Age-Related Macular Degeneration (AMD)
What Is Age-Related Macular Degeneration (AMD)?
Age-related macular degeneration (AMD) is a common condition affecting people age 50 years and older that is associated with central vision loss, which affects one's ability to read, drive, or see someone’s face if it progresses to more advanced stages.
The macula refers to the central portion of the retina. The retina is similar to film inside a camera. The image one sees is focused by the cornea and lens of the eye onto the center of the retina (macula.) Many people with AMD have minimal visual symptoms and may retain good vision indefinitely. A relatively small percentage of people with AMD will lose central vision, which may impair their ability to read and drive a car. There are two major types of AMD, a "dry" (non-neovascular) and a "wet" (neovascular) form.
Dry AMD, affecting about 90 percent of all people with AMD, is characterized by drusen. Drusen are small yellow deposits that are visible to the doctor on clinical examination of the macula and are the hallmark of AMD. Most people with drusen alone do not have significant visual changes or vision loss. A minority of people with dry AMD will advance to central vision loss due to geographic atrophy, which involves the loss of pigmented cells beneath the macula (these pigmented cells normally act to support and nourish the photoreceptor cells). There is currently no treatment or cure for geographic atrophy, though investigative research is ongoing.
Wet AMD affects only about 10 percent of people with AMD, yet accounts for the majority of central vision loss due to AMD. The word "wet" implies leakage and bleeding in the macula due to abnormal blood vessels (choroidal neovascularization) that may develop spontaneously in AMD. If left untreated, these abnormal blood vessels result in permanent scarring of macular tissue and severe central vision loss. While there is still no cure for wet AMD, we currently have a few medications that are very effective in treating this condition.
Causes And Associations
AMD is a complex, degenerative condition that becomes increasingly prevalent with advanced age. It is typically found in people ages 50 years or more, although drusen sometimes can be seen in younger people. Family history is another important association, although simply having a blood relative with AMD does not necessarily mean or guarantee that one will definitely develop AMD. Other risk factors for AMD may be modifiable or controllable, including smoking, poor nutritional intake, and high blood pressure.
Genetics And AMD
In addition to aforementioned associations, genetics play a key role in AMD, with heredity representing over 70% of the risk of developing the disease. Genetic markers have recently been identified that strongly influence the risk of progression to advanced AMD with vision loss. Several of these gene variants promote inflammation by altering activation of the complement cascade, which is an active part of our immune system. Other gene variants affect mitochondrial function and increase oxidative stress in the retina, consistent with both the role of smoking as a risk factor and the benefit of antioxidants in delaying disease progression. Cholesterol metabolizing enzyme variants are also associated with this disease, consistent with the known biochemical composition of drusen.
Early identification of higher risk patients may help prevent vision loss or slow down disease progression. Environmental risk factors can be identified, lifestyle modifications can be made, and nutritional supplementation can be instituted in these situations to further reduce risk of disease progression. Frequent monitoring of these individuals may result in early detection of wet AMD, leading to better visual outcomes through earlier treatment.
Symptoms Of AMD
Many people with mild dry AMD have little to no visual symptoms. Some people, however, will require more light to read, have difficulty adjusting between dark and light conditions, or notice mild blurring of vision. Occasionally, significant loss of central vision can occur. 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 typically not affected.
Those with wet AMD often have more rapidly progressive loss of central vision, typically over days to weeks. Visual distortion is a common symptom of this stage. Occasionally, however, people may not be aware of these visual changes because their other eye sees well. Therefore, it is important to test vision in each eye separately by covering one eye at a time when checking vision.
Amsler Grid Chart Test
An Amsler grid is a self-monitoring tool that allows people to check their vision one eye at a time to monitor for blurring or distortion that may signify the conversion from dry to wet AMD. People with AMD progression may notice changes on the Amsler grid, and if this occurs, they should contact their ophthalmologist promptly.
The Amsler Grid Chart should be used to check the central part of your visual field, the area that can be damaged by Macular Degeneration.
