Orbital cerebrospinal fluid pressure and glaucomatous optic neuropathy: Facts and or Myths?

Jost B. Jonas, MD, PhD

Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Germany

Since the lamina cribrosa of the optic nerve head forms the border between the intraocular space with a higher pressure and the retrobulbar space with a lower pressure, a pressure gradient exists across the lamina cribrosa as difference of intraocular pressure minus pressure in the retrobulbar cerebrospinal fluid and optic nerve tissue space1,2. This trans-lamina cribrosa pressure gradient is of importance for ocular diseases in which the pressure on one or on both sides of the lamina cribrosa is either abnormally high and/or abnormally low3,4. An abnormal pressure gradient influences the physiology and pathophysiology of the optic nerve head5-9, including the orthograde and retrograde axoplasmic flow10,11. In that context, it should be kept in mind, that the term “intraocular pressure” is a misnomer.  What we ophthalmologists call “intraocular pressure”, is just the transcorneal pressure difference2. The true pressure in the eye with an intraocular pressure of 20 mmHg is 780 mmHg [760 mmHg (atmospheric pressure) plus 20 mmHg].  For the optic nerve, however, it is not the transcorneal pressure difference which counts, but the trans-lamina cribrosa pressure difference and the trans-lamina cribrosa pressure gradient. 

The trans-lamina cribrosa pressure gradient depends on the pressure difference and the distance between the intraocular compartment and the retrobulbar fluid filled compartment.  The distance between both compartments markedly depends on the thickness of the lamina cribrosa12,13. Consequently, the thinning of the lamina cribrosa in highly myopic eyes may be one of the reasons, why the glaucoma susceptibility is increased in highly myopic eyes13,14. In addition, histomorphometric studies have shown that in non-highly myopic eyes the lamina cribrosa gets thinner in an advanced stage of the disease13. This glaucoma related thinning of the lamina cribrosa may be one of the reasons why the risk for further glaucoma progression in eyes with advanced glaucoma is increased15,16

The trans-lamina cribrosa pressure difference depends on the intraocular pressure and the retrobulbar cerebrospinal fluid pressure. It is elevated if either the intraocular pressure is elevated and/or if the cerebrospinal fluid pressure is reduced. More than 30 years ago, Volkov pointed out that a low cerebrospinal fluid pressure could pathogenetically be associated with glaucomatous optic neuropathy17. The same idea had already earlier been expressed by Szymansky and Wladyczko18.  In a similar manner, Yablonsky, Ritch and Pokorny postulated that an abnormally low cerebrospinal fluid pressure around the optic nerve may be the reason for a barotraumatically induced optic nerve damage in normal-pressure glaucoma19.  In an experimental study, they decreased the intracranial pressure to 5 cmH2O below the atmospheric pressure by canulation of the cisterna magna. The intraocular pressure of one eye was reduced to slightly above atmospheric pressure by cannulation of the anterior chamber.  After 3 weeks, the optic nerve heads of the eyes in which intraocular pressure was unaltered showed typical features of glaucomatous optic neuropathy.  In contrast, in the eyes in which the intraocular pressure was also lowered, no changes occurred.  The authors hypothesized that reducing intracranial pressure would have the same effect as increasing the intraocular pressure for the development of glaucoma.  Consequently, Berdahl and colleagues performed a retrospective review of medical records of more than 50,000 patients who had undergone lumbar puncture for primarily non-ophthalmological reasons20,21. The cerebrospinal fluid pressure was significantly (P<0.0001) lower in the subjects with normal-tension glaucoma (8.7±1.16 mmHg) and in the primary open-angle glaucoma group (9.1±0.77 mmHg) than in the control group (11.8±0.71 mmHg).  Additionally, the cerebrospinal fluid pressure was higher in the ocular hypertension group than in age-matched control subjects (12.6 ±0.85 mmHg versus 10.6±0.81 mmHg; P<0.05).  These results were confirmed by a prospective study by Ren and colleagues22-24. In their study, the lumbar cerebrospinal fluid pressure was significantly (P<0.001) lower in the normal-intraocular pressure glaucoma group (9.5 ± 2.2 mmHg) than in the high-intraocular pressure glaucoma group (11.7±2.7 mmHg) or the control group (12.9±1.9 mmHg).  The trans-lamina cribrosa pressure difference was significantly (P<0.001) higher in the normal-intraocular pressure glaucoma group (6.6±3.6 mmHg) and the high-intraocular pressure glaucoma group (12.5±4.1 mmHg) than in the control group (1.4±1.7 mmHg).  In a multivariate analysis, the amount of glaucomatous visual field loss was mainly associated with the trans-lamina cribrosa pressure difference (P=0.005) while intraocular pressure and cerebrospinal fluid pressure as single parameters were no longer significantly (P>0.50) associated with the perimetric loss. In a parallel study, the cerebrospinal fluid pressure was significantly (P<0.001) higher in a ocular hypertensive group of 17 patients (16.0±2.5 mmHg) than in the control group (12.9±1.9 mmHg)24. In the control group, cerebrospinal fluid pressure was significantly correlated with both systolic blood pressure (P=0.04) and intraocular pressure (P<0.001).  Since the intraocular pressure also showed a tendency towards an association with blood pressure (P=0.09), as was also shown in population-based studies25, the trans-lamina cribrosa pressure difference was not significantly (P=0.97) related with the blood pressure. In the subjects of the control group, the pressure in all three fluid compartments was thus correlated with each other, with the systemic blood pressure being the highest, followed by the intraocular pressure and finally by the cerebrospinal fluid pressure. In the control group of Ren´s study, the cerebrospinal fluid pressure (P=0.01; correlation coefficient r=-0.26), intraocular pressure (P=0.001; r=-0.34) and trans-lamina cribrosa pressure difference (P=0.004; r=-0.31) decreased significantly with higher age.  The cerebrospinal fluid pressure was additionally associated with higher body mass index (P<0.001)26. It confirmed the association between an abnormally body mass index in patients with idiopathic intracranial hypertension27.  

In conclusion, taking into account (1) that it is the trans-lamina cribrosa pressure difference (and not the transcorneal pressure difference, i.e. the so-called “intraocular pressure”) which is of importance for the physiology and pathophysiology of the optic nerve; (2) that studies have suggested physiologic associations between the pressure in all three fluid filled compartments, i.e. the systemic arterial blood pressure, the cerebrospinal fluid pressure and the intraocular pressure; (3) that an experimental investigation suggested that a low cerebrosopinal fluid pressure may play a role in the pathogenesis of normal (intraocular-) pressure glaucoma, and (4) that eventually clinical studies have reported that patients with normal (intraocular-) pressure glaucoma had significantly lower cerebrospinal fluid pressure and a higher trans lamina cribrosa pressure difference when compared to normal subjects, one may infer that a low cerebrospinal fluid pressure may be associated with normal (intraocular-) pressure glaucoma in some patients. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high trans-lamina cribrosa pressure difference (with a barotraumatically induced optic nerve damage) and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated.  This model could explain why patients with normal (intraocular-)pressure glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular-)pressure glaucoma and eyes with high-pressure glaucoma, in contrast to eyes with a direct vascular optic neuropathy, can show profound similarities in the appearance of the optic nerve head. 

 

4th Edition – May 2017