What is age-related macular degeneration?

Many people, usually after age 65, develop a "wearing out," or degeneration of the macula as part of the aging process. We don't know why some people get these changes and others do not. There appears to be an increased risk of macular degeneration with increasing age, in cigarette smokers, and in those who have other family members affected by this disease. There are 15 million people in the United States affected by age-related macular degeneration, with over 1.6 million having the more severe wet type.

There are two basic types of age-related macular degeneration. The vast majority of people have the less severe dry type. The hallmark clinical finding of dry macular degeneration consists of small aging spots or drusen.

Normal Macula.	Dry macular degeneration with drusen (yellow spots).

Eyes with geographic atrophy, a variant of dry macular degeneration, develop a wearing away of the macular pigmented tissues. The atrophy causes discrete islands of blind spots. Vision is good unless the atrophy extends into the macular center.

Geographic atrophy just spares the macular center.	The atrophy gradually enlarged, causing loss of central vision.

Some patients with macular degeneration can develop a blister, which is called a pigment epithelial detachment. These blisters often cause blurriness or distortion. Various treatments have been attempted over the years without success. The blisters can remain stable, spontaneously flatten, or can go on to develop associated choroidal neovascularization.

Pigment epithelial detachment (outlined by arrows).	Fluorescein angiogram highlights the blister.

New blood vessels (choroidal neovascularization) grow beneath the macula in the more severe wet form. These vessels cause the overlying macula to swell with fluid and blood which often causes permanent central vision loss.

End-stage wet macular degeneration with macular hemorrhaging and scarring

Choroidal neovascularization (CNVM) is invisible without a special test called fluorescein angiography. Fluorescein angiography is a photographic test, not involving x-rays, in which a colored vegetable dye is injected into an arm vein.A series of photographs are taken as the dye passes through the back of the eye. This allows us to better diagnose the presence and extent of the abnormal blood vessels and leakage in order to determine whether treatment can be offered. The abnormal blood vessels are classified as being well-defined (classic), poorly defined (minimally classic), or occult by how well the margins can be identified on angiography. The choice of treatment and the response to various therapies are often determined by how large or well-defined the lesion is.

Fluorescein angiography shows a white, well-defined CNVM (a red circle outlines the abnormal vessels).	Angiography shows a poorly-defined CNVM. There is no distinct white lesion seen.

The goals of treatment are to prevent CNVM from developing in the first place (vitamin therapy), prevent CNVM from spreading into the macular center (laser photocoagulation), or limit the size of and leakage from the CNVM once it reaches the macular center (photodynamic therapy, Macugen, Lucentis, Avastin, and Eylea).

Patients with mild dry degeneration usually notice minimal changes in their vision although there may be slow loss of reading vision over many years. If the wet form develops, leakage and bleeding may involve the macular center causing symptoms such as distortion and vision loss. Patients never go completely blind since the part of the eye responsible for peripheral (side) vision is not affected by this disease.

Normal vision.	Vision with macular degeneration.

Patients are often asked to check their central vision every day with an Amsler grid. This grid is a pattern that resembles a checkerboard. You will be asked to cover one eye and stare at a black dot in the center of the grid. While staring at the dot, you may notice that the straight lines in the pattern appear wavy to you. You may notice that some of the lines are missing. These may be signs of wet age-related macular degeneration.

Click here to view or download a full-sized Amsler grid for yourself.

Blurry areas and black spots.	Wavy or crooked lines.

How is age-related macular degeneration diagnosed?

The most important step in accurately diagnosing macular degeneration is a careful dilated eye examination by an eye doctor familiar with this disease. Further testing, including fluorescein angiography, may be necessary.

What treatments are available for age-related macular degeneration?

1. Preventive treatments.
   • Nutritional supplements. The Age-Related Eye Disease Study (AREDS), a large, randomized, multicenter prospective study sponsored by the National Eye Institute, found that taking supplements containing high levels of antioxidants and zinc significantly reduced the risk of advanced age-related macular degeneration. The nutrients are not a cure for age-related macular degeneration, nor will they restore vision already lost from the disease. However, they may play a key role in helping people at high risk for developing advanced age-related macular degeneration keep their vision. People who are at high risk for developing advanced age-related macular degeneration should consider taking the formulation used in the study and eating a diet high in vitamin C, vitamin E, zinc, and carotenoids. Your eye doctor will tell you if you would benefit from these supplements based on a dilated eye examination.
     

