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

42.Leske MC, Chylack LT Jr, He Q, et al. Incidence and progression of cortical and posterior subcapsular opacticies: the Longitudinal Study of Cataract. Ophthalmology 1997;104:1987–1993.

43.Leske MC, Chylack LT Jr, Wu SY, et al. Incidence and progression of nuclear opacities in the Longitudinal Study of Cataract. Ophthalmology 1996;103:705–712.

44.Hu TS, Zhen Q, Sperduto RD, et al. Age-related cataract in the Tibet Eye Study. Arch Ophthalmol 1989;107:666–669.

45.Chatterjee A, Milton RC, Thyle S. Prevalence and aetiology of cataract in Punjab. Br J Ophthalmol 1982; 66:35–42.

46.Minassian DC, Mehra V. 3.8 million blinded by cataract each year: projections from the first epidemiological study of incidence of cataract blindness in India. Br J Ophthalmol 1990;74:341–343.

47.Seddon JM, Christen WG, Manson JE, et al. The use of vitamin supplements and the risk of cataract among US male physicians. Am J Pub Health 1994;84:788–792.

48.Mares-Perlman JA, Klein BEK, Klein R, Ritter LL. Relation between lens opacities and vitamin and mineral supplement use. Ophthalmology 1994;101:315–325.

49.Leske MC, Chylack LT, He Q, et al. Antioxidant vitamins and nuclear opacities. The Longitudinal Study of Cataract. Ophthalmology 1998;105:831–836.

50.Mares-Perlman JA, Lyle BJ, Klein R, et al. Vitamin supplement use and incident cataracts in a popu- lation-based study. Arch Ophthalmol 2000;118:1556–1563.

51.Kuzniarz M, Mitchell P, Cumming RG, Flood VM. Use of vitamin supplements and cataract: the Blue Mountains Eye Study. Am J Ophthalmol 2001;132:19–26.

52.Jacques PF, Chylack LT Jr, Hankinson SE, et al. Long-term nutrient intake and early age-related nuclear lens opacities. Arch Ophthalmol 2001;119:1009–1019.

53.Leske MC, Wu SY, Connell AMS, Hyman L, Schachat AP, Barbados Eye Study Group. Lens opacities, demographic factors and nutritional supplements in the Barbados Eye Study. Int J Epidemiol 1997; 26:1314–1322.

54.Taylor A, Jacques PF, Chylack LT Jr, 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– 549.

55.Mares-Perlman J, Brady WE, Klein BEK, et al. Diet and nuclear lens opacities. Am J Epidemiol 1995b; 141:322–334.

56.Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107:450–456.

57.Vitale S, West S, Hallfrisch J, et al. Plasma antioxidants and risk of cortical and nuclear cataract. Ophthalmology 1993;100:1437–1443.

58.Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C., National Academy Press, 2000.

59.Mares-Perlman JA, Brady WE, Klein BEK, et al. Serum carotenoids and tocopherols and severity of nuclear and cortical opacities. Invest Ophthalmol Vis Sci 1995a;36:276–288.

60.Lyle BJ, Mares-Perlman JA, Klein BEK, Klein R, Greger JL. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol 1999;149:801–809.

61.Gale CR, Hall NF, Phillips DIW, Martyn CN. Plasma antioxidant vitamins and carotenoids and agerelated cataracts. Ophthalmology 2001;108:1992–1998.

62.Yeum KJ, Taylor A, Tang G, Russell RM. Measurement of carotenoids, retinoids, and tocopherols in human lenses. Invest Ophthalmol Vis Sci 1995;36:2756–2761.

63.Moeller SM, Taylor A, Tucker KL, et al. Overall adherence to the Dietary Guidelines for Americans is associated with reduced prevalence of early age-related nuclear lens opacities in women. J Nutr 2004;134:1812–1819.

64.Leske MC, Wu SY, Hyman L, et al. Biochemical factors in the lens opacities case-control study. Arch Ophthalmol 1995;113:1113–1119.

