Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

3.3.9. CIGARETTE SMOKING

Several studies have identified cigarette smoking as a risk factor for age-related macular degeneration (23,25,39,45,46). In a case-control study conducted in Baltimore, Maryland, cigarette smoking was identified as a significant risk factor for age-related macular degeneration among males only (OR 2.6, 95% CI 1.15–5.75) (23). Current cigarette smoking was associated with increased risk of neovascular age-related macular degeneration in the Eye Disease Case-Control Study (25). In the Copenhagen City Heart Study, smoking was associated with risk of atrophic maculopathy (39). In the Beaver Dam Eye Study, exudative macular degeneration was significantly associated with current smoking among females (OR 2.5, 95% CI 1.01–6.20) and males (OR 3.29, 95% CI 1.03–10.50) compared with ex-smokers or nonsmokers (47). Whether smoking plays a causal role in age-related macular degeneration is not clear, and potential biological mechanisms include increased atherogenesis and increased oxidative stress caused by smoking (48). In the Rotterdam Study, 36 individuals with atrophic age-related macular degeneration and 65 individuals with neovascular age-related macular degeneration were identified among 6174 persons aged 55 yr and older (49). Among subjects younger than 85 yr, current smokers had a 6.6-fold increased risk of neovascular age-related macular degeneration compared to subjects who did not smoke (49). Former smokers also had an increased risk of neovascular age-related macular degeneration compared with nonsmokers (49). Cigarette smoking was an independent risk factor for incident age-related macular degeneration in the Nurses’ Health Study (50). Smoking cigarettes for more than 40 yr was a risk factor for age-related macular degeneration in a study from Australia (51).

Lower plasma carotenoids have been described among smokers compared with nonsmokers (52,53), and as described in Chapter 7, it is well known that cigarette smokers have a lower intake of many vitamins compared with comparable nonsmokers (54–59). Smokers are less likely to consume fresh fruits, vegetables, salad, and whole grain cereals compared with nonsmokers, and the consumption of saturated fat, sugar, and alcohol are higher (58). In a case-control study, macular pigment density was compared between 34 smokers and nonsmokers matched by age, sex, dietary patterns, and overall eye, skin, and hair color pigmentation (60). Although cases and controls were matched by dietary intake of carotenoids, nonsmokers had over twice the macular pigment density of smokers (60) (Fig. 1). In a study of healthy adults in Japan, serum concentrations of zeaxanthin were inversely correlated with the number of cigarettes smoked per day (61).

3.3.10. GRIP STRENGTH

Decreased grip strength has been associated with age-related macular degeneration in both the Framingham Eye Study (20) and in a large case-control study in Baltimore (23). Grip strength is an indicator of sarcopenia, or loss of skeletal muscle mass, among older adults (62). Decreased grip strength may be associated with age-related macular degeneration because of oxidative stress may contribute to the pathogenesis of both sarcopenia and age-related macular degeneration. Oxidative stress has been hypothesized to contribute to sarcopenia in older adults because skeletal muscle and nervous tissues do not have the high repair capacities that occur in more mitotically active tissues (63). Changes in skeletal muscle that occur with aging include the accumulation of lipofuscin, which may be formed by the oxidative polymerization of lipids, greater lipid peroxidation, and

Fig. 1. Frequency distribution of macular pigment optical density for smokers and nonsmoking controls. (Reprinted from ref. 60, with permission of Elsevier.)

an increase in mitochrondrial DNA deletions (63). In sarcopenia, most of the loss in strength results from an age-related decrease in muscle mass (62).

3.3.11. NUTRITIONAL FACTORS

Dietary intake. The Beaver Dam Eye Study from Beaver Dam, Wisconsin has provided a wealth of epidemiological data regarding the relationship between nutritional factors and age-related macular degeneration. An inverse association was noted between intakes of provitamin A carotenoids and dietary vitamin E and the incidence of large drusen over 5 yr (64). An inverse association was also found between zinc intake and the incidence of retinal pigmentary abnormalities over 5 yr (64). Adults 43–86 yr of age who were in the highest quintile of dietary intake of zinc from foods had a lower risk of early age-related macular degeneration (OR 0.6, 95% CI 0.4–1.0) compared with subjects in the lowest quintile of dietary intake of zinc from foods (65). Carotenoid intake was not associated with risk of early or late age-related macular degeneration (65). A high intake of saturated fats and cholesterol were associated with a higher risk of early age-related macular degeneration (66). These data support that hypothesis that atherosclerosis and related factors are involved in the pathogenesis of age-related macular degeneration (66).

