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Overview |
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Definition |
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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. |

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Etiology |
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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. |

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Risk Factors |
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- Aging
- Formation of drusen
- Excessive exposure to sunlight
- Light-colored iris
- History of cardiovascular disease
- Cigarette smoking
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Signs and Symptoms |
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- 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
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Differential
Diagnosis |
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- Epiretinal fibrosis
- Diabetic retinopathy
- Stargardt disease
- Hypertensive retinopathy
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Diagnosis |
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Physical Examination |
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Patients are referred for full ophthalmologic examination if ARMD is
suspected. The Amsler's grid is administered to assess visual
loss. |

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Pathology/Pathophysiology |
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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
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Other Diagnostic
Procedures |
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- 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
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Treatment Options |
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Treatment Strategy |
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There is no known cure for ARMD; however, there are procedures that can help
slow vision loss. |

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Drug Therapies |
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- Tissue plasminogen activator (tPA) helps remove subretinal
hemorrhaging; given in the form of eye drops
- Thalidomide: investigational, inhibits angiogenesis
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Surgical Procedures |
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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
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Complementary and Alternative
Therapies |
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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. |

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Nutrition |
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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. |

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Herbs |
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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). |

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Homeopathy |
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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.
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Acupuncture |
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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). |

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

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Other
Considerations |
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Prevention |
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- 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.)
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Complications/Sequelae |
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- Subretinal neovascularization—serous
detachment and scarring of the pigment epithelium may make finding location
impossible.
- Blindness—low vision aids for partial
blindness may help
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Prognosis |
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- 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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References |
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Acad Sci. 2000;889:87-106.
Ausman LM. Criteria and recommendations for vitamin C intake. Nutr Review.
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Belda JI, Roma J, Vilela C, Puertas FJ, Diaz-Llopis M, Bosch-Morell F, Romero
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Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
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The reader is advised to check product information (including package inserts)
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interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |