Every four to six weeks, Larry Curtis wakes up at 4 a.m. in his home in Rockville, Maryland, then makes the long commute via the Metro and MARC train to the Wilmer Eye Institute in Baltimore.
“I come up to the appointment desk here at 8 o’clock in the morning, and they're cheerful. That’s a wonderful way to start any kind of medical procedure, especially if you're going to get a needle in both eyes,” he says. Curtis, 73, has age-related macular degeneration (AMD)—a disease that requires injections to control the rogue growth of blood vessels in the retina that causes vision loss.
After a round of preliminary exams and photos of his retinas, Curtis will see retina specialist Peter Campochiaro, M.D., the George S. and Dolores D. Eccles Professor of Ophthalmology and Neuroscience, who consults the tests and most often recommends a course of injections, which are delivered once a technician has administered antiseptics and anesthetics to Curtis’ eyes.
“Your head’s back, your eyes open. He tells you when there’s going to be some pressure,” explains Curtis. “While this is happening, for years, I have gone back to the same fishing spot in Montana in my mind, and I'm watching a trout—the same old trout,” he says. “I pretend that when the needle goes in, that’s when the fish bites.”
After his time with Campochiaro, Curtis begins his journey home to Rockville. “My vision is frosted glass,” he says. “I try not to bump into people as I leave the hospital.”
Curtis is one of the lucky ones with AMD, a condition that currently afflicts 11 million people in the United States, most of them over age 60. He can actually get to a specialist who can administer the shots of anti-VEGF (vascular endothelial growth factor) medication on a regular basis. And he has insurance to cover the $2,000 price tag of each injection.
Frequent anti-VEGF injections are effective but not practical, admits Campochiaro. “It’s pretty difficult to make all the appointments. If a patient breaks their leg, for example, they miss their shots for quite a while. And their results are not nearly as good,” Campochiaro says. For this reason, he is on the hunt for better treatments with partners from Wilmer’s Center for Nanomedicine, including Justin Hanes, Ph.D., director of the center and the Lewis J. Ort Professor of Ophthalmology, and Laura Ensign, Ph.D., the Marcella E. Woll Professor of Ophthalmology, both biomedical engineers who specialize in drug delivery.
One project began when Hanes and Ensign approached Campochiaro with a question: “If we could make an eye drop that lasted for a long time so you only have to dose it once a day and it could deliver drugs to the retina—would that be important for patients?” With patients like Curtis in mind, Campochiaro gave them an enthusiastic yes.
Ensign and Hanes had been working on a concept that they thought might solve a problem endemic to eye drops—the fact that the eye blinks them out almost as soon as they go in so that typically less than 5 percent of the medication penetrates into the eye. For eye drops to effectively deliver a drug to the retina, a high drug concentration must be maintained long enough for the drug to travel from the front of the eye all the way to the retina in the back of the eye. Achieving this feat in humans is one of the “holy grails” of drug delivery in the eye, says Ensign.
“We identified a new way to use a polymer in eye drops that rapidly distributes the drug over the surface of the eye and then forms a gel,” says Hanes. “This new method keeps the drug against the surface of the eye longer, which allows greater drug penetration.” Because the polymer forms a clear gel that acts as a protective barrier to keep medication from being cleared away by tears, the researchers call this technology the invisible therapeutic ocular bandage (ITOB).
Several aspects of the polymer contribute to its effectiveness. It is thermoreversible, which means it acts in the opposite way of normal gelling behavior. Think of Jell-O, which begins as a liquid and gels as the temperature cools. This polymer does the reverse: It is liquid at room temperature and gels as it warms up on the surface of the eye.
Such polymers exist in many medications, but typical thermoreversible polymers present a problem in eye drops. “Normally, when you use a thermoreversible polymer, it will gel and seize up right away in a clump. When you blink, it can get gummed up in your eyelashes and smear around,” Ensign says. The team manipulated a particular thermoreversible polymer to act differently, however, such that “the liquid spreads evenly over the eye surface before it gels,” explains Ensign.
The result is a thin layer that fits right under the eyelid. The thinness of the clear gel reduces refraction, which can obscure vision.
The polymer is compatible with a variety of drugs. The one used in the AMD medication the team is currently studying in preclinical trials is a small molecule, called a hypoxia-inducible factor inhibitor, which has been shown in previous studies to stop the faulty growth of blood vessels that cause the vision loss associated with AMD— possibly even more effectively than the anti-VEGF medication currently used in eye injections.
The long-term hope, says Campochiaro, is that using the ITOB as a delivery method will enable patients to administer AMD medication via eye drops, reducing their number of clinic visits and need for injections.
This is welcome news to Curtis. Should these daily eye drops become a reality for patients (see sidebar), Curtis will no longer have to plan his life around the monthly injections or worry that a missed appointment could jeopardize his sight.
“The benefit is not just my convenience; this could really have an impact on a much wider range of people,” says Curtis. Indeed, by 2020, it’s projected that 196 million people worldwide will suffer from AMD; that figure is expected to increase to 288 million by 2040. “The idea that drops can be transported to anywhere and be available to doctors who are not specialists—it would change the world.”