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What Treatments Are Available for Wet Macular Degeneration (AMD)?

By Lylas G. Mogk, M.D.

In wet (neovascular/exudative) age-related macular degeneration (AMD), abnormal blood vessels develop under the macula and break, bleed, and leak fluid. This damages the macula and if left untreated can result in rapid and severe loss of central vision. The most effective treatments to date for wet AMD are several anti-angiogenic drugs.

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti = against; angio = vessel; genic = development), and anti-neovascular (anti = against; neo = new; vascular = blood vessels).

The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein called vascular endothelial growth factor, or VEGF, that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments.

Lucentis, Avastin, and Eylea

At present, these drugs are administered by injection directly into the eye after the surface has been numbed. The needle is very small and is inserted near the corner of the eye — not the center. During the injection procedure, the doctor will ask the patient to look in the opposite direction to expose the injection site, which also allows the patient to avoid seeing the needle. Anti-angiogenic drugs currently in use include Lucentis, Avastin, and Eylea. An earlier drug, Macugen, is also used in certain circumstances.

To learn more about clinical research on treatments for macular degeneration, visit the National Eye Institute website for information on clinical studies.

Clinical Trials for Wet Macular Degeneration

In order to receive approval from the U.S. Food and Drug Administration (FDA), a new drug or treatment must be proven to be both safe and effective by undergoing a rigorous series of controlled unbiased studies. To prevent bias, neither the patient nor the examiners can know which patients received the actual treatment and which were the untreated (or "control") subjects.

These are called "double blind" or "double masked" studies and usually yield the most reliable results. The medication is coded and patients are placed at random into either the treatment or control group. When the study is concluded, the code is revealed and it is then possible to determine who received the actual drug and who received the inactive substance, or placebo.

As defined by the U.S. National Institutes of Health, most clinical trials are designated as Phase I, II, or III, based on the questions the study is seeking to answer:

  • In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
  • In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
  • In Phase III studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase IV studies, after the Food and Drug Administration has approved the drug, continuing studies will determine additional information, such as the drug's risks, side effects, benefits, and optimal use.

As the incidence of AMD increases, due primarily to the aging of the US population, a number of in-depth studies, clinical trials, and remedial interventions are presently underway:

Other Treatments for Wet AMD

Photodynamic Therapy

Photodynamic therapy (PDT) was developed by researchers at the Massachusetts Eye and Ear Infirmary and has been approved for AMD treatment by the FDA since April 2000. PDT works as follows: A 10-minute intravenous administration of Visudyne (a photosensitive drug) is followed by the application of a low-dose, non-thermal (light only) laser to the affected area of the retina. The drug circulates throughout the body's blood vessels, and is particularly attracted to new blood vessels, including the abnormal vessels under the macula.

The laser activates the drug, which selectively seals off the leaking blood vessels without damaging the surrounding healthy retinal tissue. This feature allows PDT to be used directly beneath the center of the macula, unlike thermal (heat) laser photocoagulation, which can burn and destroy normal retinal tissue.

Thermal Laser Photocoagulation

Thermal laser photocoagulation is a technique used by retinal surgeons to treat a number of eye conditions, one of which is wet AMD. A thermal (heat) laser is directed into the eye at abnormal blood vessels growing beneath the retina. The heat from the laser closes off the unwanted blood vessels, preventing further leakage and vision loss.

Thermal laser photocoagulation does not restore lost vision; therefore, in the past, it was critical that treatment be initiated as early as possible in the course of the disease. Unlike PDT, however, thermal laser can also destroy surrounding healthy retinal tissue as it seals the leakage from abnormal blood vessel growth; therefore, it is not used on vessels directly under the center of the macula. At present, thermal laser is rarely used in clinical practice.

Macular Translocation Surgery

Macular translocation is a surgery that involves detaching the retina from its base, rotating it slightly, and replacing it in a different position, so that the macula sits on a new, healthy base. While macular translocation surgery is unlikely to become standard treatment for everyone with wet AMD, it has proven effective for some when done promptly. It does not work for dry AMD because, for reasons not yet understood, the degeneration recurs in the new position.

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