Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a degenerative disease of the macula, the central part of the retina that is responsible for fine visual details. Previous classification systems referred to “wet” and “dry” manifestations of AMD. Newer terminology favors the use of “early” and “late” stages of AMD. Early AMD is characterized by the presence of small drusen, which are focal, yellow deposits in the retina. These can be visualized under dilated ophthalmologic examination. Small, infrequent deposits are virtually always found in people over age 50 and are not necessarily pathological. In conjunction with increased or decreased pigmentation in the pigmented epithelium layer of the retina, drusen are a sign of early AMD. Early AMD may be asymptomatic, or may cause blurred vision or poor vision in low light.
As AMD progresses to late stages, central vision gradually worsens until patients are no longer able to perform tasks requiring fine visual skills. AMD is the most common cause of legal blindness (20/200 or worse in both eyes) among elderly Americans. Peripheral vision is often spared until later in the disease, and if adequate, may allow limited performance of some daily activities.
The late stage is divided into neovascular AMD and nonneovascular AMD. Neovascular AMD was previously known as “wet” AMD, due to abnormal vessel growth (neovascularization) into the subretinal space. It is less common than nonneovascular AMD (10%-15% of cases), but has a worse prognosis and accounts for most cases of extensive vision loss. Because it can progress quickly, any sudden changes in vision should prompt immediate consultation with an ophthalmologist.
In addition, nonneovascular AMD can transform to neovascular AMD, and neovascular AMD may transform into nonneovascular AMD. Both forms may be seen in the same eye or each eye may have a different form. It is not clear whether neovascular and nonneovascular AMD are different manifestations of the same disease or two different entities.
AMD is thought to be caused in part by exposure to ultraviolet radiation, mainly from sunlight. Just as skin can become damaged with excessive sun exposure, the pigmented layer of the retina that protects the photoreceptors can also become damaged with excessive UV light. Blue light was also found to induce damage.
Race and Ethnicity. Non-Hispanic whites in the U.S. have a 2.5% prevalence. In contrast, the U.S. black and Hispanic populations each have a prevalence of about 0.9%.
Age. AMD r arely occurs in persons under age 55. The prevalence is 0.8% in those aged 70 and older, increasing to 16% in those over 90.
Smoking. Individuals who smoke have a relative risk of 2.0 and greater, compared with those who have never smoked. Risk may remain elevated for 15 or more years after smoking cessation.
Family history. Genetic factors are linked to AMD and, combined with smoking, substantially increase risk.
Alcohol. Heavy use increases risk for early AMD.
Sunlight. AMD is believed to be more prevalent near the equator, but this has yet to be shown to be statistically significant.
Other risk factors under investigation include hypertension and other cardiovascular comorbidities, and red meat consumption. -, , ,
The minimum age for diagnosis of AMD is 50 years. The classification system is based, not on visual acuity, but on characteristic findings on dilated retinal examination. These include changes in the retinal pigmented epithelium, periretinal hemorrhages, retinal atrophy, and retinal scarring. Drusen are not pathognomonic.
Ocular Coherence Tomography (OCT) is the gold standard in diagnosing and managing patients with neovascular AMD.
Slit-lamp photography of the macula is sometimes performed to document progression.
Fluorescein angiography detects the presence and location of any subretinal neovascularization, but its utilization has been lessened due to OCT.
Late stages of both neovascular and nonneovascular AMD can resemble other ophthalmologic diseases, which must be ruled out.
For prevention steps, see Nutritional Considerations, below.
Early AMD is typically managed by observation and lifestyle changes, especially avoidance of tobacco and alcohol. Patients should be referred to an ophthalmologist.
Regular exercise. Physical activity is beneficial for weight maintenance and overall cardiovascular function. It is also independently associated with lower risk for AMD. - 
Vitamins C and E, beta-carotene, and zinc: Foods naturally high in these antioxidants have been shown to reduce progression from early to late disease (see Nutritional Considerations).
For intermediate to advanced disease, antioxidant supplements are indicated (See Nutritional Considerations, below). However, according to the Age-Related Macular Degeneration Preferred Practice Pattern 2015 guidelines, evidence does not support the use of these supplements for patients with less than intermediate AMD.
Gingko biloba is under investigation for a possible role in treatment. It improved visual acuity in a small study and a larger, more recent study. Further investigation is warranted.
There is no specific medical or surgical treatment for nonneovascular AMD. Patients should be regularly monitored by an ophthalmologist and should report any abrupt changes in vision.
If OTC, or fluorescein angiography, reveals classic neovascularization, the first choice in treatment typically consists of intraocular injections of biologic agents, such as VEGF inhibitors. Aflibercept, ranibizumab, and bevacizumab (off-label use) are among the options for treatment. Thermal laser photocoagulation or photodynamic (laser) therapy are older options and ma y still be used in some cases. However, recurrences are common.
