What is macular degeneration?

The retina is the light-sensitive membrane lining the inside of our eye. The macula is the central retina - that portion of the retina used for "straight-ahead" vision (reading, recognizing faces, etc.). As some people get older, the macula deteriorates with age - this is called age-related macular degeneration or ARMD.

What causes macular degeneration?

There are several factors that increase the risk for developing macular degeneration. The greatest risk factor is genetic - certain people inherit genes that place them at a high risk for developing ARMD. The second most important risk factor is advancing age. The older one gets, the greater is his or her risk for ARMD. Two other factors that increase the risk for ARMD are smoking, and high blood pressure. Finally, eating a poor diet may also increase the risk for ARMD. Individuals eating a well-balanced diet rich in green, leafy vegetables, fish, and fruit have a slightly lower risk of developing ARMD.

How is macular degeneration diagnosed?

The diagnosis of ARMD is based upon the finding of characteristic abnormalities in the macula during a dilated eye exam. These findings include:

1. Drusen - small yellow deposits underneath the macula.

2. Pigment alterations - spots of increased/decreased pigment

3. Atrophy - thinning of the tissues in the macula

4. Choroidal neovascularization - abnormal blood vessel growth beneath the macula

Drusen in patient with
age-related macular degeneration

What are "dry" and "wet" macular degeneration?

ARMD is considered "dry" when drusen, atrophy, or pigment alterations are seen without any evidence of abnormal blood vessel growth. When abnormal blood vessels grow, they often cause fluid accumulation under the retina, leading to the term "wet" macular degeneration. 90% of patients with ARMD have the dry form, but "wet" ARMD causes 90% of the severe visual loss seen.

What treatments are available for "dry" AMD?

Antioxidant supplements have recently been proven to be beneficial in age-related macular degeneration. While antioxidants do not improve vision or reverse macular degeneration, they do reduce the chance of future visual loss. Laser treatment can reduce the number of drusen but it is not yet known whether this improves the visual prognosis. Current recommendations for patients with dry AMD include the following: take antioxidant supplements, don't smoke, control your blood pressure, and eat a well balanced diet rich in green leafy vegetables (like spinach), fish, and fruit.

What antioxidants are recommended?

The Age-related Eye Disease Study (AREDS) recommended that individuals older than 55 with at least moderate macular degeneration should consider taking a supplement of antioxidants plus zinc. Individuals considering supplements should discuss their use with an internist prior to beginning treatment. The oral supplements used in the study were taken twice daily with food at the following doses:

• Vitamin C 250 mg (500 mg daily)

• Vitamin E 200 IU (400 IU daily)

• Beta Carotene 7.5 mg (15 mg daily)

• Zinc 40 mg (80 mg daily), and

• Cupric Oxide 1 mg (2 mg daily) – this is given to avoid copper deficiency which zinc may cause

Researchers cautioned that individuals who smoke (or have smoked within the past 10 years) should avoid the use of beta-carotene, since two other clinical trials have suggested an increased rate of lung cancer among smokers using this supplement. The AREDS study showed no benefit of the supplements for patients with mild or no macular degeneration.

What is Lutein?

Lutein is a pigment found in the macula and also in green leafy vegetables. Studies have found that patients who eat a diet rich in green, leafy vegetables (such as spinach) have a lower risk of developing macular degeneration leading researchers to speculate that Lutein intake is beneficial. It is currently unknown whether taking Lutein in a supplement form is helpful for macular degeneration or not.

What treatments are available for "wet" AMD?

Numerous treatments are now available for patients with "wet" AMD. Traditional laser treatment is commonly recommended to treat blood vessels which are not directly under the central retina. Because laser treatment leaves a permanent blind spot, other treatments (photodynamic therapy with or without Kenalog, Macugen therapy, and Avastin therapy) are often recommended when the blood vessels grow under the central retina.

What is photodynamic therapy (PDT)?

