September 2018

COVER FEATURE

Noninvasive, nonpharmacologic, nonsurgical glaucoma therapy


by Liz Hillman EyeWorld Senior Staff Writer

“Drops and prior surgical procedures are effective at lowering IOP to a certain
level, then for those who
need additional IOP lowering,
I think the goggles would
be a great option.”
—John Berdahl, MD


Balance Goggles are based on the concept that both intraocular pressure and intracranial pressure can play a role in the development of sight-threatening glaucoma—and thus also play a role in its treatment.
Source: John Berdahl, MD

A shift in the thinking of what causes glaucoma, a chance article about astronauts, and a company developing IOP-lowering goggles was born

To say that treatment for glaucoma has undergone a revolution within the last decade is an understatement. There are new surgical options (several considered microinvasive glaucoma surgery [MIGS]) and new drug targets on the market. While there are surgical options and medications still in the pipeline, there is also a nonsurgical and nonpharmacologic option that could offer first-of-its-kind, on-demand, titratable IOP lowering—and its use could be as simple as strapping on a pair of goggles.
Currently dubbed Balance Goggles (Equinox, Sioux Falls, South Dakota), the idea is that the goggles create a vacuum over the eye to lower eye pressure. The concept of this product was born out of the idea that it’s not just IOP in glaucoma that causes damage to the optic nerve, but that it’s an imbalance between IOP and cerebrospinal fluid (CSF) pressure, and by decoupling these two pressures, a new therapeutic option would emerge.
John Berdahl, MD, Vance Thompson Vision, Sioux Falls, South Dakota, published his first paper on the role of CSF pressure and glaucoma a decade ago.1 Dr. Berdahl first got the idea about the role of cerebrospinal fluid pressure in glaucoma while scuba diving with his wife. With several hundred millimeters of mercury pressing on his body, including his eyes, he thought, why don’t scuba divers get glaucoma? It’s because that same pressure is applied all over the body, he reasoned. So was it possible that people with glaucoma had something going on with their CSF pressure and IOP?
Conducting research, Dr. Berdahl and coinvestigators found that patients with various forms of glaucoma do indeed have an imbalance of IOP and CSF (intracranial) pressure, which causes cupping of the optic disc resulting in nerve damage over time. This, Dr. Berdahl said, can explain why even patients with low IOPs can still develop glaucoma (they might have an even lower CSF pressure) and why those with high IOPs might not develop glaucoma (they have an elevated protective CSF pressure).
“Clearly, we’ve been missing a big picture in glaucoma for a long time,” Dr. Berdahl said. “In the United States, 30% of patients who have glaucoma never have a high eye pressure, and of those who have a high eye pressure, only 10% of them over 5 years go on to develop glaucoma. The story isn’t just about eye pressure in isolation. We think it is eye pressure relative to cerebrospinal fluid pressure that is the underlying cause of disease. If that is the underlying cause of the disease, how do we use that information to develop technologies that can help people?”
Dr. Berdahl’s initial paper in 2008 has since been cited nearly 300 times, indicating strong research and support to this theory in the academic and scientific field.
“On the scientific side, it’s been millions of dollars, and hundreds of studies around this topic have been performed,” Dr. Berdahl said, pointing out that he thinks most ophthalmologists think this relationship is true. At a medical meeting 5 years ago, Dr. Berdahl said the audience was asked “Do you think CSF pressure plays a role in glaucoma pressure—yes or no?” About 95% said yes.
Russell Swan, MD, Vance Thompson Vision, Bozeman, Montana, said when he was in residency 3–4 years ago the concept of CSF pressure in glaucoma was introduced but not widely discussed. Now, he added, over the last 1–3 years, he thinks there is a lot of discussion and a lot of journal articles about it.
“I think there is fairly unifying agreement that it plays a significant role,” Dr. Swan said.
“I think people are aware of it. I think they think it’s true, and they don’t have any idea what to do with that information,” Dr. Berdahl said. “[Currently,] we don’t get CSF pressures. We don’t obtain them with spinal taps on glaucoma patients, so we’re not getting that information on the front end, and even if we did, what do we do about it? We would lower eye pressure like we always do.”
There is not a practical, clinical application for this information—at least not yet.
Six years passed after Dr. Berdahl got the idea about the role of CSF pressure and glaucoma. During that time he was primarily thinking about how to measure CSF pressure noninvasively. Then, while reading an article about the visual loss that astronauts faced with long-term spaceflight, Dr. Berdahl thought he knew why a percentage were losing vision.
“It’s the opposite of glaucoma, where CSF pressure is higher than eye pressure,” he said. This led him to think that if pressure could be added to the eye, maybe the pressure differential across the optic nerve head could be balanced.