Instructions for Use:
- View the chart (with your reading glasses on) at normal reading distance.
- Completely cover one eye and look at the central dot on the chart.
- Notice if there are any areas within the grid that appear gray (or black), or if there are any areas where the straight lines appear bent, crooked, or missing.
- Check the chart regularly (daily or weekly).
- Call your doctor if new changes occur.
In addition to a dilated retinal examination and digital color photography, various retinal imaging tests may be utilized to further assess the AMD.
Fluorescein Angiography is an office-based test that can aid in determining the extent of macular degeneration and distinguishing between dry and wet AMD. Fluorescein angiography is performed by injecting sodium fluorescein dye into a peripheral vein in the arm with a small needle. This dye travels through the blood vessels of the body and eyes. Choroidal neovascularization in the macula can be visualized as a leaking blood vessel complex under the retina. It is regarded as a safe test, but people should expect some temporary and mild yellowish discoloration of the skin and urine. Most people have no difficulty with this testing, although a small percentage of people will experience some transient nausea. Any angiogram test, however, can rarely be associated with allergic or even more severe reactions, and therefore this test is typically reserved for people in whom wet AMD is noted or suspected.
Optical Coherence Tomography (OCT) is a non-invasive, office-based imaging test that uses a special light to scan the macula and determine whether there is fluid in the macula, potentially signifying wet AMD. It is commonly used in combination with fluorescein angiography to help diagnose wet AMD and is also used to monitor the response to treatment for wet AMD. There are no side effects or risks involved with OCT; there is no radiation involved.
Autofluorescence is another non-invasive imaging test is useful for evaluating the health of the pigmented cell layer beneath the macula in those who have dry AMD. The pigmented cell layer plays an important role in sustaining the health and function of retinal photoreceptor cells. Specifically, it is used to identify and track progression of geographic atrophy, which involves the loss of this pigmented cell layer and in turn, the loss of photoreceptor cells.
Most people with AMD will retain good central vision and the ability to read in their lifetime. This is because 90% of people have dry AMD. This is often associated with a more favorable prognosis compared to wet AMD, though dry AMD may also gradually progress to an advanced form with atrophy of the macula, limiting central vision. People with wet AMD will quickly suffer central vision loss if left untreated. While patients may progress to legal blindness, it is important to realize that AMD affects central vision - it typically does not lead to total loss of vision. Thankfully, there are new treatments available for those with wet AMD.
Dry AMD - There is no treatment available yet that can either halt the progression or recover vision loss from dry AMD. However, the Age Related Eye Disease Study (AREDS), sponsored by the National Eye Institute (NEI) of the National Institutes of Health (NIH), showed that a specific formulation of antioxidant vitamins and minerals had a clinically proven benefit in reducing the risk of progression of dry AMD to more advanced stages and associated vision loss by 25%. In May of 2013, the NEI proposed a modification to the original AREDS formula based on the AREDS2 study, which was an update to the original AREDS clinical trial. The AREDS2 formula contains:
- 500 mg Vitamin C
- 400 IU Vitamin E
- 10 mg Lutein
- 2 mg Zeaxanthin
- 80 mg Zinc oxide
- 2 mg Copper oxide
It is prudent to check with your primary care physician before starting this micronutrient supplement. In general, Vitamin E supplementation should not exceed 400 IU. In addition, unlike the original AREDS formula, there is no beta-carotene in the newer AREDS2 formulation (it was replaced by lutein and zeaxanthin). This is significant because some studies in the medical literature have identified increased rates of lung cancer with high levels of beta-carotene in heavy 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 has been associated with vision loss and more advanced forms of AMD.
- Eat a diet rich in colorful vegetables and fruits. These food groups have been associated with lower rates of progression to advanced AMD and contain anti-oxidants (eg. lutein) which may slow progression of disease.
- Control blood pressure. High blood pressure is associated with more advanced AMD.
- Be physically active. People with AMD who are physically active several times a week may reduce their risk for progression to advanced AMD and vision loss.
