Glaucoma may not be the disease you think it is

Take-home message: Clinicians continue to explore the relationship between IOP and cerebrospinal fluid pressure in glaucoma.

Reviewed by John P. Berdahl, MD

Sioux Falls, SD-Most ophthalmologists learned that glaucoma is a disease of elevated IOP. There is a good possibility it is something else entirely.

“We know that IOP matters in glaucoma, but perhaps the pressure differential across the cornea-which is what we measure in IOP-is only a surrogate for the pressure differential that really matters,” said John P. Berdahl, MD.

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“What matters is the pressure across the optic nerve head, the pressure gradient between the eye and the cerebrospinal fluid (CSF) 500 μm across the lamina cribrosa,” said Dr. Berdahl, of Vance Thompson Vision, Sioux Falls, SD. “There is growing evidence to support the idea that glaucoma is not a one-pressure disease, IOP, but a two-pressure disease, the difference between IOP and CSF pressure.”

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Exploring the concept

Exploring the concept

The idea that CSF pressure contributes to glaucoma was first presented in 2008. Eight years later, a growing body of retrospective and prospective data support the two-pressure model, Dr. Berdahl noted.

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Intracranial pressure (ICP) is already recognized as a factor in optic nerve dysfunction. Intracranial hypertension causes the optic nerve to bow outward. The pressure differential impedes axonal transport at the lamina cribrosa, depriving the optic nerve of nutrition. If the metabolic needs of the optic nerve are not met for a sufficiently long period, the nerve withers and vision suffers.

Dr. Berdahl suggested that glaucoma is the end result of the same situation in reverse. Pressure inside the eye is higher than intracranial pressure, which results in the posterior cupping that is seen in glaucoma. Axonal transport is impeded at the lamina cribrosa and the optic nerve, its metabolic needs unmet, eventually withers and vision is lost.

“This represents a potential redefinition of glaucoma,” he said. “This concept opens up entirely new therapeutic modalities and options for patients and physicians. And it explains physiology and pathophysiology that don’t fit the traditional one-pressure model.”

Elevated IOP might explain primary open-angle glaucoma, he continued.

But elevated IOP cannot account for normotension glaucoma. Nor can clinicians explain why elevated IOP may not lead to glaucoma in ocular hypertensives. The two-pressure model does.

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In individuals without glaucoma, the pressure differential between IOP and intracranial pressure is about four mm Hg. In individuals with glaucoma, the pressure gradient across the lamina cribrosa in greater, in the range of 13 mm Hg and higher.

“What causes cupping visual field loss in glaucoma? I believe the cupping is caused by the posteriorly directed forces generated when the IOP is greater than the ICP,” Dr. Berdahl said. “The visual field loss is caused by axonal death as the nutrient and waste transport needs of the optic nerve are not met because transport cannot get into the higher pressure environment beyond the lamina cribrosa.”

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He sees the same mechanism at work in normotension glaucoma. These individuals have normal IOP but a low ICP. The pressure gradient across the lamina cribrosa is high enough to impede axonal transport and eventually cause damage to the ocular nerve and increasing loss of vision.

Ocular hypertension

Ocular hypertension

The two-pressure model also explains ocular hypertension without glaucoma. These individuals have elevated IOP with a similarly elevated ICP that protects the optic nerve. Even though the absolute pressure on both sides of the lamina cribrosa is high, the normal pressure gradient allows for normal axonal transport.

Testing the two-pressure model at the clinical level is difficult. Ophthalmologists and other vision specialists routinely measure IOP at the cornea. But the only currently available method to measure ICP is an invasive lumbar puncture.

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Multiple research groups are working with animal models to develop noninvasive or less invasive methods to measure ICP, Dr. Berdahl continued.

Other groups are investigating multiple pharmaceutical agents known to affect ICP or CSF pressure for potential to treat glaucoma.

Dr. Berdahl is taking a different approach.

About one-half of visitors to the International Space Station suffer from vision impairment and intracranial pressure (VIIP). In a normal environment, gravity pulls fluid into the lumbar column and slightly reduces ICP, he explained.

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In a weightless or microgravity environment, such as the space station, CSF redistributes evenly throughout the cerebrospinal space, increasing ICP. In some astronauts, this increased ICP causes flattening of the eye, hyperopic shift, choroidal folds, optic disk edema, and impaired vision.

Dr. Berdahl founded Equinox LLC to develop special goggles (Balance Goggles). The goggles use physics to counteract the increased ICP of weightlessness by increasing the external pressure on the eye, which raises IOP to restore the normal pressure gradient at the lamina cribrosa.

“The goggles have a good shot at controlling eye pressure very precisely to counteract ICP,” Dr. Berdahl said.

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“The same concept can be applied to glaucoma by reducing the atmospheric pressure on the eye, which reduces IOP and reduces the pressure gradient at the optic nerve,” he said. “Redefining glaucoma as a two-pressure pathology opens a lot of physical and pharmacologic pathways to diagnose, treat, and even prevent glaucoma.”

Learn how the goggles concept was inspired by John P. Berdahl, MD, while on a scuba diving trip. Go to http://bit.ly/2aGZaFJ

John P. Berdahl, MD

E: [email protected]

This article was adapted from Dr. Berdahl’s presentation at the 2016 meeting of the American Society of Cataract and Refractive Surgery. Dr. Berdahl has financial interests with Equinox.

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