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
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.
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.
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
497
498
Delcourt et al.
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
Risk Factors for Cataract
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
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
Am J Epidemiol
Vol. 151, No. 5, 2000
499
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
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
500
Delcourt et al.
TABLE 1. Prevalence (%) of different types of cataract
(severe only) according to age and sex In the POLA* Study,
southern France, 1995-1997
TABLE 2. Distribution (% or mean) of risk factors studied in
the POLA* Study, southern France, 1995-1997
Men
(n= 1,082)
Age group (years)
Total
Men
PSC* only
Cortical only
Nuclear only
Mixed
Cataract surgery
Total
Women
PSC only
Cortical only
Nuclear only
Mixed
Cataract surgery
Total
60-69
70-79
n = 554
5.2
1.4
1.3
1.3
0.9
n = 411
9.5
3.4
6.1
6.1
7.0
n=117
6.8
6.8
17.9
17.1
13.7
n= 1,082
7.0
2.8
4.9
4.8
4.6
10.1
32.1
62.4
24.1
n=673
4.7
2.8
1.5
1.6
1.6
n=561
8.9
4.8
8.9
8.5
5.7
n=152
6.6
9.2
13.8
20.4
23.7
n= 1,386
6.6
4.3
5.8
6.5
5.7
12.3
36.9
73.7
29.0
• 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.
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)
Women
(n= 1,386)
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)
70.3 (6.8)t
11.2
6.9
5.8
22.2
36.0
3.6
2.8
11.8
35.8
5.5
1.6
9.0
1.6
7.2
5.6
24.2
5.4
7.6
41.8
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)
3.71(1.05)
40.1 (20.3)
3.83(1.06)
* 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
Am J Epidemiol
Vol. 151, No. 5, 2000
Risk Factors for Cataract 501
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
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)
Cortical
only
Nudear
only
Mixed
cataracts
Cataract
surgery
OR*
95% Cl*
OR
95% Cl
OR
95% Cl
OR
95% Cl
OR
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
—
—
1.91
1.36
0.98, 3.71
0.82, 2.28
—
2.34
3.75
1.07,5.15
2.26, 6.21
0.87,2.16
1.72, 4.28
0.78
1.47
0.30, 2.04
0.60, 3.62
0.87, 2.16
1.72, 4.28
1.37
2.72
0.87,2.16
1.72,4 28
—t
—
1.37
2.72
0.87,2.16
1.72,4.28
0.53
3.25
0.24, 1.16
1.39,7.58
—
1.17, 3.19
1.92
1.37
2.72
—
—
—
—
—
1.22,3.14
—
—
—
1.96
0.75
1.37
2.72
95% Cl
—
—
—
—
—
—
2.04
—
—
0.57
0.38, 0.87
0.66, 0.86
0.75
0.66, 0.86
0.66, 0.86
0.75
—
—
1.04,3.81
—
• 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
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
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
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
502
Delcourt et al.
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
Am J Epidemiol Vol. 151, No. 5, 2000
Risk Factors for Cataract
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
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.
Am J Epidemiol
Vol. 151, No. 5, 2000
503
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
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: Coordination—Dr. 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); Ophthalmology—Drs. Louis
Balmelle, Jacques Costeau, Jean-Luc Diaz, Fabienne
Robert, and Bernard Arnaud; Biology—Laboratoire 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;111:1041—9.
3. Flaye DE, Sullivan KN, Cullinan TR, et al. Cataracts and cigarette smoking: The City Eye Study. Eye 1989;3:379-84.
504
Delcourt et al.
4. Italian-American Cataract Study Group. Risk factors for agerelated cortical, nuclear, and posterior subcapsular cataracts.
Am J Epidemiol 1991;133:541-53.
5. Miglior S, Marighi PE, Musicco M, et al. Risk factors for cortical, nuclear, posterior subcapsular and mixed cataract: a casecontrol study. Ophthalmic Epidemiol 1994;l:93-105.
6. Harding JJ, Egerton M, van Heyningen R, et al. Diabetes, glaucoma, sex, and cataract: analysis of combined data from two
case control studies. Br J Ophthalmol 1993;77:2-6.
7. Tavani A, Negri E, La Vecchia C. Selected diseases and risk of
cataract in women: a case-control study from northern Italy.
Ann Epidemiol 1995;5:234-8.
8. Chylack LT Jr, Wolfe JK, Singer DM, et al. The Lens Opacities
Classification System HI. The Longitudinal Study of Cataract
Study Group. Arch Ophthalmol 1993;lll:831-6.
9. Catignani GL, Bieri JG. Simultaneous determination of retinol
and alpha-tocopherol in serum or plasma by liquid chromatography. Clin Chem 1983;29:708-12.
10. Tessier F, Birlouez-Aragon I, Tjani C, et al. Validation of a
micromethod for determining oxidized and reduced vitamin C
in plasma by HPLC-fluorescence. Int J Vitam Nutr Res 1996;
66:166-70.
11. Leske MC, Chylack LT Jr, Wu SY. The Lens Opacities CaseControl Study. Risk factors for cataract. Arch Ophthalmol
1991;109:244-51.
12. Klein BE, Klein R, Linton KL. Prevalence of age-related lens
opacities in a population: The Beaver Dam Eye Study. Ophthalmology 1992;99:546-52.
13. Hirvela H, Luukinen H, Laatikainen L. Prevalence and risk
factors of lens opacities in the elderly in Finland: a populationbased study. Ophthalmology 1995;102:108-17.
14. Leske MC, Connell AM, Wu SY, et al. Prevalence of lens
opacities in the Barbados Eye Study. Arch Ophthalmol 1997;
115:105-11.
15. Delcourt C, Cristol JP, Leger CL, et al. Associations of antioxidant enzymes with cataract and age-related macular degeneration: The POLA Study. Ophthalmology 1999;106:215-22.
16. Hiller R, Sperduto RD, Ederer F. Epidemiologic associations
with nuclear, cortical, and posterior subcapsular cataracts. Am
J Epidemiol 1986;124:916-25.
17. Klein BE, Klein R, Ritter LL. Is there evidence of an estrogen
effect on age-related lens opacities? The Beaver Dam Eye
Study. Arch Ophthalmol 1994;112:85-91.
18. Cumming RG, Mitchell P. Hormone replacement therapy,
reproductive factors, and cataract: The Blue Mountains Eye
Study. Am J Epidemiol 1997; 145:242-9.
19. Benitez del Castillo JM, del Rio T, Garcia-Sanchez J. