Clinical Trials: Macular Degeneration
by Jeff Worley
"The eye is an extremely unforgiving organ," says Jayakrishna Ambati, an associate professor of ophthalmology at UK. "And because of this, our work is all the more challenging."
The eye places a premium on optical clarity, he explains, and new blood vessels that grow in the eye interfere with clarity and are the main culprits in driving the disease called macular degeneration.
Why do new blood vessels grow? "The truth is, we aren't sure," says Ambati. "It could be because as the eye grows (it's about 50 percent larger when we're adults), various deposits form in the back of the eye and promote a mild degree of inflammation, which may trigger the formation of new blood vessels." As new blood vessels develop, they bleed and leak fluid because they're so fragile, and injure the retina.
"Unfortunately, all this is happening in the tiny, one-millimeter region in the center of your eye. If it happened anywhere else, it wouldn't be much of a problem."
Ambati, working with UK ophthalmologist Andrew Pearson, is trying to find answers to basic biological questions about diseases of the eye, specifically—in two ongoing clinical trials—the origin and progression of age-related macular degeneration (AMD).
"AMD is the leading cause of blindness not only among the elderly in this and other developed nations, but because of the inversion of the population pyramid in this country, it's the leading cause of blindness among adults, period," Ambati explains. "It's now a reality for the baby boomers." In the United States in 2000 there were 35 million senior citizens (12.4 percent of the population was over the age of 65), according to David Wekstein, associate director of UK's Sanders-Brown Center on Aging. This number is expected to grow to around 40 million by 2010 and to 70 million by 2030.
"We are clearly becoming a more geriatric population," says Ambati, "and therefore diseases associated with aging are of tremendous public health importance."
Currently, the only approved treatment for AMD is something called photodynamic therapy (PDT), which involves injection of the dye visudine. This drug accumulates preferentially throughout the body, but not solely, in areas of new blood vessels. "We use a laser beam to activate that drug, which then closes off blood vessels and causes them to stop leaking," Ambati explains. But this treatment, he adds, "leaves a lot to be desired."
Jayakrishna Ambati is trying to find answers to basic biological questions about diseases of the eye, specifically—in two ongoing clinical trials—the origin and progression of age-related macular degeneration, the leading cause of blindness in adults.
For one thing, only about 20 percent of people with macular degeneration are eligible for this treatment—those who fall into the category of "classic leakage." "Most patients have the other type, occult leakage, which doesn't respond well at all to photodynamic therapy." Ambati is quick to add that PDT doesn't restore vision; all it does is decrease the rate of vision loss. "Also, it's not a permanent effect—95 percent of these vessels reopen within two to three months, so treatment has to be repeated over and over again."
In one of their current clinical trials—a Phase II trial focused on patients with occult age-related macular degeneration—Ambati and Pearson are testing the effectiveness of an implant containing the steroid fluocinolone acetonide. Steroids have long been known to be potent anti-inflammatory agents, and the idea in this study is to deliver high doses to the eye and no place else, since steroids given systemically are known to have severe side effects. The doctors will target the eye by implanting a device called Envision TD, developed in part by Pearson at the UK Chandler Medical Center. The device is a tiny polymer shell containing about two milligrams of the drug.
The trial, which is scheduled to run until March 2006, is fully enrolled and is well under way, with 50 trial participants placed at random into three groups: one gets a placebo, one gets an implant, and the third gets the implant and photodynamic therapy. (Ambati did the implant procedure for those who fell into groups two and three. While the patients were awake and under local anesthetic, he inserted the device during a 15-minute procedure, suturing the polymer shell in place.)
Though he's clearly excited by the basic science of trying to better understand the causes of macular degeneration, Ambati prefers to talk about how such work can help people.
"Around 25 percent of people over 65 have some form of macular degeneration—that's a huge number," he says. "Next to life itself, vision is the most precious thing we have. When people get older and enter their retirement years, they have more time to read and to watch television, and obviously they want to continue to be able to see the faces of their grandchildren. Macular degeneration robs them of all these things. There's a lot of human suffering behind the simple statement 'the leading cause of blindness.'"
For information on how to participate in a related clinical trial, call Michele Reg in the Department of Ophthalmology at 859-323-5868.