In the first NHANES, conducted between 1971 and 1972, a high frequency of consumption of fruits and vegetables rich in vitamin A (provitamin A carotenoids and other dietary carotenoids) was associated with a lower risk of age-related macular degeneration (24). The adjusted prevalence odds ratios (95% CI) for age-related macular degeneration among those consuming fruits and vegetables rich in vitamin A one to three, four to six, and seven or more times per week, compared to less than one time per week, were 0.89 (0.80–1.00), 0.71 (0.50–1.00), and 0.59 (0.37–0.99) (24). The relationship between plasma micronutrient concentrations and age-related macular degeneration were examined in the Baltimore Longitudinal Study of Aging (67). In this study, a protective association was found between a high “antioxidant index” consisting of plasma ascorbic acid, α-tocopherol, and β-carotene,

and age-related macular degeneration, adjusting for age, sex, and nuclear opacity (67). No association was found between reported dietary intake of carotene, zinc, vitamin A, or vitamin C and age-related maculopathy in the Blue Mountains Eye Study (68). A high dietary intake of carotenoids was associated with a lower risk of age-related macular degeneration in the Eye Disease Case-Control Study (69). No relationship was found between vitamin E or vitamin C consumption and age-related macular degeneration (69). The assessment of dietary intakes was assessed using a semi-quantitative food frequency questionnaire (70). No association was found between dietary intake of carotenoids, vitamin C, zinc, and the incidence of early age-related macular degeneration in the Blue Mountains Eye Study (71).

In the Nurses’ Health Study and Health Professionals Follow-Up Study, 77,562 women and 50,866 men 50 yr of age and older were followed for 18 and 12 yr, respectively (72). There were 464 incident cases of early age-related maculopathy and 316 incident cases of neovascular age-related maculopathy. Men and women who consumed three or more servings per day of fruit had a reduced risk of neovascular age-related maculopathy (RR 0.64, 95% CI 0.44–0.93) compared to those who consumed less than 1.5 servings per day, but a similar relationship was not found for the risk of early age-related maculopathy (RR 0.86, 95% CI 0.64–1.15). Men and women who consumed four or more servings per day of vegetables did not have a reduced risk of early age-related maculopathy (RR 1.50, 95% CI 0.69–1.77) or neovascular age-related maculopathy (RR 1.06, 95% CI 0.73–1.56) compared to those who ate two or less servings of vegetables per day (72). There was no significant relationship found between quintiles of intake of lutein/zeaxanthin and risk of either early age-related maculopathy or neovascular age-related maculopathy.

Intake of dietary fat was associated with an increased risk for age-related macular degeneration. In a prospective study of participants in the Nurses’ Health Study and Health Professionals Follow-up Study, those in the highest quintile of total fat intake had an increased risk of developing age-related macular degeneration (RR 1.54, 95% CI 1.17–2.01) compared to those in the lowest quintile of intake. Higher intake of linoleic acid was also associated with an increased risk of developing age-related macular degeneration (73). In a multicenter case-control study of 349 subjects with advanced neovascular age-related macular degeneration and 504 subjects without age-related macular degeneration but with other ocular diseases, higher vegetable fat consumption was associated with an elevated risk of age-related macular degeneration (OR 2.22, 95% CI 1.32–3.74) for those in the highest vs the lowest quintile of intake (74). A higher intake of vegetable, monounsaturated, and polyunsaturated fats and linoleic acid, rather than total fat intake, was associated with a greater risk of advanced age-related macular degeneration, and the diets that were high in omega-3 fatty acids and fish were inversely associated with risk for age-related maculopathy when intake of linoleic acid was low (74). In a prospective cohort study of 261 adults with nonexudative age-related macular degeneration who had mean followup of 4.6 yr, higher total fat intake was associated with an increased risk of progression to more advanced age-related macular degeneration (75). Those in the highest quartile of total fat intake had an increased risk of progression (RR 2.90, 95% CI 1.15–7.32) compared to those in the lowest quartile. Intake of animal fats was also associated with an increased risk of progression (RR 2.29, 95% CI 0.91–5.72) in comparing the highest quartile with the lowest quartile. Consumption of nuts was also protective against progression of macular degeneration (75).

In the Rotterdam Study, dietary intake was assessed at baseline (1990–1993) using a semi-quantatitive food frequency questionnaire (76). Incident age-related macular degeneration was assessed over follow-up until 2004. Of 4170 people who participated in the follow-up and were at risk of age-related macular degeneration, incident disease occurred in 560 subjects. An above-median intake of β-carotene, vitamin C, vitamin E, and zinc was associated with a 35% reduced risk (hazard ratio [HR] 0.65, 95% CI 0.46–0.92) of developing age-related macular degeneration (76).

Supplement use. In the Physician’s Health Study I, during mean 12.5 yr of follow-up of 21,120 men, 279 incident cases of age-related maculopathy were observed (77). Those who used vitamin E supplements had a decreased risk of age-related maculopathy (RR 0.87, 95% CI 0.53–1.43) and users of multivitamin supplements had a reduced risk (RR 0.90, 95% CI 0.68–1.19), but none of the results reached statistical significance. It appeared that those who take certain types of supplements were unlikely to show large reductions in age-related maculopathy (77).

