Technology advances so rapidly, sometimes it's hard to keep up. Like computer technology, vision technology is also advancing at an increasingly rapid clip. Though many of the most exciting advances in vision technology are still in the experimental phase, and won't be available for years, here are two advancements that are just about ready for prime time, which is to say they are about to begin actual clinical trials. The first is a new medication that takes a different approach to treating advanced macular degeneration (AMD), and the second is the first step toward creating vision without an optic nerve, or even an eye.
A Different Approach to Treating AMD
In the September 2017 issue of AccessWorld we introduced you to UK research fellow Felicity de Cogan, who is working toward creating an eye drop that can deliver AMD medication. Today the only effective treatment for AMD is regular intravitreal (back-of-the eye) injections of a class of drugs known as Vascular Endothelial Growth Factor (VEGF) inhibitors. VEGF is the protein that promotes new blood vessel growth, also called angiogenesis. Angiogenesis is necessary for normal body maintenance, such as new vessel growth associated with wound healing, but when it misfires in overstressed retinal cells, it can lead to excessive vessel formation in the macula, causing the permanent damage known as wet AMD. Currently approved VEGF inhibitors are antibodies that bind to the VEGF protein itself and suppress vessel formation. Unfortunately, currently approved VEGF inhibitors are relatively large—too large to be administered via eye drops. The only way for them to reach their target is by injections, which can be a burdensome process for both patients and their caregivers.
"These injections are generally well-tolerated, but do carry a few serious risks, such as retinal detachment and infection, as well as occasional pain and discomfort. But the need for chronic retreatment also increases the burden on patients and their caregivers, and in time may lead patients to stop treatment," says Paul Chaney, President and Chief Executive Officer of New Jersey-based PanOptica Pharma.
While de Cogan is working to develop a way to transport these large molecules to the retina using eye drops that bind the antibodies to special peptides, Chaney and his team of researchers are working toward an alternate treatment. Recently PanOptica received $11 million in new funding 1 to begin a Phase 1/2 safety and efficacy testing of a new formulation of an experimental medication that shows promise of treating wet AMD with a compound one thousand times smaller than currently approved VEGF inhibitors. The new compound, currently known simply as PAN-90806, is a different kind of anti-VEGF medication. Here?s what that means:
VEGF receptors are located in tissues throughout the human body, including the blood vessels in the retina. In order for retinal blood vessels to grow, VEGF needs to fit into one of those receptors—kind of like a key fitting into a keyhole. The current VEGF inhibitors work by binding themselves to the keys, so that they no longer fit inside the lock and thus cannot unleash damaging vessel growth. In PanOptica's new "small molecule" approach, instead of disabling the key, the drug blocks the keyhole, preventing angiogenesis.
Small molecule anti-VEGFs are also used in cancer therapies, with drugs like Sutent (sunitinib) and Nexavar (sorafenib) as important treatment options. "There are a number of these agents available, but as cancer therapies, they were developed to be administered orally – as a pill," says Chaney. "Our mission was to find one that can be administered in an eye drop that delivers the drug to its intended VEGF receptor target in the back of the eye. The drug does not go through the eye, as one might suppose, say, in the way that glaucoma drops work. PAN-90806 is not absorbed through the cornea but rather "is absorbed by blood vessels in the conjunctiva and is carried by the blood vessels around the outside of the eye to the central choroid and retina, where the damage from wet AMD occurs," Chaney explains.
In a previously completed study, 45 percent of subjects with wet AMD treated with two very low doses of a first-generation formulation demonstrated measurable improvements. However, at higher dosages some recipients experienced corneal irritation. "The new generation version recently developed shows the potential for significantly better corneal safety, which suggests we should be able to safely employ higher and more effective doses in a once-a-day eye drop," says Chaney.
The company is planning to enroll up to 60 patients for up to three months of treatment with eye drops in 2018 clinical trials. Test subjects must be newly diagnosed patients who have not yet received VEGF inhibitor treatment, although if no improvement is seen, patients will be offered standard treatment. "This is the only way we can gauge effectiveness," notes Chaney.
One Step Closer to a Bionic Eye
It's been over four years since our very first vision tech article, Four Emerging Vision-Enhancing Technologies, in which we mentioned the Argus II retinal implant from Second Sight Medical Products, which was approved by the FDA in February of that year for the treatment of late-stage retinitis pigmentosa. The Argus II uses special eyeglasses with a mounted camera that sends its electronic data to a small receiver/computer. This unit codes the stream and sends the information to a retina-implanted chip, which forwards the signal through the optic nerve and into the brain.
More recently, in the March 2016 AccessWorld, we described the work of Professor Arthur Lowery, from Australia's Monash University, who is developing an implantable chip that can receive signals and bypass the retina completely and send visual images directly to the brain. Presently, Lowery is preparing to submit an ethics application for human trials.
At the convergence of these two technologies, Second Sight has now received permission to begin preliminary human clinical trials of a skull-implantable visual prosthesis known as Orion. Orion will use the same type of external glasses and processor as the Argus, but instead of sending the signal to a retinal chip, the signals will be delivered to a chip designed to stimulate the visual cortex of the brain—similar to but with differences from the one Lowery works with.
According to Second Sight founder and current Chairman Dr. Robert Greenberg, the company is hoping to enroll five patients split between The University of California, Los Angeles, and Baylor College of Medicine in Houston. Also according to Greenberg, "The Orion was in our original roadmap when we began developing the Argus." The Argus took over 20 years to develop—whereas work on the Orion began in earnest in 2014. "As things turned out, the eye was an excellent place to work out the technical details for the Orion," says Greenberg.
One of the most important things the company learned was that individuals could make considerable use of a lot less vision than people thought. "Just a tiny bit of restored vision could have a tremendous impact on a person?s life," says Greenberg. They also learned how little it takes to provide that sight. "A group in Germany is working with 1500-pixel chips, but with our software, the 64 pixels we use can provide basically the same amount of visual acuity."
The Argus external hardware has been completely redesigned for 2018, and all current Argus users will be eligible for upgrades. "The glasses were designed 15 years ago, and were in need of an update. The new processing unit will also be 25 times more powerful than the current model."
According to Greenberg, another technical achievement that helped propel the Orion's development is their work with miniaturizing the electronics while having them work inside the high-salt environment of the body. "The environment inside the human body is as salty as the ocean," he explains. "Imagine tossing a TV into the sea and expecting it to work. Now, shrink that TV down to the size of an aspirin and you have some idea of the technical challenge we faced."
The company spent many years and millions of dollars trying to develop a coating for their retinal chip. "We finally settled on a modified pacemaker solution, which is to put the chip inside a very small container, with sixty-four tiny inert metal rods that conduct the signal through to the retina in the Argus, and now the brain itself in the Orion."
The Argus encircles the eye with an antenna that receives both wireless signals and induction power. The Orion will implant this equipment under the skin near the ear—much as a cochlea implant does. The signal and power will then travel through a tiny cable to connect to the electrode array, which will lie against the brain atop the visual cortex.
The company's eventual goal is to miniaturize the processing unit so that it fits inside the glasses. Asked if there are any plans to incorporate the entire unit into a prosthetic, creating a "bionic" eye, Greenberg demurs. "When cochlear implants were first designed they were hoping eventually to shrink them down so they could fit inside the ear—and that was twenty years ago. Our thinking is that if we can give you the ability to regain vision by putting on a pair of glasses, our goal near-term then isn't to make it smaller, it's to increase the resolution and acuity of that vision. Eventually, these products will be fully implantable."
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