Intracranial pressure may play significant role in glaucoma

Thomas W. Samuelson, MD, interviews John P. Berdahl, MD, the lead author of a study on the role of ICP in glaucoma.

Introduction

Thomas W. Samuelson

In the May issue of Ophthalmology, Berdahl and colleagues published the results of their study pertaining to cerebrospinal fluid pressure and its relationship to primary open-angle glaucoma. In this retrospective study, the authors found a positive correlation between manifest glaucoma and an increased pressure differential across the lamina cribrosa. Although further study is needed, the pressure differential across the lamina cribrosa may be an underappreciated factor in patients with glaucoma.

This paper has received considerable attention in recent months. In addition to the article in Ophthalmology, the study was published in the August issue of Investigative Ophthalmology and Visual Science. Dr. Berdahl also presented his findings in September at the International Congress of Eye Research in Beijing.

Thomas W. Samuelson, MD
OSN Glaucoma Section Editor

Thomas W. Samuelson, MD: What was the genesis of your project?

John P. Berdahl, MD: While on a scuba dive, I began to think about the tremendous pressures my eyes must be experiencing and wondered why I was suffering no adverse effects. This led me to carefully consider two basic questions: What is IOP, and why does it matter?

IOP is not the pressure inside the eye; it is the pressure difference across the cornea, that is, pressure inside the eye minus atmospheric pressure. In the example of scuba diving, the absolute pressure inside the eye goes up tremendously, but so does the surrounding atmospheric pressure, resulting in an IOP — pressure difference across the cornea — that remains unchanged. Stated differently, the absolute pressure in the eye changes significantly, but the pressure in the eye relative to its surroundings remains unchanged. This is also true in high altitudes or when a low-pressure weather systems rolls through. The implications are that absolute pressure in the eye is of little importance, but the pressure difference between the eye and its surroundings is critical.

We routinely measure the pressure difference across the cornea – the IOP – but we know the site of damage in glaucoma is the optic nerve, far from the cornea. Perhaps it is the local pressure difference experienced by the optic nerve that matters. Because the retrolaminar optic nerve is exposed to cerebrospinal fluid, we chose to investigate if intracranial pressure (ICP) is lower in glaucoma patients.

Dr. Samuelson: Why would ICP matter in glaucoma?

Dr. Berdahl: The optic nerve is exposed to two pressurized regions that are separated by the lamina cribrosa, yet we have only rigorously studied one of them — IOP. Anteriorly, the intraocular space has a typical pressure of 10 mm Hg to 21 mm Hg, while posteriorly, the subarachnoid space has a typical pressure of 5 mm Hg to 15 mm Hg. The pressure difference between them, the translaminar pressure difference, can cause changes in the optic disc if it becomes abnormal. For example, optic nerve head swelling can occur if the relative pressure is greater posterior to the lamina cribrosa as observed in pseudotumor cerebri or hypotony.

If the IOP is high relative to the ICP, either due to a high IOP or a low ICP, axonal flow would need to surmount a large pressure difference in order to pass across the lamina cribrosa and into the eye. Over time the axonal flow may not be able to meet the metabolic demand of the nerve.

Dr. Samuelson: Describe your study.

Dr. Berdahl: We sought to determine if ICP was lower in patients with glaucoma and higher in patients with ocular hypertension. We identified more than 62,000 patients who had lumbar puncture at the Mayo Clinic over the last 20 years. We cross-matched this list with 66 patients who had a diagnosis of glaucoma and 27 patients who had a diagnosis of ocular hypertension and compared them with a control group of patients who did not have glaucoma.

Dr. Samuelson: What did you discover?

Dr. Berdahl: When compared with appropriate control groups, we found that ICP is lower in patients with glaucoma and normal tension glaucoma. Additionally, we found that ICP is higher in patients with ocular hypertension. The average ICP was 9.1 mm Hg in glaucoma and 8.6 mm Hg in the normal tension glaucoma subset compared with 11.8 mm Hg in the control group (P < .0001). ICP was 12.6 mm Hg in ocular hypertension compared with 10.6 mm Hg in age-matched controls (P < .05).

Dr. Samuelson: What is the clinical relevance of this finding?

Dr. Berdahl: IOP may not be the only pressure that matters in glaucoma. ICP may play a critical role in the development of glaucoma. Potentially, low ICP could explain why so-called “normal tension” glaucoma develops. Conversely, elevated ICP could protect ocular hypertensives from progressing to glaucoma.

Dr. Samuelson: Would noninvasive ways to measure ICP be beneficial?

Dr. Berdahl: Noninvasive ICP measurements would be a tremendous aid to studying this concept. If the concept is true, it could also be helpful to identify patients at the highest risk of glaucomatous progression.

For more information:

• John P. Berdahl, MD, can be reached at Minnesota Eye Consultants, 710 E. 24th St., Suite 100, Minneapolis, MN 55404; 612-813-3600; fax: 612-813-3636; e-mail: johnberdahl@gmail.com.
• Thomas W. Samuelson, MD, can be reached at Minnesota Eye Consultants, 701 E. 24th St., Suite 100, Minneapolis, MN 55404; 612-813-3628; fax: 612-813-3656; e-mail: twsamuelson@mneye.com.

References:

• Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5):763-768.
• 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 [published online ahead of print Aug. 21, 2008]. Invest Ophthalmol Vis Sci.