Serum or plasma nutrients. In the Eye Disease Case-Control Study, serum concentrations of carotenoids, vitamin C, vitamin E, and selenium were compared between 421 cases with neovascular age-related macular degeneration and 615 controls (25,78). A reduced risk of age-related macular degeneration was found in the upper two tertiles of carotenoids compared with the lowest tertile (25,78). Of all the case-control studies of its kind, the Eye Disease Case-Control Study had the largest sample size of adults with age-related macular degeneration and therefore the greatest statistical power for discerning differences in different nutrients between cases and controls. No significant association was found between vitamin C, vitamin E, or selenium and age-related macular degeneration (25). No relationship was found between plasma carotenoids, including plasma lutein, α-tocophe- rol, vitamin A, and age-related maculopathy in a case-control study involving 65 cases and controls seen at Moorfields Eye Hospital (79). In a case-control study from the Beaver Dam Eye Study, serum β-carotene, lutein, zeaxanthin, and α-tocopherol were not associated with age-related macular degeneration (80). The statistical power to examine a relationship between serum lutein/zeaxanthin and age-related maculopathy and age-related macular degeneration may have been more limited because these carotenoids were only measured in a subsample of case-control pairs (80). No inverse relationship was found between lutein and zeaxanthin in the diet or serum and any for of age-related maculopathy in NHANES III (81). In a case-control study of subjects from the Blue Mountains Eye Study, no relationship was found between serum α-tocopherol concentrations and age-related macular degeneration (82). A borderline association was found between plasma α-tocopherol and late age-related macular degeneration in a population-based study of macular degeneration in France (83). In a case-control study involving 46 people with age-related macular degeneration and 46 controls, no relationship was found between total carotenoids, vitamin C, vitamin E, zinc, and age-related macular degeneration (84). The relationships between nutritional status and age-related macular degeneration in some of these studies are highlighted in Table 2.

Macular pigment. Several methods have been used for the in vivo measurement of macular pigment and have been reviewed in detail elsewhere (85). These methods include heterochromatic flicker photometry, in which a subject tries to eliminate the flicker in a visual stimulus that alternates between two different wavelengths, and photographic measurement of macular pigment by comparison of images obtained using blue and green

illumination (86). In a case-control study of 56 donor eyes with age-related macular degeneration and 56 control eyes without age-related macular degeneration, the concentrations of lutein and zeaxanthin in concentric regions centered on the fovea was significantly less in eyes with age-related macular degeneration than eyes that did not have the disease (87). An age-related decline in macular pigment optical density has been observed in healthy subjects (88). Subjects with age-related macular degeneration in one eye only had lower macular pigment density in the unaffected eye compared with healthy controls with no history of age-related macular degeneration (88).

Obesity. In the POLA Study, conducted among 2584 residents of Sète, in the south of France, aged 60–95 yr, high body mass index (>30 kg/m2) was associated with a twofold increased risk of late age-related macular degeneration (40). A recent prospective study showed that body mass index was associated with the risk of developing age-related maculopathy (89). The relationship between body mass index in four categories (lean, <22.0; normal 22.0–24.9; overweight, 25.0–29.9; and obese, ≥30) and incident age-related maculopathy was examined in 21,121 men participating in the Physicians’ Health Study. After adjusting for age, aspirin and β-carotene treatment, and cigarette smoking, the RR of visually significant dry age-related maculopathy was lowest in men with normal body mass index. Compared with normal men, the RR (95% CI) among men who were lean, overweight, and obese was 1.43 (1.01–2.04), 1.24 (0.93–1.66), and 2.15 (1.35–3.45), respectively, suggesting a J-shaped relationship between body mass index and incidence of dry age-related maculopathy (89). In a prospective cohort study in a hospital-based retinal practice, progression of age-related macular degeneration was associated with higher body mass index, higher waist circumference, and higher waist–hip ratio (90).

3.3.12. SUNLIGHT EXPOSURE

In the Beaver Dam Eye Study, the amount of leisure time spent outdoors during the summer was associated with exudative macular degeneration (OR 2.26, 95% CI 1.06–4.81) but no association was found between estimated ambient ultraviolet (UV)-B exposure and age-related macular degneration (91). No association was found between age-related macular degeneration and the amount of ocular UV-A and UV-B light exposure among 838 Maryland watermen in the Chesapeake Bay (92), but a history of greater exposure to blue and visible light were associated with a higher risk of disease (93). In a case-control study involving 409 cases and 286 control subjects in Australia, cases with age-related macular degeneration were found to have lower median annual sun exposure than controls (94). In a small study involving 26 cases and 24 controls, the extent of dermal elastosis in sun-protected dermis was associated with age-related macular degeneration, suggesting to the investigators that increased susceptibility of elastic fibers to photic degenerative stimuli was a new risk factor (95).

3.3.13. OTHER FACTORS

Moderate wine consumption was associated with decreased odds of developing agerelated macular degeneration in the first NHANES (96). In the Beaver Dam Eye Study, consumption of beer in the past year was related to greater odds of developing increased retinal pigment degeneration (OR 1.13, 95% CI 1.05–1.88), and wine consumption was not related to either early or late age-related macular degeneration (97). In the Blue Mountains Eye Study, no relationship was found between beer or wine intake and early or late age-related macular degeneration, but an increased risk of early age-related macular