Cerebrospinal fluid (CSF) pressure and glaucoma

[caption id="attachment_5897" align="alignnone" width="750"] Subarachnoid space of the optic nerve with trabeculae between arachnoid and pia layer[/caption] Cerebrospinal fluid (CSF) pressure is attractive as a potential target for surveillance or modification in eyes with glaucoma, but its true value in those terms will not be known until accurate means are devised to measure the pressure locally in the optic nerve head, said Hanspeter Esriel Killer MD, Kantonsspital Aarau and University of Basel, Switzerland. “The concept is still in the Platonic and infancy stage and really needs to be refined in order to fulfil the laws of physics and mathematics,” he told the 12th European Glaucoma Society Congress in Prague, Czech Republic. He noted that pressure is scalar, obtained by dividing the force applied by the area to which it is applied. However, in the case of CSF pressure, neither the amount of force applied nor the size of the area involved can be determined accurately with current technology. MATCH THE MODEL Intracranial CSF pressure is one of two components of the translaminar pressure gradient, a measure of the forces applied to the lamina cribrosa. The laminar pressure gradient is calculated by subtracting intracranial CSF pressure from intraocular pressure (IOP). In a theoretical model, when the two pressures are equal, the translaminar pressure gradient would be zero. Whereas when CSF pressure exceeds IOP, the gradient will have a negative value and the papilloedema might occur, and if IOP exceeds intracranial CSF, the gradient will have a positive value and glaucoma might occur. However, the optic nerve’s subarachnoid space has a complex anatomy. For example, the area where CSF would be applying pressure to the lamina cribrosa has an annular shape, segmented into many tiny compartments, each with different amounts of compliance to pressure. In addition, scanning electron microscopy shows that the subarachnoid space right behind the lamina cribrosa is filled with trabeculae unlike a Bernoulli tube. CSF is not homogenous at different sites. Unlike a Newtonian fluid, it contains up to 20,000 peptides with a variety of biochemical functions. “What we need is hyperbolic geometry so that we can actually model to the formation of this area behind the lamina cribrosa, and then we could get more accurate measurement of actual CSF pressure,” Dr Killer said. One way to calculate the dynamics of the ocular pressure within the optic nerve is to use Alan Turing’s reaction diffusion equation. Using partial differential equations, it calculates the surface area of a torus composed of segments of varying diameter. NEW TECHNOLOGY Dr Killer noted that, to obtain the measurements necessary to perform those calculations in patients, he and his associates are in the process of creating a three-dimensional reconstruction of the whole optic nerve subarachnoid space. Another problem they are working on overcoming is the actual measurement of CSF pressure in the optic nerve subarachnoid space. The conventional means of measuring CSF pressure is to use a lumbar puncture. That approach assumes that CSF pressure is equal throughout the body in a manner akin to a Bernoulli tube. In fact, studies using computed tomography (CT) cisternography show herniations and blockages to the flow of CSF in different parts of the spinal canal and the subarachnoid space of the optic nerve, as well as different concentrations of contrast-loaded CSF and in different parts around the optic nerve. (HE Killer et al, Br J Ophthalmol 2012; 96:544-548; HE Killer et al, The optic nerve: a new window into cerebrospinal fluid composition. Brain 2006; 129:1027-1030; HE Killer et al, Cerebrospinal fluid dynamics between the intracranial – and the subarachnoid space of the optic nerve. Is it always bidirectional?; Brain 2007 129(4):1027-1030) “The reason is simply because the anatomy throughout the optic nerve is not the same in every location. If you are behind the lamina cribrosa or in the middle portion, or if you are in the connector portion, the size of the subarachnoid space is variable,” Dr Killer said. To help determine the contribution of CSF to the translaminar pressure, he and his associates have developed a technique for measuring the velocity of the CSF in different positions in the subarachnoid space surrounding the optic nerve, using an MRI diffusion sequence, he said. He added that in order to accurately measure translaminar pressure, the measurements of IOP and CSF need to be simultaneous, whereas currently they are generally performed at separate times. Moreover, account has to be taken of the fact that IOP and CSF have independent cycles of peaks and troughs that do not coincide. Hanspeter Esriel Killer: killer@ksa.ch