Articles

Macular Degeneration

Introduction

Macular degeneration is a major cause of gradual, painless, central vision loss in the elderly. (1) It occurs as a result of geographic atrophy, serous detachment of the retinal pigment epithelium, and/or choroidal neovascularization. There are two forms that occur. One is a nonexudative or dry form, which begins with the accumulation of extracellular deposits, called drusen, underneath the retinal pigment epithelium. When examined ophthalmoscopically, they appear as discrete, small, yellow lesions, clustered in the macula. As the process continues, they become larger, more numerous, and confluent. Generally, they cluster in the posterior pole, but may occur anywhere in the fundus. Drusen in an extramacular location are of no visual consequence. The drusen alone do not cause visual loss, although mild metamorphopsia (distortion), loss of reading speed, and impaired contrast sensitivity may occur. They do represent a significant risk factor for subsequent geographic atrophy and choroidal neovascularization. Vision becomes impaired when the retinal pigment epithelium becomes focally detached and atrophic, interfering with photoreceptors.

In the exudative, or wet form, which actually occurs much less frequently, neovascular vessels from the choroids grow through a defect in Bruch’s membrane into the potential space beneath the retinal pigment epithelium. Blurring of vision and distortion occurs as leakage from these vessels produces elevation of the retina and retinal pigment epithelium. Although it is widely accepted that the primary loci of the disease are the choriocapillaris, Bruch’s membrane, and the retinal pigment epithelium, the visual loss in age-related macular degeneration results from dysfunction and death of the overlying photoreceptors. (2) The onset of symptom is usually gradual, however, acute vision loss may occur if bleeding from subretinal choroidal neovascular membranes occurs. Neovascular membranes are not easily seen on fundus examination because they are behind the retina, so flurorscein angiography is extremely useful for their detection. Occasionally, laser oblation may be performed to halt the exudative process, however, the process is usually a recurring one requiring vigilance and often repeated photocoagulation. Major or repeated hemorrhage from neovascular membranes results in fibrosis, development of a disciform macular scar and permanent loss of central vision.

The disease is one found primarily in the elderly, as implied by the name. Previously known as "senile macular degeneration," the name has been changed to age-related macular degeneration, (ARMD), due to the unflattering reference to advanced age. The average age at onset of visual loss is about 75 years. After the age of 50 years, the incidence steadily increases; over one-third of people in their ninth decade of life are affected. (3) The actual incidence of the disease depends upon how it is defined.

The Framingham Eye Study revealed that ARMD affects about 2% of Americans aged 52-64 years: 11% aged 65-74 years; and 28% aged 75 years and older. (4)

Despite its prevalence and extensive ocular morbidity, the pathogenesis of the disease remains unclear. Arteriosclerosis, oxidative damage, photic damage, inflammation, diet, vitamin and rare element deficiencies, and genetics have been implicated by various researchers. Genetic factors become very hard to quantify due to the fact that parents and siblings may not be alive, and children may be too young to manifest clinical findings. It has been determined that systemic arterial hypertension and cigarette smoking are associated with an increased risk of neovascular ARMD. Other suggested risk factors include hyperopia and increased horizontal cup-to-disc ratio, and risk factors associated with cardiovascular disease. Another relationship to ARMD was suggested in an evaluation of 51 older patients with recent-onset bilateral ARMD. This study noted that the prevalence of depression in these patients was substantial and that it exacerbated the effects of ARMD, suggesting that treatment of depression may lead to improved outcomes. (5) Early studies implicated a relationship between light and the development of ARMD, however, more recent studies found no correlation to either visible light or a light iris color an increased risk. The role of ocular blood flow in ARMD is under study – affected patients may show impaired choroidal perfusion. (6)

Statistic

World Health Organization, 2004.

  • Age-related macular degeneration (AMD) ranks third on the global scale.
  • However, in developed countries, AMD is the leading cause of blindness.

New Zealand Medical Association, 2001.

