Healthy Diets and the Subsequent Prevalence of Nuclear Cataract in WomenHealthy Diets and Nuclear Cataract in Women FREE

Cataracts, which increase in prevalence with age, are the most important cause of blindness in the world.¹ In the United States, cataract is the most prevalent cause of visual impairment due to eye disease,² and surgery to remove lenses with cataracts accounts for approximately 60% of vision-related Medicare expenditures.³ The number of Americans affected by cataract and undergoing cataract surgery is expected to increase dramatically in the next 20 years as the US population ages.⁴ As more aging Americans need cataract surgery, there is concern about the ability of health care systems, particularly Medicare, to fund cataract surgery.³ Therefore, identifying modifiable risk factors is of critical importance to improving health of older Americans and to the economic stability of the health care system.

Nuclear cataract is the most common type of cataract among older Americans⁵ and the most common type of cataract for which surgical extraction is performed.⁶ This type of cataract is frequently more common in women^{4 ,7 - 8} and in people with brown eyes,^{7 - 8} myopia,^{8 - 10} diabetes,^{8 - 9 ,11} or low education.⁷ Many modifiable risk factors have been suggested. Smoking is the most commonly and consistently reported modifiable risk factor in population studies (previously reviewed¹² ). Others that are sometimes observed in population studies include having a higher^{13 - 15} or lower^{13 ,16} body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), heavy use of alcoholic beverages,^{17 - 19} and diets low in 1 or more nutrients or high in fat or refined carbohydrates.^{20 - 30}

Several aspects of diet may lower risk for nuclear cataract by lowering oxidative stress or systemic inflammation (which can lead to oxidative stress). Having adequate or high intakes or blood levels of lutein and zeaxanthin^{20 - 27} and the use of multivitamin supplements (recently reviewed^{28 - 29} ) have been most consistently related to lower risk for cataract. Often, but less consistently, high diet or blood levels of vitamins C and/or E (recently reviewed³⁰ and subsequently reported^{21 - 22 ,31} ) have been associated with lower risk. A few studies have also suggested many other aspects of diet associated with lower risk for nuclear cataract or cataract extraction, including high intake of long-chain³² or total³³ ω-3 fatty acids or low intake of carbohydrates,³⁴ refined carbohydrates (as indicated by a low glycemic index score),³⁵ overall fats,³⁶ or certain types of fat.³⁷ Only 1 previous study³⁸ has directly evaluated the overall impact of a healthy diet on the occurrence of cataract. The investigators observed that adherence to the 1990 dietary guidelines for Americans, as reflected by Healthy Eating Index (HEI) scores for diets over a 10-year period, was associated with lower risk for early nuclear lens opacities.³⁸

The Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI),³⁹ was designed in part to evaluate the relationships of the carotenoids lutein and zeaxanthin with the prevalence of age-related nuclear cataract and age-related macular degeneration. We previously reported that high dietary and blood levels of lutein and zeaxanthin were associated with lowered risk for nuclear cataract in this cohort.³⁶ There are limited studies published to date in which nutritional risk factors are evaluated concurrently with a comprehensive set of other lifestyle, ocular health, and physical risk factors. The availability of extensive risk factor data from the WHI and CAREDS investigations permits the description of the relationships of overall diet patterns, use of supplements, and an extensive set of other potential risk factors related to low prevalence of nuclear cataract in this article.

The WHI Observational Study³⁹ is a prospective cohort study of the most common causes of mortality and morbidity among 93 676 postmenopausal women, aged 50 to 79 years at enrollment, at 40 sites around the United States. The original cohort was recruited to the WHI at each of these sites through regional mass mailings and mass media strategies among women ineligible for or uninterested in participation in the WHI Clinical Trials. Participants were followed up an average of 6 years after enrollment. Women were excluded if they had medical conditions that predicted survival shorter than 3 years, alcoholism, drug dependency, or mental illness.^{40 - 41}

The CAREDS population consists of women who were enrolled in the observational study of the WHI at 3 of 40 sites (the University of Wisconsin, Madison; the University of Iowa, Iowa City; and the Kaiser Permanente Center for Health Research, Portland, Oregon) and had self-reported intakes of lutein plus zeaxanthin that were either higher than the 78th percentile or lower than the 28th percentile as assessed at baseline enrollment into the WHI in 1994 to 1998, as previously described.³⁶ Of 3143 women who fulfilled these criteria and formed the recruitment pool, 96 died or were lost to follow-up between sample selection in 2000 and enrollment in the CAREDS from May 1, 2001, to January 31, 2004. Those remaining were sent letters inviting them to participate in the CAREDS. A total of 1042 women declined participation and 2005 (66%) were enrolled. Of those enrolled, we excluded women from the present analyses for the following reasons: the WHI found that the diet data were unreliable (n = 1), history of trauma to both eyes (n = 32), reported cataract extraction before age 40 years (n = 1), missing or ungradable nuclear lens photographs (n = 132), and missing covariate data (n = 31). Thus, 1808 women composed the analysis data set for this investigation. All procedures conformed to the Declaration of Helsinki and were approved by the institutional review board at each university.

Estimates of daily food and nutrient intake were made from responses to a previously validated, semiquantitative food frequency questionnaire⁴² at the WHI baseline (1994-1998). Adherence to the 1990 dietary guidelines for Americans and the 1992 food guide pyramid, reflecting dietary recommendations at the time women entered the WHI, was estimated by the 1995 HEI (HEI-1995) scores⁴³ adapted to this questionnaire as previously described.⁴⁴ The HEI-1995 score includes 10 components, each with a possible score range of 0 to 10. A summary of score components is given in Table 1. For the food group components (grains, vegetables, fruits, milk, meat), scores were based on intake of the recommended servings of each food group for women older than 55 years. Scores between 0 and 10 were given proportionally according to the frequency with which the participant reported eating each food, compared with the dietary guidelines' recommended number of servings. For total fat, energy intake of 30% or less from fat was given the maximum score of 10; energy intake of 45% or more from fat was given a score of 0. For saturated fat, energy intake of less than 10% from saturated fat was given a score of 10; energy intake of 15% or more from saturated fat was given a score of 0. For cholesterol, intake less than 300 mg/d was given a score of 10; intake of 450 mg/d or more was given a score of 0. Sodium intake less than 2400 mg/d was given a score of 10; sodium intake of 4800 mg/d or more was given a score of 0. For variety, intake of at least 16 different food items over 3 days was given a score of 10; intake of 6 or fewer different types of food over 3 days was given a score of 0.

The dietary guidelines for Americans and the food guide pyramid were updated in 2005.⁴⁵ Therefore, we also explored relationships of nuclear cataract with estimated adherence to these more recent guidelines using the HEI-2005 score, developed by Guenther et al.⁴⁶ Briefly, the HEI-2005 score includes 12 components, with maximum component scores ranging from 5 to 20 per component and a maximum total composite score of 100. A summary of score components is given in Table 1. The component scores were based on nutrient density values rather than on absolute levels of foods eaten, using energy estimates for women older than 55 years. They also reflect guidance about specific foods to consume within larger food groups. For example, the 2005 guidelines recommend that in addition to 5 to 9 serving of fruits and vegetables per day, one should specifically eat dark green leafy vegetables, dark orange vegetables, and legumes several times per week. The 10 points devoted to the vegetable score included 5 points for total servings of vegetables and 5 points for the specific servings of dark green vegetables, orange vegetables, and legumes. In addition, points for fat intake were assigned differently. The recommendation for fat intake was between 20% and 35% of energy, with most fats coming from sources of polyunsaturated and monounsaturated fats such as fish, nut, and vegetable oils. Thus, points were given for low intake of saturated fat (<7% of energy) and low energy from solid fat, sugars, and alcohol and for high intake of oils (≥12 g/1000 kcal).

Supplement use was queried at the WHI baseline (1994-1998). In addition, detailed data on the frequency and duration of multivitamin and high-dose antioxidant intakes were queried in questionnaires submitted at the CAREDS study visit (May 1, 2001, to January 31, 2004). Use of high-dose antioxidants at the CAREDS baseline was defined as daily intake of at least 2 of the following 3 antioxidant supplements: 120 mg or more of vitamin C, 60 IU (40 mg) or more of vitamin E, and 10 000 μg or more of beta carotene. Women using these supplements for 2 years or less before photographs were taken were compared with women using supplements for longer than 2 years, longer than 5 years, and longer than 10 years (>2-5 years, >5-10 years, and >10 years).

