Overview and Risk Factors
Age-related macular degeneration (ARMD) is a degenerative disease of the macula, the central part of the retina. There are two forms of ARMD: a "dry" form marked by degenerative changes in the macula without bleeding or leakage of fluid; and a "wet" form, which often occurs in association with dry ARMD and exhibits leakage and/or bleeding from new blood vessel growth beneath the retina. Central vision, which is necessary for fine visual tasks and many daily activities, is threatened by ARMD. Consequently, ARMD is the most common cause of legal blindness (20/200 or worse in both eyes) among elderly Americans. ARMD pathogenesis is not well understood.
Changes usually seen in early stages of dry ARMD include subretinal yellowish deposits (drusen) and chorioretinal atrophy. Visual loss in dry macular degeneration tends to have a slow progression and uncommonly results in severe loss of central vision. In addition, dry ARMD can transform to wet ARMD. The wet form of ARMD involves abnormal vessel growth (neovascularization) into the subretinal space, causing leakage of fluid and/or bleeding. Resultant vision loss can occur suddenly or over the course of a few weeks.
Dry ARMD may occur in both eyes, whereas wet ARMD usually occurs unilaterally.1 Acute (days to weeks) or unilateral changes require immediate ophthalmologic evaluation. Dry ARMD may cause slow recovery of vision after leaving sunlight and going indoors. Symptoms of wet ARMD include distortion of straight lines (although this may also occur in dry ARMD), and (rarely) changes in color perception. As the disease progresses, a central scotoma may occur. For example, when looking directly at one's face, the nose (or larger area) may appear absent or distorted.
Risk Factors
Persons of white, non-Hispanic race/ethnicity generally have a higher prevalence of ARMD.2,3 Blacks have the lowest risk.3
Established risk factors include:
Age. ARMD rarely occurs in persons under age 55 years old. The prevalence is 0.8% in those aged 70 and older, increasing to 16% in those over 90.4
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.5
Family history.
An additional probable risk factor is nutritional deficiency (see Nutritional Considerations).
Studies of the relationship of hypertension and sunlight exposure on macular degeneration show conflicting results. Cataract surgery as a possible risk factor needs further research.
Diagnosis and Treatment
Diagnosis
ARMD is diagnosed by the characteristic appearance of the macula, as examined after dilation, and with direct ophthalmoscope or with a fundus lens at the slit lamp.
Slit-lamp photography of the macula is sometimes performed to document progression.
Fluorescein angiography detects the presence and location of any subretinal neovascularization.
Treatment
Vitamins C, E, beta-carotene and zinc are potentially valuable therapies (see Nutritional Considerations).
Dry ARMD
No specific medical or surgical treatment for the dry form of ARMD exists. Laser therapy needs further study.
Gingko biloba improved visual acuity in a small study (with unmasked assessment of outcome),6 and a larger more recent study.7 Further investigation is warranted.
Wet ARMD
If fluorescein angiography reveals classic neovascularization, thermal laser photocoagulation or photodynamic (laser) therapy may be used. 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 wet ARMD.8
For neovascular ARMD, a VEGF inhibitor, pegaptanib, has shown modest benefit. In addition, ranibizumab (a VEGF inhibitor that awaits FDA approval) and off-label bevacizumab injections show promise for treatment of neovascular ARMD.
Submacular surgery is generally not recommended, except possibly when large hemorrhages are present.
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.
Nutritional Considerations
Dietary factors appear to play an important role in ARMD. 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 ARMD in association with measures of adiposity, including body mass index (BMI) and waist/hip ratio.9-11 Regular exercise is associated with lower risk for ARMD.9,12
Low fat intake. Studies have found associations between high intakes of saturated fat and cholesterol and ARMD.13,14 Other studies have implicated vegetable fat and total fat intake in ARMD.15-17 Regular consumption of processed baked goods increased risk for ARMD twofold compared with those who did not regularly consume these foods, possibly through adverse effects on blood lipids or inflammation.15 In contrast, fish intake is associated with reduced prevalence of ARMD, at least among certain populations.13, 15-17
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.18 Several studies have found that people with high intake of fruits and vegetables had a significantly lower risk for ARMD compared with those who have low intakes.19,20 The Eye Disease Case Control Study found that individuals in the highest quintile of carotenoid intake had a 43% lower risk for ARMD compared with those in the lowest quintile. Intakes of collard greens and spinach, both rich in lutein, were found to be the most protective. The Health Professionals Follow-Up Study and Nurses' Health Study found inverse associations between higher fruit intakes (3 or more servings per day) and lower risk for neovascular age-related maculopathy.21
Antioxidant supplements. In the Age-Related Eye Disease Study, individuals with moderate or advanced ARMD 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.22 Caution is advised, however, given evidence that beta-carotene supplementation may increase lung cancer risk among smokers, and that daily doses of vitamin E 400 IU and greater may increase cardiovascular and all-cause mortality.23
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.24 Lutein supplementation also improved visual performance (visual acuity and glare sensitivity) in other controlled trials.25 Patient-specific recommendations should be made by an ophthalmologist, 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.
Orders
Emphasize fresh fruits and vegetables, collard or turnip greens, kale, spinach.
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 as per ophthalmologist recommendations.
Smoking cessation.
What to Tell the Family
Appropriate medical care and self-care can slow the loss of vision due to ARMD. 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. This diet is also beneficial to family members, who may have a higher risk of ARMD. 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.
References
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2. Klein R, Clegg L, Cooper LS, et al. Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 1999;117:1203-1210.
3. Klein R, Klein BE, Knudtson MD, et al. Prevalence of age-related macular degeneration in 4 racial/ethnic groups in the multi-ethnic study of atherosclerosis. Ophthalmology. 2006;113:373-380.
4. Weih LM, VanNewkirk MR, McCarty CA, Taylor HR. Age-specific causes of bilateral visual impairment. Arch Ophthalmol. 2000;118:264-269.
5. Seddon JM, Willett WC, Speizer FE, Hankinson SE. A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA. 1996;276:1141-1146.
6. Lebuisson DA, Leroy L, Rigal G. Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo study [In French]. Presse Med. 1986;15:1556-1558.
7. Fies P, Dienel A. Ginkgo extract in impaired vision--treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration [in German]. Wien Med Wochenschr. 2002;152:423-426.
8. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Arch Ophthalmol. 1999;117:1329-1345.
9. Seddon JM, Cote J, Davis N, Rosner B. Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio. Arch Ophthalmol. 2003;121:785-792.
10. Schaumberg DA, Christen WG, Hankinson SE, Glynn RJ. Body mass index and the incidence of visually significant age-related maculopathy in men. Arch Ophthalmol. 2001;119:1259-1265.
11. Smith W, Mitchell P, Leeder SR, Wang JJ. Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol. 1998;116:583-587.
12. Klein R, Klein BE, Tomany SC, Cruickshanks KJ. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 2003;110:1273-1280.
13. Smith W, Mitchell P, Leeder SR. Dietary fat and fish intake and age-related maculopathy. Arch Ophthalmol. 2000;118:401-404.
14. Mares-Perlman JA, Brady WE, Klein R, VandenLangenberg GM, Klein BE, Palta M. Dietary fat and age-related maculopathy. Arch Ophthalmol. 1995;113:743-748.
15. Seddon JM, Cote J, Rosner B. Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol. 2003;121:1728-1737.
16. Cho E, Hung S, Willett WC, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001;73:209-218.
17. Seddon JM, Rosner B, Sperduto RD, et al. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol. 2001;119:1191-1199.
18. Ribaya-Mercado JD, Blumberg JB. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr. 2004;23(suppl 6):567S-587S.
19. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MOM. Factors associated with age-related macular degeneration: an analysis of data from the First National Health and Nutrition Examination Survey. Am J Epidemiol. 1998;128:700-710.
20. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994;272:1413-1420.
21. Cho E, Seddon JM, Rosner B, Willett WC, Hankinson SE. Prospective study of intake of fruits, vegetables, vitamins, and carotenoids and risk of age-related maculopathy. Arch Ophthalmol. 2004;122:883-892.
22. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417-1436.
23. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.
24. Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004;75:216-230.
25. Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study. Nutrition 2003;19:21-24.
