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Current and Emerging Therapies for Macular Degeneration

Age Related Macular degeneration (AMD) is a degenerative condition of unknown cause affecting the center of the retina. The central part of the retina is called the macula and it is this region of the retina that is responsible for our detailed straight-ahead vision for tasks such as reading, driving and near work. AMD is the leading cause of blindness in people over the age of 60 in the United States. An estimated 8 million Americans are afflicted with this disease and as more and more people live beyond the age of 85 we can expect a precipitous rise in the incidence of macular degeneration. In fact the number of people with AMD is expected to double by the year 2020.

Over the last decade there has been a veritable explosion in macular degeneration research, and although there is no cure for AMD, our patients are now reaping the benefits of that hard work. This section will deal primarily with current and emerging treatments for “wet” (blood vessel growth) AMD. There are a number of good resources addressing background information on macular degeneration and these are listed below:

• American Academy of Ophthalmology
• National Eye Institute
• Research to Prevent Blindness, Inc.
• AMD Alliance International
• Macular Degeneration Foundation
• Macular Degeneration Partnership

“Wet” Macular Degeneration

In approximately 10-15% of cases of AMD, abnormal blood vessels begin to grow under the macula resulting in leakage of fluid and bleeding. This leakage is very harmful and since the cells in the macula are so sensitive there is a rapid degeneration of this tissue resulting in an abrupt decline in central vision. While “wet” AMD (also known as advanced AMD) affects a minority of patients with AMD it is responsible for nearly 90% of cases of severe visual loss. Keep in mind that the abnormal vessels are essentially touching the overlying retina and thus the goal of treatment is to selectively eradicate the vessels without harming the sensitive cells in the macula. We are considerably closer to the Holy Grail of treatment as we are now better able to knock out the abnormal blood vessels without further harming the macula cells. However, we have a long way to go before we will be able to restore function to the already damaged macula tissue. This is why when we speak of treatments our goal is to stabilize or slow the disease process. Recovery of lost vision unfortunately still occurs in only a minority of patients.

Laser Surgery
Until 2000, conventional thermal laser surgery was the only treatment available for patients with wet AMD. This treatment utilizes heat from a high-energy beam of light to cauterize abnormal blood vessel growth. Because of the high energy that is necessary, the overlying retina is irreversibly damaged after this treatment. One can imagine the consequences of this treatment when the blood vessels are in the center of the macula (known as the fovea), which is responsible for 90% of our detailed central vision. Conventional laser is no longer employed when the blood vessel growth is directly beneath the center of the macula because the treatment destroys this tissue and usually worsens the vision. On the other hand, when the growth is outside the center, laser surgery is oftentimes very useful but the recurrence rate is high and patients must be monitored very closely.

Photodynamic Therapy (PDT)
In 2000, verteporfin (Visudyne) became available which is the first drug ever to be approved by the FDA for the treatment of wet macular degeneration. This treatment is used when the blood vessel growth involves the center of the macula. The drug, which is injected intravenously in the doctor’s office, accumulates in the abnormal vessels under the retina (see picture below). Since the drug is light-activated it only works when light of a certain wavelength is aimed at the abnormal vessels. This causes the drug to come to life resulting in selective closure of the abnormal vessels without harming the overlying retina (see picture below). Recurrent leakage is common and retreatment is often necessary with most people requiring 4 or 5 treatments over the course of 12 – 18 months.

Cortisone
Recently, cortisone has been found to beneficial in slowing leakage from abnormal blood vessels. Triamcinolone, a form of cortisone, is sometimes injected into the eye to reduce leakage and vessel growth. Depending on the situation, this may be administered in conjunction with photodynamic therapy or alone. The precise role of cortisone in the treatment of wet AMD remains to be seen as we are still learning about this new therapy.

Transpupillary Thermotherapy (TTT)
In this treatment, a low energy laser beam heats the abnormal vessels enough to close them but not enough to significantly damage the overlying retina. By preserving the retinal tissue it is hoped that the vision will stabilize or improve. This treatment may be helpful in situations where the blood vessel growth is large and “occult” or difficult to see. Studies comparing TTT with other newer treatments are pending and to date there has been no evidence to suggest that TTT is any better than standard treatment with PDT. Presently, few retina specialists are performing this treatment.

New Drugs
As we learn more about the mechanism of abnormal blood vessel growth, newer so called targeted therapies are emerging. Several new drugs for the treatment of wet macular degeneration are in various stages of clinical trials. These new medications work by blocking the chemicals that cause blood vessel growth under the retina. Depending on the specific drug these so called anti-angiogenesis medications are either injected into the eye or into the tissue around the eye. Although these new drugs are a more elegant way of treating wet AMD it remains to be seen if they are more effective than conventional therapy. The drugs furthest along in clinical trials are Macugen, Lucentis, and Anecortave Acetate, with Macugen slated for approval sometime in 2005 and the others 1 or 2 years later.

Surgery
Theoretically, if one could surgically remove the abnormal blood vessel growth you could potentially cure the problem and restore vision. Innovative microsurgical instruments and techniques have been developed for this purpose but unfortunately the research results have not been very encouraging. Another intriguing concept is macular translocation in which the surgeon “moves” the macula away from the abnormal blood vessel growth and places it in a more healthy location. This procedure is highly technical and complex and is performed by only a small number of retina surgeons. As we develop more effective drugs, interest in these intricate and potentially risky surgical procedures will likely wane.

“Dry” Macular Degeneration

When the cells in the macula slowly breakdown the result is blurred central vision which at times is associated with blind spots around the center. Reading and other tasks may require more light and facial recognition can become difficult. Unlike the wet variety, dry AMD has a gradual onset and progression. It typically involves both eyes but one eye may be more affected than the other. Dry AMD can progress on its own resulting in thinning of the macula and significant loss of central vision. It can also suddenly convert to wet AMD but unfortunately it is impossible to predict when this might occur.

Vitamin and Mineral Supllements
For many years doctors debated whether taking vitamins and/or mineral supplements help prevent or slow the progression of AMD. In 2001, the Age-Related Eye Disease Study (AREDS), a major study sponsored by the National Eye Institute, determined that a regimen of high dose antioxidant vitamins and zinc reduced the risk of advanced AMD and its associated vision loss. Only people at high risk of developing advanced AMD should take this regimen, as the study found no benefit in people who had early stage AMD.

The specific daily amounts of antioxidants and zinc used in the study were:
· Vitamin C 500 mg
· Vitamin E 400 International Units
· Beta-carotene 15 mg (may be labeled as Vitamin A 25,000 International Units)
· Zinc Oxide 80 mg
· Copper 2 mg as cupric oxide to prevent zinc-induced copper deficiency anemia
Smokers and ex-smokers should probably not take beta-carotene as studies have shown a link between beta-carotene use and lung cancer in smokers.

The AREDS formulation is not a cure for AMD. It cannot restore lost vision from AMD but it can delay progression to advanced AMD in high risk patients. You should talk to your Eye MD before beginning any high dose vitamin regimen to see if it is appropriate for you.

This article was written for the NEOS Website by Robert H. Janigian, Jr, MD

Updated 7/22/08