(08-29) 17:39 PDT SAN FRANCISCO -- Virginia Knepper-Doyle has had about 45 injections into her left eye over the past two years to prevent her from going blind. But last week, her doctor gave her disappointing news.

"It's not working," said Knepper-Doyle, 80, frustration obvious in her voice. "The injections had stopped any further deterioration. But suddenly I had no central vision left, and I guess that means the medications don't work anymore."

Knepper-Doyle, an artist who lives with her husband and son in Belvedere, has age-related macular degeneration, which causes the rods and cones that sense light and send visual signals to the brain to stop working. Age-related macular degeneration is the most common cause of blindness among adults in the United States, afflicting about 2 million people.

And those numbers are only going to climb as the Baby Boomers reach their 70s and 80s. The National Eye Institute estimates there will be 3 million people with age-related macular degeneration by 2020.

There are drug treatments that can protect the rods and cones, which are called photoreceptors, for a time. But for the vast majority of patients, there no treatment to restore vision once it's been lost. At least one drug, Lucentis, appears to restore vision in some patients with a type of age-related macular degeneration.

Struggling for answers

So doctors and scientists are scrambling to come up with treatments - from the relatively mundane, like drugs already on the market that might prevent further vision damage, to the seemingly outrageous, like telescopes implanted into the eye.

In the Bay Area alone, researchers are studying chemicals that have helped blind mice see, and they're developing prosthetic devices that would replace the rods and cones with electronic chips. Other scientists are looking at stem cells as a novel technique for protecting or replacing cells in the retina.

"As our population is aging, the number of people affected is going to grow. And you have people who are otherwise healthy but they can't read, they can't drive - that's a huge burden on society," said Ingrid Caras, a science officer at the California Institute for Regenerative Medicine, which has pumped about $50 million into funding for stem cell research to treat macular degeneration.

"Macular degeneration is very high on the priority list of diseases that need attention," Caras said.

Prevalence after 80

More than 1.3 million people older than 40 are blind in the United States, according to Prevent Blindness America. Most of those people - almost 950,000 of them - become blind after age 80.

Other conditions that cause vision impairment are more prevalent than age-related macular degeneration, but they're also less likely to cause legal blindness, often because treatments exist that slow or stop entirely the vision loss. Diabetic retinopathy, for example, afflicts about 7.7 million Americans, but can be controlled with good treatment for diabetes. And cataracts affect more than 24 million Americans, but cataracts can be removed fairly easily through surgery.

There are two forms of age-related macular degeneration, called dry AMD and wet AMD. Both types affect cells in the retina, where all of the work sensing light and sending visual signals to the brain takes place. Macular degeneration can be inherited but isn't always. Another type of degenerative blindness, called retinitis pigmentosa, is an inherited condition that also attacks the cells in the retina.

Roughly 90 percent of age-related macular degeneration cases are the dry version, which occurs when the retinal pigment epithelial (RPE) cells that nourish and support the photoreceptor cells die. Without the RPE cells, the photoreceptor cells also eventually fail.

In wet AMD, which always starts as the dry type, blood vessels grow abnormally in the back of the eye and eventually cause bleeding and swelling. There are drugs to treat wet AMD - which is what Knepper-Doyle was being treated for - but they usually don't restore vision and don't appear to help dry AMD patients.

Part of the reason that both forms of age-related macular degeneration are so disabling is that they attack a critical area of the eye called the macula, which is a tiny patch of cells in the center of the retina. The macula is jammed with photoreceptors and responsible for the sharp vision that allows us to read, see faces, drive and watch TV.

So patients may not ever lose all of their sight, but they often will end up legally blind.

"It's sort of like a completely foggy day, and you're on the Golden Gate Bridge," Knepper-Doyle said. "And it's really hard to see the car in front of you, but you can see it a little, just the outline, or this blob of darkness in the fog."

Where to start?

Restoring vision to those who have lost it - or better yet, preventing people from ever developing macular degeneration - is the ultimate goal. But with few clues as to what sets off the chain of events that causes the photoreceptors to die, scientists don't know where to start preventing it.

And repairing or replacing the photoreceptors, which are complex neural cells that communicate with the optic nerve and, in turn, the brain, is widely considered beyond our scientific capabilities for now. Therefore, much of the research into macular degeneration is focused on treatments to protect the vision that remains or finding ways to bypass the damaged photoreceptors.