     AREDS researchers found that people at high risk of developing advanced stages of macular degeneration lowered their risk by about 25 percent when treated with a high-dose combination of vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), and zinc (as 80 mg zinc oxide), and copper (2mg cupric oxide which was also added to prevent a zinc-induced copper deficiency which may be associated with high levels of zinc supplementation). This treatment also reduced the risk of vision loss by about 19 percent. The supplements did not provide any apparent benefit for those with either early macular degeneration (those with either several small drusen or a few medium-sized drusen in one or both eyes) or no macular degeneration.

     Some people with intermediate macular degeneration may wish to consider whether or not they wish to take large doses of the supplements for medical reasons. For example, beta-carotene has been shown to increase the risk of lung cancer among smokers. Taking supplements with zinc may cause a copper deficiency. The study also found high zinc levels were associated with genitourinary tract problems. Patients may want to discuss the best combination of supplements to take with their primary care physician.

     Supplements based on the AREDS study include Ocuvite Preservision, Icaps AREDS formula, Viteyes and Visvite.

     The value of other supplements, such as lutein and bilberry, are completely unknown since none have been adequately studied in randomized, prospective studies. They may be helpful, have no benefit, or might even prove to be harmful. The National Institutes of Health is currently sponsoring the AREDS 2, which will evaluate the benefits of oral supplementation with lutein (10 mg/day), zeaxanthin (2 mg/day), and omega-3 long-chain polyunsaturated fatty acids (1 gram/day).
   • Life-style modifications. Discontinuing smoking, weight loss, and regular exercise appear to be both good for your heart and your eyes.
2. Laser photocoagulation.

   A laser is an instrument that produces a pure, high-intensity beam of light energy. The laser light can be focused onto the retina, selectively treating the desired area while leaving the surrounding tissues untouched. The absorbed energy heats, or photocoagulates, the retina creating a microscopic spot.

   Laser surgery is performed in our office while you are awake and comfortable. The laser is used to seal the leaking vessels beneath the retina. The laser treatment usually takes less than 15 minutes to complete, and you can go home immediately following surgery. Arrangements for transportation should be made in advance since you may not be able to drive right away.

   Choroidal neovascularization with surrounding hemorrhage.	Dry laser scar following successful laser photocoagulation surgery.

   It takes several weeks to months before we can tell whether treatment has been successful. Patients usually require more than one laser surgery to control the macular leakage, often within the first month or two of treatment. Recurrences need to be promptly diagnosed and treated in order to maintain reading vision. For this reason, you will need to return for examinations every few weeks until the outcome is known. Although laser surgery decreases the risk of severe central vision loss by about 50%, some people will eventually lose reading vision.

3. Photodynamic therapy.

   Laser photocoagulation surgery has traditionally been the standard treatment for patients with wet age-related macular degeneration and choroidal neovascularization outside the macular center. When choroidal neovascularization is beneath the center of the macula, laser not only destroys these abnormal vessels but also permanently damages the overlying retina. Patients are thus left with a dry scar but no central vision. Newer therapies such as photodynamic therapy allow treatment of these central lesions while minimizing retinal damage.

    
   This video explains the unique mechanism by which photodynamic therapy occludes the abnormal blood vessels in eyes with wet age-related macular degeneration.

   The 2-year findings from the Treatment of AMD with Photodynamic Therapy (TAP) showed that photodynamic therapy appeared to work best for patients with either mostly well-defined choroidal neovascularization or purely poorly-defined choroidal neovascularization. Verteporfin (Visudyne), a photodynamic dye developed by Novartis Ophthalmics and QLT Phototherapeutics Inc, stabilized or improved vision in 59% of treated eyes with primarily well-defined choroidal neovascularization compared to 31% of patients who received placebo. Legal blindness developed in 41% of treated eyes compared to 55% of untreated eyes. Patients often required multiple treatments to control recurrent choroidal neovascularization.

   OCT scans before (top) and following (bottom) photodynamic therapy. The swollen, cystic appearing macula returns to its normal configuration following treatment.