65.Rouhiainen P, Rouhiainen H, Salonen JT. Association between low plasma vitamin E concentration and progression of early cortical opacities. Am J Epidemiol 1996;144:496–500.

66.Nadalin G, Robman LD, McCarty CA, Garrett SKM, McNeil JJ, Taylor HR. The role of past intake of vitamin E in early cataract changes. Ophthal Epidemiol 1999;6:105–112.

67.McCarty CA, Mukesh BN, Fu CL, Taylor HR. The epidemiology of cataract in Australia. Am J Ophthalmol 1999;128:446–465.

68.Knekt P, Heliövaara M, Rissanen A, Aromaa A, Aaran RK. Serum antioxidant vitamins and risk of cataract. BMJ 1992;305:1392–1394.

69.Ohta Y, Niwa T, Yamasaki T. Effect of prolonged marginal ascorbic acid deficiency on lenticular levels of antioxidants and lipid peroxide in guinea pigs. Int J Vitam Nutr Res 2001;71:103–109.

70.Jacques PF, Taylor A, Moeller S, et al. Long-term nutrient intake and 5-year change in nuclear lens opacities. Arch Ophthalmol 2005;123:517–526.

71.Jacques PF, Chylack LT Jr, McGandy RB, Hartz SC. Antioxidant status in persons with and without senile cataract. Arch Ophthalmol 1988;106:337–340.

72.Christen WG, Liu S, Schaumberg D, Buring JE. Fruit and vegetable intake and the risk of cataract in women. Am J Clin Nutr 2005;81:1417–1422.

73.Lu M, Taylor A, Chylack LT Jr, et al. Dietary fat intake and early age-related lens opacities. Am J Clin Nutr 2005;81:773–779.

74.Schaumberg DA, Liu S, Seddon JM, Willett WC, Hankinson SE. Dietary glycemic load and risk of age-related cataract. Am J Clin Nutr 2004;80:489–495.

75.Hankinson SE, Seddon JM, Colditz GA, et al. A prospective study of aspirin use and cataract extraction in women. Arch Ophthalmol 1993;111:503–508.

76.Glynn RJ, Christen WG, Manson JE, Bernheimer J, Hennekens CH. Body mass index: an independent predictor of cataract. Arch Ophthalmol 1995;113:1131–1137.

77.Tavani A, Negri E, LaVecchia C. Selected diseases and risk of cataract in women. A case-control study from northern Italy. Ann Epidemiol 1995;5:234–238.

78.Hiller R, Podger MJ, Sperduto RD, et al. A longitudinal study of body mass index and lens opacities: the Framingham studies. Ophthalmology 1998;105:1244–1250.

79.Schaumberg DA, Glynn RJ, Christen WG, Hankinson SE, Hennekens CH. Relations of body fat distribution and height with cataract in men. Am J Clin Nutr 2000;72:1495–1502.

80.Klein BEK, Klein R, Moss SE. Incident cataract surgery: the Beaver Dam Eye Study. Ophthalmology 1997;104:573–580.

81.Younan C, Mitchell P, Cumming R, Rochtchina E, Panchapakesan J, Tumuluri K. Cardiovascular disease, vascular risk factors and the incidence of cataract and cataract surgery: the Blue Mountains Eye Study. Ophthalmic Epidemiol 2003;10:227–240.

82.Schaumberg DA, Ridker PM, Glynn RJ, Christen WG, Dana MR, Hennekens CH. High levels of plasma C-reactive protein and future risk of age-related cataract. Ann Epidemiol 1999;9:166–171.

83.Karasik A, Modan M, Halkin H, Treister G, Fuchs Z, Lusky A. Senile cataract and glucose intolerance: the Israel Study of Glucose Intolerance Obesity and Hypertension (The Israel GOH Study). Diabetes Care 1984;7:52–56.

84.Clayton RM, Cuthbert J, Duffy J, et al. Some risk factors associated with cataract in S. E. Scotland: a pilot study. Trans Ophthalmol Soc UK 1982;102:331–336.

85.Cottam DR, Mattar SG, Barinas-Mitchell E, et al. The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes Surg 2004;14:589–600.