Serum samples were obtained from participants at the WHI baseline examinations (1994-1998) after a 12-hour or longer fast and were stored at −80°C.³⁹ Serum levels of lutein, zeaxanthin, and tocopherols were determined at Tufts University (2004-2005) by reverse-phase high-performance liquid chromatography.⁴⁷

Lens photography and eye examinations were part of the CAREDS study visits that took place between 2001 and 2004 using the standardized Early Treatment for Diabetic Retinopathy Study protocol⁴⁸ modified as in the Age-Related Eye Disease Study, for which grading reliability has been previously reported.⁴⁹ Briefly, both eyes were examined with slitlamp biomicroscopy. After pharmacological dilation of the pupils, a single nonstereoscopic photograph was taken of each eye with a modified Topcon slitlamp camera (Topcon Corp, Tokyo, Japan) to grade nuclear sclerosis and nuclear color using the Age-Related Eye Disease Study protocol.⁵⁰ Optical density of nuclear opacity was graded against a series of 7 standard photographs producing continuous scores on a decimal scale that can range from 0.9 to 7.1. Severity of nuclear sclerosis was determined in eyes that had not previously undergone cataract extraction. Dates of cataract extraction in each eye, trauma to eyes, and physician-diagnosed histories of cataract, glaucoma, and macular degeneration as well as treatments and lifestyle changes that accompanied these conditions were queried in questionnaires collected at the time of lens photography.

The primary outcome was the presence of nuclear cataract, defined as a nuclear sclerosis severity score of 4 or greater in the worse eye and/or a history of cataract extraction in either eye. It was previously determined in a similar population that the incidence of cataract surgery was highest among people with photographically evident cataracts in the nuclear region of the lens,⁶ suggesting that nuclear cataracts in women who had received cataract extractions were likely. Nuclear sclerosis, defined as a severity score of 4 or greater, was a secondary outcome among women who had at least 1 natural lens for which lens photographs were gradable (1577 women were eligible for this outcome).

The following were queried at the CAREDS study visit: age, family history of cataract (immediate family member aged <65 years when diagnosed), and UV-B sunlight exposure (since age 18 years and in last 20 years, based on outdoor activities during weekday, weekend, and vacation periods, living location, use of protective gear [hats or sunglasses], and time on water). Iris color was classified from photographs and refractive error from examination at the CAREDS eye examination. Additional demographic, lifestyle, and health history data were available from questionnaires completed at the WHI study entry (education, smoking, physical activity, height, weight, hormone replacement therapy use, alcohol use, pulse pressure, and history of diabetes, hypertension, and cardiovascular disease). Histories of smoking, alcohol use, and diabetes were updated at CAREDS study visits.

Odds ratios (ORs) and 95% confidence intervals (CIs) for nuclear cataract and for nuclear sclerosis scores of 4 or higher (yes or no) were calculated by exposure categories in models adjusted for age (continuous variable) using logistic regression (PROC LOGISTIC in SAS version 9.1 statistical software; SAS Institute, Inc, Cary, North Carolina). A multivariate cataract risk factor model was constructed, including age and all risk factors that could biologically cause cataracts if they were related (P < .10) to either nuclear sclerosis or nuclear cataract in univariate analyses. The strongest OR was entered first and other covariates were reentered until no other covariates fell into the model at P < .10.

In this study sample, there was a wide range of intakes of many different foods: an approximately 3-fold or greater difference between the 10th and 90th percentile cut points for intakes of most individual food components that compose HEI-1995 scores (Table 1). Women whose overall scores for the HEI-1995 were in the highest quintile had diets that were lower in fat, saturated fat, and sodium and higher in lutein and zeaxanthin, vitamin C, and vitamin E (Table 2) and all other vitamins and minerals estimated (data not shown) compared with women whose overall scores were in the lowest quintile. Women with high HEI-1995 scores were also more likely to be older and have schooling beyond high school. In addition, they were more likely to have characteristics that are often associated with Americans who adopt healthy lifestyles: being more likely to take supplements, have lower body fat (as reflected by BMI), and have higher levels of physical activity and being less likely to smoke (Table 2).

Nuclear cataract was common in this sample; it was present in 454 of 1577 women (29%) who had lenses in at least 1 eye. An additional 282 of 1808 women (16%) had reported cataract extractions in either eye. Overall, 736 women (41%) either had nuclear cataracts evident from lens photographs or reported having a cataract extracted. The prevalence increased steeply with age, about 5-fold with each increasing decade (Table 3).

Table 3 describes age-adjusted and multivariate-adjusted ORs and 95% CIs for nuclear cataract by healthy diet scores and other potential risk factors identified in Table 2. Because the risk factors were nearly identical for nuclear sclerosis defined in women with intact lenses and for nuclear cataract, including cataract extractions, ORs are given only for the latter and more common end point. Minor exceptions are noted later.

