What is Macular Degeneration?

Age-related macular degeneration (AMD) is a common condition affecting people age 50 years and older. The condition can be associated with loss of central vision, leading to the loss of your ability to read, to drive a car, or even see someone's face. Macular degeneration is the most common cause of blindness in the United States for people over the age of 60 years.

The Macula is central part of the retina that provides you with the sharpest vision. The retina is a thin layer of tissue that lines the interior of the eye. It acts like the film in a camera, allowing the eye to see. Conditions that affect the macula can impair your central vision. Many people with AMD have no visual symptoms and may retain normal 20/20 vision. A small percentage of people with AMD will lose central vision and the ability to read and drive a car. Although AMD can cause central vision loss, it does not typically lead to complete blindness.

There are two major types of AMD, a “dry” (non-neovascular) and a “wet” (neovascular) form. Although both can cause vision decline, the wet form is the more aggressive and rapidly progressive type.

In dry macular degeneration, yellowish material accumulates under the retina and can damage the sensitive retinal nerve cells. This yellow material collects in mounds that are called drusen. In many cases, the drusen only cause minor damage and result in mild vision loss. If there are many drusen that are also large, antioxidant vitamins and minerals may reduce the chance of more damage. These vitamins can be bought in drug stores and supermarkets and are sold as Ocuvite or I-CAPS as well as many other brands. If there are only a few drusen, or if the drusen are very small, then benefit of these vitamins are less certain. Similarly, if you do not have any findings of macular degeneration, the vitamins offer no proven benefit.

In wet macular degeneration, abnormal blood vessels grow and leak blood and fluid under the retina. These blood vessels usually cause more severe damage to the nerve cells. Certain imaging tests are performed to help identify and characterize these abnormal blood vessels. In the last decade major advances have occurred for the treatment of wet macular degeneration. New drugs such as Avastin, Lucentis, and Eylea can stop the growth of these abnormal blood vessels in the macula. Photodyamic Therapy with Visudyne, also know as a “Cold Laser” may help to make these drugs more durable in selected cases.

For a vast majority of patients, the newest treatments can stabilize their vision. For many others, we can now actually improve vision with treatment, a goal that was not imaginable previously. Immediate treatment is critical to achieve the best results with these new treatments for wet macular degeneration.

For very advanced macular degeneration where the abnormal blood vessels have formed a scar, no medical or surgical treatment currently available will be helpful. However, an evaluation by a low vision specialist might help to allow you to maximize your function with whatever vision you still retain despite the damage to your retina.

Dry Macular Degeneration

Dry age-related macular degeneration (AMD) is the early stage and is the most common form of AMD. There is usually little or no vision loss during this stage. Some individuals, however, can have severe vision loss from an advanced form of “dry” macular degeneration.

Dry age-related macular degeneration results from the deterioration of the outer layers of the retina, which causes an accumulation of waste material underneath the macula. These waste deposits, called drusen, are yellow in color and cause damage to the sensitive retinal tissues by impeding the flow of oxygen and nutrients. Drusen are the hallmark of AMD and can be visualized by your doctor when looking at the macula in a clinical exam.

Most people with drusen alone do not have significant visual changes or vision loss. A minority of people with dry AMD will progress to central vision loss due to geographic atrophy, which is the loss of the pigment layer under the macula. Unfortunately, there is no treatment or cure for geographic atrophy and the associated vision loss. Research using stem cell implantation is attempting to help treat this type of macular degeneration.

Wet Macular Degeneration

The wet form of AMD is a late stage of the condition and affects about 10 percent of all people with the condition. Although it is the less common form, wet AMD is responsible for the majority of central vision loss due to AMD.

Wet AMD is caused when abnormal blood vessels called Choroidal neovascular membranes, begin to grow under the macula. These abnormal vessels can bleed and leak fluid in the macula, causing the vision to become distorted of blurry. If not treated quickly, these blood vessels can grow larger and eventually cause scarring with permanent and often severe central vision loss. The newest treatments of wet AMD can allow many patients to retain good vision, and even regain some vision they have lost from this disease.

Symptoms of Dry AMD

Most individuals with dry AMD have no visual symptoms at all. Some people, have difficulty seeing well in dim lighting, and will require more light to read or see clearly. Mild blurring of the vision can also occur as dry AMD progresses.. Occasionally, significant loss of central vision can occur from severe dry macular degeneration. Vision loss associated with dry AMD is usually gradual or slow. Because AMD affects the macula, the symptoms are typically related to central vision tasks such as reading or driving. Peripheral vision is usually not affected.

Early signs of dry AMD are few and regular eye exams may identify this condition before symptoms occur. As dry AMD progresses, patients can have an increase in blurred or distorted vision, and a difficulty seeing in dim light. There are currently no treatments available to reverse damage done to vision by dry age-related macular degeneration. Studies show that smoking, high blood pressure and poor diet can be contributing factors in worsening vision from macular degeneration, and vitamin supplements may be recommended. While a vitamin supplement regimen is different for every patient, some of the recommended types include:

Symptoms of Wet AMD

People with wet AMD often have rapid progressive loss of central vision typically over weeks or months. Occasionally, patients can experience sudden loss of central vision that can occur overnight. Other symptoms of wet AMD include blurred vision, distorted vision (Straight lines look wavy), or blind spots. Patients may not be aware of visual changes because the other eye may see well. Therefore, it is very important that patients with macular degeneration regularly test the vision of each eye separately by covering one eye at a time.

To check their vision, a patient can simply read something with one eye covered, and then alternate to check the other eye. Alternately, you can use an Amsler grid to monitor any changes in your vision.

An Amsler grid is a pattern made of straight vertical and horizontal lines with a dot in the middle. It is a self-monitoring test that is performed with only one eye open at a time. If you notices that the lines have become wavy, distorted, or blurry, this could indicate a progression of their macular degeneration. Should this occur, you should contact your retina specialist promptly.

Evaluation

Early diagnosis and proper treatment can be beneficial in delaying the progression of wet AMD and saving vision. A complete and comprehensive ophthalmic examination is important in the assessment of AMD. During your visit, you will receive vision testing, eye drops to dilate the pupils, and a complete examination of the front and back of the eye. Pupillary dilation may create blurred vision, and therefore, it is best if a driver accompanies the patient, although it is not absolutely required.

Many advances in imaging the retina have taken place to help in the diagnosis and management. Several test maybe performed on patients with AMD and other retinal conditions. These include color photos to document and categorize drusen, macular pigment changes, blood, and other characteristic of AMD. Additional tests that are commonly performed include fluorescein angiography (FA) and Indocyanine Green angiography (ICG), and High Resolution Optical Coherence Tomography (OCT). These tests are performed for initial diagnosis of wet AMD, and are often repeated to guide treatment over the course of the disease.

Fluorescein angiography is a safe, commonly used, office-based diagnostic test that can aid in determining the extent of macular degeneration and help distinguish between the dry and wet forms of the condition. Fluorescein angiography has been used since the 1960's, and is performed by injecting a small amount of sodium fluorescein dye into a peripheral vein with a small needle. This dye travels through the blood vessels of the body and into the eyes. Choroidal neovascularization in the macula can be visualized as leaking blood vessels under the retina. Fluorescein angiography is regarded as a safe test, but people should expect some yellowish discoloration of the skin and orange urine for 1 to 2 days. Most people have no difficulty with this testing, although a low percentage of people will experience some nausea. Any angiogram test, however, can be associated with allergic or even more severe reactions.

Indocyanine Green angiography (ICG) is a similar to a fluorescein angiography, except a different type of dye is used. The different molecular properties of ICG dye allow for better detection of certain macular conditions, including wet macular degeneration. Individuals with an allergy to Iodine or with severe liver disease cannot undergo this due to the possibility of serious side effects. ICG angiography is especially helpful in cases where there is a significant amount of blood in the macula that limits visualization with other available testing.

Optical Coherence Tomography (OCT) is a non-invasive, office-based imaging technique that uses light to scan the retina and produce a 3-deminisional picture of the macula. It can show the detailed layers and thickness of the macula, helping also to identify an fluid within the macular area. It is commonly performed with a fluorescein angiography to help diagnose wet AMD. It can also be used to assess the response to treatment for wet AMD and help guide future treatments. OCT is fast and performed with no risk to the patient.

Macular Degeneration Prognosis

The prognosis for AMD has improved dramatically for many patients with this condition. Most people with AMD will retain good central vision and the ability to read for their lifetime. Most of these patients have the dry form of AMD, which is associated with a better prognosis. Patients with wet AMD can lose central quickly and permanently, but immediate treatment can help to reduce vision loss. A small percentage of patients with dry AMD will still lose central vision. With the use of the latest treatments, vision can be preserved and improved even in advanced cases.

Causes of Macular Degeneration

The specific cause of AMD is not known but many risk factors have been established. AMD is a degenerative condition that usually affects individuals over the age of 50, and is typically progressive with time. The greatest risk factor for developing AMD is age. Other include:

1. Family History of Age-related Macular Degeneration
2. Race: More common in Whites
3. Gender: More common in Females
4. Smoking: Increases the risk of AMD significantly
5. Hypertension: Associated with AMD
6. Poor Nutrition: Associated with increased risk of AMD

Treatments for Macular Degeneration

There is no treatment or cure for Dry AMD. A landmark clinical trial conducted by the National Institute of Health (NHS) and the National Eye Institute (NIH) found a significant benefit in preserving vision and slowing disease progression in patients with AMD that were taking dietary supplements containing high doses antioxidants and Zinc. This study was the Age-related Eye Disease Study (AREDS) and demonstrated that high-risk patients can reduce the risk of progression of dry AMD to more advanced stages and associated vision loss by consuming the following vitamins and minerals

AREDS

• 500 mg Vitamin C
• 400 IU Vitamin E
• 15 mg Beta-carotene
• 80 mg Zinc oxide
• 2 mg Copper oxide

AREDS 2

A new clinical trial, the AREDS 2 study, is re-evaluating the original AREDS formula to possibly establish an improved nutritional formulation for dry AMD. The AREDS 2 study will assess the effects of supplementation of lutein and Zeaxanthin and omega-3 fatty acids on the progression to advanced AMD. Additionally, the study will assess whether an AREDS formula with reduced zinc and/or no beta-carotene works as well as the original AREDS formula in reducing the risk of progression of AMD. The results of this study are scheduled to be available in 2013.

It is important to check with your medical doctor before starting AREDS supplement. In general, Vitamin E supplementation should not exceed 400 IU, and smokers should not be on any Beta-carotene supplementation due to an increase risk of lung cancer. There are AREDS formula vitamins available that do not have Beta-carotene that are appropriate for smokers.

Based on epidemiologic studies, certain lifestyle and nutritional changes may be beneficial. Based on what is known to date, the following recommendations may be made in hopes of improving the prognosis of dry AMD:

• Stop Smoking: Smoking is the strongest modifiable risk factor for advanced macular degeneration and vision loss.
• Nutrition: Eat a diet rich in dark, leafy green vegetables. This includes spinach, broccoli, kale, collards, turnip greens, swiss chard, mustard greens, and lettuce. The darker green leaf, the more nutritious it is.
• Vitamins: Take a general multivitamin and multimineral supplement. See you eye care specialist to determine if you should also take the AREDS formula vitamins.
• Exercise regularly and keep a healthy weight. People with macular degeneration who are physically active several times a week may reduce their risk of progression to advanced AMD and vision loss.
• Omega-3 Fatty Acids: Consuming omega-3 oils has been shown in many studies to help reduce the risk of progression of macular degeneration. Foods rich in omega-3 oils include: Flax seed, fish (salmon, halibut, cod), chia seeds, walnuts, cauliflower, cabbage, brussel sprouts, oregano, and cooked soybeans.
• Control blood pressure and cholesterol. High blood pressure has been strongly associated with advanced macular degeneration.

Treatment for Wet AMD

The prognosis for people with wet AMD is improving. There are more effective treatments now than was available just a few years ago but still no cures exist for AMD. Treatments include new drugs aimed at blocking growth factors, nondestructive laser-drug combinations, and traditional laser photocoagulation.