Photodynamic therapy (PDT), which is performed after intravenous injection of verteporfin that differentially enters neovascular tissue, offers limited benefit to patients with several forms of neovascular AMD. It does not restore vision, but rather is used to limit vision loss. Thanks to more effective medical therapy, this option is less commonly used.
Intravitreal steroid injections are under study and have achieved mixed results.
Submacular surgery is generally not recommended, and has not been shown to prevent vision loss at one year.
Macular translocation surgery has many complications, but could be a viable alternative for those who are not candidates for laser therapy. However, it remains unclear which patients, if any, are best served by this invasive approach. Long term studies are being conducted.
Dietary factors appear to play an important role in AMD. In epidemiologic studies, the following factors are associated with reduced risk of onset or progression of the disease:
Maintenance of ideal weight. Studies have found a higher risk for AMD in association with metabolic syndrome and measures of adiposity, including body mass index (BMI) and waist/hip ratio., ,
Low fat intake. Studies have found associations between high intakes of saturated fat and cholesterol and AMD. , Other studies have implicated vegetable fat and total fat intake in AMD. -, , People who regularly consumed processed baked goods had double the risk of AMD, compared with those who did not regularly consume these foods; the effect may relate to adverse effects on blood lipids or inflammation., However, the Age-Related Eye Disease Study 2 (AREDS2), a randomized, double-masked, placebo-controlled study found no protective benefit of DHA or EPA at five-year follow-up and a recent systematic review supported these findings. Genetics may influence the effect of fatty acids on AMD; more research is warranted. - 
High consumption of fruits and vegetables. Lutein and zeaxanthin are the principal carotenoids in the macular region of the retina. They are abundant in dark-green, leafy vegetables and appear to play an important role in prevention of macular degeneration. , Several studies have found that people with high intake of fruits and vegetables had a significantly lower risk for AMD compared with those who have low intakes. -  The Health Professionals Follow-Up Study and Nurses’ Health Study found an inverse association between fruit intake and risk for neovascular age-related maculopathy.
Antioxidant supplements. In the Age-Related Eye Disease Study, individuals with moderate or advanced AMD who received 500 mg of vitamin C, 400 IU of vitamin E, 15 mg of beta carotene, and 80 mg of zinc oxide (and 2 mg cupric oxide to prevent copper deficiency) had significantly reduced progression of their disease, compared with subjects receiving a placebo. Caution is advised, however, for several reasons: This evidence derives from a single study. Also, beta-carotene supplementation may increase lung cancer risk among smokers. Finally, daily doses of vitamin E exceeding 400 IU may increase cardiovascular and all-cause mortality.
In the lutein antioxidant supplementation trial (LAST), a 10-mg supplement of lutein taken daily, alone or with an antioxidant vitamin combination, increased macular pigment density and improved visual function when compared with a placebo. Lutein supplementation also improved visual performance (visual acuity and glare sensitivity) in other controlled trials. Due to a saturation of transport mechanisms for these carotenoids, some individuals do not achieve increases in macular pigment density, in spite of increases in blood levels of lutein and zeaxanthin following supplementation. Other individuals may not benefit if they are overweight, because lutein and zeaxanthin will be taken up by adipose tissue, rather than by the macula. An ophthalmologist should make patient-specific recommendations, because the age of the patient, disease severity, duration of treatment, and potential inhibitory effect of lutein supplementation on other carotenoids should be taken into account.
See Basic Diet Orders Chapter
Emphasize fresh fruits and vegetables, particularly leafy greens, such as collard or turnip greens, kale, and spinach. Orange peppers, corn and squash are also good sources of lutein and zeaxanthin.
Consider the following supplements in consultation with an ophthalmologist: Vitamin C 500 mg, vitamin E 400 IU, beta-carotene 15 mg, zinc oxide 80 mg, and cupric oxide 2 mg daily.
Lutein, dosed per ophthalmologist recommendations.
What to Tell the Family
Appropriate medical care and self-care can slow the loss of vision due to AMD. It is helpful to encourage smoking cessation and a diet that is low in fat and cholesterol and high in fruits and vegetables. That means including at least 1 serving daily of a dark leafy green vegetable, such as spinach, kale, collards, or turnip greens, along with 3 servings of fresh fruit per day. This diet is also beneficial to family members, who may have a higher risk of AMD. Supplemental lutein and certain vitamins and minerals (C, E, beta-carotene, and zinc/copper oxide) may be beneficial, but their use should be supervised by an ophthalmologist. Low-vision aids (such as special lighting and magnifiers) are available through eye clinics.
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