The strongest modifiable risk factor in this sample was having a high overall diet quality score as reflected by the HEI-1995 score. After adjustment for other risk factors, being in the third to fifth quintiles for the HEI-1995 score (having HEI-1995 scores >68) was associated with 37% lower odds for nuclear cataract (Table 3). This was not influenced by further adjustment for energy, which was unrelated to nuclear cataract (data not shown). Odds did not decrease linearly with increasing score; HEI-1995 scores above quintile 3 did not further lower odds for nuclear cataract.

Having a better diet as reflected by a higher HEI-1995 score was associated with many other aspects of healthy lifestyle or potential protective factors for nuclear cataract (Table 2). However, the association of the HEI-1995 score with nuclear cataract did not appear to be completely explained by other measured aspects of healthy lifestyle as it remained significant after adjusting for smoking and BMI (Table 3) as well as supplement use and physical activity (data not shown).

This association was also not driven by any single dimension of diet. The prevalence of nuclear cataract was related to low values for most subscale scores (vegetables, fruits, milk, grains, total fat, saturated fat, and variety [data not shown]). Exceptions were for subscores for meat intake, which were directly related to nuclear cataract (data not shown; P trend = .07) and for subscores for sodium and cholesterol intake, for which there was little variability and no relation to nuclear cataract (data not shown).

We conducted additional exploratory analyses to further consider which nutrients or single components of diet may have contributed to the overall inverse associations of the HEI-1995 score to nuclear cataracts. As previously described,³⁶ levels of lutein and zeaxanthin in diet and in serum were inversely associated with nuclear cataract. The HEI-1995 score is correlated with dietary lutein and zeaxanthin (Spearman correlation coefficient = 0.4; P < .001). Adjusting for lutein and zeaxanthin in the diet (multivariate OR = 0.69; 95% CI, 0.97-1.02) only slightly attenuated the association between the HEI-1995 score and nuclear cataract, suggesting that higher intakes of these carotenoids only partly explained the associations between nuclear cataract and HEI-1995 scores.

Women with higher HEI-1995 scores had higher vitamin C intakes than those with lower scores (median, 169 vs 67 mg/d among women in the high vs low quintile for HEI-1995 score, respectively). Further adjustment of the OR for nuclear cataract among women with high vs low HEI-1995 scores for vitamin C intake from foods attenuated the ORs (multivariate OR = 0.76; 95% CI, 0.50-1.15), suggesting that higher vitamin C intakes partly explained the associations with HEI-1995 scores. However, there was a significant linear trend for a protective association of vitamin C intake from foods alone but not from foods and supplements combined even after multivariate adjustment including the HEI-1995 score, suggesting the possibility of remaining protective associations of vitamin C–containing foods rather than vitamin C itself.

The level of α-tocopherol (vitamin E) in foods, foods and supplements combined, or serum was not significantly related to nuclear cataract (Table 2). Also, adjusting for vitamin E from foods did not alter the association of the HEI-1995 score with nuclear cataract (data not shown).

We previously reported that the prevalence of nuclear cataract in this sample was associated with diets high in fat³⁶ and speculated that this might reflect the possibility that dietary fat intake is a marker for diet poor in a wide variety of micronutrients. Indeed, dietary fat intake was highly correlated with the HEI-1995 score (r = 0.7; P < .001), and adjusting associations for dietary fat attenuated the OR more than adjusting for any other nutrient (multivariate OR = 0.86; 95% CI, 0.54-1.37).

Nuclear cataract was not related to highest scores on a diet pattern that was intended to reflect adherence to more recent dietary guidelines (HEI-2005), even though the odds for nuclear cataract decreased with increasing quintile for HEI-2005 scores from quintiles 2 through 4 (Table 3). We explored associations between nuclear cataract and subscale scores for the HEI-2005 to understand the reason for the discrepancy between results for the 2 HEI scoring systems. Women in the highest quintile for HEI-2005 scores had higher rather than lower intakes of oils (liquid oils such as corn or canola oil) (median, 7.6 g/d) than women in quintile 4 for HEI-2005 scores (median, 5.4 g/d) and quintile 5 for HEI-1995 scores (median, 4.5 g/d). Oil intake above the median was associated with a higher prevalence of nuclear cataract than oil intake below the median (adjusted OR = 1.60; 95% CI, 1.22-2.11). Furthermore, after excluding the oil subscore from the HEI-2005 index and recomputing the HEI-2005 score, women in the highest quintile had lower odds for nuclear cataract than women in the lowest quintile (multivariate, Table 3).