Lucentis (ranibizumab) is a very effective treatment developed for wet AMD and was FDA approved in 2006. This was the first treatment shown to improve vision in many people with wet AMD. Lucentis is a humanized antibody fragment that works by blocking an important growth factor of choroidal neovascularization called vascular endothelial growth factor (VEGF.) By blocking VEGF, both the growth and leakiness of the abnormal blood vessels is reduced. Studies with patients on a course of Lucentis showed that over 90% of people on treatment will at least maintain vision, and 30% to 40% will have a large improvement in their vision. However, there can still be vision loss despite ongoing Lucentis therapy.

Lucentis is administered in the office by an intraocular injection and typically dosed monthly for the first few treatments. The eye is prepped with antiseptic solutions and topical anesthetic drops. The injection is very well tolerated being relatively painless and only rarely associated with any complications. Treatment may need to continue indefinitely depending on the nature of the wet AMD and response to treatment, although the frequency and total number of injections may vary considerably among patients.

The risks of intraocular injections such as with Lucentis include bleeding, retinal tear, and infection, all of which are very rare. Anyone who receives an injection and subsequently has increased pain or loss of vision should contact their doctor immediately as these symptoms could indicate one of these rare complications.

Avastin (bevacizumab) is another drug used to treat wet AMD. Avastin is FDA-approved for use in people with certain types of cancer by intravenous infusion. Like Lucentis, Avastin is an antibody that blocks the effects of VEGF. Retina specialists have been performing intraocular injections of Avastin to treat wet AMD for about as long as Lucentis. Although the use of Avastin injected into the eye is considered off-label, there are studies, including a large national clinical trial, that show Avastin to be as safe and effective to Lucentis.

Eylea (aflibercept) was approved in November of 2011 by the FDA to treat wet AMD. Eylea is a fusion protein that acts like an antibody to bind VEGF. In clinical trials it had similar efficacy and safety to Lucentis. This new medication may allow extending treatments for every 2 months after a initial period of monthly treatments, however, clinical studies are still underway.

Macugen (pegaptanib) is growth inhibiting drug that blocks VEGF to some degree and can also slow the growth of choroidal neovascularization and to reduce leakage in the macula. Macugen was the first approved in December of 2004 as an intraocular injection therapy for wet AMD. It is generally considered to be less effective than the other anti-VEGF agents and not used in practice much anymore.

Photodynamic therapy (PDT) with Visudyne (verteporfin), also know as a “Cold Laser,” is another treatment for wet AMD. It utilizes an intravenous injection of a photosensitizing drug called Visudyne (verteporfin) and a non-thermal laser light to try and reduce leakage from abnormal blood vessels. It typically does not improve vision as when used alone, however, it is being explored as an adjunctive agent to anti-VEGF therapy, and to intraocular steroid therapy. Currently PDT is not the primary treatment for wet macular degeneration.

Laser photocoagulation, or “Hot Laser” may be used in certain, rare cases of choroidal neovascularization where the abnormal blood vessels are not beneath the center of the macula. Thermal laser treatment attempts to heat and destroy choroidal neovascularization but also damages overlying cells that can be important for vision. Accordingly, this procedure is typically considered only when the abnormal blood vessels are far from the center of the macula. A major problem with thermal laser treatment is recurrent choroidal neovascularization which can develop in 50-60% of people.

An Implantable miniature telescope was approved by the FDA in July 2011. The telescope is surgical implanted into the eye, and has been found to be useful in certain patients with advanced untreatable AMD. This device is currently intended for those patients with poor vision from advanced macular degeneration in both eyes, and requires a specialized team of surgeons. Patients also have to go visual training after the implantation to correctly use the implanted telescope.

Stem cells have been studied for macular degeneration and other retinal degenerative disease for many years. Although no current treatment using stem cells for macular degeneration is available, there are experimental trials being conducted that are studying stem cell technology to help treat certain forms of macular degeneration.

For patients with permanent visual impairment that limits important functions in their daily lives, low vision aids may allow them to regain the ability to perform some activities. Low vision therapy involves using specific optical devices and lighting aids to assist in performing specific vision functions. Even patients with a moderate limitation in vision can benefit from low vision rehabilitation, which may help them to improve their ability to read and write.