantly (P<0.001) higher in both the normal-IOP glaucoma group (6.6 Â} 3.6 mmHg) and the high-IOP glaucoma group (12.5 Â} 4.1mmHg) as compared to the control group (1.4 mmHg) (Ren et al Ophthalmology 2010; 117: 259-266).

Other evidence includes the marked thinning of the laminar cribrosa that occurs in eyes with glaucoma and the resulting decrease in the distance between the intraocular compartment on one side, and the optic nerve and the CSF space on the other, Dr Jonas noted. “If the distance between these two compartments is decreased, trans-lamina cribrosa pressure gradient gets steeper at any given IOP and CSF pressure,” he added.

Non-invasive CSF calculation

To test the theory further, Dr Jonas and his associates have developed a non-invasive means of estimating the orbital CSF pressure that uses magnetic resonance imaging (MRI) of the orbital subarachnoid space surrounding the optic nerve as a surrogate. After an independent group confirmed a correspondence between MRI images and lumbar CSF pressure measurements, they devised a formula for using the MRI-based measurements to calculate CSF pressure. The formula took into account other variables including age, diastolic blood pressure and body mass index ( Xie et al. Crit Care. 2013;17(4):R162).

The researchers then applied the calculation formula to data from participants in the Beijing Eye Study and other medical studies. They found that, in glaucoma patients, the IOP was significantly higher (p=0.008) and the CSF pressure was significantly lower (p<0.001) than they were in those without glaucoma. The trans-laminar pressure difference was also significantly higher in glaucoma patients. Moreover, the intergroup difference was highest for the trans-laminar cribrosa pressure difference, followed by CSF pressure and IOP. Furthermore, in a binary regression analysis there was a statistically significant association between open-angle glaucoma and translaminar cribrosa pressure difference (p<0.001), but there was no statistically significant relationship between openangle glaucoma and IOP.

Similarly, retinal nerve fibre layer thickness had a statistically significant positive association trans-laminar cribrosa pressure but not with IOP in eyes with open-angle glaucoma, after adjusting for gender, age, religion, region of habitation, optic disc area and refractive error. On the other hand, angle-closure glaucoma was significantly associated with higher IOP but not with translaminar cribrosa pressure difference after adjustment for age and anterior chamber depth.

“In open-angle glaucoma, but not in angle-closure glaucoma, the calculated trans-laminar cribrosa difference versus IOP showed a better association with glaucoma presence and the amount of glaucomatous optic neuropathy. Our findings support the notion of a potential role of low cerebrospinal fluid pressure in the pathogenesis of open-angle glaucoma,” Dr Jonas said.