- Consider eating food rich in Omega 3 fatty acids. Omega 3 fatty acids are found in cold water fish such as tuna and salmon along with nuts. Studies show that a diet with high omega 3 fatty acid intake is associated with less advanced AMD.
Wet AMD - In that past, laser-based therapies were used to target the abnormal blood vessels that cause wet AMD. However, the laser burns typically resulted in scarring and damage to central vision. Fortunately, there are now anti-vascular endothelial growth factor (anti-VEGF) medications available for the treatment of wet AMD. These medications, injected into the eye as an office-based procedure, are currently the preferred therapy for wet AMD due to their unprecedented efficacy. They represent the first therapy that has ever been clinically proven to help improve vision in a substantial proportion of patients with wet AMD. Timing is important, as earlier identification and treatment of wet AMD is associated with better visual outcomes.
Anti-Vascular Endothelial Growth Factor (VEGF) Agents
In 2006, the FDA approved Lucentis (ranibizumab) for the treatment of wet AMD. This was the first treatment shown to improve vision in many people with wet AMD. 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 will continue to some degree on an indefinite basis in most patients 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 hemorrhage, 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 a serious infection.
Lucentis (ranibizumab) 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 the vast majority of patients maintained vision and that 30-40% experienced relatively large degrees of visual improvement. However, vision loss can still occur despite ongoing therapy with any anti-VEGF agent. For instance, a patient's underlying dry AMD (atrophy) is not treated by anti-VEGF medication.
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 to 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 now studies that show Avastin is as effective as Lucentis in most cases.
Eylea (aflibercept) was approved in November 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. In some cases it can be given less frequently.
Macugen (pegaptanib) is a 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 intraocular injection therapy for wet AMD, but is generally considered to be less effective than the other anti-VEGF agents and is not used in practice much anymore.
Photodynamic Therapy (PDT) with Visudyne (verteporfin) is another treatment for wet AMD. It utilizes an intravenous injection of a photosensitizing drug called verteporfin (Visudyne) and a non-thermal laser light to try and reduce leakage from certain types of choroidal neovascularization. It typically does not improve vision as when used alone, however, it is being explored as an adjunctive agent to anti-VEGF and to intraocular steroid therapy.
PDT is a timed, office-based procedure. The Visudyne drug is infused into a vein in the arm over 10 minutes and then allowed to collect within the choroidal neovascularization over another 5 minutes. The choroidal neovascularization is then exposed to a low energy laser light for about 90 seconds to activate the drug only within abnormal blood vessels in the macula. This produces a chemical reaction within these abnormal blood vessels to reduce blood flow and leakage. The treatment is often repeated at 3 month intervals. Visudyne clears itself completely from the body over several days, during which the skin and eyes must be protected from sunlight with clothing and special sunglasses. No driving is allowed while wearing the sunglasses. Sometimes PDT is combined with other treatments such as anti-VEGF agents or steroids to attack choroidal neovascularization using several different mechanisms of action.
Laser photocoagulation may be used in uncommon, specific 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 vision cells to some degree. 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.
Low vision aides may help improve the quality of life for people whose vision is impaired to the point that they cannot carry out important visual activities of daily living such as reading mail or writing checks. Low vision rehabilitation with a qualified low vision specialist can help identify special magnifying optical devices and lighting aids that can assist a patient in performing specific vision functions. Low vision centers can also be a good resource for non-optical aids such as books on tape, large print reading materials, and writing guides. Computers and electronic readers (iPad, Kindle, etc) are often found to be very useful in the setting of vision loss from AMD.
In July 2010, an implantable miniature telescope was FDA approved for select patients with advanced end-stage macular degeneration in both eyes. This device has been shown to improve both vision and quality of life in select patients who have lost central vision in both eyes due to advanced AMD. It is implanted in one eye and magnifies images onto the healthy areas of the retina outside of the central area that has been damaged by AMD. This magnification aims to reducethe effect that the blind spot has on central vision. For additional information, please visit www.centrasight.com.