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Device manufacturers presenting new implants and technologies to treat glaucoma. As the industry moves from 1.0 devices to 2.0 devices, this will be a transformative time in the way physicians treat patients.
Minimally invasive glaucoma surgery devices (MIGS) are no longer new. The iStent and Trabectome have been on the market for several years and other devices are nearing approval in European and the United States.
“The next device will probably be the CyPass (Transcend Medical), which we hope will be on the market late this year or in the first quarter of 2017,” said Steven D. Vold, MD, who is in private practice in Fayetteville, AR. “On the horizon is the Xen implant (Allergan). And farther off are other implants and new technologies. We are starting to see real progress in treating glaucoma. As we move from 1.0 devices to 2.0 devices, this is going to be a transformative time in the ways we take care of patients.”
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Dr. Vold co-moderated “New Horizons in Glaucoma Devices” at the 2016 Glaucoma 360 meeting with Malik Y. Kahook, MD, professor of ophthalmology and director of the Glaucoma Service, University of Colorado. Some of the companies that presented are already in human trials and some have yet to produce a prototype, but all are pushing the boundaries of glaucoma care.
Conventional wisdom says glaucoma is the result of elevated intraocular pressure (IOP). What if conventional is wrong, or at least incomplete? The latest data suggest that the optic nerve damage seen in glaucoma results from an imbalance between IOP and intracranial pressure, not from elevated IOP alone. The pressure imbalance inhibits axonal transport that supports the metabolic needs of the optic nerve.
“If the IOP is too high or the intracranial pressure is too low, there is a pressure gradient across the optic nerve and its metabolic needs cannot be met,” said John Berdahl, MD, founder and CEO of Equinox. “The nerve slowly withers and dies. If we can decouple IOP from intracranial pressure, we can restore balance to the optic nerve and treat glaucoma.”
In glaucoma, IOP is higher than intracranial pressure, blocking axonal transport. Astronauts aboard the International Space Station have the opposite problem, intracranial pressure being higher than IOP. But the effect is the same, impaired axonal transport and potential damage to the optic nerve.
Dr. Berdahl’s solution is to restore the pressure balance using goggles to provide negative or positive pressure to the eyes.
Reducing ambient pressure reduces the elevated IOP seen in glaucoma, reducing the pressure gradient across the optic nerve and restoring axonal transport. If the problem is elevated intracranial pressure, increasing ambient air pressure on the eye increases IOP, likewise reducing the pressure gradient at the optic nerve to restore axonal transport.
The process works in cadaver eyes, Dr. Berdahl said. The next step is a device that can deliver the precise ambient air pressure needed to offset differences between intraocular and intracranial pressures to restore axonal transport function.
InnFocus has a simple goal, said Russ Trenary, president and CEO. It wants to treat the entire gamut of glaucoma, mild to severe, bringing IOP to 15 mm Hg or lower with a single device, the MicroShunt.
“We want patients who are coming in with a high IOP on maximum medications and get them below 15 mm Hg so they don’t lose vision any longer,” Trenary said. “And be able to get these patients off their eye drops.”
Early clinical data suggest it can be done. The MicroShunt uses a 70-µm lumen to tap the trabeculectomy aqueous drainage pathway. The key is the stent material, poly(styrene-block-isobutylene-block-styrene) or SIBS, that has more than 15 years of human use, including more than 8 years in ocular use, Trenary noted.
The device meets American Glaucoma Society IOP goals even without cataract removal, Trenary said, with a greater than 40% IOP lowering from baseline on full medications to less than 15 mm Hg. International trials show more than 80% of eyes with an IOP of less than 15 mm Hg, more than 80% reduction in glaucoma medications to a mean of 0.6 medications per patient and more than 70% of patients free of glaucoma medications 3 years after implantation with no long-term, sight-threatening adverse events.
The company enrolling patients for a phase III trial in the United States against trabeculectomy. A U.S. reimbursement code is already in place and the trabeculectomy trial is designed to meet pan European reimbursement requirements.
“This is a game changer,” Trenary said. “We are the only device that will be able to say this is what happens compared to trabeculectomy.”
