Yousry Naguib05.01.05
The eye is a complex organ that provides us with the sense of sight, allowing us perform countless every day activities, whether working, reading, writing, driving a car or watching television. The human eye works in a manner similar to a camera, with the cornea behaving much like a lens cover. The cornea takes widely diverging rays of light and bends them through the pupil, the dark, round opening in the center of the colored iris. The iris and pupil function like the aperture of a camera. The lens functions similarly to the lens in a camera, helping to focus light to the back of the eye. The lens is the part that can become cloudy and is removed during cataract surgery.
The retina could be likened to the film of the camera. It is a membrane containing photoreceptor nerve cells that lines the inside back wall of the eye. The photoreceptor nerve cells of the retina change the light rays into electrical impulses and send them through the optic nerve to the brain where an image is perceived. The center of the retina, called the macula, is most sensitive and is responsible for sharp vision.
Due to the aging of the population, the number of Americans with major eye diseases is increasing and vision loss is becoming a major public health problem. Blindness or low vision affects 3.3 million Americans over age 40. This figure is projected to reach 5.5 million by the year 2020. Blindness and low vision increase significantly with age, particularly in people over age 65. Consequently, vision loss interferes with quality of life and lessens an individual's sense of independence.
A report published in the April 2004 issue of the Archives of Ophthalmology identified age-related macular degeneration (AMD), glaucoma, cataracts and diabetic retinopathy as the most common eye diseases in Americans age 40 and over1.
AMD is the leading cause of blindness in persons 65 years or older in the U.S. It affects more than 10 million Americans, and perhaps an equal number of persons in Europe. As the baby boomers get older these figures will likely increase.
AMD occurs when the cells of the macula become damaged and stop functioning. Its symptoms include blurred vision, colors appearing dim and difficulty reading. Oxidative stress has been implicated in AMD. The retina is highly susceptible to oxidative stress because of its high consumption of oxygen, its high content of polyunsaturated fatty acids and its exposure to light.
Cataracts are the leading cause of low vision among all Americans. In fact, an estimated 20 million Americans 40 or older have a cataract in either eye. A cataract forms when the eye's lens becomes cloudy and blocks some light from reaching the retina and interferes with vision.
Approximately four million Americans 40 years and older have diabetic retinopathy, and in actual fact, one in every 12 people with diabetes mellitus in this age group has vision-threatening diabetic retinopathy.
Glaucoma is the second leading cause of blindness worldwide. The overall prevalence of open-angle glaucoma in the U.S. population 40 years and older is estimated to be more than 2 million, with 1.5 million white and 0.4 million black persons affected. The pathogenesis of primary open-angle glaucoma-the most common type-is poorly understood. Intraocular pressure is the only risk factor identified that is modifiable.
The correlation between diet and eye health is not new. For example, the need to obtain adequate vitamin A to prevent xerophthalmia (a term used for a grouping of eye diseases) and night-blindness has been known for decades. More recently, interest has been directed at dietary supplements that may prevent loss of vision caused by degenerative conditions that become more common with age.
Oxidative damage to the retina has been proposed as a risk factor for AMD and its associated vision loss. It is thought that antioxidants may prevent cellular damage in the retina by reacting with free radicals produced in the process of light absorption. In this case, antioxidants may play a protective role.
The evidence backing the effectiveness of long-term supplementation with antioxidant vitamins C and E, beta-carotene and high dose zinc in halting the progression of AMD is dominated by one large trial known as the Age-Related Eye Disease Study (AREDS). The particular supplement formula used in the study showed a modest benefit in people with moderate to severe signs of the disease.
AREDS, which was sponsored by the Federal government's National Eye Institute (NEI), Bethesda, MD, found that taking high levels of antioxidants and zinc could reduce the risk of developing advanced AMD by about 25%. In this 11-center double-blind trial, approximately 3600 participants, aged 55-80 years with varying stages of AMD, were randomly assigned to receive daily oral tablets containing either antioxidants (C, 500 mg; vitamin E, 400 IU; and beta-carotene, 15 mg, often labeled as equivalent to 25,000 International Units of vitamin A); or zinc (80 mg, as zinc oxide, plus 2 mg copper, as cupric oxide); or antioxidants plus zinc; or placebo. (Copper was added to the formulations containing zinc to prevent copper deficiency anemia, a condition associated with high levels of zinc intake.) Study participants were closely followed for just over six years.