86.Leske MC, Sperduto RD. The epidemiology of senile cataracts: a review. Am J Epidemiol 1983;118: 152–165.

87.West SK, Valmadrid CT. Epidemiology of risk factors for age-related cataract. Surv Ophthalmol 1995; 39:323–334.

88.Hodge WG, Whitcher JP, Satariano W. Risk factors for age-related cataracts. Epidemiol Rev 1995;17: 336–345.

89.Hiller R, Sperduto RD, Ederer F. Epidemiologic associations with cataract in the 1971–1972 National Health and Nutrition Examination Survey. Am J Epidemiol 1983;118:239–249.

90.Leske MC, Connell AM, Wu SY, Hyman L, Schachat A. Prevalence of lens opacities in the Barbados Eye Study. Arch Ophthalmol 1997;115:105–111.

91.West SK, Muñoz B, Schein OD, Duncan DD, Rubin GS. Racial differences in lens opacities: the Salisbury Eye Evaluation (SEE) project. Am J Epidemiol 1998;148:1033–1039.

92.Cruickshanks KJ, Klein BEK, Klein R. Ultraviolet light exposure and lens opacities: the Beaver Dam Eye Study. Am J Pub Health 1992;82:1658–1647.

93.Burton M, Fergusson E, Hart A, Knight K, Lary D, Liu C. The prevalence of cataract in two villages of northern Pakistan with different levels of ultraviolet radiation. Eye 1997;11:95–101.

94.Minassian DC, Mehra V, Reidy A. Childbearing and risk of cataract in young women: an epidemiologic study in central India. Br J Ophthalmol 2002;86:548–550.

95.Harding JJ, van Heyningen R. Drugs, including alcohol, that act as risk factors for cataract, and possible protection against cataract by aspirin-like analgesics and cyclopenthiazide. Br J Ophthalmol 1988;72:809–814.

96.Flaye DE, Sullivan KN, Cullinan TR, Silver JH, Whitelocke RAF. Cataracts and cigarette smoking. The City Eye Study. Eye 1989;3:379–384.

97.West S, Muñoz B, Emmett EA, Taylor HR. Cigarette smoking and risk of nuclear cataracts. Arch Ophthalmol 1989;107:1166–1169.

98.Hankinson SE, Willett WC, Colditz GA, et al. A prospective study of cigarette smoking and risk of cataract surgery in women. JAMA 1992;268:994–998.

99.Klein BEK, Klein R, Linton KLP, Franke T. Cigarette smoking and lens opacities: the Beaver Dam Eye Study. Am J Prev Med 1993;9:27–30.

100.Cumming RG, Mitchell P. Alcohol, smoking, and cataracts: the Blue Mountains Eye Study. Arch Ophthalmol 1997;115:1296–1303.

101.Ederer F, Hiller R, Taylor HR. Senile lens changes and diabetes in two population studies. Am J Ophthalmol 1981;91:381–395.

102.Kinoshita JH. A thirty year journey in the polyol pathway. Exp Eye Res 1990;50:567–573.

103.Varma SD, Mizuno A, Kinoshita JH. Diabetic cataracts and flavonoids. Science 1977;195:205–206.

104.Brilliant LB, Grasset NC, Pokhrel RP, et al. Associations among cataract prevalence, sunlight hours, and altitude in the Himalayas. Am J Epidemiol 1983;118:250–264.

105.Taylor HR, West SK, Rosenthal FS, et al. Effect of ultraviolet radiation on cataract formation. N Engl J Med 1988;319:1429–1433.

106.Bochow TW, West SK, Azar A, Muñoz B, Sommer A, Taylor HR. Ultraviolet light exposure and risk of posterior subcapsular cataracts. Arch Ophthalmol 1989;107:369–372.

107.West SK, Duncan DD, Muñoz B, et al. Sunlight exposure and risk of lens opacities in a populationbased study: the Salisbury Eye Evaluation project. JAMA 1998;280:714–718.