Most MIGS devices reduce IOP by shunting aqueous within the eye. MicroOptx shunts directly the tear film. The is no bleb, encapsulation is not a problem, and episcleral venous pressure cannot cause nighttime IOP increases.
“Our device is engineered to achieve an IOP of 8 to 10 mm Hg,” said Chief Executive Officer Chris Pulling. “Our goal is to halt progression to blindness rather than simply slowing progression to blindness.”
Implantation takes about a minute using a small stab incision, Pulling said. The actual device is about 1.5 mm wide and protrudes about 300 µm above the conjunctiva.
The lumen is coated with a hydrophilic coating that binds with the aqueous and effectively prevents adherence by proteins, cells, or bacteria. The sheer stress from constant laminar flow inhibits any bacterial encroachment.
Testing in pig eyes shows no infection and minimal inflammation with rapid healing. The device quickly and consistently lowers IOP from 14 to 15 mm Hg in control eyes to 8 to 10 mm Hg in test eyes.
“We have a very small size, very simple design, and very low risk that produces very consistent, predictable and dramatic reductions in IOP,” Dr. Pulling said. “We will be starting our first human trials in the United States in July or August (2016).”
The Kahook Dual Blade, or KDB, made by New World Medical, continues to move toward broader testing and eventual commercialization. The hand-held instrument penetrates to the eye and the trabecular meshwork to the inner wall of Schlemm’s canal. A ramp elevates the meshwork to a pair of blades that excise the lifted tissue to restore drainage.
“This device allows for a very clear and efficient ab interno trabeculectomy,” said Ahmad A. Aref, MD, professor of ophthalmology, University of Illinois Chicago. “There is very little collateral damage to the surrounding ocular structures and very little remnant trabecular tissue.”
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Early clinical testing by 11 surgeons at 9 sites has been promising, Dr. Aref pointed out. Clinical results were positive. Patients had a mean IOP of 18.3 mm Hg before surgery despite a mean of 2.0 IOP-lowering medications. The day after surgery mean IOP had fallen to 11.29 mm Hg with a mean of 0.7 medications. At 3 months, the mean IOP was 12.1 mm Hg with 1.1 medications.
Surgeons overwhelmingly agreed that the KDB is straightforward to use, provides uncomplicated entry into Schlemm’s canal and has easy advancement along the canal. There were no serious adverse events and a 48% rate of intraoperative hyphema indicated a functional collector system, Dr. Aref noted. Additional studies are planned.
“This is a cost-effective procedure that is within existing procedure codes that restores the eye’s natural drainage pathway,” he said. “We can use the existing code for goniotomy and it can be done with or without cataract surgery.”
Most MIGS devices involve implants, stitches, and the associated surgical concerns. Sanoculus has taken a different path by developing minimally invasive micro sclerostomy, or MIMS. The device was inspired by the glaucoma treatment challenge issued by Sir Peng Khaw, MD, PhD, Moorfields Eye Hospital, London, a 10-minute technique that will reduce IOP to 10 mm Hg for at least 10 years.
“I call this the 103 challenge and it has been our vision,” said Chief Executive Officer Nir Israeli. “MIMS creates a scleral corneal channel to drain aqueous into the subconjunctival space. It is safe, efficient, and easy to perform. We hope it will become the standard procedure for treating glaucoma and combined glaucoma-cataract surgery.”
The handheld device is essentially a small drill that is inserted through the conjunctiva about 10 mm from the limbus and through the scleral corneal junction. Once in place, it rotates for 5 seconds to create a 50-µm channel to drain aqueous. The entire procedure takes less than 2 minutes.
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First in-human studies with 23 procedures in 19 patients provided promising results, Israeli said. Patients showed clinically significant drops in IOP, typically from the 20 to 40 mm Hg range down to 10 to 16 mm Hg at 3 and 6 months. The channels remained stable for at least 6 months.
“Our competitors are all using implants and some of them require complex operations,” he added. “MIMS is different. It is an efficient, 2-minute surgery that suits the vast majority of glaucoma patients. We believe it will last for many years.”
The company expects to get its CE mark later in 2016 and launch European sales by mid-2017. The U.S. timeline is longer, with an IDE expected in early 2017, pivotal studies in 2019 and approval later that year.