Comparison with placebo demonstrated a statistically significant reduction (approximately 25%) for the development of advanced AMD with antioxidant plus zinc. Those in the "zinc alone" or "antioxidant alone" groups also reduced their risk of developing advanced AMD, but at moderate rates (by 21% and 17%, respectively) compared to the "antioxidants plus zinc" group.
Results of AREDS suggest that nutritional supplements may be one of the most promising means of delaying end-stage AMD. However, this supplement combination had no effect on the development of cataracts2. In addition, a Cochrane study has argued caution in generalizing these findings to other populations with different nutritional status, suggesting that some harm may be caused by long-term micronutrient supplementation, particularly in smokers3.
Oxidative stress may also contribute to glaucoma etiology and progression, and dietary antioxidants are suggested as promising means of prevention for primary open-angle glaucoma. A recent observational study prospectively examined the role of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, zeaxanthin), along with vitamins E and C in relation to primary open-angle glaucoma risk among 116,484 participants followed for at least 10 years. The researchers analyzed their food questionnaire data and found little evidence those intakes of dietary carotenoids, vitamins C or E, or supplements substantially reduce the risk of developing primary open-angle glaucoma4.
A few years ago the relationship between dietary antioxidant intake and age-related cataracts was examined in 492 non-diabetic women aged 53-73 years, who were without previously diagnosed cataracts. Their nutrient intake was calculated from food frequency questionnaires collected over 13-15 years. Researchers found that the study results supported the role of vitamin C in diminishing the risk of cataracts in women who were less than 60 years old. The results were also favorable for carotenoids in diminishing the risk of cataracts in women who never smoked5.
By far the most biologically plausible micronutrients to have a potential protective role in AMD are the carotenoids lutein and zeaxanthin, which are also potent antioxidants. They are abundant in the retina of the eye and are also found in high concentrations in the macula.
Lutein and zeaxanthin are oxygen-containing carotenoids known as xanthophylls and are commonly found in green leafy vegetables such as spinach and Brussels sprouts. Additionally, egg yolk is a highly bioavailable source of lutein and zeaxanthin6. But these eye health ingredients are also found in supplement form.
Observational studies have indicated that high intake of lutein and zeaxanthin from food, such as spinach and broccoli, is associated with a reduced risk of both AMD and cataracts. These findings have fueled high public interest in the health benefits of lutein and zeaxanthin and the proliferation of supplements containing them, as seen on pharmacy and health food store shelves.
The main physiological functions of lutein and zeaxanthin in the eye are protection against oxidative damage and as blue-light (harmful) filters. Low plasma lutein and zeaxathin concentrations or dietary intake are associated with low macular pigment density. And there is a growing body of evidence suggesting a connection between AMD and low levels of macular pigment.
A case control study involving 56 subjects with AMD and 56 without AMD showed that people in the highest quartile of lutein and zeaxanthin level had an 82% lower risk for AMD compared with those in the lowest quartile7.
In another study, the relationship between macular pigment and risk for AMD was examined in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in nine healthy subjects known to be at a high-risk for AMD. There was an age-related decline in the optical density of macular pigment among subjects with healthy eyes. Eyes predisposed to AMD had significantly less macular pigment than eyes at no such risk. The study concluded that supplementation with lutein and zeaxanthin may delay, avert or modify the course of AMD8.
In a recent, randomized, double-masked, placebo-controlled trial, known as the LAST study (Lutein Antioxidant Supplementation Trial), 90 patients with atrophic AMD were divided into three groups. Group 1 received 10 mg lutein, group 2 received 10 mg lutein plus a combination of antioxidants and minerals, and group 3 received a maltodextrin placebo over 12 months. The mean eye macular pigment optical density, visual acuity, contrast sensitivity and glare recovery improved in groups 1 and 2. Patients who received the placebo (group 3) had no significant changes in any of the measured parameters. The study concluded that visual function is improved with lutein alone or lutein together with other nutrients9.