108.Minassian DC, Mehra V, Jones BR. Dehydration crises from severe diarrhoea or heatstroke and risk of cataract. Lancet 1984;1:751–753.

109.Minassian DC, Mehra V, Verry JD. Dehydrational crises: a major risk factor in blinding cataract. Br J Ophthalmol 1989;73:100–105.

110.Zodpey SP, Ughade SN, Khanolkar VA, Shrikhande SN. Dehydrational crisis from severe diarrhoea and risk of age-related cataract. J Indian Med Assoc 1999;97:13–15, 24.

111.Van Heyningen R, Harding JJ. A case-control study of cataract in Oxfordshire: some risk factors. Br J Ophthalmol 1988;72:804–808.

112.Bhatnagar R, West KP Jr, Vitale S, Sommer A, Joshi S, Venkataswamy G. Risk of cataract and history of severe diarrheal disease in southern India. Arch Ophthalmol 1991;109:696–699.

113.Kahn MU, Kahn MR, Sheikh AK. Dehydrating diarrhoea & cataract in rural Bangladesh. Indian J Med Res 1987;85:311–315.

114.Muñoz B, Tajchman U, Bochow T, West S. Alcohol use and risk of posterior subcapsular opacities. Arch Ophthalmol 1993;111:110–112.

115.Ritter LL, Klein BEK, Klein R, Mares-Perlman JA. Alcohol use and lens opacities in the Beaver Dam Eye Study. Arch Ophthalmol 1993;111:113–117.

116.Phillips CI, Clayton RM, Cuthbert J, Qian W, Donnelly CA, Prescott RJ. Human cataract risk factors: significance of abstention from, and high consumption of, ethanol (U-curve) and non-significance of smoking. Ophthalmic Res 1996;28:237–247.

117.Black RL, Oglesby RB, von Sallmann L, Bunim JJ. Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. JAMA 1960;174:166–171.

118.Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8–14.

119.Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA 1998;280:539–543.

147.Velasco PT, Lukas TJ, Murthy SNP, Duglas-Tabor Y, Garland DL, Lorand L. Hierarchy of lens proteins requiring protection against heat-induced precipitation by the α crystallin chaperone. Exp Eye Res

1997;65:497–505.

148.Fu S, Dean R, Southan M, Truscott R. The hydroxyl radical in lens nuclear cataractogenesis. J Biol Chem 1998;273:28603–28609.

149.Palmquist BM, Philipson B, Barr PO. Nuclear cataract and myopia during hyperbaric oxygen therapy. Br J Ophthalmol 1984;68:113–117.

150.Brown NP, Harris ML, Shun-Shin GA, Vrensen GFJM, Willekens B, Bron AJ. Is cortical spoke cataract due to lens fibre breaks? The relationship between fibre folds, fibre breaks, waterclefts and spoke cataract. Eye 1993;7:672–679.

151.Merriam JC. The concentration of light in the human lens. Trans Am Ophthalmol Soc 1996;94:803– 918.

152.Duindam JJ, Vrensen GFJM, Otto C, Greve J. Cholesterol, phospholipid, and protein changes in focal opacities in the human eye lens. Invest Ophthalmol Vis Sci 1998;39:94–103.

153.Dillon J, Ortwerth BJ, Chignell CF, Reszka KJ. Electron paramagnetic resonance and spin trapping investigations of the photoreactivity of human lens proteins. Photochem Photobiol 1999;69:259–264.

154.Dillon J, Zheng L, Merriam JC, Gaillard ER. The optical properties of the anterior segment of the eye: implications for cortical cataract. Exp Eye Res 1999;68:785–795.

155.McCarty CA, Taylor HR. Recent developments in vision research: light damage in cataract. Invest Ophthalmol Vis Sci 1996;37:1720–1723.

156.Streeten BW, Eshaghian J. Human posterior subcapsular cataract: a gross and flat preparation study. Arch Ophthalmol 1978;96:1653–1658.

157.Palva M, Palkama A. Ultrastructural changes in x-ray induced cataract of the rat. Acta Ophthalmol 1978; 56:587–598.

