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New Treatments for Wet AMD
By Richard Spaide, MD
What Is Wet AMD?
Wet age-related macular degeneration (AMD) is a term that describes a process where blood vessels and other cells invade the area under the macula, the part of the retina used for detail vision. The invading tissue can leak, bleed and cause scar tissue to form, damaging the macula and causing vision loss.
The most important aspect about wet AMD is that the body wants, and actively tries, to make these blood vessels grow. In many diseases, doctors help the body do what it already wants to do. For example, if you get an infection, your doctor prescribes an antibiotic that works together with your body's immune system to clear the infection. Once you're better, you stop taking the antibiotic. Macular degeneration is quite different. Your doctor is trying to oppose what your body wants to do. The body wants to make blood vessels grow, while your doctor tries to prevent that growth. Treatment for wet AMD can suppress the body's ability to make blood vessels in the eye, but sooner or later the medicine wears off and the body will try to make blood vessels grow again. Then, the treatment needs to be repeated.
If you're diagnosed with wet AMD, it is a life-changing event. You will need chronic treatment. Currently, there is no cure; however, conscientious follow-up and treatment are usually successful in keeping these blood vessels in check.
Evolving Treatments
While a cure for wet AMD is not yet a reality, there are now more treatment choices, and the field is changing rapidly. Recommendations made only a few years ago no longer hold today.
For example, doctors previously used a laser to treat wet AMD. Although lasers may sound high-tech, the strategy for their use was fairly simple. The doctor used the laser to burn the blood vessels in order to make them go away. Since the body actively tries to make blood vessels grow, it isn't hard to figure out the problem with lasers - even if a doctor could successfully "cook" these blood vessels, new ones often quickly regrew to take their place. Unfortunately, each laser treatment destroys retinal cells.
The next development used a drug called Visudyne® that specifically binds to blood vessels. When Visudyne® is activated with a special cold laser in a process called photodynamic therapy, the drug damages blood vessels and causes them to close down. In the process, the treatment caused inflammation but not as much damage to the retina as the hot laser. Yet again, the same difficulty exists: blood vessels regrow after treatment. While photodynamic therapy can be repeated without causing too much damage, it does have several drawbacks: it causes some damage to normal tissue, and doesn't work for many subtypes of wet AMD.
To avoid some of the problems with photodynamic therapy, doctors began to use triamcinolone - a corticosteroid injected directly into the eye. Triamcinolone reduces inflammation specifically caused by photodynamic therapy and suppresses the regrowth of vessels. In addition, triamcinolone lasts for up to six months in the eye. Patients treated with a combination of triamcinolone and photodynamic therapy appeared to have better visual outcomes with fewer treatments per year. Unfortunately, triamcinolone has many side effects, including glaucoma and cataract formation.
Anti-VEGF Treatments
The need emerged to develop a way to suppress blood vessel growth without causing so many side-effects. The answer came from cancer therapy. Tumors grow, and to grow past a certain size, they need blood vessels to feed them. Cancer research has focused a lot of attention on inhibiting this process. The most important chemical that causes blood vessel growth is a protein made by the body called Vascular Endothelial Growth Factor (VEGF). Various drugs have been developed to block the effects of VEGF so that blood vessel growth can be stopped or, at least, restrained.
Injecting VEGF blockers (anti-VEGF agents) into the eye was a huge breakthrough in treating wet AMD. The first drug used was Macugen® developed by (OSI) Eyetech, which could only block some forms of VEGF. Patients treated with Macugen® did better than those not having treatment, but they still lost vision. Later development of two closely related drugs, Avastin® and Lucentis® by Genentech, brought macular degeneration treatment to a new level. Patients treated with Lucentis® have a small improvement, on average, in visual acuity. Until now, no other treatment had resulted in a net gain in vision. Some doctors are using Avastin® and, while the cost differs, the results to date are very similar. Both drugs are significant advances, producing much better results than no treatment or previous treatment. Lucentis® is FDA-approved for wet AMD. Avastin® is FDA-approved for colorectal cancer and is being used "off-label" to treat wet AMD. Both drugs continue to be evaluated in ongoing clinical trials.
Initial clinical studies used monthly injections of Lucentis® in patients with wet AMD with impressive results. Various strategies are being used to try to reduce the number of injections needed, as monthly treatment is a difficult regimen for patients. We don't know the right approach for everyone, but we are finding that it's possible to use less frequent dosing in many patients. About one-third of patients treated will have a significant improvement in vision, which retinal specialists define as being able to read three lines more on the eye chart than before treatment. However, many patients lose more lines than this when they initially develop the disease, so a three line improvement in a minority of patients still isn't the desired outcome.
What we would like is for a greater proportion of patients to have a greater amount of vision gained. To accomplish this, treatment trials are underway to combine other drugs or treatments with Lucentis® or Avastin® For instance, the use of Lucentis® with a drug that blocks a factor called Platelet Derived Growth Factor (PDGF) is under investigation to see if the results are better than using Lucentis® alone. Most studies of this type focus on newly diagnosed, previously untreated patients. Another goal is to reduce the number of required treatments. Some new research is investigating various strategies to reduce the treatment frequency, but the visual outcomes of these approaches are not known at present.
It's important to work with your doctor to stay informed and assess your treatment options. Early treatment is critical. Although the results of treatment are better than ever before, we continue to look for even more promising results in the future.
Richard Spaide, MD, is an ophthalmologist with Vitreous Retina Macula Consultants of New York, and is affiliated with the Manhattan Eye, Ear and Throat Hospital.
This article originally appeared in the Fall/Winter 2007 edition of Sharing Solutions. To download the entire newsletter, click here