Ophthalmologists have long been aware that IOP is the biggest risk factor for glaucoma. They also know, however, that IOP is not the entire story. Up to 30% of patients with glaucoma may not have an elevated IOP, whereas only a small percentage of individuals with high IOP ultimately develop glaucoma.1,2 Clearly, there are factors at play other than IOP. Neurodegeneration, ocular perfusion, and a lack of neurotrophic factors have all been suggested as major factors in the development of glaucoma. Recent data suggest that cerebrospinal fluid pressure (CSFp) may play an important role in the disease3,4(Figure 1).

DIFFERENCES IN PRESSURE

When we clinicians measure IOP, we are really measuring the pressure difference across the cornea. We apply a force to the external cornea to flatten (applanate) the cornea so that the pressure inside the eye equals the pressure outside the eye. Although we use the term intraocular pressure, a more appropriate term would be transcorneal pressure difference, because that is actually what we are measuring. Obviously, glaucoma does not occur at the cornea but at the optic nerve head, which has led to explorations of whether the pressure difference across the optic nerve head may be the key factor in defining glaucoma.

CSF fills the subarachnoid space and bathes the optic nerve all the way to its insertion through the lamina cribrosa. The IOP is separated from the CSFp by the lamina cribrosa, which is roughly 500 μm thick but thins with glaucoma. If the IOP is high or if the CSFp is low, then a pressure differential exists across the optic nerve head, and glaucomatous damage can occur. The relatively low CSFp or relatively elevated IOP will generate a net force on the optic nerve, causing posterior bowing of the lamina cribrosa and the cupping that is characteristic in eyes with glaucoma.

Studies have shown that patients with glaucoma have a lower CSFp, whereas those with ocular hypertension have a higher and possibly protective CSFp (Figure 2). These retrospective and prospective studies suggest that glaucoma could be a two-pressure disease.3-5 Other research has demonstrated a decrease in CSFp with increasing age, consistent with the rising incidence of glaucoma with increasing age6 (Figure 3). If these theories prove true, they may have implications beyond glaucoma.

OF ASTRONAUTS AND PRESSURE

The National Aeronautics and Space Administration has been investigating the role of CSFp in astronauts who have engaged in long-term space flight on the international space station. It had been shown that astronauts can develop optic nerve head edema and flattening of the posterior globe, resulting in decreased vision and a hyperopic shift.7 The changes could be due to the lack of gravity in space, which would result in a higher-than-normal CSFp at eye level.8

On Earth, CSF pools in the caudal spinal column, resulting in a zero or negative CSFp at eye level (Figure 4). IOP is therefore higher than CSFp at the lamina cribrosa. The lack of gravity in space allows CSF to diffuse throughout the spinal column and intracranial space, resulting in a higher CSFp at eye level. The CSFp can thus be higher than IOP, reversing the pressure gradient at the lamina cribrosa and causing the optic nerve to bow forward and swell.

CONCLUSION

CSFp can only be accurately measured by a spinal tap. Using imaging modalities, ophthalmodynamometry, or postural changes, many companies have tried to develop a noninvasive method by which to measure ICP. Success in this area could unlock numerous possibilities for research to determine if CSFp truly plays a role in the development of glaucoma. It would also further characterize the role of CSFp in space flight and help to permit further human exploration of other planets.

John P. Berdahl, MD, is a clinician and researcher with Vance Thompson Vision in Sioux Falls, South Dakota. Dr. Berdahl may be reached at johnberdahl@gmail.com.

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  2. Musch DC, Gillespie BW, Niziol LM, et al. Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study. Ophthalmology. 2011;118:1766-1773.
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  8. Berdahl JP, Yu D-Y, Morgan WH. The translaminar pressure gradient in sustained zero gravity, idiopathic intracranial hypertension, and glaucoma. Med Hypotheses. 2012:1-6.