158.Sperduto RD, Hu TS, Milton RC, et al. The Linxian cataract studies. Two nutrition intervention trials. Arch Ophthalmol 1993;111:1246–1253.

159.Chylack LT, Brown NP, Bron A, et al. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiol 2002;9:49–80.

160.Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss. AREDS Report No. 9. Arch Ophthalmol 2001;119:1439–1452.

161.Teikari JM, Rautalahti M, Haukka P, et al. Incidence of cataract operations in Finnish male smokers unaffected by α tocopherol or β carotene supplements. J Epidemiol Community Health 1998;52:468– 472.

162.Christen WG, Manson JE, Glynn RJ, et al. A randomized trial of beta carotene and age-related cataract in US physicians. Arch Ophthalmol 2003;121:372–378.

163.McNeil JJ, Robman L, Tikellis G, Sinclair MI, McCarty CA, Taylor HR. Vitamin E supplementation and cataract: randomized controlled trial. Ophthalmology 2004;111:75–84.

pigmentation in the macula was likely related to the wavelength of light that was used in the ophthalmoscope, as the yellow color was more readily visible with the use of redfree light (9). In 1945, George Wald (1906–1997) observed that the macular pigment in humans had the same absorption spectrum as crystalline leaf xanthophyll. The extramacular portions of the retina were also noted to contain some xanthophyll, but at a lower concentration per unit area than the macula. Extraction of the yellow pigment from human maculas yielded a hydroxy-carotenoid that Wald believed was lutein or leaf xanthophyll itself, noting “this marks the first appearance of a carotenoid of this type in a mammalian retina” (12).

3. EPIDEMIOLOGY

3.1. Definitions

The epidemiology of age-related macular degeneration has been fairly well characterized among different populations worldwide in the last three decades. Comparisons between studies, especially the earlier studies, has been somewhat limited because of the different definitions of age-related macular degeneration, lack of agreement in grading the disease, and variable use of standardized fundus photographs or examination alone. Consensus on an international classification and grading system was only reached in 1995 (13). The term “age-related maculopathy” refers to a disorder of the macular area of the retina characterized by soft or confluent drusen, areas of increased pigment in the outer retina or choroid associated with drusen, and areas of depigmentation or hypopigmentation of the retinal pigment epithelium. Late stages of age-related maculopathy are called age-related macular degeneration and include dry or geographic atrophy and wet, also known as neovascular, disciform, and exudative age-related macular degeneration (13).

3.2. Incidence and Prevalence

3.2.1. INCIDENCE

The incidence of age-related macular degeneration has been studied in risk groups and population-based studies (14–18). Two hundred patients with macular drusen were followed for an average of 4 yr, and the highest rate of visual loss occurred in those in the seventh decade and beyond (14). Of 71 patients who presented with bilateral macular drusen alone, the 5-yr cumulative risk of developing severe visual loss due to maculopathy was 12.7% (15). In a prospective study of 126 patients with bilateral drusen seen at Moorfields Eye Hospital, the cumulative incidence of new exudative or nonexudative lesions was 23.5% by 3 yr follow-up (16). In the Beaver Dam Eye Study, the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late agerelated maculopathy were studied over 5 yr among 3583 adults, aged 43–86 yr of age (18). The incidence of age-related maculopathy lesions was higher among adults 75 yr of age or older, and after adjusting for age, the incidence was 2.2 times higher among women than men (18). The 5-yr incidence of late age-related maculopathy, defined by the new appearance of either exudative macular degeneration or pure geographic atrophy at follow-up, was 0.9%. In the Chesapeake Bay Waterman Study, a cohort restricted to men of a particular occupation with half the men under 50 yr of age, the 5-yr incidence of late age-related maculopathy was 0.2% (17).