Scientists are working with stem cells on several possibilities for preventing vision loss. Much of the funding from the California Institute for Regenerative Medicine, for example, is going toward a program to replace the damaged retinal pigment epithelial cells that nourish the photoreceptors.

Injecting stem cells

Scientists at StemCells Inc. in Newark are taking a different approach. Early studies of human neural stem cells - the precursors to cells that make up the nervous system - revealed that those stem cells seemed to protect the nerve cells around them. Now they're hoping to tap into that protective trait by injecting the stem cells into the eyes of patients with macular degeneration, and seeing if the cells will protect the photoreceptors.

The technique has worked in rats, and soon the company, working with a vision research center in Texas, will begin injecting the cells into human patients. Researchers with StemCells Inc. hope that their relatively simple approach - using stem cells for protection, rather than to rebuild or replace damaged cells - will offer more immediate benefits than the more aggressive techniques proposed by other scientists.

"If you start by trying to swing for the fences and pick the most difficult pathway, that is admirable, but it's going to take some time to get there," said Dr. Stephen Huhn, vice president and head of the Central Nervous System Program at StemCells Inc. "You might learn a lot of useful things and have a very effective therapy with a much simpler presence."

A chemical solution

A few miles north at UC Berkeley, scientists are studying a chemical that, when given to mice, works with a protein in the damaged cells of the retina to make them sensitive to light again. The chemical has temporarily restored vision to blind mice, and may someday be useful for patients with the most debilitating forms of degenerative blindness.

Retinal prostheses - devices that can be implanted into the eye to bypass the damaged photoreceptors - similarly are being studied as a means of restoring some small degree of sight to those who are totally blind. First conceived in the '60s, early models were made in the '80s, and versions are being sold commercially in Europe. A type of retinal prosthesis is under review by the U.S. Food and Drug Administration.

Retinal prostheses are similar to cochlear implants, in that a device is implanted into the sensory organ - the eye or the ear - to pick up light or sound and translate it into signals that can be picked up by nerve cells and transmitted to the brain.

At Stanford, scientists have developed a type of retinal prosthesis involving a silicon chip implanted just behind the retina. Patients would wear goggles that collect and process visual data and then transmit that data, via near-infrared light that is not visible to humans, directly to the chip. The chip would, in turn, produce electric currents that would be picked up by other layers of the retina and sent to the brain.

The prosthesis has been shown to work in rats, and now the Stanford scientists are refining their work to develop higher-resolution images. Much as cochlear implants can't re-create normal hearing, retinal prostheses won't result in normal vision. And at least for now, the vision that's restored is minimal - allowing completely blind people to see fuzzy shapes or maybe the edge of a sidewalk.

'Nothing to something'

That's a potentially huge improvement for someone who's totally blind, but not necessarily useful for someone who's legally blind and wants to be able to read or watch TV again. If scientists can improve the resolution, the prosthetic devices could be made much more useful, said Jim Loudin, a physicist who's been working on the Stanford prosthesis since 2005.

"In the entire retinal prosthesis field, the person who's responded best has not really been able to see that E on the eye chart," Loudin said. "It's helping people who are going from nothing to something."

Knepper-Doyle isn't expecting any of the current experimental treatments to be available in time to save her vision, which has declined steadily since she was diagnosed six years ago. The drugs helped for a while, or at least slowed the progression.

But she can't read text on the Internet anymore, and she stopped driving some time ago. Her vision loss has made it difficult to socialize too, because she has a hard time recognizing faces or seeing cards when she plays bridge with friends.

"I've asked my doctor what's coming up the pike with treatments for AMD. And he says the exciting stuff won't happen for about 10 years," Knepper-Doyle said. "But I'm 80, so I don't know whether I'll see that happen or not, and I'm sorry it isn't coming sooner."

The abstract artist

Ironically, perhaps, the vision loss has had a charmingly positive effect on her art. Before she started to go blind, most of her art was impressionist, and she had an eye for details. Now, her paintings are all abstracts and full of color. She regularly shows her work in galleries.

"I couldn't do the kind of art I was doing before, so I changed to be very loose. And people seem to like them," she said. "I work outside, with the birds all around. I can still see colors. They may be different than what you see, but I can see them."