Age-related macular degeneration

Normal vision compared to vision in AMD. Blurred central field vision is characteristic in people suffering AMD.

Age-related macular degeneration is the leading cause of blindness in the Western world for people of advanced age, and the incidence of disease is growing as elderly populations increase.

AMD is a progressive deterioration of the macula, the central portion of the retina, and usually affects people 60 years of age or older. Because the macula is responsible for high-resolution visual acuity, AMD often leads to loss of detailed object recognition in the central field of vision. This is the reason why people suffering with AMD often cannot resolve the face of a person, but can still see objects in the background of the field.

Figure 3: Prevalence of AMD. The incidence of AMD increases rapidly after age 50, and strikes a large segment of the population 70 years and older.

The yellow color of the macula lutea of the eye is the result of selective accumulation of the yellow carotenoids lutein and zeaxanthin, an accumulation which is specific for this part of the retina. For this reason, these carotenoids are often referred to as the yellow macular pigments.

There are two forms of age-related macular degeneration: the "dry" form and the "wet" form.

•  "Dry" AMD

"Dry" AMD is the most common form of AMD and accounts for approximately 90% of all cases. The form is characterized by deposits of cellular debris, and changes in the photoreceptors and retinal pigment epithelium. The progression of the disease is thus slow and painless, and often develops unnoticed. Unfortunately, the problem is compounded by the fact that no treatment is available.

•  "Wet" AMD

The "wet" form results when blood vessels grow under the macula, and begin to leak fluid and blood into the retina thereby causing damage to the photoreceptors. The progression of this form of AMD can be rapid, with dramatic losses in visual acuity occurring within weeks. The most beneficial treatment for “wet” AMD is the destruction of the newly formed blood vessels by laser photocoagulation. While laser treatment results in loss of visual acuity, the extent of visual loss is less than without treatment. The "wet" form of AMD is a rare complication, and represents only about 10% of all AMD cases.

Age-related macular degeneration is a multifactorial disease, which means it has many causes that have to come together in concert in order to produce disease manifestation. Certain risk factors, however, have been identified:

Age -- Age is the major risk factor in acquiring AMD. In the US for example, about 5% of the population 60 years of age suffer with AMD, which increases to 20% for the 70 year olds, peaking at approximately 20% for all individuals over 80, refer to Sun and Nathans [1].

Family history -- AMD can be inherited. This means that if a close relative acquires the disease there is a greater likelihood that you will also. Of the inherited forms of the disease, juvenile AMD is the most common.

Gender -- Women have a greater probability of developing AMD than men, and this risk increases to double of that of men over age 75. A decrease in estrogen levels after the menopause appears to be a confounding factor.

Iris Color -- People with a light iris color have a higher risk for AMD than the ones with a dark iris.

Smoking -- is an important factor in developing AMD because the numerous toxic substances of smoke draw on the eye’s supply of antioxidants

Alcohol consumption -- especially in connection with a diet high in saturated fats and cholesterol, appears to contribute to the depletion in antioxidants protecting the eye. People who consume high amounts of alcohol often neglect fruits and vegetables in their diet, foods that contain high amounts of natural antioxidants, such as carotenoids.

Sun exposure -- Excessive sun exposure can also act as a contributing factor in AMD, because the macula is sensitive to harmful blue light, and the reactive free radicals it can produce.

Cardiovascular disease -- Any form of cardiovascular disease, such as high blood pressure, can facilitate the development of AMD, because the blood circulation to the retina is reduced.

Several recent epidemiological studies have associated frequent consumption of foods containing lutein and zeaxanthin, such as maize or corn and spinach, and high plasma levels of zeaxanthin and lutein with a reduction in risk for AMD.

Additional studies suggest that people with AMD have lower levels of lutein and zeaxanthin in the macula than those without AMD. For example, in a study by Landrum et al. [2], analysis of postmortem eyes of 12 normal subjects and 24 subjects with AMD revealed that the average lutein and zeaxanthin concentrations were approximately 30% lower in the retinas of AMD patients than in the healthy control group.

Figure 4: Total carotenoid concentration in normal and AMD retinae. People suffering AMD have approximately 30% lower concentrations of lutein and zeaxanthin in the inner retina than do normal individuals.

A case-control investigation published in 1993 by the Eye Disease Case-Control (EDCC) Study Group [3] compared the antioxidant status and the progress of age-related macular degeneration in a population of 356 subjects with a specific form of AMD compared to 520 control subjects. They were able to show a statistically significant inverse relationship between plasma levels of zeaxanthin and lutein and the risk of developing AMD. This means that low amounts of plasma zeaxanthin and lutein may be risk factors for AMD.

Seddon et al. [4] have shown in a later paper from the same study group that the relative risk for AMD is approximately 60% lower in subjects consuming 5.7 mg of lutein and zeaxanthin per day.

Figure 5: Studies suggest that the risk of AMD decreases significantly as the average dietary intake of lutein and zeaxanthin increase from approximately 1.5 mg per day to approximately 5.7 mg per day.

The world’s population may not be consuming sufficient amounts of lutein and zeaxanthin to maintain their eye health. Modern, hectic, lifestyles have impacted eating habits, and have encouraged a fast-food diet. Changing these habits is difficult, if not impossible, and for this reason dietary supplements or fortified foods containing lutein and zeaxanthin are viable alternatives for increasing the widespread consumption of these carotenoids of vision.

Observational and experimental studies suggest that antioxidants may delay the progression of AMD and loss of vision. The Age-Related Eye Disease Study Research Group investigated the effects of supplements containing high-dose vitamin C, E, beta-carotene, zinc and copper on AMD progression and visual acuity. The Group’s Age-Related Eye Disease Study (AREDS) Report No. 8 [5], which was published in the October 2001 issue of the Archives of Ophthalmology, describes an 11-center, double-blind clinical trial in which 3,640 well-nourished elderly participants received either (1) an antioxidant supplement containing 500 mg vitamin C, 400 IU vitamin E and 15 mg Beta-carotene, (2) a supplement containing 80 mg zinc and 4 mg copper, (3) the antioxidant and the zinc supplement, or (4) control tablets (placebo). After a follow-up period of approx. 6.3 years, the authors of this investigation conclude that both zinc and the antioxidants + zinc significantly reduced the odds of developing advanced AMD in the group at highest risk for the disease.

Cataracts are characterized by a slow, but continuous, clouding of the lens. The lens is less transparent because its proteins become oxidized, and their structures begin to break down. Age-related cataracts is the second most prevalent eye disease in the Western world, and like AMD, it mainly hits the aging population. By becoming increasingly opaque, the lens prevents visual light from reaching the macula. The result is a loss of light sensitivity, combined with blurred vision. Visual acuity, or the ability to see an object sharply, is thus affected, but also a distortion in the perception of color.

Compounding factors observed in AMD are also relevant in cataracts, such as smoking, diet, sun exposure and age. Although cataracts can be treated surgically by replacing the natural lens, the procedure is costly, and not available in all parts of the world.

A recent epidemiological study published in 1999 by Brown et al. [6], a group of clinical nutritionists from Harvard University and the University of Massachusetts, offers evidence that lutein and zeaxanthin may reduce the incidence of acquiring age-related cataracts. This large study was designed to assess the daily intake of carotenoids and other dietary antioxidants in 36,644 US male health professionals, 45-75 years of age, during an eight year follow-up period in which negative factors - such as smoking - were controlled. The results demonstrated an approximately 20% lower risk of developing age-related cataracts in men who consumed higher amounts of vegetables (broccoli and spinach) containing lutein and zeaxanthin. The authors point out that since carotenoids can act as effective antioxidants at low partial pressures of the eye, and lutein and zeaxanthin are the only carotenoids accumulated by the retina and other ocular tissues, these two carotenoids may be particularly effective in maintaining your eye health. Brown et al. conclude that dietary carotenoids, especially lutein and zeaxanthin, may lower the incidence of age-related cataracts and that their findings support the consumption of fruits and vegetables high in carotenoids.

Figure 6: The relative risk for cataract extraction decreases from 1.00 in men consuming 1.3 mg per day to 0.80 when 8.7 mg per day of the macular carotenoids are consumed daily. This means a risk reduction of approximately 20%.

References

1. Sun H, Nathans J (2001, October) The challenge of macular degeneration. Scientific American. 285: 68-75

2. Landrum JT, Bone RA, Kilburn MD (1996) The macular pigment: A possible role in protection from age-related macular degeneration, in Advances in Pharmacology, Vol 38, Sies H, ed., Academic Press, London, pp. 537-556

3. EDCC (Eye Disease Case-Control) Study Group (1993) Antioxidant status and neovascular age-related macular degeneration. Arch. Ophthalmol. 111: 104-109

4. Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, Yannuzzi LA, Willett W (1994) Dietary carotenoids, vitamins A, C and E and advanced age-related macular degeneration. J. Am. Med. Assoc. 272: 1413-1320

5. AREDS Report No. 8 (2001) 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. Arch. Ophthalmol. 119: 1417-1436

6. Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE (1999) A prospective study of carotenoid intake and risk of cataract extraction in US men. Am. J. Clin. Nutr. 70: 517-524

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