The potential impact of healthy diet on age at which a visually significant cataract was present was estimated in the subsample of women who had at least 1 lens (1577 women) by examining the linear fit line for the relationship between nuclear sclerosis severity score and age at photography among women with HEI-1995 scores above vs below the 20th percentile cut point (59 points). (We omitted women aged <55 years at photography because there were too few cases of nuclear sclerosis with severity scores ≥4 to make this comparison.) The mean age at which visually significant nuclear cataract (nuclear sclerosis severity score ≥4) was present was 2.9 years earlier for women with healthy diet scores greater than this cut point than for women with healthy diet scores less than this cut point (76.4 vs 73.5 years, respectively) after adjusting for nonmodifiable risk factors (iris color and pulse pressure). After further adjusting for nondietary modifiable risk factors (BMI, smoking, physical activity), the mean age at which this level of severity was observed was slightly lowered to 2.4 years earlier (76.3 vs 73.9 years, respectively). This relationship between diet and nuclear sclerosis severity score of 4 or greater was consistent across all ages and can be observed in the linearized curves (Figure) and in curves in which all data points were fit with spline curves (not shown). The slopes of the lines were not significantly different (P interaction = .39), but a sample size of more than 7500 people would be required to detect an interaction with 90% power at α = .05.

Risk factors for cataract have been previously evaluated in the absence of adjustment for broad health diet patterns and were therefore evaluated here along with risk factors that have not been extensively studied (UV light exposure and physical activity). Some risk factors were associated with the prevalence of nuclear cataract in this sample even after adjustment for having high scores on the HEI-1995 (Table 3). This included some directly modifiable risk factors (smoking and having a BMI >35), pulse pressure, and several nonmodifiable risk factors (myopia and having dark brown eyes).

There were not clear associations with supplement use. The prevalence of nuclear cataract, including cataract extractions, was lower in women who used multivitamin supplements for longer than 2 years prior to lens photographs as compared with those who used them for less than 2 years (OR = 0.82; 95% CI, 0.67-1.02); however, the association was not significant, even after multivariate adjustment (Table 3). Moreover, the association did not strengthen with increasing duration of use (multivariate-adjusted OR = 1.05; 95% CI, 0.76-1.43) in 272 women who reported consuming these supplements for longer than 10 years compared with 896 women who reported taking supplements for less than 2 years prior to lens photography. Regular use of multivitamins at the WHI baseline was also not related to nuclear cataract (multivariate OR = 0.96; 95% CI, 0.77-1.19) among the 874 women who regularly used multivitamins at the WHI baseline compared with the 934 women who did not.

The use of high-dose antioxidant supplements was not related to nuclear cataract (Table 3). This remained true when comparing 160 women who had used such supplements for longer than 10 years with those who did not use high-dose antioxidants or had used them for less than 2 years before eye photographs were taken (multivariate OR = 1.16; 95% CI, 0.79-1.70).

Having a family history of cataracts before age 65 years was not associated with risk for nuclear cataract. Some risk factors for nuclear cataract that have been identified in other samples were not observed in this study. These included ocular exposure to UV-B light (Table 2), low education, history of arthritis, diabetes, or asthma, hypertension, use of cholesterol-lowering medication, hormone replacement therapy use, or heavy alcohol use (data not shown).

Results from this study indicate that healthy diets, which reflect adherence to the US dietary guidelines at the time of entry in the WHI study, are more strongly related to the lower occurrence of nuclear cataracts than any other modifiable risk factor or protective factor studied in this sample of women. Being above the 20th percentile for scores that reflect adherence to the US dietary guidelines in 1995 was associated with a 37% lower risk for nuclear cataract after adjusting for other nondietary risk factors. The HEI was originally developed by the US Department of Agriculture as an index of overall diet quality that incorporated the nutrient needs of healthy Americans and US dietary guidelines in 1990 for reduction of risk of major chronic diseases.⁴³ These indices were based on scientific knowledge of relationships between diet and only the major chronic diseases of cardiovascular disease and cancer and did not address risk for eye diseases, which were less well understood at that time. The results of our study indicate that higher scores on this index also relate to reduced risk for the most common type of cataract in the United States.

The median HEI-1995 score for US women older than 50 years in the National Health and Nutrition Examination Survey, conducted close to when the WHI baseline diets were assessed (1988-1994), was 64 as it was in this sample. These data suggest that diets “more nutritious than average” might be related to a similar magnitude in reduction in risk for nuclear cataract among American women. (However, this estimate in primarily white women may not approximate the impact in women of other ethnicities or men.)

It was previously estimated that a 10-year delay in the onset of cataracts could reduce the number of cataract operations needed by half.⁵¹ We attempted to evaluate the impact of healthy diets on the age at which visually significant cataracts develop in an exploratory analysis using a subsample of the women in the present study (Figure). We estimated that healthy diet, controlled for other healthy lifestyles, could be related to a 2.4-year delay in the presence of visually significant nuclear cataract. While this is the best available estimate to date, for several reasons it is likely to be an underestimate of the delay in cataracts in which healthy diets might result. First, these analyses use a subsample and have less statistical power than associations presented for the entire group of women in Table 3. Second, attenuation of risk estimates that occur by inevitable measurement error usually biases the association toward the null. This includes error due to imperfect measurement of diet at entry into the WHI study as well as error due to the estimation of diet over a shorter period than might influence the development of nuclear opacities. (Nuclear opacities are detected as early as the third decade of life in some people and may develop over many decades.) Third, the different intercepts in the Figure suggest the possibility that women with healthy diets had less severe opacities before this relationship was assessed in this study. Fourth, some modifiable risk factors that were controlled for (BMI, for example) likely reflect, to some extent, better diets at earlier ages. Also, in practice, improvement in one aspect of healthy lifestyles (such as being more physically active or stopping smoking) often accompanies improvement in diet. There are only a few existing study samples with photographic evidence of the severity of nuclear sclerosis in which such estimates can be made. The impact of diet and healthy lifestyles on delaying cataracts and cataract surgery might be better estimated from existing large, long-term, prospective studies, particularly if data from these samples are pooled.

No further reduction in prevalence of nuclear cataract was associated with having HEI-1995 scores higher than 59 points (Table 1) even though it was associated with higher intakes of many nutrients thought to protect against cataract (Table 2), suggesting that once adequate levels of intake are attained, further increases may not be protective. However, some aspects of diet, such as that reflected by a general trend for low prevalence of nuclear cataract with higher intake of vitamin C from foods, remained associated with further reduced risk. This suggests that the HEI-1995 score may not have captured all protective aspects of foods.

These data confirm results in a separate sample of relatively healthy older women that indicated that HEI-1995 scores above the median were associated with lower risk for nuclear cataracts.³⁸ In both studies, a design that is a hybrid between cross-sectional studies and prospective studies is used. That is, in both cases, dietary data were assessed years before lens status was assessed (4-7 years in our study and 9-11 years in the other study). This increases the likelihood of a temporally correct relationship. The fact that this end point is determined by photographs rather than by diagnosis or self-report in our study strengthens the likelihood that the data reflect a temporal relationship (poor diet leads to nuclear cataract rather than the other way around). Finally and importantly, the association between healthy diet patterns and nuclear cataract does not disappear or markedly weaken in younger women in the sample as we would expect if poor diet occurred as a result of cataract or comorbid conditions. (The youngest women in this sample would have been less likely than older women to have had cataracts or other comorbid conditions for many years prior to when diet was assessed) (data are not shown for the entire cohort but can be visualized for a subsample in the Figure). However, prospective studies over a decade or longer and studies that include men can provide more precise estimates of risk reduction in the general population that can be achieved with healthy diets.

The lack of association of nuclear cataract with the HEI-2005 score does not necessarily suggest that adhering to the current (2005) US dietary guidelines is less protective against nuclear cataract; instead, it might reflect a limitation in the diet scoring system. After removing the score for high oil intake, similar results were obtained with either score. Although oil intake is recommended to achieve an adequate vitamin E intake and might be related to low risk for other chronic diseases, it was related to higher rather than lower risk for nuclear cataract in this sample. A separate scoring system that reflects adherence to the 2005 US Department of Agriculture food guide pyramid has been developed.⁵² It is not known whether scores using this alternative system are more strongly related to nuclear cataract risk. This is a newly developing field, and improved ability to estimate diet quality may improve our ability to study the impact of diet on cataract.

These results did not appear to be influenced by other measures of a healthy lifestyle that were associated with having healthy diets. Smoking (reviewed¹² ), obesity,^{13 - 15} physical activity,⁵³ and supplement use (reviewed^{28 - 29} ), also associated with higher prevalence of nuclear cataract or cataract extraction in this and other studies, did not explain the associations with healthy diets in this study. However, in practice it is recognized that all aspects of healthy lifestyles are interrelated and that improvement in each tends to increase the chances for improvement in other aspects.

There is a large body of observational studies suggesting that use of multivitamins is associated with lower risk for nuclear cataract (previously reviewed^{28 - 29} ). However, multivitamins were not associated with lower risk for cataract in this study, even after considering longer-term use of multivitamins. The use of multivitamins is associated with diets higher in many nutrients and with other healthy behaviors.⁵⁴ The lack of association in this sample of relatively healthy women could reduce the magnitude of confounding by healthy diet and lifestyle. Alternatively, multivitamins may only protect against nuclear cataract in people who already have poor diets. In the Linxian cataract studies⁵⁵ conducted in a region of China with known high prevalence of micronutrient deficiencies, there was a 36% reduction in nuclear cataract among people aged 65 to 74 years who used multivitamins. Recently, multivitamin use for approximately 9 years in a double-masked, placebo-controlled trial was observed to lower the development of nuclear opacities but increase risk for posterior subcapsular opacities.⁵⁶ The lack of a protective association in our study could result from the relatively healthy diets of women sampled.

The following additional limitations should be considered in drawing conclusions from this study. Because the prevalence rather than incidence of nuclear cataract was assessed, the findings may theoretically represent poor diets that occur as a result of having nuclear cataracts or comorbid conditions associated with them. However, this explanation for the protective association of diet and nuclear cataract is unlikely. Receiving a diagnosis of a chronic disease is most likely to result in improved rather than worsened diet. Moreover, the associations of diet with nuclear cataract did not differ in older women, who would have been more likely to have chronic disease, compared with younger women. Also, because the severity of nuclear sclerosis was assessed photographically, most women (52%) who had nuclear opacities with a severity score of 4 or greater had not been told by a doctor that they had a cataract. The HEI-1995 scores in women who were told that they had a cataract (mean score, 69) did not differ significantly (P = .16) from those who were not told that they had a cataract (mean score, 68). If anything, these data suggest that we may have underestimated the magnitude of associations between healthy diets and the presence of nuclear cataract. Data from a few existing large, long-term, prospective studies could potentially provide better estimates of the magnitude of these relationships, and we hope these results will be forthcoming. Second, some risk factors were not measured, such as lead exposure,⁵⁷ or may be unknown and may explain the associations observed. However, further adjusting for education, a marker of socioeconomic status that could reflect this or other unmeasured confounders, did not alter ORs (data not shown). Third, associations were limited to women in this study and may not reflect the protective influence of diet in men. However, associations of single nutrients with nuclear cataract in men have been similar or stronger in other populations.^{20 ,23} Finally, even though surgery for most cataracts in older white women can be presumed to result from cataracts in the nuclear region after age 50 years,⁶ some misclassification of nuclear cataract would have resulted from cataracts extracted due to opacities in the posterior subcapsular or cortical regions of the lens, possibly attenuating the associations between diet and nuclear cataracts. However, associations of the diet index score with nuclear cataracts determined photographically in women with intact lenses in this sample were nearly identical (data not shown).

In conclusion, this study adds to the body of literature suggesting that healthy diets are associated with lower risk for cataract. Diet was the strongest risk factor related to reduced risk of nuclear cataract in this sample of postmenopausal women. Smoking and obesity were also contributors. Lifestyle improvements that include healthy diets, smoking cessation, and avoiding obesity may substantively lower the need for and economic burden of cataract surgery in aging American women.

Correspondence: Julie A. Mares, PhD, Department of Ophthalmology and Visual Sciences, University of Wisconsin, 610 N Walnut St, 1063 WARF Bldg, Madison, WI 53726-2336 (jmarespe@wisc.edu).

Submitted for Publication: July 21, 2009; final revision received October 7, 2009; accepted November 24, 2009.

