For years now, there has been considerable evidence indicating that glaucoma should be considered a neurological disease and not an entity isolated to the eyes alone. Perhaps the most compelling evidence for such a characterization is the fact that the retinal ganglion cells affected by glaucoma do not synapse until they arrive at the midbrain (specifically, the lateral geniculate nucleus).
For years now, there has been considerable evidence indicating that glaucoma should be considered a neurological disease and not an entity isolated to the eyes alone.1
Perhaps the most compelling evidence for such a characterization is the fact that the retinal ganglion cells affected by glaucoma do not synapse until they arrive at the midbrain (specifically, the lateral geniculate nucleus).
Evidence of damage in the midbrains of simian models after induction of ocular hypertension2 furthers the evidence for glaucoma to be classified as a neurological disease. One other (rather contemporary) notion regarding glaucoma and its relationship to the brain is a plausible correlation between glaucoma and low cerebrospinal fluid (CSF).
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As the optic nerve exits the globe and begins its journey through the retrobulbar space, it fenestrates through the lamina cribrosa. It is at this point that there exists a pressure gradient between intraocular pressure (IOP) within the globe and CSF pressure within the subarachnoid space (or, as I tell my patients, “eye pressure and brain pressure”).
If this trans-laminar pressure gradient is high (specifically meaning a higher drop in pressure as the optic nerve goes from the globe to the retrobulbar space), then there is a greater chance for glaucomatous optic nerve damage to occur.3
There is more than one way for this scenario to occur. First, if IOP is high and CSF pressure is normal, then there would exist a drop in pressure along this gradient. Second, if IOP is normal and CSF pressure is low, the net effect would be the same kind of drop in pressure as in the first example.
So, the net effect is that a relatively low CSF pressure is a risk factor for glaucoma. Further, high IOP combined with low CSF pressure would seemingly be a greater risk factor for the development of glaucoma than the first two scenarios.
While lumbar punctures and facsimiles thereof will likely never become part of a glaucoma evaluation, this causal relationship between CSF pressure and IOP at the location of the lamina cribrosa does well to possibly (and at least in part) explain a few aspects of glaucoma that remain somewhat elusive.
First, we have thin central corneal thickness as a strong and independent risk factor for the development of glaucoma.4 The cornea and lamina cribrosa both derive from the neuro-ectoderm in utero. So, perhaps a thin central cornea (along with other hysterics) correlates with a lamina cribrosa that isn’t as apt to handling a significant pressure gradient between IOP and CSF pressure.
Second, we have the separate clinical entity known as normal or low-tension glaucoma (NTG) in which glaucomatous damage occurs in the presence of statistically normal IOP. Perhaps the presence of relatively low CSF pressure would at least partially explain the pathogenesis in this disease entity.
Third, we have ocular hypertension with no signs or symptoms that would lead us to suspect glaucoma (i.e. labeling a patient as having ocular hypertension rather than labeling that patient as a glaucoma suspect). We all know that ocular hypertension is the number-one risk factor for the development of glaucoma.
Yet, we all have patients with this condition (and some with markedly high IOP) who just never go on to develop any signs of glaucoma. Perhaps some of these patients also have protectively high CSF pressures, thus lowering their trans-laminar pressure gradients between IOP and CSF pressure.
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Whatever the reason may be, we understand that high IOP doesn’t automatically mean glaucoma, and low IOP doesn’t automatically mean not glaucoma.
While more research is obviously needed (and currently being undertaken) to explore this plausible correlation of low CSF pressure and its potentially causal relationship with glaucoma, the implications seem rational and sensible.
With respect to NTG, the fact that patients are typically diagnosed at relatively older ages points to vascular and hemodynamic dysfunction as another contributing factor. Yet, low CSF pressure as a potential risk factor would do well to possibly explain why some patients develop glaucoma at lower IOPs than others.
The future of glaucoma holds considerable promise of new horizons on both the diagnostic and therapeutic sides of this increasingly common disease.
However, the future will also entail an increasingly more common discussion of non-IOP risk factors, whether those factors can be modified or not. The notion of CSF pressure and its relationship with glaucoma, at the very least, continues a conversation about glaucoma as a neurological disease and not something contained solely within the eyes.
1. Yu L, Xie L, Dai C, et al. Progressive thinning of visual cortex in primary open-angle glaucoma of varying severity. PLoS One. 2015 Mar 27;10(3):e0121960.
2. Dai Y1, Sun X, Yu X, et al. Astrocytic responses in the lateral geniculate nucleus of monkeys with experimental glaucoma. Vet Ophthalmol. 2012 Jan;15(1):23-30.
3. Jost jb et al. Cerebrospinal fluid pressure and glaucoma. J ophthal vis res. July 2013 8(3): 257-263.
4. Brandt JD, Beiser JA, Kass MA, et al. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001 Oct;108(10):1779-88.