Lutein and zeaxanthin are the only dietary carotenoids present in the eye lens and epidemiological studies suggest that consumption of vegetables rich in lutein and zeaxanthin reduces the risk for developing age-related cataracts. In a test tube experiment, both lutein and zeaxanthin were shown to protect human lens epithelial cells against ultraviolet B light insult10.
In a recent study, 17 patients with age-related cataracts were randomly assigned to receive either lutein (15 mg), alpha-tocopherol (100 mg) or placebo three times a week for up to two years. Visual performance (visual acuity and glare sensitivity) was monitored every three months throughout the study. Only the lutein group showed improvement in the visual performance, suggesting that a high intake of lutein may have beneficial effects on the visual performance of people with age-related cataracts11.
Animal toxicology studies have established the safety of lutein as a nutrient, and it is also generally recognized as safe (GRAS) for use in foods and beverages.
Bilberry extracts have been used in ophthalmology for their properties in enhancing night vision acuity. This property was first reported in World War II; pilots at the British Royal Air Force who ate bilberry jam experienced an improvement in nighttime visual acuity, faster adjustment to darkness, and faster restoration of visual acuity after exposure to glare. Later studies confirmed these effects. However, there are other studies that cast doubt on the proposition that bilberry supplementation, in the forms currently available and in doses recommended, is an effective treatment for the improvement of night vision in young males with good vision12.
In a 2002 study, a statistically significant improvement in long distance visual acuity was observed in patients with macular degeneration after treatment with ginkgo biloba extract EGb 76113. The therapeutic efficacy of EGb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg per day (group I = 50 patients) or 60 mg per day (group II = 49 patients) of EGb 761. Marked improvement of the study participants' vision was observed in both treatment groups after four weeks, with more pronounced improvements in group I.
The omega 3 fatty acid docosahexaenoic acid (DHA) is abundant in the retina of the eye and is an essential nutrient for eye development in infants. Research has shown that dietary supplementation with omega 3 fatty acids results in an improvement in visual function of premature infants. In a randomized, double-blind trial, infants were supplemented with DHA and arachidonic acid (AA) in a formula designed to closely match that of mother's milk. Infants in the supplemented group showed an improvement in the visual performance at 12 months of age14.
A prospective cohort study with an average follow-up time of 4.6 years, involving 261 individuals age 60 years and older with early or intermediate stages of AMD, showed that higher intake of fish and nuts was associated with a lower risk of AMD progression15.NW
About the author: Yousry Naguib is manager of new product development at Soft Gel Technologies, Los Angeles, CA. He can be reached at 323-726-0700; Fax: 323-726-7065; E-mail: yousryn@soft-gel.com; Website: www.soft-gel.com.
References
1. Special Issue: Blindness. Arch Ophthalmol, 2004: volume 122.
2. 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.
3. Evans JR, Henshaw K. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev, 2000;(1):CD000253.
4. Kang JH et al. Antioxidant intake and primary open angel glaucoma: A prospective study. Am J Epidemiology, 2003;158:337.
5. Taylor A et al. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. Am J Clin Nutr, 2002;75:540.
6. Handelman GJ et al. Lutein and Zeaxanthin concentrations in plasma after dietary supplementation with egg yolk. Am J Clin Nutr, 1999;70:247.
7. Bone RA et al. Macular pigment in donor eyes with and without AMD: A case-control study. Investigative Ophthalmology & Visual Science, 2001;42:235.
8. Beatty S et al. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci, 2001;42:439.
9. Richer S et al. 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.
10. Chitchumroonchokchai C et al. Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. J Nutr, 2004;134:3225.
11. Olmedilla B et al. 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.
12. Canter PH, Ernst E. Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision a systematic review of placebo-controlled trials. Surv Ophthalmol, 2004;49:38.
13. Fies P, Dienel A. Ginkgo extract in impaired vision-treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration. Wien Med Wochenschr. 2002;152:423.
