American Journal of Epidemiology Copyright O 2000 by The Johns Hopkins University School of Hygiene and Public Health All

rights reserved

vol.151, No. 5

Printed in USA.

Risk Factors for Cortical, Nuclear, and Posterior Subcapsular Cataracts

The POLA Study

Cecils Delcourt,1 Jean-Paul Cristol,2 Fr6deric Tessier,3 Claude L. Leger,2 Francoise Michel,2 Laure Papoz,1 and the POLA Study Group4 The POLA (Pathologies Oculaires Li6es a i'Age) Study is a population-based study of cataract and agerelated macular degeneration and their risk factors being carried out among 2,584 residents of Sete, southern France, aged 60-95 years. Recruitment took place between June 1995 and July 1997. Cataract classification was based on a standardized lens examination by slit lamp, according to Lens Opacities Classification System III. This paper presents results obtained from cross-sectional analysis of the first phase of the study. In polytomous logistic regression analyses, an increased risk of cataract was found for female sex (cataract surgery: odds ratio (OR) = 3.03; cortical cataract: OR = 1.67), brown irises (cortical, nuclear, and mixed cataracts: OR = 1.61), smoking (cataract surgery: OR = 2.34 for current smokers and OR = 3.75 for former smokers), known diabetes of 10 or more years' duration (posterior subcapsular, cortical, and mixed cataracts and cataract surgery: OR = 2.72), use of oral corticosteroids for at least 5 years (posterior subcapsular cataract: OR = 3.25), asthma or chronic bronchitis (cataract surgery: OR = 2.04), cancer (posterior subcapsular cataract: OR = 1.92), and cardiovascular disease (cortical cataract: OR = 1.96). Decreased risk of cataract was found with higher education (all types of cataract and cataract surgery: OR = 0.59), hypertension (cataract surgery: OR = 0.57), and high plasma retinol levels (nuclear and mixed cataracts and cataract surgery: OR = 0.75 for a 1standard-deviation increase). Most of the risk factors identified in this study confirm the findings of other studies. The association of cataract with plasma retinol level requires further investigation. Am J Ep/cfem/o/2000;151: 497-504. cataract; cortisone; cross-sectional studies; diabetes mellitus; eye diseases; risk factors; smoking; vitamin A

Cataract is the leading cause of blindness, accounting for 50 percent of blindness worldwide (1). With the global aging of populations, particularly in industrialized countries, the prevalence of this condition is increasing rapidly. The only therapy currently available is lens extraction. The growing need for surgical resources is particularly critical in developing countries, but it also affects industrialized countries. For instance, cataract surgery has become the most common surgical procedure among people aged 65 years or more in the United States, with an estimated $3.4 billion cost to Medicare in 1991 (2). An increased understanding of cataract etiology may lead to the
Received for publication December 30, 1998, and accepted for publication May 18, 1999. Abbreviations: LOCS III, Lens Opacities Classification System III; OR, odds ratio; POLA, Pathologies Oculaires Liees a I'Age. 1 1nstitut National de la Sante et de la Recherche Medicate (INSERM), Unite 500, Montpellier, France. 2 Laboratoire de Biologie et Biochimie des LJpides, University Hospital of Montpellier, Montpellier, France. 3 InstHut National Agronomique, Paris, France. 4 Members of the POLA Study Group are listed in the Acknowledgment Reprint requests to Dr. Cecile Delcourt, INSERM Unite 500, 39 Avenue Charles Flahault, 34093 Montpellier, Cedex 5, France.

development of nonsurgical strategies for delaying or preventing cataract. In the United States, the National Eye Institute estimates that a 10-year delay in the onset of cataract would result in a 50 percent reduction in the prevalence of cataract (1). The POLA (Pathologies Oculaires Liees a I'Age) Study is an epidemiologic study being conducted in southern France that is designed to identify risk factors for cataract and age-related macular degeneration. Most of the epidemiologic studies on this subject have been conducted in the United States; our study is one of the few European studies on this subject (3-7) and is, to our knowledge, the first to be carried out in France. We present here the associations of age-related posterior subcapsular, cortical, nuclear, and mixed cataracts with demographic, medical, and nutritional risk factors.
MATERIALS AND METHODS Study population

