Blind World Magazine

Macular Degeneration.
Doctors tracking cancer drug’s use on incurable disease.

November 14, 2005.
The Journal Gazette.

Age-related macular degeneration – AMD – is the leading cause of blindness for people age 55 and older in the United States. An incurable eye disease, it affects more than 10 million Americans, and as baby-boomers age, that figure is expected to increase significantly.

That is not good news, but, typically, the news about macular degeneration is never good. It strikes, it advances and central vision is destroyed. Even the best available treatment might only slow its progress.

Still, there are reasons to be hopeful. Greater awareness can lead to early detection and early treatment. Education about controllable risk factors might prevent or delay AMD, and new treatments could one day not only stop the disease but improve vision. Avastin, a drug used to treat cancer, is being used experimentally to treat AMD and results so far are promising. More about that later.

How do you know if AMD is attacking your eyes?

If you notice any distortion in your vision, such as waviness or lines not being straight, or if there’s unusual blurriness or any sudden change in your vision, you should get your eyes checked right away.

“Don’t sit around and ignore it for two months and hope it goes away,” ophthalmologist and surgeon Dr. Jon Walker says.

In that period of time, if it’s AMD, it will only get worse.

There are two kinds of macular degeneration: dry, the most common form, in which vision is lost gradually over time, and wet, which is more severe and can happen suddenly.

The degeneration of the macula, which is in the center of the retina that lines the back of the eye, happens because of a buildup of age spots, or drusens, underneath the retina. Walker, of Farber and Walker Diseases & Surgery of the Retina and Vitreous, 7900 W. Jefferson Blvd., explains what’s happening.

“Your body has only one way to fix anything and that’s to grow a blood vessel. If you scrape your knee, you don’t tell your body to fix your knee – your body knows there’s a hole there, grows a blood vessel and patches you up. Your body’s always looking for trouble.

“Well, as you get older, you start to build up aging spots underneath the retina and that’s usually not a big problem, but sometimes the body will misinterpret the problem and then it will treat the back of the eye like a scraped knee. … These microscopic blood vessels – the wet macular degeneration – sprout like weeds growing through cracks in a sidewalk. They sprout up and spread around to try to get rid of the aging spots … but the problem is the retina is sitting on top of this, so as soon as the blood vessel sprouts, it pushes the retina up and suddenly the image of the world projected on this irregular retina is bent.”

Damage to the macula in that case happens rapidly and loss of central vision can occur quickly.

Early detection is key for treatment to be effective. The American Academy of Ophthalmology recommends a routine eye exam every two to four years for people 40 to 64 and every one to two years for those 65 and older. Regular, at-home monitoring of vision with an Amsler grid, a chart that resembles graph paper, also can help detect trouble early by revealing signs of distortion.

Long-term avoidance of controllable risk factors also can help. Research has shown that AMD occurs two to three times more often among tobacco smokers than non-smokers, and the risk correlates with the amount used. The more a person smokes, the greater the risk and the faster the progress of the disease if it starts.

Walker says smoking is “the No. 1 modifiable risk factor. You can’t control your genetics; you can’t control your age. Smoking clearly makes macular degeneration worse.”

Other controllable risk factors are hypertension, excessive sun exposure, obesity and poor nutrition. The AMD Alliance says a high-fat, high-cholesterol diet can lead to fatty plaque deposits in the macular vessels, which can impede blood flow and increase the risk of AMD, while a diet low in fat promotes good eye health.

Risk factors that can’t be controlled include age, genetics, gender, skin and eye color and severe farsightedness.

The U.S. National Eye Institute estimates that people in their 50s have a 2 percent chance of getting AMD but the risk increases to nearly 30 percent in those older than 75.

In general, AMD is most prevalent in white women older than 60, occurs more often in Caucasians than in other races and is more prevalent in blue-eyed people. People with a family history of AMD are at higher risk of getting it. Severe farsightedness is uncommon, but because it is related to extreme distortion of the eye’s shape, it can affect the retina.

While there is no treatment for advanced dry AMD, when it reaches the intermediate stage, a specific high-dose formulation of antioxidants and zinc was found in a National Eye Institute Age-Related Eye Disease Study to reduce the risk of advanced AMD and its associated vision loss. The specific amounts used in the AREDS research were 500 milligrams of vitamin C, 400 international units of vitamin E, 15 milligrams of beta-carotene, 80 milligrams of zinc as zinc oxide and two milligrams of copper as cupric oxide.

