t is frightening for many patients. “I felt as if the lights were dimming and I couldn’t make it brighter,” Cooper says.

Until recently, treating wet AMD could only delay the inevitable, giving patients a few more months or years of vision. One of the first therapies was thermal laser photocoagulation, which involves sealing blood vessels with a hot laser but often leads to scarring of tissues in and around the macula—a dense layer of photoreceptors and neurons in the retina.

Since 1996, Rosenfeld has led numerous trials of another widely used treatment, photodynamic therapy. A light-sensitive dye is injected into the patient’s arm, travels throughout the body and collects in the abnormal blood vessels under the macula. Then a non-burning laser light shined into the eye activates the medication, causing blood clots to form in the abnormal blood vessels and prevent leaking.

In the early 2000s, anti-angiogenesis drugs launched what Carmen Puliafito, M.D., professor and chairman of Bascom Palmer, describes as “a new era in macular degeneration treatment.” These drugs are based on the finding that patients with wet macular degeneration have high levels of a substance called vascular endothelial growth factor (VEGF) in their affected eyes. VEGF, which is also produced by cancer cells, prompts abnormal growth of blood vessels, also known as angiogenesis. The new drugs, including the one Betty Cooper used, bind with VEGF and interfere with its ability to stimulate blood vessel growth. Macugen, one such drug investigated at Bascom Palmer and nationwide, was the first one proven effective in halting the progression of wet AMD. Approved by the FDA in late 2004, Macugen slowed vision loss in 70 percent of patients and led to a mild vision gain in 6 percent.

Bascom Palmer physicians also participated in a subsequent trial of Lucentis, an even more effective anti-angiogenesis drug that also is injected directly into the eye. “Results were announced last spring, and for the first time we had a treatment that could improve vision significantly in 30 to 40 percent of our patients,” Rosenfeld says. “That was groundbreaking.”

But since Lucentis isn’t commercially available, most Bascom Palmer patients couldn’t take advantage of the new drug. So Rosenfeld and his colleagues turned to another drug, Avastin, an FDA-approved colon cancer drug that, like Lucentis, is manufactured by Genentech and is able to inhibit VEGF. If Avastin prevented the abnormal growth of blood vessels in colon cancer, Rosenfeld reasoned, wouldn’t it work with wet macular degeneration? The answer was a resounding “yes.” By the end of summer this year, 250 patients had been treated with Avastin with remarkable results. Betty Cooper was among an initial trial of 18 patients treated with systemic Avastin. “Within a week or so, it was amazing,” recalls Cooper, whose vision went from 20/80 to 20/20 in her right eye.

Avastin was initially given as an intravenous injection, which required multiple doses of 400 to 500 milligrams each and cost between $2,200 and $2,750 per dose. Based on concerns about side effects of systemic treatment over time, Rosenfeld and colleagues tried injecting Avastin directly into the eye, like Lucentis and Macugen. This off-label approach, made possible with help from Bascom Palmer pharmacist Serafin Gonzalez, worked well. Only one milligram is needed every two months, and it costs only $13 an injection. “We’ve taken a treatment that could not be afforded by most people in the world,” Rosenfeld says, “and made it accessible to everyone.”

Since June 2005, when Bascom Palmer physicians published the results of their initial 12-week Systemic Avastin for Neovascular Age-Related Macular Degeneration (SANA) study and reported their success in treating patients with an injection of Avastin into the eye, physicians in Europe, South and Central America, the Middle East, South Africa, Australia, and Asia have begun treating patients with Avastin. Since the drug isn’t FDA approved for macular degeneration, Bascom Palmer physicians are using it only as “salvage therapy,” giving it to patients going blind despite use of approved drugs. Once the FDA gives the green light, Rosenfeld and his colleagues plan to launch a multicenter trial of Avastin in the eye.

“I predict that Avastin will be used extensively in ophthalmology, fueled by its efficacy and the low cost of the therapy,” Rosenfeld says. “This drug has the potential to save Medicare billions of dollars.”

espite progress in the treatment of wet AMD—which must begin in the first year after the diagnosis of new blood vessels and before vision loss becomes permanent—there is little that can be done for the dry form, largely because scientists still don’t know why the photoreceptors in the macula die.

Wen-Hsing Lee, M.D., assistant professor of ophthalmology, is launching a project to investigate whether cellular byproducts that accumulate in the macula over time contribute to cell degeneration. She also plans to study a series of retinal enzymes that scavenge the harmful byproducts that predispose the cells to AMD.

Abigail S. Hackam, assistant professor of ophthalmology, is bringing her experience with photoreceptor biology and nerve cell degeneration to bear. Using an innovative tool called a gene chip or microarray, she has been looking at which genes are turned on and off as photoreceptor death progresses in dry AMD.

George Inana, M.D., is using gene array profiling to compare the activity of genes in cells from patients with and without the disease. Inana notes that macular degeneration is likely influenced by the interaction of a combination of genes, rather than a single identifiable gene. “If we know which genes play a role,” he says, “we’ll be able to attack the disease at the most fundamental level.”

Macular degeneration is widely believed to be a genetic disease, but one that’s influenced by lifestyle and environment. Several studies have shown that a diet rich in green, leafy vegetables and certain nutrients (zinc, lutein, zeaxanthin, and vitamins A, C, and E) lower the risk or slow progression of the dry form. Caucasians and women are more likely to lose vision, and there appears to be a link between obesity and AMD progression. Of particular interest to Bascom Palmer professor of pharmacology and cell biology Maria E. Martin-Castano, M.D., is the contribution of cigarette smoking and hypertension to dry AMD. She has identified several oxidants present in tar that may play a role.

While scientists and physicians still don’t have cures for macular degeneration, Bascom Palmer’s team is confident it has entered a new era in treatment of the disease. And, if the fact that U.S. News & World Report rated Bascom Palmer the nation’s No. 1 eye hospital two years running is any indicator, University of Miami faculty will remain on the leading edge.