Treating Wet Amd - Age Related Macular Degeneration Amd: Eye Care

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Treating wet AMD

The only option for treating wet AMD used to be laser surgery. But this approach had limited effectiveness, because laser surgery cannot prevent the growth of new blood vessels, and because it results in destruction of both diseased and healthy retina. Also, laser surgery does nothing to correct or slow the underlying disease process in wet AMD. In the search for better options, researchers now believe the most promising results are coming from medications called anti-vascular endothelial growth factor drugs, or anti-VEGF. Although they work in different ways, these drugs inhibit angiogenesis, the formation of new blood vessels.

Laser treatments

Because anti-VEGF drugs are fast becoming the treatment of choice for many people with wet AMD, laser treatments are being used less frequently. In general, lasers are used only in situations where the leaking blood vessels are located at the periphery rather than in the central portion, or fovea, of the macula.

Laser photocoagulation. In this procedure, the doctor aims a laser beam at leaky blood vessels to seal them and prevent further seepage. People reap the most benefits when the procedure is done on newly formed vessels that haven't yet encroached on the fovea. In such cases, sealing off the leaking blood vessels may be able to restore vision. As with other laser surgeries, laser photocoagulation can be done in a doctor's office. The laser procedure itself takes only a few minutes, although the entire office visit may take significantly longer, and sometimes multiple treatments are necessary. You may experience some mild discomfort and sensitivity to light afterward. Frequent checkups will be scheduled, during which the doctor may repeat the fluorescein angiography to assess the status of the blood vessels. The surgery is often helpful, but in about half the cases, the condition recurs and may require more laser treatments.

Photodynamic therapy. Another option is Visudyne therapy, a type of photodynamic therapy (see Figure 10), which uses light-activated drugs to treat medical conditions ranging from cancer and heart disease to autoimmune conditions and eye diseases, including wet AMD. The FDA approved Visudyne therapy in 2000. This treatment has been used much less frequently since the introduction of anti-VEGF drugs (see below).

Figure 10: Photodynamic therapy for macular degeneration To treat wet AMD, a light-activated chemical, which is given intravenously, settles in blood vessels behind the retina. Next, the doctor uses a low-intensity laser to activate the chemical in the blood vessels, vaporizing the leaking vessels that cause AMD. Several treatments are necessary.

Visudyne therapy is a two-step, 15-minute process that can be done in a doctor's office. First, the drug verteporfin (Visudyne) is injected into a vein in the arm through an intravenous line over a 10-minute period. During the next 5 minutes, the drug travels through the body and accumulates in the abnormal blood vessels in the eye. The doctor then activates the drug by shining a low-intensity laser into the eye for about 90 seconds. This produces a highly energized form of oxygen that kills abnormally growing cells, closing off the abnormal blood vessels without damaging surrounding healthy eye tissue. Visudyne therapy alone rarely restores vision; more often, it simply slows retinal damage and decline in vision caused by wet AMD. To preserve vision, patients usually need more than one Visudyne treatment per year.

Research is now under way to determine whether combining photodynamic therapy with steroid injections might increase the effectiveness of this approach. Such steroid injections should suppress the formation of new blood vessels, thus decreasing the risk of recurrence and preserving vision — but the jury remains out until the study results are reported.

If you undergo Visudyne therapy, stay out of the sun for two to five days after treatment; you'll want to avoid exposing your skin or eyes to direct sunlight or bright light. Your eyes may be especially sensitive to light. Speak to your eye doctor about other steps you'll need to take following this therapy.

Anti-VEGF drugs

VEGF, or vascular endothelial growth factor, stimulates the formation of new blood vessels in the eyes (see Figure 11) and elsewhere in the body. Anti-VEGF drugs not only inhibit new blood vessel formation, but also appear to decrease vascular permeability — that is, they reduce the amount of leakage from abnormal blood vessels.

Figure 11: Targets for anti-VEGF therapy The wet form of age-related macular degeneration injures healthy tissue in the retina. The blood vessels and photoreceptor cells of a healthy eye are seen in the top illustration (A). When VEGF molecules stimulate abnormal blood vessel development, healthy blood vessels sprout tentacles that extend under and into the retina, toward the macula (B). These new vessels are prone to leak fluid and blood, which injure tissue and photoreceptor cells. Anti-VEGF drugs counteract the action of VEGF molecules, thereby inhibiting blood vessel proliferation. They also appear to decrease vascular permeability, which decreases the amount of leakage from abnormal blood vessels.