The POLA Study is a prospective study taking place in Sete, a town of 40,000 inhabitants located on the
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Mediterranean Sea in southern France. The objective of this survey is to study age-related eye diseases (cataract and macular degeneration) and their risk factors. Inclusion criteria were 1) being a resident of the town of Sete and 2) being aged 60 years or over on the day of the baseline examination. According to the 1990 population census, there were almost 12,000 residents eligible for participation; the objective was to recruit 3,000. The population was informed of the study through the local media (television, radio, and newspapers). We also contacted 4,543 residents individually by mail and by telephone, using the electoral roll. Between June 1995 and July 1997, we recruited 2,584 participants, including 1,133 men and 1,451 women, with an average age of 70.4 years. This paper presents results obtained from cross-sectional analysis of the first phase of the study. We are currently undertaking a follow-up examination, 3 years after baseline. The baseline examination took place in a mobile unit equipped with ophthalmologic devices (a projector of the Snellen chart, a decimal scale (L28 IR; Luneau S.A., Chartres, France), an autorefractometer (RM-A7000; Topcon Optical Company, Tokyo, Japan), a slit lamp (SL7F; Topcon), and a retinal camera (TRC 50 XF; Topcon)). We moved the mobile unit from one area to another to be in the proximity of the contacted participants. Participants gave written consent for participation in the study. The study's design was approved by the Ethical Committee of Montpellier University Hospital (Montpellier, France).
Cataract classification

Four ophthalmologists performed the ophthalmologic examinations. The examination included a recording of the participant's ophthalmologic history (particularly lens extraction and the year of extraction); a measure of the best corrected far visual acuity in the right and left eyes; after pupil dilation, a quantitative assessment of nuclear, cortical, and posterior subcapsular lens opacities by slit lamp, according to the Lens Opacities Classification System EQ (LOCS IJT) (8); and one 50 color photograph of each eye, centered on the macular area. The type and degree of lens opacification were graded by slit lamp following LOCS HI procedures (8). The LOCS i n system, which is based on standard photographs, provides decimal, nearly continuous grades separately for nuclear opalescence (NO) (ranging from 0 to 6.9, using six standards), nuclear color (NC) (ranging from 0 to 6.9), cortical opacities (C) (ranging from 0 to 5.9, using five standards), and posterior subcapsular opacities (P) (ranging from 0 to 5.9, using five standards).

Severe cataract. We chose to classify as severe cataracts lens opacifications which led to significant visual impairment in most participants (grades of NO 4 or NC > 4 for nuclear cataract, C > 4 for cortical cataract, and P > 2 for posterior subcapsular cataract). Participants were classified as having a single type of cataract (nuclear, cortical, or posterior subcapsular) when only one type of opacity was present. The nuclear group, for instance, consisted of participants with nuclear cataract only in both eyes, or nuclear cataract only in one eye and moderate or no cataract in the other eye. The mixed cataract group consisted of participants with various combinations of nuclear, cortical, and posterior subcapsular opacities in one or both eyes. Moderate cataract. We chose to classify participants as having moderate cataract if they were free of severe cataract and had moderate opacities (2 < NO < 4 or 2 <, NC < 4 for nuclear opacities, 2 < C < 4 for cortical opacities, and 1 < P < 2 for posterior subcapsular opacities). It was not possible to distinguish among moderate nuclear cataract only, moderate cortical cataract only, moderate posterior subcapsular cataract only, and mixed moderate cataracts, because there would have been too many groups for the analyses. No cataract. Participants were classified as free of cataracts if they had neither severe nor moderate cataract. Therefore, this group also includes participants with minimal changes (NO < 2 and NC < 2, C < 2, a n d P < l ) . Finally, participants who had already had bilateral lens extractions were placed into a separate group (bilateral cataract surgery). Participants with unilateral lens extraction (n = 100) were classified according to the status of their other eye. Information on lens examination in both the right eye and the left eye was lacking for 25 participants (1.0 percent), in 13 cases because of lack of dilation (eight participants refused and five had contraindications) and in 12 cases because of technical failure. We excluded one case of traumatic cataract. Thus, cataract status could be determined for 2,558 (99 percent) of 2,584 participants. The vast majority of participants (n = 1,726) were classified as having moderate cataract, while relatively few (n = 131) had no cataract according to the above criteria. Thus, in the analyses discussed below, persons with severe types of cataract have been compared with the group "moderate or no cataract."
Interview data

Data were collected by trained study personnel who were unaware of cataract status. A standardized interview was carried out for assessment of sociodemoAm J Epidemiol Vol. 151, No. 5, 2000

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graphic variables (marital status, educational level, main lifetime occupation, etc.), medical history (treated hypertension, cardiovascular diseases, diabetes mellitus, knee or hip osteoarthritis, etc.), all medications currently being used, smoking history, and occupational and leisure-time exposure to sunlight. The interviewer then measured height, weight, waist and hip circumferences, and systolic and diastolic blood pressures. Participants were considered to have a high level of education if they had reached at least the end of high school. History of cardiovascular disease was defined as a history of myocardial infarction, stroke, or angioplasty. Hypertension was defined as known treated hypertension confirmed by current use of antihypertensive medication and/or systolic blood pressure >160 mmHg and/or diastolic blood pressure ^95 mmHg. Body mass index was defined as weight (kg)/height (m)2.
Biochemical data

blood cell glutathione, 356 (14.4 percent) measurements could not be made because of technical failure; this left 2,112 subjects for the analysis. Ascorbic acid was measured only in subjects recruited after November 20, 1995 (n = 2,020).
Statistical analysis

Biologic measurements were made from fasting blood samples taken at the participant's home on the morning of the examination. They included measurements of plasma (cholesterol, triglycerides, and vitamins A, E, and C) and red blood cells (reduced glutathione). Plasma triglyceride and total cholesterol levels were measured by routine enzymatic methods with a reagent purchased from Boehringer Laboratories (Norristown, Pennsylvania). Plasma high density lipoprotein cholesterol was assayed in the supernatant after precipitation of apolipoprotein B-containing lipoproteins by magnesium phosphotungstate kit (bioM6rieux S.A., Marcy-1'Etoile, France). Retinol and a-tocopherol were measured by high performance liquid chromatography according to the method previously described by Catignani and Bieri (9). In each series of measurements, one sample of the liotrol mixture was measured as an internal standard, to prevent any shift during the study. Ascorbic acid was measured by high performance liquid chromatography according to the method described by Tessier and BirlouezAragon (10). Red blood cell reduced glutathione was measured by colorimetric assay (Bioxytech GSH-400; OXIS International, Inc., Paris, France).
Missing data

Among the 2,558 participants for whom cataract status was available, 46 subjects (1.8 percent) refused blood sampling. For an additional 44 subjects (1.7 percent), some data were missing in the standardized interview. Therefore, the analyses discussed below were performed in 2,468 subjects. Concerning red
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The associations of the different types of cataract with the potential risk factors were estimated by polytomous logistic regression. Patients without any severe opacities constituted the reference group in all analyses. We used a strategy similar to that of other studies of cataract (4,11), as follows. 1) Age- and sex-adjusted odds ratios were calculated for all potential risk factors. All variables with an odds ratio that differed from 1 (p < 0.10) for at least one type of cataract were retained for the next phase of analysis. 2) A full multivariate analysis was carried out. 3) A reduced multivariate analysis was conducted, and those variables which did not show any significant (p < 0.05) association with any of the cataract types were excluded. 4) Coefficients for a given variable were constrained to be equal across selected cataract types when their estimates in the reduced model were not significantly different. 5) Coefficients for certain variables for selected cataract types were constrained to be 0 when their estimates in the reduced model were not significantly different from 0. The comparisons between the full model and the reduced model and between the reduced model and the final model were made with a %2 test of the improvement in the log-likelihood. Concerning diabetes, because of a known effect of duration for any physiologic change, we chose to create two duration groups (<10 years and >10 years, a 10-year duration being about the median) before performing any statistical analysis. By contrast, educational level and iris color were recorded as three-class variables: primary, secondary, and superior for education and blue, green/light brown, and dark brown for iris color. Since primary and secondary educational levels on the one hand and light brown and dark brown iris color on the other hand did not show any difference for any type of cataract in step 2, we chose to pool these categories in order to simplify the analysis. These analyses were performed using Statview (SAS Institute, Cary, North Carolina) and BMDP (BMDP, Inc., Berkeley, California) (for the constrained polytomous logistic regression).
RESULTS

As table 1 shows, among men the prevalence of cataract increased from 10.1 percent below age 70

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TABLE 2. Distribution (% or mean) of risk factors studied in the POLA* Study, southern France, 1995-1997
Men (n= 1,082) Women (n= 1,386)

TABLE 1. Prevalence (%) of different types of cataract (severe only) according to age and sex In the POLA* Study, southern France, 1995-1997
Age group (years) Total 60-69

70-79
n = 411 9.5 3.4 6.1 6.1 7.0 32.1 n=561 8.9 4.8 8.9 8.5 5.7 36.9 n=117 6.8 6.8 17.9 17.1 13.7 62.4 n=152 6.6 9.2 13.8 20.4 23.7 73.7 n= 1,082 7.0 2.8 4.9 4.8 4.6 24.1 n= 1,386 6.6 4.3 5.8 6.5 5.7 29.0

Men PSC* only Cortical only Nuclear only Mixed Cataract surgery Total Women PSC only Cortical only Nuclear only Mixed Cataract surgery Total

n = 554 5.2 1.4 1.3 1.3 0.9 10.1 n=673 4.7 2.8 1.5 1.6 1.6 12.3

Personal characteristics Mean age (years) High educational level (%) Brown irises (%) Medical history Smoking (%) Current smoker Former smoker Body mass indexf Known diabetes mellitus (%) Duration of <10 years Duration of 10 years Cardiovascular disease (%) Hypertension (%) Use of oral corticosteroids (%) <5 years 5 years Asthma or chronic bronchitis (%) Cancer (%) Knee or hip osteoarthritis (%) Biochemical variables (mean level) Cholesterol (mmol/liter) HDL* cholesterol (mmol/liter) Apolipoprotein A1 (g/liter) Apolipoprotein B (g/liter) Triglycerides (mmol/liter) a-tocopherol (nmot/liter) Retinol (umol/liter) Ascorbic addH (umol/liter) Erythrocyte glutathione* (nmol/mg of hemoglobin)

70.3 (6.8)t 11.2

74.9

70.5 (6.9) 3.8 80.0

14.9 59.9 26.7 (3.6)

5.1 10.0 26.2 (4.5) 3.6 2.8 11.8 35.8

6.9
5.8 22.2 36.0

5.5 1.6 7.2 5.6 24.2

9.0 1.6
5.4 7.6 41.8

POLA, Pathologies Oculaires Liees a I'Age; PSC, posterior subcapsular cataract.

years to 62.4 percent at age 80 years or more. The prevalence of cataract was slightly higher in women, and it increased from 12.3 percent below age 70 years to 73.7 percent at age 80 years or more. While posterior subcapsular cataract was the most frequent type of cataract below age 70 years (5.2 percent in men and 4.7 percent in women), nuclear and mixed cataracts were the most frequent types at and above age 80 years (17.9 percent and 17.1 percent, respectively, in men and 13.8 percent and 20.4 percent in women). Overall, 43.1 percent of posterior subcapsular opacities were associated with other opacities, and therefore were classified under "mixed cataracts." This proportion increased to 71.0 percent among participants aged 80 years or more. This explains the decrease in the prevalence of posterior subcapsular cataract alone over age 80 years, the vast majority of posterior subcapsular opacities being classified as mixed cataracts. Similarly, 45.9 percent and 46.6 percent of cortical and nuclear opacities, respectively, were classified as mixed cataracts. Table 2 presents the distribution of the studied risk factors in the POLA Study. In this Mediterranean population, the majority of the participants had brown irises. Three fourths of the men had smoked during their lives, versus only 15 percent of the women. Known diabetes, cardiovascular disease, and asthma were more frequent in men, while cancer, knee or hip osteoarthritis, and treatment with oral corticosteroids were more frequent in women. Levels of total and high density lipoprotein cholesterol, apolipoprotein Al, and a-tocopherol were higher in women.

5.51 (1.02) 1.23 (0.32) 1.46(0.25) 1.12(0.25) 1.37(1.01) 33.1 (10.1) 2.45 (0.66) 29.3(18.6)

5.91 (1.12) 1.50(0.37) 1.68(0.28) 1.11 (0.25) 1.20(0.76) 35.5(10.0) 2.27 (0.60)

40.1 (20.3) 3.83(1.06)

3.71(1.05)

* POLA, Pathologies Oculaires Uees a I'Age. t Numbers in parentheses, standard deviation. t Weight (kg)/height (m). Plasma measurements unless otherwise stated. D n= 895 for men; n= 1,125 for women. # n= 924 for men; n= 1,188 for women.

Table 3 presents the results from the final polytomous model. Age remained a major factor for all types of cataracts. Women had a threefold higher rate of cataract extraction, a significant 1.7-fold higher rate of cortical cataract, and nearly significant 1.47- and 1.39-fold increased rates of nuclear and mixed cataracts, respectively. A high level of education was associated with lower risk of all types of cataract (odds ratio (OR) = 0.59). Having brown irises was associated with higher risks of cortical, nuclear, and mixed cataracts but not of posterior subcapsular cataract or cataract surgery. Current and former smoking were significantly associated with higher odds of cataract surgery (OR = 2.3 for current smoking and OR = 3.7
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TABLE 3. Odds ratios for cataract estimated by multlvariate polytomous logistic regression (final model) among adults aged 60-95 years, POLA* Study, southern I-ranee, 1995-1997 Posterior subcapsuiar cataract only OR* Personal characteristics Age (per 1-year Increase) Female sex High educational level Brown irises Medical history Smoking Current smoker Former smoker Known diabetes mellltus Duration of <10 years Duration of 210 years Use of oral corticosterotds <5 years 25 years Asthma or chronic bronchitis Cancer Cardiovascular disease Hypertension Biochemical variables Plasma retinol level (per 1-standard deviation Increase) 95% Cl* OR Cortical only 95% Cl OR Nudear only 95% Cl OR Mixed cataracts 95% Cl OR Cataract surgery 95% Cl

1.09 1.01 0.59

1.06, 1.12 0.73, 1.41 0.37, 0.93

1.12 1.67 0.59 1.61

1.08, 1.16 1.06,2.63 0.37, 0.93 1.18,2.20

1.20 1.47 0.59 1.61

1.17, 1.24 0.90, 2.38 0.37, 0.93 1.18,2.20

1.22 1.39 0.59 1.61

1.19, 1.25 0.95, 2.03 0.37, 0.93 1.18,2.20

1.24 3.03 0.59

1.20, 1.28 1.83,5.00 0.37, 0.93

1.37 2.72 0.53 3.25 1.92 0.87,2.16 1.72,4.28 0.24, 1.16 1.39,7.58 1.17, 3.19 1.96 1.37 2.72

1.91 1.36 0.78 1.47

0.98, 3.71 0.82, 2.28 0.30, 2.04 0.60, 3.62 1.37 2.72

2.34 3.75 1.37 2.72

1.07,5.15 2.26, 6.21 0.87,2.16 1.72,4 28 1.04,3.81 0.38, 0.87

0.87,2.16 1.72, 4.28 1.22,3.14

0.87, 2.16 1.72, 4.28

2.04

0.57

0.75

0.66, 0.86

0.75

0.66, 0.86

0.75

0.66, 0.86

POLA, Pathologies Oculalres Uees a I'Age; OR, odds ratio; Cl, confidence Interval, t These odds ratios were constrained to be equal to 1 (see "Materials and Methods").

for former smoking), while current smoking was associated with a 1.9-fold higher rate of nuclear cataract, although this finding was at the limit of significance. Known diabetes of long duration (>10 years) was significantly associated with a 2.7-fold increased risk of all types of cataract except nuclear cataract, while known diabetes of short duration was not significantly associated with cataract. History of cardiovascular disease was associated with a twofold increased risk of cortical cataract, while hypertension was significantly associated with a decreased risk of cataract surgery (OR = 0.57). The use of oral corticosteroids for 5 years or more was associated with a 3.2-fold increased risk of posterior subcapsular cataract, while a history of asthma or chronic bronchitis was associated with a twofold increased risk of cataract surgery. History of cancer was associated with a 1.9-fold increased risk of posterior subcapsular cataract. Finally, plasma retinol level was inversely associated with the combined risks of nuclear and mixed cataracts and cataract surgery (OR = 0.75). This association was highly significant (p< 0.0001).
DISCUSSION

ences in the etiology of different types of cataract (posterior subcapsular, cortical, and nuclear). Various personal, medical, and biochemical factors appear to play a role in the development of lens opacities.
Age

The results of this study confirm most of the risk factors identified in other studies, despite differences in study design (cataract classification, country, population, etc.). The results are also consistent with differAm J Epidemiol Vol. 151, No. 5, 2000

As table 1 illustrates, age is a major risk factor for the development of cataract. In men, the prevalence of any type of cataract increased from 10.1 percent below age 70 years to 62.4 percent over age 80 years. The prevalence of any cataract was slightly higher in women, increasing from 12.3 percent below age 70 years to 73.7 percent over age 80 years. Several methodological considerations must be taken into account. First, cataract development is a continuous process, and some opacification occurs systematically with age. The choice of the threshold for defining cataract is therefore a problem. For the moment, no international standard exists for the definition of cataract, which impedes comparisons among studies (12-14). The development of an international grading and classification system for cataracts would facilitate the comparison of prevalence rates among studies. Our main objective was to identify risk factors for cataract and age-related macular degeneration rather than to estimate the prevalence of age-related eye diseases. Our aim was to recruit a large sample of persons from the general population, with a high diversity of

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potential risk factors. To assess possible bias in recruitment, we previously compared our sample with the entire eligible population according to age, sex, and social class. Although the sex distribution was similar in both populations, our sample underrepresented older persons and overrepresented the middle and upper social classes (15). Bias from self-selection may therefore have affected cataract prevalence rates.
Personal characteristics

After adjustment for other risk factors, women had threefold higher odds of cataract surgery than men. They also had 1.7-fold higher odds of cortical cataract, which is consistent with results from three other studies (4, 11, 16). These sex differences were already present before adjustment and were increased by the adjustments for smoking and diabetes, both of which were much more prevalent in men. The factors explaining the excess risk of cataract, particularly cortical cataract, in women remain to be identified. They may relate to sex differences, particularly to hormone levels (17-19), or to differences in lifestyle or other environmental exposures. Participants with a high level of education had a 40 percent lower risk of all types of cataract. The association of lower socioeconomic status with cataract is a general finding that has been seen in studies with various settings (4, 11, 16, 20-22). This very consistent finding suggests, in particular, an influence of lifestyle on the etiology of cataracts. Participants with brown irises were at higher risk for cortical, nuclear, and mixed cataracts, which is consistent with the findings of two case-control studies (4, 11). However, in a prospective study, iris color was not associated with nuclear cataract (22). The mechanism by which iris color is linked to cataract remains unclear. The same mechanism may explain the excess prevalence of cortical cataract found in Black populations (11, 16).
Medical history

Consistent with the findings of a number of studies, smoking was a strong risk factor for cataract, the risk being mostly confined to nuclear cataract (and cataract extraction) (3, 11, 22-27). In observational studies, the possible existence of a confounding factor responsible for the relation cannot be completely dismissed. However, the strength of the relation, the specificity of its association with nuclear cataract, and the consistency of the relation across populations with different lifestyles and exposures all favor a causal association. The mechanism by which smoking is related to cataract is unclear. Smoking may cause damage to the

lens by increasing oxidative stress, by lowering levels of circulating antioxidants, or by increasing lens cadmium levels (28-31). Diabetes was strongly associated with the risk of all types of cataract, except nuclear cataracts. Again, this finding is very consistent with the literature (5-7, 11, 16, 20, 32). As we found in our study, the four studies which have distinguished between the different types of cataract (5, 11, 16, 32) found associations with subcapsular posterior and/or cortical cataract, but none found a significant relation with nuclear cataract. Finally, as expected, our study showed that the risk of cataract increases strongly with the duration of diabetes. The use of oral corticosteroids was a strong risk factor for subcapsular posterior cataract, confirming the results of three other studies (4, 5, 11). Recently, an association has also been reported between use of inhaled corticosteroids and subcapsular posterior cataract (33) and cataract extraction (34). This may explain our finding that asthma and chronic bronchitis were associated with increased risk of cataract extraction. We also found an association of subcapsular posterior cataract with a history of cancer. To our knowledge, this is the first report on this association, since history of cancer was not recorded in the other studies. This association of subcapsular posterior cataract with cancer may be mediated by an adverse effect of radiotherapy or chemotherapy on the lens. In our study, we did not have enough cases of cancer to distinguish between radiotherapy and chemotherapy. Further research is needed to confirm this finding. Finally, cardiovascular disease was associated with an increased risk of cortical cataract, while hypertension was associated with a reduced risk of lens extraction. These results conflict with those of the other studies on the subject: None of the four existing studies (4, 11, 22, 35) have found a relation between history of cardiovascular disease and any type of cataract. Four studies (4, 11, 22, 36) did not find significant relations of hypertension with cataract, while two studies (7, 37) found a significant increased risk of cataract in cases of hypertension. Globally, these results do not favor the possibility of a major effect of cardiovascular disease and hypertension in the etiology of cataract. Given the number of comparisons made in this analysis, it is possible that the associations of cataract with cardiovascular disease and hypertension are chance findings.
Biochemical variables

The only significant association among biochemical variables and cataract in this study concerned plasma retinol. A strong, highly significant inverse relation was found between plasma retinol level and nuclear
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and mixed cataracts, as well as cataract surgery (for a 1-standard-deviation increase, OR = 0.75; 95 percent confidence interval: 0.66, 0.86). Three studies have found a significant inverse relation between total vitamin A intake and nuclear cataract (11, 38, 39). Relations with other types of cataract or with all cataracts were less clear (11, 38-41). The relation of nuclear cataracts with dietary preformed vitamin A (i.e., retinol) was less strong than the relation with total dietary vitamin A (4, 38, 41). This suggests that carotenoids may be more important in the risk of nuclear cataract than retinol. To our knowledge, only two previous studies have assessed the association of plasma retinol with nuclear cataract (42, 43). These studies did not find any significant association. However, one study had little statistical power and used a crude evaluation of lens status (43). The other found a nonsignificant negative association of plasma retinol with nuclear cataract and a significant positive association with cortical cataract (42). The results of this study strongly suggest that vitamin A may be protective for cataract. Our findings are supported by those of previous dietary studies (11, 38, 39), while the two available studies on plasma retinol (42, 43) gave inconsistent results. Possible confounding of the cataract-retinol association by carotenoids must be evaluated. Measurement of plasma carotenoid levels is currently being performed in our study. Alternatively, the nucleus of the lens may be sensitive to nutrient deficiencies. Indeed, apart from low levels of vitamin A, low levels of protein and amino acids, riboflavin, niacin, thiamine, and folate have been found to be associated with higher risk of nuclear cataract in other studies (38, 39, 44).
Methodology

Since information on many of the studied risk factors was obtained by interview, recall bias might also have produced these results. However, since most of our findings are specific to each type of cataract and consistent with the literature, the effect of such biases was probably limited. Because the majority of the studies conducted to date have been case-control or crosssectional in design, prospective studies will be needed to confirm these results.
Summary

Our study confirmed most of the risk factors for cataract identified in other studies, including lower economic status, smoking, use of corticosteroids, diabetes, and brown irises. We also found a strong association of nuclear and mixed cataracts with low plasma retinol levels, which requires further evaluation.

ACKNOWLEDGMENTS

Our study had several methodological limitations. Our method of selecting participants led to underrepresentation of older persons and overrepresentation of the middle and upper social classes in comparison with the entire eligible population (15). Bias from selfselection may therefore have occurred. However, most of our findings concerning the identified risk factors (eye color, smoking, diabetes, corticosteroids) and their relations with each type of cataract are in complete consistency with those of other studies in the literature. It is therefore unlikely that less consistent findings, particularly associations of cataract with plasma retinol, are only a result of selection bias. Since this analysis was cross-sectional, we cannot assume that the presence of the risk factors identified preceded the development of cataract. It is possible that the development of cataract caused changes in lifestyle, inducing changes in some of the risk factors.
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Financial support for this study was provided by the Institut National de la Sant6 et de la Recherche M&licale (Paris, France), die Fondation de France, Department of the Epidemiology of Aging (Paris), the Region LanguedocRoussillon (Montpellier, France), the Fondation pour la Recherche M6dicaJe (Paris), the Association Retina-France (Toulouse, France), Rh6ne Poulenc S.A. (Paris), Essilor International (Paris), and the Centre de Recherche et d'Information Nutritionnelle (Paris). The POLA Study Group: CoordinationDr. Cecile Delcourt, Annie Lacroux, Sylvie Fourrey, Marie-Jose' Covacho, Pierre Paillard, Alice Ponton-Sanchez, Dr. Roselyne Defay, Dr. Alain Colvez, and Dr. Laure Papoz (Principal Coordinator); OphthalmologyDrs. Louis Balmelle, Jacques Costeau, Jean-Luc Diaz, Fabienne Robert, and Bernard Arnaud; BiologyLaboratoire de Biologie et Biochimie des Lipides, Montpellier: Dr. JeanPaul Cristol, Dr. Martine Delage, Dr. Marie-Heiene Vernet, Gilles Fouret, Dr. Francoise Michel, Dr. Claude Leger, and Dr. Bernard Descomps; Laboratoire de Toxicologie Biophysique, Montpellier: Drs. Pierre Mathieu-Daude and Jean-Claude Mathieu-Daude"; Institut National Agronomique, Paris: Drs. Fr6d6ric Tessier and Ines BirlouezAragon.

REFERENCES 1. Javitt JC, Wang F, West SK. Blindness due to cataract: epidemiology and prevention. Annu Rev Public Health 19%; 17: 159-77. 2. Steinberg EP, Javitt JC, Sharkey PD, et al. The content and cost of cataract surgery. Arch Ophthalmol 1993;111:10419. 3. Flaye DE, Sullivan KN, Cullinan TR, et al. Cataracts and cigarette smoking: The City Eye Study. Eye 1989;3:379-84.

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