14. Birch EE et al. Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatric Research, 1998;44:201.
15. Seddon JM et al. Progression of age-related macular degeneration. Arch Ophthalmol, 2003;121:1728.
The retina could be likened to the film of the camera. It is a membrane containing photoreceptor nerve cells that lines the inside back wall of the eye. The photoreceptor nerve cells of the retina change the light rays into electrical impulses and send them through the optic nerve to the brain where an image is perceived. The center of the retina, called the macula, is most sensitive and is responsible for sharp vision.
Due to the aging of the population, the number of Americans with major eye diseases is increasing and vision loss is becoming a major public health problem. Blindness or low vision affects 3.3 million Americans over age 40. This figure is projected to reach 5.5 million by the year 2020. Blindness and low vision increase significantly with age, particularly in people over age 65. Consequently, vision loss interferes with quality of life and lessens an individual's sense of independence.
A report published in the April 2004 issue of the Archives of Ophthalmology identified age-related macular degeneration (AMD), glaucoma, cataracts and diabetic retinopathy as the most common eye diseases in Americans age 40 and over1.
AMD is the leading cause of blindness in persons 65 years or older in the U.S. It affects more than 10 million Americans, and perhaps an equal number of persons in Europe. As the baby boomers get older these figures will likely increase.
AMD occurs when the cells of the macula become damaged and stop functioning. Its symptoms include blurred vision, colors appearing dim and difficulty reading. Oxidative stress has been implicated in AMD. The retina is highly susceptible to oxidative stress because of its high consumption of oxygen, its high content of polyunsaturated fatty acids and its exposure to light.
Cataracts are the leading cause of low vision among all Americans. In fact, an estimated 20 million Americans 40 or older have a cataract in either eye. A cataract forms when the eye's lens becomes cloudy and blocks some light from reaching the retina and interferes with vision.
Approximately four million Americans 40 years and older have diabetic retinopathy, and in actual fact, one in every 12 people with diabetes mellitus in this age group has vision-threatening diabetic retinopathy.
Glaucoma is the second leading cause of blindness worldwide. The overall prevalence of open-angle glaucoma in the U.S. population 40 years and older is estimated to be more than 2 million, with 1.5 million white and 0.4 million black persons affected. The pathogenesis of primary open-angle glaucoma-the most common type-is poorly understood. Intraocular pressure is the only risk factor identified that is modifiable.
The correlation between diet and eye health is not new. For example, the need to obtain adequate vitamin A to prevent xerophthalmia (a term used for a grouping of eye diseases) and night-blindness has been known for decades. More recently, interest has been directed at dietary supplements that may prevent loss of vision caused by degenerative conditions that become more common with age.
Antioxidants
Oxidative damage to the retina has been proposed as a risk factor for AMD and its associated vision loss. It is thought that antioxidants may prevent cellular damage in the retina by reacting with free radicals produced in the process of light absorption. In this case, antioxidants may play a protective role.
The evidence backing the effectiveness of long-term supplementation with antioxidant vitamins C and E, beta-carotene and high dose zinc in halting the progression of AMD is dominated by one large trial known as the Age-Related Eye Disease Study (AREDS). The particular supplement formula used in the study showed a modest benefit in people with moderate to severe signs of the disease.
AREDS, which was sponsored by the Federal government's National Eye Institute (NEI), Bethesda, MD, found that taking high levels of antioxidants and zinc could reduce the risk of developing advanced AMD by about 25%. In this 11-center double-blind trial, approximately 3600 participants, aged 55-80 years with varying stages of AMD, were randomly assigned to receive daily oral tablets containing either antioxidants (C, 500 mg; vitamin E, 400 IU; and beta-carotene, 15 mg, often labeled as equivalent to 25,000 International Units of vitamin A); or zinc (80 mg, as zinc oxide, plus 2 mg copper, as cupric oxide); or antioxidants plus zinc; or placebo. (Copper was added to the formulations containing zinc to prevent copper deficiency anemia, a condition associated with high levels of zinc intake.) Study participants were closely followed for just over six years.
Comparison with placebo demonstrated a statistically significant reduction (approximately 25%) for the development of advanced AMD with antioxidant plus zinc. Those in the "zinc alone" or "antioxidant alone" groups also reduced their risk of developing advanced AMD, but at moderate rates (by 21% and 17%, respectively) compared to the "antioxidants plus zinc" group.
Results of AREDS suggest that nutritional supplements may be one of the most promising means of delaying end-stage AMD. However, this supplement combination had no effect on the development of cataracts2. In addition, a Cochrane study has argued caution in generalizing these findings to other populations with different nutritional status, suggesting that some harm may be caused by long-term micronutrient supplementation, particularly in smokers3.
Oxidative stress may also contribute to glaucoma etiology and progression, and dietary antioxidants are suggested as promising means of prevention for primary open-angle glaucoma. A recent observational study prospectively examined the role of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, zeaxanthin), along with vitamins E and C in relation to primary open-angle glaucoma risk among 116,484 participants followed for at least 10 years. The researchers analyzed their food questionnaire data and found little evidence those intakes of dietary carotenoids, vitamins C or E, or supplements substantially reduce the risk of developing primary open-angle glaucoma4.
A few years ago the relationship between dietary antioxidant intake and age-related cataracts was examined in 492 non-diabetic women aged 53-73 years, who were without previously diagnosed cataracts. Their nutrient intake was calculated from food frequency questionnaires collected over 13-15 years. Researchers found that the study results supported the role of vitamin C in diminishing the risk of cataracts in women who were less than 60 years old. The results were also favorable for carotenoids in diminishing the risk of cataracts in women who never smoked5.
Lutein and Zeaxanthin
By far the most biologically plausible micronutrients to have a potential protective role in AMD are the carotenoids lutein and zeaxanthin, which are also potent antioxidants. They are abundant in the retina of the eye and are also found in high concentrations in the macula.
Lutein and zeaxanthin are oxygen-containing carotenoids known as xanthophylls and are commonly found in green leafy vegetables such as spinach and Brussels sprouts. Additionally, egg yolk is a highly bioavailable source of lutein and zeaxanthin6. But these eye health ingredients are also found in supplement form.
Observational studies have indicated that high intake of lutein and zeaxanthin from food, such as spinach and broccoli, is associated with a reduced risk of both AMD and cataracts. These findings have fueled high public interest in the health benefits of lutein and zeaxanthin and the proliferation of supplements containing them, as seen on pharmacy and health food store shelves.
The main physiological functions of lutein and zeaxanthin in the eye are protection against oxidative damage and as blue-light (harmful) filters. Low plasma lutein and zeaxathin concentrations or dietary intake are associated with low macular pigment density. And there is a growing body of evidence suggesting a connection between AMD and low levels of macular pigment.
A case control study involving 56 subjects with AMD and 56 without AMD showed that people in the highest quartile of lutein and zeaxanthin level had an 82% lower risk for AMD compared with those in the lowest quartile7.
In another study, the relationship between macular pigment and risk for AMD was examined in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in nine healthy subjects known to be at a high-risk for AMD. There was an age-related decline in the optical density of macular pigment among subjects with healthy eyes. Eyes predisposed to AMD had significantly less macular pigment than eyes at no such risk. The study concluded that supplementation with lutein and zeaxanthin may delay, avert or modify the course of AMD8.
In a recent, randomized, double-masked, placebo-controlled trial, known as the LAST study (Lutein Antioxidant Supplementation Trial), 90 patients with atrophic AMD were divided into three groups. Group 1 received 10 mg lutein, group 2 received 10 mg lutein plus a combination of antioxidants and minerals, and group 3 received a maltodextrin placebo over 12 months. The mean eye macular pigment optical density, visual acuity, contrast sensitivity and glare recovery improved in groups 1 and 2. Patients who received the placebo (group 3) had no significant changes in any of the measured parameters. The study concluded that visual function is improved with lutein alone or lutein together with other nutrients9.
Lutein and zeaxanthin are the only dietary carotenoids present in the eye lens and epidemiological studies suggest that consumption of vegetables rich in lutein and zeaxanthin reduces the risk for developing age-related cataracts. In a test tube experiment, both lutein and zeaxanthin were shown to protect human lens epithelial cells against ultraviolet B light insult10.
In a recent study, 17 patients with age-related cataracts were randomly assigned to receive either lutein (15 mg), alpha-tocopherol (100 mg) or placebo three times a week for up to two years. Visual performance (visual acuity and glare sensitivity) was monitored every three months throughout the study. Only the lutein group showed improvement in the visual performance, suggesting that a high intake of lutein may have beneficial effects on the visual performance of people with age-related cataracts11.
Animal toxicology studies have established the safety of lutein as a nutrient, and it is also generally recognized as safe (GRAS) for use in foods and beverages.
Bilberry
Bilberry extracts have been used in ophthalmology for their properties in enhancing night vision acuity. This property was first reported in World War II; pilots at the British Royal Air Force who ate bilberry jam experienced an improvement in nighttime visual acuity, faster adjustment to darkness, and faster restoration of visual acuity after exposure to glare. Later studies confirmed these effects. However, there are other studies that cast doubt on the proposition that bilberry supplementation, in the forms currently available and in doses recommended, is an effective treatment for the improvement of night vision in young males with good vision12.
Ginkgo Biloba
In a 2002 study, a statistically significant improvement in long distance visual acuity was observed in patients with macular degeneration after treatment with ginkgo biloba extract EGb 76113. The therapeutic efficacy of EGb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg per day (group I = 50 patients) or 60 mg per day (group II = 49 patients) of EGb 761. Marked improvement of the study participants' vision was observed in both treatment groups after four weeks, with more pronounced improvements in group I.
Omega 3 Fatty Acids
The omega 3 fatty acid docosahexaenoic acid (DHA) is abundant in the retina of the eye and is an essential nutrient for eye development in infants. Research has shown that dietary supplementation with omega 3 fatty acids results in an improvement in visual function of premature infants. In a randomized, double-blind trial, infants were supplemented with DHA and arachidonic acid (AA) in a formula designed to closely match that of mother's milk. Infants in the supplemented group showed an improvement in the visual performance at 12 months of age14.
A prospective cohort study with an average follow-up time of 4.6 years, involving 261 individuals age 60 years and older with early or intermediate stages of AMD, showed that higher intake of fish and nuts was associated with a lower risk of AMD progression15.NW
About the author: Yousry Naguib is manager of new product development at Soft Gel Technologies, Los Angeles, CA. He can be reached at 323-726-0700; Fax: 323-726-7065; E-mail: yousryn@soft-gel.com; Website: www.soft-gel.com.
References
1. Special Issue: Blindness. Arch Ophthalmol, 2004: volume 122.
2. 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.
3. Evans JR, Henshaw K. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev, 2000;(1):CD000253.
4. Kang JH et al. Antioxidant intake and primary open angel glaucoma: A prospective study. Am J Epidemiology, 2003;158:337.
5. Taylor A et al. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. Am J Clin Nutr, 2002;75:540.
6. Handelman GJ et al. Lutein and Zeaxanthin concentrations in plasma after dietary supplementation with egg yolk. Am J Clin Nutr, 1999;70:247.
7. Bone RA et al. Macular pigment in donor eyes with and without AMD: A case-control study. Investigative Ophthalmology & Visual Science, 2001;42:235.
8. Beatty S et al. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci, 2001;42:439.
9. Richer S et al. 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.
10. Chitchumroonchokchai C et al. Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. J Nutr, 2004;134:3225.
11. Olmedilla B et al. 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.
12. Canter PH, Ernst E. Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision a systematic review of placebo-controlled trials. Surv Ophthalmol, 2004;49:38.
13. Fies P, Dienel A. Ginkgo extract in impaired vision-treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration. Wien Med Wochenschr. 2002;152:423.
14. Birch EE et al. Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatric Research, 1998;44:201.
15. Seddon JM et al. Progression of age-related macular degeneration. Arch Ophthalmol, 2003;121:1728.