   The 2-year results of the Visudyne In Photodynamic (VIP) Therapy Trial found this therapy to also be effective for patients with purely poorly-defined choroidal neovascularization. At the 24-month examination, 46% of those patients treated with Visudyne therapy lost less than 3 lines of vision (moderate vision loss) compared to 33% of patients on placebo. Seventy percent of Visudyne treated patients lost less than 6 lines of vision (severe vision loss) compared to 53% of patients receiving placebo. The benefit of Visudyne therapy appeared to be greatest in patients presenting with relatively small lesions or lower levels of visual acuity (less than 20/50). Patients treated with Visudyne received an average of five treatments during the 24-month period.

   Subsequent analysis of the TAP and VIP data showed photodynamic therapy to be effective for most eyes with smaller choroidal neovascularization regardless of how well- or poorly-defined the lesion.

   Standard photodynamic therapy rarely improves vision. However, combining photodynamic treatment with injection of VEGF inhibitors or anti-inflammatory steroid medication (Kenalog) into the eye (a painless in-office procedure) appears to dramatically improve results. Patients appear to require far fewer photodynamic treatments and the vision often improves.

4. Vascular Endothelial Growth Factor (VEGF) Inhibitors.

   In 1989 scientists identified a growth factor (vascular endothelial growth factor, or VEGF) that plays a major role in stimulating "neovascularization" or new blood vessel growth. VEGF causes the cells lining blood vessels (vascular endothelium) throughout the body to multiply and form new vessels. In the macula, VEGF is produced in response to inflammation and lack of oxygen. The VEGF binds to the choroidal endothelial cells, which then proliferate and form choroidal neovascularization, the hallmark of wet macular degeneration. Blocking the VEGF molecule is currently the most effective treatment against choroidal neovascularization. Macugen, Lucentis and Eylea are the three VEGF-inhibitors currently approved for ocular use. Avastin, another VEGF inhibitor initially approved for the treatment of colorectal cancer, is also in wide use for macular degeneration. All of these medications are injected into the eye in a painless, in-office procedure. Although VEGF inhibitors are not curative, they have transformed wet macular degeneration from an untreatable disease into a chronic one where the vast majority of patients maintain vision.

   • Macugen. In December 2004 Macugen (Eyetech and Pfizer Pharmaceuticals) became the first FDA-approved anti-VEGF treatment for wet macular degeneration. Macugen consists of a synthetic fragment of genetic material that specifically binds to the VEGF molecule and blocks it from stimulating the receptor on the surface of endothelial cells. Macugen injections are given every 6 weeks. The results of treatment are similar to photodynamic therapy. Combining photodynamic therapy with intravitreal steroids or other VEGF inhibitors, or monotherapy with either Lucentis, Avastin, or Eylea are all more effective than Macugen alone. The future role of Macugen therapy is therefore uncertain at best.
   • Lucentis. Genentech produced an antibody fragment, Lucentis, that binds to VEGF and prevents it from interacting with the VEGF receptor on the surface of endothelial cells. Approved by the FDA in June 2006, the injections are given up to every 4 weeks indefinitely. Lucentis is superior to both photodynamic therapy and Macugen in maintaining and improving vision for a broad-spectrum of eyes with wet age-related macular degeneration. Approximately 90 to 95% of patients treated with Lucentis maintained or improved vision (<3 lines of vision loss) compared to 62 to 68% of those treated with photodynamic therapy. After 12 months, vision improved by about 1 to 2 lines in patients treated with Lucentis compared to a loss of about 2 lines in patients treated with photodynamic therapy. Vision was at least 20/40 in about one-third of patients receiving Lucentis compared to only 3 to 11% of those who received photodynamic therapy. Unfortunately, patients appear to require monthly intraocular injections for at least a year or two for best visual results.
   • Avastin. Avastin (bevacizumab) is an anti-VEGF compound, also produced by Genentech, that originally was approved for treating colorectal cancer. Its chemical structure is very similar to Lucentis. The cost per treatment is a fraction of other available therapies, including photodynamic therapy and other anti-VEGF drugs. The CATT study showed monthly Avastin and Lucentis to be equally effective, making the choice of drug an individual one determined by the patient, doctor and insurance industry.
   • Eylea. Eylea (aflibercept), produced by Regeneron, is an anti-VEGF compound that mimics the target cell's VEGF receptors, tightly 'trapping' or binding VEGF molecules. Approved by the FDA in November 2011, 3 monthly injections followed by injections every 2 months is just as effective as monthly Lucentis or Avastin treatment. Eylea thus becomes a more attractive option when compared to the other anti-VEGF dugs since patients can be examined and treated less often.
5. Subretinal surgery.