CAREDS Group: The CAREDS Group Investigators include Catherine Allen, PhD, Barbara Blodi, MD, Matthew Davis, MD, Larry Hubbard, MAT, Tara LaRowe, PhD, University of Wisconsin, Madison; Karen M. Gehrs, MD, Robert B. Wallace, MD, University of Iowa, Iowa City; Elizabeth Johnson, PhD, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts; Michael Klein, MD, Casey Eye Institute, Oregon Health and Science University, Portland; Cheryl Ritenbaugh, PhD, MPH, University of Arizona, Tucson; D. Max Snodderly, PhD, University of Texas, Austin; Amy E. Millen, PhD, University at Buffalo, Buffalo, New York; Niyati Parekh, PhD, New York University, New York; and Bill Wooten, PhD, Brown University, Providence, Rhode Island. The CAREDS staff include Paula Smith, BS, Susan K. Nolte, BS, Debora Vahrenwald, BS, Portland; Kelly O’Berry, BS, Heather Stockman, BS, Steven Wallace, BS, Lindsey Fuhrmeister, BS, Iowa City; and Jane Armstrong, BS, Michael Neider, BS, Hugh Wabers, BS, Janet Rowley, BS, Tanya Judge, BS, Lisa Oxton, BS, Rick Voland, PhD, Gail Ostrowski, BA, Scott Burfield, BS, Julie Ewing, BA, Tracy Perkins, BS, Madison.

Financial Disclosure: Dr Gehrs has served as an advisory board consultant for Eyetech and as a speaker for Alcon resident surgery course.

Funding/Support: This research was supported by grants EY016886, 13018, and DK 07665 from the National Institutes of Health and by Research to Prevent Blindness. It was part of the Carotenoids and Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI). The National Eye Institute provided funding for the CAREDS, and the National Heart, Lung, and Blood Institute provided funding for the WHI program.

Additional Contributions: The following WHI investigators, staff, and participants contributed their time and effort in obtaining the WHI data that were presented in this article: at the program office, Barbara Alving, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller (National Heart, Lung, and Blood Institute, Bethesda, Maryland); at the clinical coordinating center, Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan (Fred Hutchinson Cancer Research Center, Seattle, Washington), Sally Shumaker (Wake Forest University School of Medicine, Winston-Salem, North Carolina), Evan Stein (Medical Research Labs, Highland Heights, Kentucky), and Steven Cummings (University of California, San Francisco); and at the clinical centers, Sylvia Wassertheil-Smoller (Albert Einstein College of Medicine, Bronx, New York), Jennifer Hays (Baylor College of Medicine, Houston, Texas), JoAnn Manson (Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts), Annlouise R. Assaf (Brown University), Lawrence Phillips (Emory University, Atlanta, Georgia), Shirley Beresford (Fred Hutchinson Cancer Research Center), Judith Hsia (George Washington University Medical Center, Washington, DC), Rowan Chlebowski (Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles Medical Center, Torrance), Evelyn Whitlock (Kaiser Permanente Center for Health Research, Portland); Bette Caan (Kaiser Permanente Division of Research, Oakland, California); Jane Morley Kotchen (Medical College of Wisconsin, Milwaukee), Barbara V. Howard (MedStar Research Institute/Howard University, Washington, DC), Linda Van Horn (Northwestern University, Chicago, Illinois), Henry Black (Rush Medical Center, Chicago), Marcia L. Stefanick (Stanford Prevention Research Center, Stanford, California); Dorothy Lane (State University of New York at Stony Brook), Rebecca Jackson (Ohio State University, Columbus), Cora E. Lewis (University of Alabama at Birmingham), Tamsen Bassford (University of Arizona), Jean Wactawski-Wende (University at Buffalo), John Robbins (University of California, Davis, Sacramento), F. Allan Hubbell (University of California, Irvine), Howard Judd (University of California, Los Angeles), Robert D. Langer (University of California, San Diego, La Jolla), Margery Gass (University of Cincinnati, Cincinnati, Ohio), Marian Limacher (University of Florida, Gainesville), David Curb (University of Hawaii, Honolulu), Robert B. Wallace (University of Iowa), Judith Ockene (University of Massachusetts/Fallon Clinic, Worcester), Norman Lasser (University of Medicine and Dentistry of New Jersey, Newark), Mary Jo O’Sullivan (University of Miami, Miami, Florida), Karen Margolis (University of Minnesota, Minneapolis), Robert Brunner (University of Nevada, Reno), Gerardo Heiss (University of North Carolina, Chapel Hill), Lewis Kuller (University of Pittsburgh, Pittsburgh, Pennsylvania), Karen C. Johnson (University of Tennessee, Memphis), Robert Brzyski (University of Texas Health Science Center, San Antonio), Gloria E. Sarto (University of Wisconsin, Madison), Denise Bonds (Wake Forest University School of Medicine), and Susan Hendrix (Wayne State University School of Medicine/Hutzel Hospital, Detroit, Michigan).