Macular degeneration, also called age-related macular degeneration (ARMD), is a painless, degenerative eye disease. Because the macula is the primary site affected by this condition, central visual acuity is affected while peripheral vision may be completely spared. There are two forms of ARMD. Nonexudative or dry ARMD involves the accumulation of drusen (debris deposits) between the pigment epithelium and the underlying basement membrane (Bruch's membrane). The exudative or wet form involves the additional presence of blood vessels that form in response to the degenerative changes (neovascularization).

ARMD is the leading cause of legal blindness in the United States in persons over the age of 55. It affects more than 10 million Americans, and this number will increase as "baby boomers" age.

ARMD occurs when the health of the pigment epithelium in the macula deteriorates and compromises the health of the retinal photoreceptors. First, one of three types of drusen forms (see Pathology/Pathophysiology). Drusen alone do not cause visual loss. However, as the eye degenerates the Bruch's membrane thickens and is weakened, resulting in detachment of the retinal epithelium. This detachment causes the overlying photoreceptors to atrophy. New blood vessels may form, in a process called neovascularization. The blood vessels leak or bleed, which causes serous or hemorrhagic detachment of the pigment epithelium and, possibly, fibrovascular scarring.

• Aging
• Formation of drusen
• Excessive exposure to sunlight
• Light-colored iris
• History of cardiovascular disease
• Cigarette smoking

• Sudden or gradual loss of central visual acuity in elderly persons
• Distortion of visual images (metamorphopsia) usually indicates neovascularization
• Amsler's grid distortions or missing lines
• Irregularity of color, transparency, and increased pigmentation of the fovea
• Presence of drusen, atrophy, neovascularization

• Epiretinal fibrosis
• Diabetic retinopathy
• Stargardt disease
• Hypertensive retinopathy

Patients are referred for full ophthalmologic examination if ARMD is suspected. The Amsler's grid is administered to assess visual loss.

Three types of drusen occur with ARMD:

• Hyaline or hard drusen—small, globular, refractile bodies; attach to the inner surface of Bruch's membrane; pigment epithelial cells above the hyaline drusen may atrophy; severe photoreceptor degeneration is rare
• Soft or granular drusen—large, irregularly shaped, pale yellow subretinal plaques; may coalesce or disappear; degeneration of pigment epithelium occurs
• Calcified, diffuse, or confluent drusen—gold, glittering bodies; calcified and inspissated remnants of soft drusen

Pigment epithelium degeneration:

• Phagocytosis of outer segment discs by pigment epithelium becomes impaired—pigment epithelium and Bruch's membrane are overloaded with undigested material
• Atrophy, scarring, and serous detachment occur

Subretinal neovascularization:

• Growth of new blood vessels from the choriocapillaris into the subpigment epithelium and then into the subretinal space
• Hemorrhaging, fibrosis, further degeneration of pigment epithelium, photoreceptor atrophy, central scarring

• Amsler's grid—10x10 cm card with white dot in center, grid with black background and white lines spaced 5 mm apart; patients with neovascularization report central or paracentral distortion or paracentral blind spot
• Intravenous fluorescein angiography—hyperfluorescence and staining can reveal presence and type of drusen; neovascularization is indicated by cartwheel-shaped pattern or by a cluster of irregular spots from which fluorescein leaks into subretinal space
• Indocyanine green videoangiograph—reveals neovascularization
• Contact lens biomicroscopy—reveals serous detachment into the fovea; flecks of intraretinal blood or lipid exudates near serous membrane indicate neovascularization

There is no known cure for ARMD; however, there are procedures that can help slow vision loss.

• Tissue plasminogen activator (tPA) helps remove subretinal hemorrhaging; given in the form of eye drops
• Thalidomide: investigational, inhibits angiogenesis

Argon laser photocoagulation therapy:

• For neovascularization that is 200 mm from the fovea (otherwise risk of destroying photoreceptor cells is too great) reduces central vision loss over at least 2 years
• May damage the overlying neurosensory retina, possibly causing visual loss
• Many patients do not qualify because of location, size, or poorly demarcated boundaries
• Benefits are greater in patients without hypertension

Photodynamic therapy:

• Photosensitized tissue irradiated with a low-powered nonthermal laser light at an absorption peak of the photosensitizer (verteporfin, a benzoporphyrin derivative, with an absorption peak near 690 nm; FDA approval received in April, 2000).
• Excited photosensitizer generates reactive intermediates, such as singlet oxygen, that damage cellular membranes.
• Controlling photosensitizer dose, light dose, and timing of irradiation allows selective therapeutic effect, with minimal damage to surrounding retina and tissue.

Vitrectomy:

• Removes neovascularization
• Removes subretinal blood if performed within 7 days

Nutrition is a valuable intervention for nonexudative (dry) macular degeneration; in contrast, exudative (wet) macular degeneration is treated most effectively with conventional therapies. Nutrition is also useful to prevent both types of age-related macular degeneration.

Oxidative stress is believed to be a contributing factor in ARMD; nutrients that protect retinal pigment epithelium (RPE) from oxidant-induced apoptosis may delay or prevent the onset of ARMD (Cai et al. 2000). Studies of antioxidant protection in ARMD have focused on carotenoids, selenium, zinc, and vitamins C and E. Additional areas of investigation include dietary factors such as carotenoid-rich foods and red wine, which is high in flavonoids (Head 1999). Examples of vegetables rich in carotene include orange and yellow squash as well as dark, leafy greens such as kale, collards, spinach, and watercress. Dark berries, such as blueberries, blackberries, and dark cherries are high in flavonoids.

The thiol antioxidant, glutathione, and its precursors, N-acetyl cysteine and selenium, protect RPE cells from oxidative damage (Cai et al. 2000). Recommendations of 200 to 500 mcg/day of selenium may be considered (Ames 2000).

