Analysis of Translaminar Pressure Gradient Using Noninvasive Cerebrospinal Fluid Pressure Monitoring

The pathophysiology of primary open-angle glaucoma (POAG) remains unclear, with potentially a multifactorial etiology. Intraocular pressure (IOP) is the only known modifiable risk factor, yet two clinical conundrums remain - patients with elevated IOP who do not develop glaucoma (ocular hypertension, OHTN) as well as patients with IOP <21 mmHg who still develop glaucoma (normal tension glaucoma, NTG). The etiology of these two scenarios remains unclear.

The role of cerebrospinal fluid pressure (CSFp) in glaucomatous optic neuropathy was initially raised 30-40 years ago. This concept has garnered more interest recently due to new findings in this area. Patients who underwent lumbar puncture (LP) and had POAG were found to have lower CSFp compared to controls in a chart review. Further studies demonstrated a positive correlation between optic nerve damage and the translaminar pressure gradient (TPG), calculated as the CSFp subtracted from the IOP. In 2010, a Chinese group suggested that normal-tension glaucoma (NTG) patients have significantly lower CSFp compared to POAG, and that TPG is greater in NTG and POAG patients compared to controls. The same group also showed that OHTN patients have higher CSFp than POAG patients, suggesting a protective effect of high CSFp when IOP is elevated. Thus, a role for CSFp in the pathophysiology of glaucoma may exist.

One can consider IIH as a model for these forms of glaucoma; CSFp is elevated in IIH, as measured by lumbar puncture (LP). Visual field loss in this disease follows an arcuate pattern, similar to glaucomatous loss. This would seem to suggest that glaucomatous optic neuropathy and IIH optic neuropathy share similar mechanisms (i.e., increased TPG due to either elevated IOP or CSFp).

One of the main hindrances to testing these hypotheses further has been the invasive nature of LP, which involves inserting a large-bore needle into the spinal column. This procedure has a relatively high risk of complications given its proximity to the spinal cord and the potential for traumatic nervous system injury if improperly performed. In contrast to this invasive procedure, a non-invasive computational device was recently developed and CE mark approved to measure CSFp using a two-depth transcranial Doppler device (TDTCD). The underlying principle of the device involves the ophthalmic artery. When originating from the internal carotid artery, the ophthalmic artery is within the subarachnoid space and thus is mildly compressed by CSFp. After exiting the intracranial space into the orbit, the ophthalmic artery loses its subarachnoid surrounding, and is no longer affected by CSFp. The TDTCD applies minimal external pressure to the orbit such that the pressure exerted externally on the extracranial segment is equivalent to the CSFp exerted on the intracranial segment (as measured by Doppler signals of both vessels.) The safety of the device has been demonstrated and verified; it has obtained CE certification in Europe, and is currently awaiting FDA approval with a "Non-Significant Risk" categorization. Further details regarding the device can be viewed at www.vittamed.com.

The device has been shown to correlate extremely well with the gold standard of LP. Multiple clinical trials utilizing this device in noninvasive CSFp monitoring in neurosurgical patients are underway at various other institutions, including Johns Hopkins University, NASA, and Baylor College of Medicine.

The investigators propose utilizing TDTCD to non-invasively measure CSFp in glaucoma/OHTN patients, IIH patients, and controls at various stages in treatment in order to further delineate the possible role of TPG in the pathophysiology of these conditions. The investigators believe this non-invasive approach has the potential to alter our current understanding and management of these disease processes, thereby assisting in the identification of at-risk patients more accurately, improving patients' quality of life.