So far, research shows that injecting anti-VEGF drugs into the eyes can slow vision loss, and in some cases even restore vision, in people with wet AMD. But the treatment is long-term, involving injections at regular intervals for at least a year and often longer. Possible side effects include eye pain, irritation, discharge, and seeing spots or floaters — although most people don't develop such problems.

Although the thought of eye injections may make you shudder, people who have undergone the treatments have found them tolerable and generally painless. The doctor numbs the eye ahead of time, and people say the injection itself feels a bit like touching their eye in search of a lost contact lens.

The FDA has approved two such drugs for use in wet AMD, while another is being prescribed off-label (although this is controversial). A number of other agents are in the drug development pipeline. Although the studies so far have involved long-term injections with anti-VEGF drugs, studies under way now are investigating whether it is possible to reduce the number of injections needed to achieve good results.

Keep in mind that these drugs can be expensive, so it's important to check your insurance plan or Medicare coverage to see how much of the cost you will need to shoulder if you decide to go ahead with this therapy.

Pegaptanib (Macugen). The FDA approved pegaptanib, the first anti-VEGF drug for wet AMD, in December 2004. Results from the VISION study and other analyses have found that pegaptanib is effective at slowing the progression of vision loss in many people and can actually restore it in a small number of people. In the VISION study, for example, 6% of those treated with pegaptanib for 54 weeks had gained three or more lines of vision when tested with a vision chart at the end of the study period.

But while pegaptanib is considered a step in the right direction, it does not restore vision in most people with wet AMD. This drug may be more effective for people with early-stage wet AMD. The VISION data also indicated that between 12% and 20% of people with early-stage wet AMD gained three lines or more on a vision chart, compared with 6% for the study group over all.

Pegaptanib injections usually take place every six weeks and are recommended for two years, although individual schedules may vary.

Ranibizumab (Lucentis). The FDA approved another anti-VEGF drug, ranibizumab, in June 2006. Ranibizumab is generating much more enthusiasm than pegaptanib, because research so far shows not only that it improves vision in a greater number of people treated, but also that the improvements are significant enough in many cases to improve quality of life.

Results of the MARINA study, a phase 3 clinical trial of ranibizumab (the last stage of the hurdles required before a drug can be submitted to the FDA), were reported at the July 2005 meeting of the American Society of Retina Specialists. The yearlong study involved 716 people with AMD. By the end of the study, on average the people treated with ranibizumab gained 7 letters in visual acuity, while those in the control group lost 10.5 letters. Analyzing the data another way, researchers found that 95% of people treated with ranibizumab either lost fewer than 15 letters or gained letters, compared with 62% of those treated with sham injections. What's more, 25%–34% of people treated (depending on the dose) improved their vision (gained 15 letters or more), compared with 5% in the control group.

Researchers also reported that roughly 40% of people taking ranibizumab improved to the point of achieving at least 20/40 vision, compared with 11% of those in the control group. This sort of improvement can affect someone's quality of life in practical terms—allowing someone with wet AMD to drive again, for example.

Results from another phase 3 trial, the ANCHOR study, reported in January 2006, were also impressive. The ANCHOR trial compared two doses of ranibizumab with photodynamic therapy, a type of laser treatment. After one year of treatment, people treated with ranibizumab gained an average of 8.5–11 letters (depending on the dose taken) on a vision chart, while people treated with the photodynamic therapy lost an average of 9.5 letters.

Bevacizumab (Avastin). This drug is currently FDA-approved for the treatment of colorectal cancer, but its mode of action in the body is similar to ranibizumab. Because anecdotal reports indicate that bevacizumab is effective in treating wet AMD, some ophthalmologists have begun to prescribe it "off-label" to their patients.

Although such off-label prescribing is legal, and it happens for other types of medical problems, it's wise to know the risks before agreeing to take bevacizumab for wet AMD. Most important, the drug has not been studied specifically for use in AMD. Although some ophthalmologists are concerned that questions remain about the long-term safety and effectiveness of bevacizumab, at this point it has been used in thousands of patients, and few safety concerns have been reported. If you are interested in learning more about whether bevacizumab may be appropriate for you, talk with your doctor.

Last updated:	June 19, 2007