Table 1

Risk Factors for Age-Related Macular Degeneration

Increasing age

Race

Female gender

Family history

Iris color

Hyperopia

Cardiovascular disease

Cigarette smoking

Inflammation

Low grip strength

Low carotenoid status

Obesity

Sunlight exposure

3.2.2. PREVALENCE

The prevalence of age-related macular degeneration increases with age. Among adults <55, 55–64, 65–74, 75–84, and ≥85 yr of age in the Blue Mountains Eye Study in Australia, the prevalence of end-stage age-related macular degeneration (neovascular disease or geographic atrophy) was 0, 0.2, 0.7, 5.4, and 18.5%, respectively (19). Data from the Framingham Eye Study suggest that the prevalence of age-related macular degeneration is 8.8% in one or both eyes in adults over age 52 yr (20). In the Beaver Dam Eye Study involving 4685 adults 42 to 84 yr old, drusen were found in the macula of at least one eye in 95.5% of subjects (21). Late age-related macular degeneration, defined as the presence of exudative disease or geographic atrophy, was found in 0.1, 0.6, 1.4, and 7.1% of individuals aged 43–54, 55–64, 65–74, and ≥75 yr, respectively (21).

3.3. Risk Factors

The epidemiology of age-related maculopathy and age-related macular degeneration has been examined in some large major surveys, including the Framingham Eye Study (20,22), a case-control study in Baltimore (23), the first National Health and Nutrition Examination Survey (NHANES) (24), the Eye Disease Case Control Study (25), and the Blue Mountains Eye Study (19). Some risk factors for age-related macular degeneration are shown in Table 1.

3.3.1. AGE

Increasing age is a strong risk factor for age-related macular degeneration (19,26,27). In the first NHANES, individuals aged 55–64 yr and 65–74 yr had an adjusted prevalence odds ratio (OR) (95% confidence interval [CI]) for age-related macular degeneration of 2.13 (1.67–2.71) and 4.54 (2.80–7.36) compared with individuals aged 45–54 yr (24).

3.3.2. RACE

Age-related macular degeneration appears to be more common and severe among whites than blacks (28). In a study of 3444 black adults, aged 40 to 84 yr, from the Barbados Eye Study, early age-related macular degeneration was found in 23.5% of subjects

(28). Late age-related macular changes, the most visually disabling for of age-related macular degeneration, was found in only 0.6% of black adults, suggesting that the severity of age-related macular degeneration is less among blacks than whites (28). Race was not found to be a significant risk factor for age-related macular degeneration in the first NHANES (24), but the study relied on clinical examination by individuals with varying levels of experience and a standardized diagnosis of age-related macular degeneration was not certain (28). The prevalence of age-related macular degeneration in the noninstitutionalized US population ≥40 yr of age was 9.2%, based on NHANES III, and the prevalence was higher among non-Hispanic whites (9.3%) compared with non-Hispanic blacks (7.4%) and Mexican Americans (7.1%) (29).

3.3.3. FEMALE GENDER

Most epidemiological studies suggest that women are at higher risk of advanced agerelated macular degeneration and visual loss than men (19,25,26). In the Beaver Dam Eye Study, women had a higher risk of developing neovascular age-related macular degeneration than men (18).

3.3.4. FAMILY HISTORY

A family history of macular disease has been identified as a strong risk factor for agerelated macular degeneration in a large case-control study in Baltimore (OR 2.9, 95% CI 1.5–5.5) (23). In two case reports, age-related macular degeneration was described in monozygotic twins (30). In nine twin pairs with age-related macular degeneration, the fundus appearance and the incidence of visual impairment were similar (31). Other factors, including diet, geographical background, and medical history, were also essentially the same in the twin pairs (31). In a study of 119 unrelated subjects with age-related macular degeneration in Boston, age-related macular degeneration had a higher prevalence among relatives of subjects, suggesting that age-related macular degeneration has a familial component and that genetic or shared environmental factors may contribute to its development (32).

3.3.5. IRIS COLOR

Blue iris color has been associated with increased risk of age-related macular degeneration (23). In a case-control study involving 102 cases and 103 controls in the United Kingdom, light stromal iris pigmentation was associated with age-related macular degeneration (33). Light-colored irises were identified as one of six major risk factors for age-related macular degeneration in a case-control study involving 1844 cases and 1844 matched controls in France (34). In a study of 650 white patients with age-related macular degeneration and 363 control patients, light-colored irides were found in 76% of patients compared with 40% of controls (35). Light iris pigmentation was associated with more extensive retinal disease in patients who had unilateral neovascular age-related macular degeneration (36).