Photodynamic therapy is an FDA-approved treatment for certain types of choroidal neovascularization under the central retina. A photosensitizing dye (verteporfin) is injected into a vein in the arm and allowed to concentrate in the choroidal neovascularization in the eye. A specially tuned "cold" laser is then shined onto the blood vessels a few minutes later. This treatment activates the dye causing a chemical reaction which damages the blood vessels. Unlike traditional laser, the treatment does not burn the retina and so no blind spot is caused. Unfortunately, the blood vessels often grow back and most patients require retreatment with PDT 3-5 times over the following 1-2 years. PDT has been proven to reduce the risk of further visual loss but visual improvement is uncommon. PDT is most effective for treating abnormal blood vessels of the “classic” variety (a particular growth pattern seen on fluorescein angiography).

What is Kenalog?

Kenalog is a long acting steroid that is often injected inside the eye in combination with PDT. Several studies suggest that patients treated with the combination of PDT and Kenalog are more likely to improve and less likely to worsen than patients treated with PDT alone. Unfortunately, Kenalog is known to speed the development of cataracts and may cause an elevation of intraocular pressure.

What is Macugen?

Macugen is the first anti-angiogenesis drug approved by the FDA to treat wet macular degeneration. Macugen inhibits a chemical known as Vascular Endothelial Growth Factor (VEGF), which is known to play an important role in the growth of abnormal blood vessels. Macugen is injected inside the eye in a relatively painless 5 minute office procedure. Like PDT, this treatment has been proven to reduce the risk of further visual loss but visual improvement is uncommon. Injections usually need to be repeated every 6 weeks for 1-2 years. Macugen is effective for treating both “classic” and “occult” varieties of blood vessels.

What is Avastin?

Like Macugen, Avastin is an anti-angiogenesis drug which inhibits VEGF. Avastin is FDA-approved for the treatment of patients with colorectal cancer, but has not yet been rigorously studied in patients with wet macular degeneration. As a result, it is not yet FDA-approved for this indication. Avastin is a more potent inhibitor of VEGF than Macugen, and many retina specialists believe it will prove to be a more effective treatment for wet macular degeneration than Macugen or Photodynamic Therapy. A recently published study of 81 eyes treated with Avastin injections inside the eye showed an improvement in average vision among treated patients (a finding not seen with either Macugen or PDT). Medicare and other insurance companies will not yet pay for Avastin – the average cost per injection is approximately $300.

What is Lucentis?

Lucentis is another anti-angiogenesis drug which inhibits VEGF. Lucentis is derived from Avastin which was chemically modified to be smaller and to have a higher affinity for VEGF. While not yet available, Lucentis is in the final phases of FDA approval and is expected to come on the market in the latter part of 2006.

What research is being done?

Macular degeneration is one of the most intensively studied diseases of the eye, and research holds real promise for more effective treatments in the near future. In addition to the numerous anti-angiogenesis drugs mentioned above, a whole new class of drugs based on small interfering RNA (siRNA) molecules seems to hold real promise in early studies.

Genetic research may hold the key to the greatest treatment of all - prevention! Identifying the specific genetic abnormalities that cause ARMD will open many doors towards developing a treatment. Last year, the first such genetic abnormality was identified – a mutation in the complement factor H gene. A mutation in this gene may be the cause of almost 50% of cases of macular degeneration. Because this gene is important in the regulation of inflammation in the body, inflammation is now thought to play a significant role in the etiology of macular degeneration. Research in transgenic animals (animals bred to carry specific genetic abnormalities) will allow testing of various medications in expedited fashion. Furthermore, genetic screening may allow identification of individuals at risk for ARMD long before they ever develop visual loss. This will allow preventative treatment to be instituted far earlier.

Common misconceptions about ARMD

Myth #1: ARMD is just normal aging of the eye. FALSE. While aging plays an important role in the cause of macular degeneration, it is not the only important factor (genetics is much more important). Many people over the age of 90 have no signs of ARMD, while other people under 50 have advanced ARMD.

Myth #2: ARMD is a single disease. FALSE. Macular degeneration is a term which encompasses numerous distinct diseases that look very similar. It is likely that several different genetic abnormalities exist which are capable of causing changes in the macula diagnostic of ARMD. It is the task of researchers to identify these distinct subtypes of ARMD since different treatments may be required for different ARMD subtypes.

Myth #3: Everyone with ARMD goes blind. FALSE. The majority of patients with ARMD maintain relatively good vision throughout their life. Furthermore, while a small portion of patients with ARMD may experience severe loss of central vision, peripheral vision is almost never affected. As a result, ARMD patients almost never require a seeing-eye dog or white cane.

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