Leaning forward, bearded chin firmly on the chin rest, Dr. B. Prescott Edmunds Jr. kept his eyes steady through a brilliant flash of light that flooded into his dilated pupil. A digital photograph of his retina- round and red-orange with branching blood vessels- filled the flat computer screen, with only a small gray shadow to reveal the damage that brought him under the care of retinal specialist Dr. Robert Vogel of Lynchburg.

Just about three months ago Edmunds became one of the 1.8 million Americans diagnosed with wet macular degeneration- a destructive process of the central vision.  But he’s among far fewer who are undergoing treatment with direct injections into the eye with a drug developed for colon cancer. That puts Vogel and Edmunds in the middle of a national groundswell of “off-label” use of a drug, meaning the Food and Drug Administration approved it for one purpose but it is being used for another. Many believe Genentech’s Avastin™ is a break-through drug in the treatment of this leading cause of blindness. And they believe it and similar drugs hold out hope for other eye diseases as well. 

Avastin™ is similar to another Genentech drug, Lucentis™, under review by the Food and Drug Administration and expected to be released this summer specifically for treatment of wet macular degeneration. Off-label use is a medical treatment issue between doctors and patients, and not a matter for FDA regulations. Drug companies are prohibited from making any claims for a drug beyond uses for which the FDA approval was sought.

For Edmunds, a retired physician, the disease came suddenly into his life. Edmunds had stepped out of the shower and noticed that the top edge of a familiar framed picture on the wall looked curved to him- and he knew it wasn’t curved. He thought it was distortion from a beginning cataract. But the next morning, he noticed that not only did the straight edge of the picture seem curved, but it seemed blurry above the line. When it didn’t improve over several days, he called his ophthalmologist, who examined Edmunds, and referred him to Vogel, who diagnosed wet macular degeneration. The macula is a group of cells in the retina at the back of the eye responsible for central vision. In its center is a kind of dimple, the fovea, where instantaneous perception of the finest details is made possible. “In wet macular degeneration, abnormal vessels grow beneath the retina, break through and cause mini-detachments of the retina in the macula”, Vogel said. The curve that Edmunds had first seen in the picture frame’s edge was a distortion from the fluid bulge under the macula.

The timing of Edmund’s diagnosis gave him options others did not have even a few years ago: “anti-angiogenesis” drugs injected into the eye. The word describes the function: anti (work against) angiogenesis (formation of new blood vessels). For Edmunds, two were available. One was FDA approved. The other choice was a colon cancer drug used “off-label” for macular degeneration. Edmund’s first chose the FDA-approved treatment, an injection of Macugen™, a Pfizer drug. When it didn’t make a difference in his vision, he asked Vogel if he could try the Avastin™ by Genentech. As a retinal specialist, Vogel had followed the injected Avastin™ issue with interest. “It was not something I pictured myself as ever doing, because of the side effects and the setting - it is more of an academic pursuit,” said Vogel. Then Vogel attended a retina specialist seminar, and heard the report, first hand. “There was literally a gasp in the room,” said Vogel. Patients with wet macular degeneration were improving. Over the past 10 years, the treatment goal has been to stop the loss in patients, said Vogel. Now, he said, “We’re looking more at how many we can get to gain vision.”

Several drugs have similar targets to stop blood vessel growth. They are Anti-VEGF (Vascular Endothelial Growth Factor) drugs like Macugen™, or soon-to-be released Lucentis™. Anti-VEGF drugs work by blocking a biological component needed for production of the abnormal blood vessels, which leak, creating a fluid-filled space where none should be. Blocking that process, said Vogel, is like turning off a spigot, which allows the body “to do what it does so well, which is to remove fluid from space it’s not supposed to be in. You end up with no fluid.” Anti-VEGF treatment is different from what’s been done in the past. “For retinal specialists this is a big shift in the way we think, because it’s always been destroy, destroy, destroy,” said Vogel. Hot lasers and cold lasers plus light sensitive chemicals were part of the weaponry. But researchers found that the body responds to destruction by increasing the very substance, VEGF, that causes the vessels to grow.  That meant other medications had to be given to control it. More than one factor promotes the undesirable growth.

Vogel has other patients using Macugen™, and some who are trying Avastin™. He isn’t doing as much laser treatment as in the past- but a lot more injections. “This is changing my practice,” he said. Dawn Kalmar, spokeswoman for Genentech, said the company has worked for years to develop Lucentis™ as a safe and effective drug for wet macular degeneration. Its development generated much excitement, she said, but a regulatory path lag time creates a gap for physicians in need. “Physicians found a way to fill the gap,” she said. “Some used Avastin™ off-label to treat patients.” Edmunds wanted to try Avastin™ even though it has risks. He’s had three injections. His vision is at about 20/40 with some ability to read letters on the 20/30 line. After a few weeks, he’ll be back to Macugen™ injections every six weeks for perhaps as long as two years. Edmunds knows what he’s dealing with. And he knows that macular degeneration can progress and can also appear without warning in the other eye. “It’s been stable,” said Edmunds. “But there are no guarantees.”