  • 4984 New Zealanders registered blind have AMD in the 55 year and over age group.

Macular Degeneration Foundation, 1999.

    1 in 3 Americans are affected. Macular Degeneration is the leading cause of central vision loss and blindness in the Western World. Over 15 million victims have this disease.

American Academy of Ophthalmology, 1999.

    90% of cases are "Dry" form. 10% of cases are "Wet" form.

The Schepens Eye Research Institute, 1999.

    "Wet" form accounts for 90% of all cases of legal blindness.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Age related macular degeneration is bilateral, occasionally treatable, not preventable, and is generally progressive. While some patients may be asymptomatic, the symptoms most commonly seen include blurred vision or metamorphopsia in one or both eyes, decreased reading ability, especially in dim light, and trouble with dark adaptation. It most frequently occurs in patients over 50 years of age. Ophthalmic evaluation shows the presence of drusen, geographic atrophy, and eventual retinal pigment epithelial detachment.

General

  • Patients may be asymptomatic
  • Blurred vision or metamorphopsia in one or both eyes
  • Decreased reading ability, especially in dim light
  • Trouble with dark adaptation
  • Generally over 50 years of age
  • Drusen present
  • Geographic atrophy
  • Bilateral
  • Serous retinal pigment epithelial detachment

Treatment Options

Conventional

For non-neovascular age-related macular degeneration, no proven treatment for visual loss has been found. While vitamin supplementation (especially antioxidants) and zinc supplementation have been proposed, at present no proven benefit exists, (7) and potential harm has not been ruled out. (8)

Laser photocoagulation is the only proven treatment of neovascular ARMD. Without exception, every study that showed benefit from laser coagulation in eyes that have CNV (choroidal neovascularization) with well demarcated boundaries. However, only 15 to 20 percent of neovascular ARMD consists of well-defined CNV. The goal of laser coagulation to CNV is to decrease the risk of additional vision loss beyond the damage that the patient already has on presentation to the ophthalmologist. Visual restoration is rare.

Nutritional Supplementation


Zinc

Studies have reported lower serum zinc levels in individuals with macular degeneration. (9) , (10) However, other authors report finding either no association, or elevated serum zinc levels in patients with macular degeneration, so there is some uncertainty surrounding this issue. (11) , (12)

Zinc plays a role in the metabolic function of several important enzymes in the retinal area of the eyes, which may affect the macular degenerative process. In 1988, a prospective, randomized, double-masked, placebo-controlled trial was conducted to investigate the effects of oral zinc administration on the visual acuity in 151 subjects with either macular degeneration or drusen (a type of pathological growth in the eye). Although the eyes in some of the zinc-treated patients lost vision, these patients had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months. The Age Related Eye Disease Study (AREDS) Report # 11 found that if individuals at risk for ARMD took antioxidant supplements with zinc, their risk would be lessened and over a 5 year period of time the impact on public health would be significant. (13)


Lutein, Zeaxanthin

Lutein and zeaxanthin are the primary carotenoids comprising the macular pigment of the eyes. In addition to acting as optical filters, evidence suggests that they also function as antioxidants in the human retina by inhibiting the peroxidation of long-chain polyunsaturated fatty acids. (14)

Inverse relationships have been reported between the incidence of age-related macular degeneration (AMD) and the combined levels of lutein and zeaxanthin intake in the diet, and also their concentration in the blood serum. The results of a study that evaluated these associations supported the hypothesis that low concentrations of lutein and zeaxanthin in the macular pigment may be associated with an increased risk of age-related macular degeneration. (15) However, this issue is not completely settled because the authors of another study reported finding no association between the serum levels of lutein and zeaxanthin and age-related macular degeneration (16) which has been further supported by data collected from the third National Health and Nutrition Examination Survey (NHANES). NHANES did find an association between higher levels of lutein and zeaxanthin in the diet and lower rates of pigmentary abnormalities, a common precursor to age-related maculopathy. (17)

Foods with high lutein and zeaxanthin content include green leafy vegetables, egg yolk, corn, orange peppers, kiwi fruit, grapes, spinach, orange juice, zucchini, and different kinds of squash. (18)


Lycopene

Lycopene is the most abundant carotenoid in the serum. One study reported that individuals with levels of lycopene in the lowest quintile were twice as likely to have age-related macular degeneration. Surprisingly, this study also reported finding that serum levels of the carotenoids that predominate in the macular pigment (lutein and zeaxanthin) were unrelated to ARMD. (19)


Vitamin E

Much of the research on the etiology of age-related macular degeneration and other eye diseases has focused on the role of nutritional antioxidants. Evidence from epidemiological studies suggests that nutritional antioxidants, such as vitamin E, may play a role in delaying the onset of these age-related vision disorders. (20) It is now known that vitamin E is distributed within retinal tissues. (21) Some research results indicate that patients with age-related macular degeneration have significantly lower serum vitamin E levels compared to age-matched controls. (22)


Vitamin C

Evidence from epidemiological studies indicates that vitamin C is one of the antioxidant nutrients that may play a role in delaying the onset of age-related macular degeneration and other visual disorders. (23) However, other studies report finding that vitamin C levels are not associated with a reduced risk to macular degeneration. (24) , (25) The multicenter Eye Disease Case-Control Study involved 356 case subjects and 520 control subjects. The results from this study found no statistically significant protective effects for vitamin C or E or selenium individually, but an antioxidant index that combined the micronutrients revealed statistically significant risk reductions with increasing levels of the index. (26)

A similar study with 827 participants reported that an antioxidant index including vitamin C, vitamin E and beta-carotene suggested possible risk reductions with higher index levels of the combined antioxidants. (27)

Many of the studies evaluating the association between antioxidants and age-related macular degeneration have conflicting outcomes. There are currently five large ongoing trials and the results of these studies are eagerly anticipated.

Herbal Supplementation


Bilberry

Bilberry is one of the most popular herbs on the market today. During World War II when British air pilots ate bilberries, they reported an improved ability to adjust to glare and an increase in their visual acuity and nighttime vision. (28) Bilberry extracts show promise in the areas of diabetic retinopathy, macular degeneration, cataracts, glaucoma, and varicose veins. (29) Bilberry is an excellent antioxidant. (30) Bilberry is claimed to exert a collagen stabilizing activity. (31) Collagen is responsible for the integrity of tendons, ligaments, and cartilage. In conditions such as arthritis, where the connective tissue is attacked and vascularized, anthocyanosides may be helpful. Bilberry reportedly strengthens the cross-linking of the collagen matrix and stimulates the production of collagen and mucopolysaccharides. (32) Bilberry compounds reportedly inhibit mediators of inflammation such as histamine, protease, leukotrienes, and prostaglandins. (33) Anthocyanosides may also decrease capillary permeability. (34) This is of particular importance because of the heightened integrity which occurs at the blood/brain barrier. By strengthening collagen, brain capillary integrity can be improved, as well as a reduction in infiltration by potential toxins. Anthocyanosides reportedly inhibit platelet aggregation. (35) Platelet aggregation tendencies relate to atherosclerotic and blood clotting tendencies. Bilberry has the ability to stimulate gastric mucus production which may be of value for those on nonsteroidal anti-inflammatory drugs. (36) Although all of the above effects are exciting, the most exciting is its potential effect on the eyes. With age, oxidative stress due to free radicals increases in some people more than in others. This damage to ocular tissues may lead to various eye pathologies. If it improves the oxygenation of tissue, bilberry may show promise in the areas of prevention for diabetic retinopathy, minimizing the advance of macular degeneration, and arresting cataract progression. (37) , (38)