3.3.6. HYPEROPIA

Hyperopia was identified as a risk factor for age-related macular degeneration in the first NHANES (24) and in a large case-control study in Baltimore, Maryland (23). In the Eye Disease Case Control Study, hyperopes (greater than +1 diopter) had an increased risk of neovascular age-related macular degeneration (25). One potential but rather speculative explanation for the association between hyperopia and age-related macular degeneration may relate to the use of eyeglasses. Myopes, who may wear eyeglasses for most

of their lives, could have possible reduced sunlight exposure compared to hyperopes, who may wear eyeglasses largely after middle age.

3.3.7. CARDIOVASCULAR DISEASE

Cerebrovascular disease was identified as a risk factor for age-related macular degeneration in the first NHANES (24). Individuals with a systolic blood pressure of 130–149, 150–169, and ≥170 mmHg had adjusted prevalence odds ratios (95% CI) of 1.15 (1.02– 1.29), 1.31 (1.04–1.66), and 1.50 (1.06–2.13), respectively compared with individuals with a systolic blood pressure of <130 mmHg (24). In a case-control study in Baltimore, individuals with low hand grip strength and a positive history of cardiovascular disease had a higher risk of age-related macular degeneration (OR 1.9, 95% CI 1.03–3.34), and a history of cardiovascular diseases was defined as myocardial infarction, angina, other heart problems, arteriosclerosis, hypertension, other circulatory problems, stroke, and/or transient ischemic attacks (23). In a large case-control study in France, arterial hypertension (OR 1.28, 95% CI 1.09–1.50) and coronary artery disease (OR 1.31, 95% CI 1.02– 1.68) were associated with age-related macular degeneration (34). In the Rotterdam Study, age-related macular degeneration was associated with plaques in the carotid bifurcation, plaques in the common carotid artery, and lower extremity arterial disease (37). Elevated plasma fibrinogen levels were associated with late age-related macular degeneration in the Blue Mountains Eye Study (38).

Epidemiological studies have not shown a consistent relationship between cardiovascular disease and late age-related macular degeneration (18,20,25,26,39). In the Pathologies Oculaires Liées à l’Age (POLA) Study conducted among 2584 adults aged 60–95 yr in Sète, France, a history of cardiovascular disease was associated with a decreased risk of soft drusen (40). No association was found between cardiovascular disease and late age-related macular degeneration (40). Systemic hypertension was found to be a significant risk factor for choroidal neovascularization in the fellow eye among patients who had known choroidal neovascularization from age-related macular degeneration in one eye (41). Severe hypertension was associated with neovascular age-related macular degeneration in a case-control study involving 182 patients with neovascular disease and 235 control subjects (42).

3.3.8. INFLAMMATION

In the Age-Related Eye Disease Study, elevated C-reactive protein was associated with increased risk of age-related macular degeneration (43). C-reactive protein was measured using a high sensitivity assay in 183 adults without any maculopathy, 200 adults with mild maculopathy, 325 adults with intermediate disease, and 222 with advanced age-related macular degeneration. After adjusting for age, sex, and other variables including smoking and body mass index, C-reactive protein concentrations were associated with increased risk of intermediate and advanced age-related macular degeneration (43). In a prospective study, 251 adults aged 60 yr and older with nonexudative age-related macular degeneration with visual acuity of 20/200 or better in at least one eye were followed for an average of 4.6 yr. Participants in the highest quartile of C-reactive protein had an increased risk of progression of age-related macular degeneration (relative risk [RR] 2.10, 95% CI 1.06–4.18) compared to those in the lowest quartile of C-reactive protein (44). Elevated interleukin-6 was also related to an increased risk of progression of age-related macular degeneration (RR 1.81, 95% CI 0.97–3.36).