When I first heard John Berdahl, MD, a clinician and researcher at Vance Thompson Vision, in Sioux Falls, SD, speak about the relationship between IOP and cerebrospinal fluid (CSF), I found it intriguing. Now, as a patient who has a spontaneous CSF leak, I am even more intrigued. Here, Dr. Berdahl details his story of discovery. -April Jasper, OD, chief optometric editor, Optometric Management.

AN EPIPHANY

When I was a first-year resident at Duke University, my wife and I travelled to the Caribbean on the one vacation residents can take and went scuba diving. I was 30 feet below the ocean’s surface when I had a realization: “There is all this weight of the water pushing on my eye — 760 mmHg of pressure — but I drill a hole in a patient’s eye for 50 mmHg. Why doesn’t this make sense?”

Instead of enjoying our vacation and a Corona, I couldn’t stop thinking about this and wondered whether it is not the absolute pressure inside the eye, but a balance between IOP and intracranial pressure (ICP) that keeps glaucoma at bay. After all, those pressures move together in lockstep when we dive or when we move to a higher elevation. Could this be why scuba divers aren’t at higher risk for glaucoma?

IN PURSUIT OF RESEARCH

I returned from vacation excited to tell my idea to R. Rand Allingham, MD, the first Richard and Kit Barkhouser professor of Ophthalmology and chief of the Glaucoma Service from 1996 to 2015 at Duke University. (Dr. Allingham passed away in 2018.) He replied, “That’s interesting. I’m not sure you’re right, but let’s go study it.”

So, we did. Specifically, we assessed more than 55,000 medical records to find patients who had glaucoma and had undergone spinal taps.^1,2 Once we identified the patients who had both, we compared them to patients who had spinal taps and did not have glaucoma. Our findings: Indeed, CSF pressure was lower in patients who had glaucoma and even lower in patients who had normal-tension glaucoma (NTG), explaining why people who have normal IOP still develop glaucoma. Additionally, CSF pressure was higher in patients who had ocular hypertension and high IOP, but no glaucoma, which explained that, too.

We wanted to dig deeper: We know that elevated IOP is a well-known risk factor for glaucomatous optic neuropathy, but we also know that elevated IOP is not always present in patients who have glaucomatous optic neuropathy. Also, we know that a small percentage of people who have high IOP go on to develop glaucoma, and 50% of people with glaucomatous optic neuropathy never have IOP over 22 mmHg.³

Further, we know that ICP, which is the pressure of the CSF that surrounds the brain, can cause swelling of the optic nerve head when it becomes higher than the IOP in patients who have pseudotumor cerebri. So, if the balance between IOP and ICP is the critical factor, then patients who have ocular hypertension and do not develop glaucoma may be protected by an elevated ICP, whereas patients who have NTG may develop glaucoma because of an abnormally low ICP. Maybe, eye care providers should be comparing IOP inside the eye with ICP. That said, getting an accurate ICP measurement currently requires a spinal tap, which is only done in unusual cases.

Since the publication of those first findings, I have published related papers.^4,5 Other investigators have looked at this research, and nearly every one of their studies has confirmed there is a balance between IOP and CSF pressure that is part of the pathogenesis of glaucoma.^6-8

CSF LEAK AND NTG

The aforementioned findings beg the question, “are those who have chronic CSF leak at an increased risk of NTG?” The pathogenesis of CSF leak, which can be iatrogenic, trauma-induced, spontaneous or from a heritable disorder, points to yes.

Specifically, a spinal CSF leak, which happens when the spinal dura mater has a hole or tear, results in intracranial hypotension, or a low volume of CSF remaining around the brain and spinal cord. Clinical and experimental studies show patients who have NTG had significantly lower CSF pressure and a higher trans lamina cribrosa pressure difference vs. normal subjects. Additionally, NTG patients have a significantly narrower orbital CSF space vs. those who have high-pressure glaucoma.⁹

A low volume of CSF creates numerous symptoms, with the most common being a positional or orthostatic headache. This is a headache (ranging from mild to disabling) that is worse while in the upright position and less severe laying (or in a horizontal position). There are a range of other symptoms, such as nausea, muffled hearing or tinnitus, imbalance, photophobia, pain between the shoulders, pain or numbness in the arms, and more. Given this information, doctors should refer such patients to a low CSF pressure expert (usually a neurologist) who might consider some pharmacological or interventional therapies, like a blood patch. OM

REFERENCES

1. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5):763-768. doi:10.1016/j.ophtha.2008.01.013
2. Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci. 2008;49(12):5412-5418. doi:10.1167/iovs.08-2228
3. Kim KE, Park KH. Update on the Prevalence, Etiology, Diagnosis, and Monitoring of Normal-Tension Glaucoma. Asia Pac J Ophthalmol (Phila). 2016;5(1):23-31. doi: 10.1097/APO.0000000000000177.
4. Berdahl JP, Ferguson TJ, Samuelson TW. Periodic normalization of the translaminar pressure gradient prevents glaucomatous damage. Medical Hypotheses. 2020;144:110258. doi:10.1016/j.mehy.2020.110258
5. Fleischman D, Berdahl JP, Zaydlarova J, Stinnett S, Fautsch MP, Allingham RR. Cerebrospinal fluid pressure decreases with older age. PLoS One. 2012;7(12):e52664. doi: 10.1371/journal.pone.0052664.
6. Matuoka ML, Santos KS, Cruz NF, Kasahara N. Correlation between ocular perfusion pressure and translaminar pressure difference in glaucoma: Evidence for a three-pressure disease? Eur J Ophthalmol. 2021;31(5):2412-2417. doi: 10.1177/1120672120960584.
7. Jonas JB, Wang N, Yang D, Ritch R, Panda-Jonas S. Facts and myths of cerebrospinal fluid pressure for the physiology of the eye. Prog Retin Eye Res. 2015;46:67-83.doi: 10.1016/j.preteyeres.2015.01.002.
8. Lindén C, Qvarlander S, Jóhannesson G, et al. Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions. Ophthalmology. 2018;125(3):361-368. doi: 10.1016/j.ophtha.2017.09.022.
9. Jonas JB, Wang N. Cerebrospinal Fluid Pressure and Glaucoma. J Ophthalmic Vis Res. 2013;8(3): 257–263.

DR. BERDAHL is in private practice at Vance Thompson Vision in Sioux Falls, S.D. He may be reached via email at john.berdahl@vancethompsonvision.com.