   Using advanced microsurgical techniques, hemorrhage and abnormal blood vessels growing beneath the macula can be removed. Unfortunately these techniques can benefit only a small minority of patients with age-related macular degeneration and carry a risk of major complications such as retinal detachment and total blindness. The Submacular Surgery Trial, the definitive National Eye Institute sponsored study, unfortunately failed to show any significant benefits for these techniques.

6. Implantable Miniature Telescope (IMT).

   The Implantable Miniature Telescope, a pea-sized lens inserted in the eye during a cataract-like operation, was approved for use in patients on July 6, 2010. Acting like a telescope, this device enlarges images by about 2 to 3 times, making it easier for those who have already permanently lost central vision to recognize images at distance. One-year efficacy data from a prospective, multicenter trial showed patients had a mean improvement of over 3 lines of vision at both distance and near and three-quarters went from severe to moderate vision impairment. The main complication was clouding of the cornea, with 4% of patients requiring corneal transplant surgery. Persons eligible to receive the telescope will be those over 75 years of age without prior cataract surgery and stable severe to profound vision impairment (best-corrected distance visual acuity 20/160 to 20/800) due to end-stage macular degeneration. Preoperatively patients will need to go through the CentraSight Treatment Program to ensure that they are good candidates for this surgery. The IMT should be available for widespread use by the second quarter of 2011.

7. Investigational treatments.

   Although there have been great strides over recent years in treating macular degeneration, we are still far from being able to prevent macular degeneration from developing in the first place, as well as curing choroidal neovascularization once it develops. There are a multitude of new treatments being investigated, although we will not know if they are helpful or harmful until ongoing clinical studies are completed. 

What happens if I lose my reading vision?

Except for airplane pilots, military personnel, etc., most patients who lose reading vision in one eye continue their normal lifestyle without change. Patients should be able to drive a car as long as their vision in the other eye is at least 20/60 in Kentucky and 20/40 in Indiana.

Low Vision services and ex amination.

We may recommend that you see a specialist for a low vision examination. Magnifying lenses or other devices can be prescribed to help with reading and other central vision tasks.

For those living in the Kentuckiana area, the See the World Store, located at 1832 Frankfort Avenue in Louisville, has a wide range of special products including magnifiers, canes, talking clocks and watches, money identifiers and more. They can be contacted at (502) 447-2458.

Radio Eye is a non-profit 24-hour radio service that broadcasts the reading of current newspapers and other everyday literature, offering greater independent living to people who are blind, visually impaired or physically handicapped. Radio Eye radio listeners hear the reading of dozens of newspapers, magazines, health materials, grocery ads and much more. The audio stream can be accessed on a special (free) Radio Eye radio, on Library Channel 20 on Lexington Insight Cable TV, in area homes and hospitals, and on the internet at www.RadioEye.org.

The low vision experts at Lighthouse International have created Living Better at Home: A Guide for People with Vision Loss. This is a national campaign to promote safety, independence, and accessibility in the home. Please click here to learn more about available online content and a free printed kit filled with useful information and products.

What are the chances of my other eye developing wet age-related macular degeneration?

Patients who have no signs of abnormal blood vessels in either eye have a minimal chance of losing central vision. This risk is increased, however, if abnormal blood vessels have already affected one eye. The yearly risk for the second eye becoming involved increases to approximately 1 in 20.

What can I do to prevent vision loss?

There is nothing that any of us can do to prevent our eyes from aging. Vitamin supplements are helpful in decreasing the risks of vision loss and wet macular degeneration from developing in high-risk eyes. The most important thing is to check the central vision of each eye every day and have frequent, regular eye examinations. Any sudden change in the vision requires an immediate examination by your eye doctor.