“The study showed that the vitamins only work if you have a certain amount of aging change in the eye,” Walker says. “It doesn’t mean that everyone should take high-dose vitamins. For instance, we aren’t completely sure it’s safe for younger patients to take those high doses for many years. We think it is safe for appropriate patients, but the AREDS vitamins are only for very specific subjects. Go to your eye-care professional and have them look in your eye and tell you before you run to the store and buy them.”

Treatment for wet AMD used to be destruction of the encroaching blood vessels with a laser, leaving a permanent blind spot. That still might be done in some situations, but newer treatments cause less damage.

Walker says the first breakthrough came with a treatment called Visudyne.

“With that treatment, we inject a special dye and we can use a milder laser and try to get the blood vessel to shrivel up without damaging the retina. So instead of destroying retina to save their vision, we can treat the blood vessel directly.”

It amounts to controlling the damage, so there will be a gradual decline.

The next advance came with Macugen, which works by targeting the chemicals that trigger abnormal blood vessel growth and leakage. Delivered by injection into the eye every four to six weeks, Macugen reduced vision loss in 70 percent of clinical trial patients.

“What we try to do with this is the same as we do with the laser – we try to stop the blood vessel from getting huge. It’s real hard to stop it from growing, period, but our goal is to control the damage,” Walker says.

A new treatment called Lucentis, from Genetech, has not yet been approved by the FDA, although clinical trials have eye-care professionals excited.

“For the average patient with macular degeneration, we’re happy if our treatment can control the disease so they get worse slowly, although there has always been a small subset of patients that do improve with any treatment,” Walker says. “Lucentis may be the first treatment where a larger subset of patients may actually get better. To actually be able to tell a patient that there’s a small chance or even a medium chance that they might improve is pretty unusual. We’re going against Mother Nature here. Once the blood vessels grow, the body’s decided you’re going blind, so for us to go against that and win is pretty exciting.”

Lucentis is based on a chemotherapy drug called Avastin, which is used to stop blood vessel growth in certain cancers.

“(Genentech) thought the Avastin molecule was too big to get through the retina if they injected it into the eye, so they chopped it up to make Lucentis,” Walker says. “Then they spent million and millions of dollars going through the trial stage.”

But a breakthrough earlier this year at the Bascom Palmer Eye Institute in Miami has changed the picture. Doctors there decided not to wait for Lucentis.

“Avastin is a chemo-therapeutic agent – it can have severe side effects – and they told patients we think Avastin might work like Lucentis,” Walker says. “ ‘We have to give it to you in your body and you have to risk severe health problems. Do you want to risk those problems to possibly see better?’

“To be very blunt, these patients were risking their life to see better. These heroic patients and doctors tried it and they did well. Then they decided to try to avoid the risk of using the drug on the whole body, so they injected it directly into the patient’s eye, and lo and behold, it worked extremely well. A lot of retina specialists around the world are now mixing up Avastin in their pharmacies and starting to give it to patients, while we’re waiting to see what happens with Lucentis.”

Walker and his partner have been using Avastin for a couple of months..

“We tend to be pretty conservative … but the results with Avastin were so impressive that we and many, many others are trying it in selected cases, because it’s so exciting to have a patient get better. People must understand, however, that this is not an FDA-approved treatment, and there may be complications that we do not know about yet.”

Walker emphasizes the Avastin treatment applies to only a small number of people with AMD.

Tom Cook, 72, of Fort Wayne has had two Avastin treatments in his left eye.

Macular degeneration started in his right eye four years ago. Visudyne slowed its progress but he still lost central vision in that eye. Then, last December, he noticed distortion in his left eye and that was treated with Macugen.

“That seemed to slow it down some,” Cook says. “But with the Avastin, basically, it has stopped the growth (of blood vessels). It seems to have stabilized and that’s great. … If the new drug had been available last December, it might have stopped this one.”

Cook still reads with the aid of a magnifying glass and says he is “thankful to still have some sight. To me, it was not a great risk at all. I’m very pleased.”

Anna Mae Miller, 86, of LaGrange, has not been so fortunate. She lost vision in her right eye in the late 1990s and most of the vision in her left eye in 2001. She can see images, light and dark, but can no longer see to read.

“I’m thankful for what I’ve got,” she says.

“I did try one of the new drugs last December, but it didn’t work for me. The new (people) that come in and get it right away are the ones it helps,” Miller says.

Her statement embodies Walker’s primary message to people who notice distortion in their vision – get checked and get treatment early.

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