“How could we do that?” he wondered. “You could push on the eye with a thumb or something to raise the eye pressure, but maybe you could put on a pair of goggles and pressurize them. … Those goggles will essentially pressurize the eye, and the pressure in the eye would go up. … Then I thought, why couldn’t we depressurize the eye, creating a vacuum.”
As a physics major, Dr. Berdahl said this idea is a simple application of Pascal’s law and hydrostatic physics.
“The goggles act by changing atmospheric pressure,” explained Malik Kahook, MD, director of the glaucoma service and glaucoma fellowship, Slater Family Endowed Chair in Ophthalmology, University of Colorado, Aurora. “The localized suction allows for control of the atmospheric pressure in and around the eye, potentially leading to a new set point pressure between the eye and the CSF pressure present in the optic nerve. In the case of suction, this may lead to a rebalance of the translaminar pressure (pressure on either side of the lamina cribrosa) and ease stress on the axons traveling through this space. In the case of added pressure, the rebalancing of translaminar pressure is intended to counteract higher CSF pressure that may occur, for example, during space flight when optic nerve swelling can lead to loss of vision.”
In December 2015, Dr. Berdahl founded Equinox, the company developing the goggles, which he said should enter clinical multicenter trials within the next year. The trials will first test the goggles on a low-risk patient population that could be helped the most, Dr. Berdahl said. But because the concept of the goggles is physics, he and others involved with the company think the treatment could apply to any type of glaucoma.
Dr. Berdahl thinks that treatment with the goggles, which would be set to a specific IOP-lowering level by the ophthalmologist, customized to patient needs, will be used as adjunctive therapy.
“Drops and prior surgical procedures are effective at lowering IOP to a certain level, then for those who need additional IOP lowering, I think the goggles would be a great option,” he said.
Could the goggles eliminate the need for pharmacologic therapy? Dr. Berdahl said he thinks there is the potential but “I wouldn’t hang my hat on it yet.”
“It’s easy to put in a drop, and drops work well when they’re used properly,” he said. “[The goggles] give doctors one more tool in the toolkit to treat glaucoma, and I think the goggles will help us treat some of the toughest forms of glaucoma.”
He envisions that the goggles would be worn primarily at night when patients are sleeping and most vulnerable to nocturnal pressure spikes.
“We think that is a time when patients are quite vulnerable to their eye pressure, so we can help during that difficult-to-treat time, and perhaps those with the most severe forms of glaucoma would wear them longer,” he said.
If born out in clinical trials, the Balance Goggles would provide a “nonsurgical, nonpharmacologic, on-demand, titratable way to set the person’s eye pressure right where we want it to be,” Dr. Berdahl said.
Dr. Swan thinks this technology could be especially useful in hard-to-treat glaucoma.
“I think it has broad utilization and opportunity in all areas of glaucoma. … For patients with normal tension glaucoma, who we have struggled to find reasonable options for and some of the surgical options like a trabeculectomy or a tube put them at significant risk, it’s nice to have something in the pipeline that decreases patients’ risk but still allows them to get to their IOP goal,” Dr. Swan said.
“My message to people would be to keep an open mind in terms of the opportunity. Having seen the clinical results and having worn them myself, knowing what the tolerability of them is, I think it’s a unique opportunity for patients that has a high safety profile but also a high level of comfort,” Dr. Swan said.
“We have a dearth of new treatment mechanisms for glaucoma,” said Dr. Kahook, a member of the Equinox Advisory Board. “I will be excited to see data from a longer- term treatment with the Balance Goggles, and I think the company is completing these studies in a systematic and precise way. They have a top-notch engineering and clinical team who are all meticulous.”

Reference

1. Berdahl JP, et al. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115:763–8.

Editors’ note: The physicians have financial interests with Equinox.

Contact information

Berdahl
: john.berdahl@vancethompsonvision.com
Kahook: malik.kahook@gmail.com
Swan: russell.swan@vancethompsonvision.com
 

 

Vision 4 Mars

Dr. Berdahl and Equinox were included in the Vision 4 Mars Challenge, sponsored by the National Space Biomedical Research Institute, which awarded grants in 2015. Dr. Berdahl said he thinks travel to Mars will be “the most unifying moment in human history during our lives, but it won’t happen if astronauts can’t see.”
Projects spearheaded by Dr. Berdahl and others are playing a role in better understanding the pathologic process and developing countermeasures to protect astronauts’ eyesight. In doing so, Dr. Berdahl said, he thinks “we played a small role in one of the most momentous moments in human history.”

Noninvasive, nonpharmacologic, nonsurgical glaucoma therapy Noninvasive, nonpharmacologic, nonsurgical glaucoma therapy
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