Zinc is found in high concentrations in the retina and choroid and is involved in retinal metabolism. Zinc is also instrumental in the production of visual pigments (Congdon 1999). Zinc can be taken in supplement form up to 50mg/day (Hambridge 2000).

Carotenoids, specifically lutein and zeaxanthin, are highly concentrated in the macula. It is hypothesized that these nutrients prevent retinal damage by absorbing high-energy blue light or by providing antioxidant protection (Cooper et al. 1999). Carotenoids can be taken in supplement form as, for example, mixed carotenoids 25,000 to 50,000 IU/day or the specific carotenoid lutein 5 mg/day.

In one study of 356 patients with advanced ARMD, high dietary intake of carotenoids was associated with a 43% lower risk of ARMD. Lutein and zeaxanthin were most strongly associated with the reduced risk. There was no associated risk reduction with vitamins A or E, although possible protection was suggested among those with a higher dietary intake of vitamin C (Seddon et al. 1994). A study of 25 ARMD patients revealed significantly lower serum levels of antioxidant nutrients compared to subjects without ARMD (Belda et al. 1999). Another study evaluated the relationship between fasting plasma levels of retinol, ascorbic acid, alpha-tocopherol, and beta-carotene in 226 patients with ARMD over two years. High plasma levels of alpha-tocopherol and an antioxidant index composed of ascorbic acid, alpha-tocopherol, and beta-carotene were associated with a protective effect for ARMD (West et al. 1994).

Not all epidemiological studies have been conclusive, however; three large studies found no statistically significant associations between age-related maculopathy and dietary or supplementary intake of carotene, zinc, or vitamins A, C, and E (Christen et al. 1999; Pratt 1999; Smith et al. 1999; VandenLangenberg et al. 1998).

In order to minimize risk of ARMD, research reviews advocate diets high in vitamins C and E and carotenoids, especially spinach, kale, and collard greens (Jacques 1999; Pratt 1999; Segasothy and Phillips 1999). Again, supplementation for primary or secondary prevention of ARMD remains controversial. If supplementation is going to be undertaken, recommendations for carotenoid, zinc and selenium were discussed earlier. Recommended doses of vitamin E may be as low as 50 IU and as high as over 1000 IU (Ames 2000); most frequent dose range of vitamin E is 400-800 IU. The recommended daily allowance (RDA) of vitamin C is 60 mg – 2000mg/day in divided doses (Carr and Frei 1999); however, many recommend not exceeding 1000 mg/day due to risk of gastrointestinal disturbances including nausea and diarrhea (Ausman 1999).

As mentioned earlier, flavonoids may also play a role in ARMD prevention. A case control study of 3072 adult patients with macular changes indicative of ARMD reported a statistically significant but negative association between ARMD and moderate wine consumption; in other words, moderate wine consumption may offer some protection against the development or progression of ARMD (Obisesan et al. 1998). Please see first paragraph in Nutrition section for foods rich in flavonoids.

Ginkgo (Ginkgo biloba) has been shown to inhibit or minimize functional retinal impairments resulting from photodegeneration, diabetic complications, and ischemia-reperfusion injury. In addition, clinical studies suggest that ginkgo may be useful in treating visual deficits in ARMD specifically (Clostre 2000; Diamond et al. 2000). Patients concurrently using anticoagulants should be monitored closely.

Ginkgo, bilberry (Vaccinium myrtillus), and grape seed (Vitis vinifera), all of which are high in flavonoids, may play a role in the prevention and treatment of ARMD. Clinical studies have demonstrated their efficacy in inhibiting visual loss and possibly improving visual acuity. Bilberry extracts standardized to 25% anthocyanidin content have a strong affinity for RPE; the recommended dose is 120 to 240 mg BID. Ginkgo, standardized to 24% ginkgo flavonglycoside content, is recommended in cases of concurrent cerebral insufficiency; the recommended dose of gingko biloba is 120 mg QD or BID. Grape seed is most useful when there is photophobia or loss of night vision; 50 to 150 mg QD or BID is recommended (Murray and Pizzorno 1998).

While scientific literature regarding the application of homeopathy for the treatment or prevention of ARMD has not specifically been reported, a trained and certified homeopathic doctor would take the individual into consideration when determining the value of and appropriateness of treatment.

In a study of 51 patients with maculopathies, researchers found little change in visual acuity or mitigation of symptoms after 12 treatments of acupuncture (Wong and Ching 1980). In another study, an evaluation of cephalic blood pressure revealed an association between patients with cephalic hypotension and ARMD. Restoring normal blood pressures with electrical stimulation resulted in significantly improved vision (Omura 1983).

Monitor for early detection of vision loss and for recurrent neovascularization after laser treatment—Amsler's grid, fluorescein angiography.

• Daily home use of Amsler's grid and immediate reporting of any distortion reduces the frequency of vision loss from 60% to 25% in patients with neovascularization.
• A high dietary intake of lutein and zeaxanthin carotenoids (e.g., spinach, collard greens), vitamin C, vitamin E, and flavonoids (e.g. dark berries) may lower risk of ARMD.
• Use ultraviolet eye protection.
• Estrogen replacement therapy (at least 4 years.)
• Moderate red wine consumption (likely secondary to the flavonoids present.)

• Subretinal neovascularization—serous detachment and scarring of the pigment epithelium may make finding location impossible.
• Blindness—low vision aids for partial blindness may help

• Subretinal neovascularization—prognosis for preserving central vision is poor; the larger the membrane and the closer it is to the fovea, the worse the prognosis; occurs in approximately 20% of ARMD and small areas may occur in up to 20% of all individuals over the age of 60; high incidence of recurrence after laser treatment

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