Grape Seed Extract

Proanthocyanidins (PCO's), the active constituent in grape seed, is a flavonoid-rich compound which is being heavily touted as one of the most potent free radical scavengers. It has been reported to enhance the absorption of and work synergistically with vitamin C. (39) PCO's have been reported to inhibit the release of mediators of inflammation, such as histamine and prostaglandins. (40) , (41) Proanthocyanidins are claimed to support collagen structures and inhibit the destruction of collagen. (42) PCO's reportedly protect 1-antitripsin, a chemical that keeps enzymes for breaking down collagen, elastin and hyaluronic acid (43) , (44) and directly inhibit these from damaging enzymes. Proanthocyanidins are believed to neutralize lipid peroxidation damage to cell membranes through their free radical activity. (45) , (46) Collagen protection is claimed to be very important for ocular health because it allows red blood cells to penetrate into the microcapillary system and prevent fluids from leaking out. (47) , (48) PCO's may strengthen the capillary walls and skin. Proanthocyanidins are reported to neutralize many free radicals, including hydroxyl, lipid peroxides and iron-induced lipid peroxidation. (49) , (50) , (51) They may inhibit the enzyme xanthine oxidase. (52) PCO's have been used in allergies because of their reported ability to inhibit degradation of mast cells and the subsequent release of histamine and other mediators of inflammation.


Green Tea

Green tea has long been used in much of the world as a popular beverage and a respected medicinal agent. An early Chinese Materia Medica lists green tea as an agent to promote digestion, improve mental faculties, decrease flatulence and regulate body temperature.

The earliest known record of consumption is around 2700 B.C. Green tea is an antioxidant that is used in promoting cardiovascular health (53) , (54) reducing serum cholesterol levels in laboratory animals and humans. (55) , (56) Studies suggest that green tea contains dietary factors that help decrease the development of some infectious diseases and dental caries. (57) , (58) , (59) Green tea also has diuretic, stimulant, astringent and antifungal properties. (60) Green tea has also been reported to enhance immunity. (61)

Green tea reportedly has antioxidant properties (62) and the ability to protect against oxidative damage of red blood cells. (63) Antioxidants protect cells and tissues of many biological systems including the eyes against oxidative damage and injury. (64) Green tea’s antioxidant effects seem to be dependent upon the polyphenol (catechin) fraction. (65) , (66) It is important to note that the addition of milk to any tea may significantly lower the antioxidant potential. (67)


Gotu Kola

Gotu kola is reported to have a positive effect on tissues, specifically skin, connective tissue, lymph and mucous membranes. (68) , (69) , (70) It does not contain any caffeine and is not related in any way to kola nut. Gotu kola has been used primarily for venous insufficiency, soft tissue inflammation and infection and for postsurgical wound healing. (71) , (72) Asiaticosides are reported to exert a preferential stimulation of collagen synthesis, in addition to stimulating glycosaminoglycan synthesis. (73) Also, gotu kola affects the connective tissue by strengthening weakened veins. (74) Gotu kola may assist in the maintenance of connective tissue. In the treatment of scleroderma, gotu kola may also assist in stabilizing connective tissue growth, reducing its formation. (75) It reportedly stimulates the formation of hyaluronidase and chondroitin sulfate, as well as exerting a balancing effect on the connective tissue. (76) It is believed to have an effect on keratinization, which aids in thickening skin in areas of infection. (77) Gotu kola is used topically and internally for skin conditions including psoriasis and eczema. (78)

Homeopathic

Carbo vegetabilis

Typical Dosage: 6X or 6C, 30X or 30CCirculatory debility

Secale cornutum

Typical Dosage: 6X or 6C, 30X or 30CPoor circulation

Diet & Lifestyle

Avoid smoking

Avoid excess UV sunlight

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Oxidative Stress

Many experts believe that macular degeneration is a result of free radical damage. Oxidant levels increase in relationship to inflammatory processes and cell apoptosis. The theory of free radical damage as the cause for aging has been studied at great length for almost 50 years. (79) It has been postulated that a mechanism of aging is a triggering of genetic expression through free radical proliferation. (80) It is reasonable, in any event, to assume that inhibition of oxidation through the use of antioxidants can slow the aging process. (81)

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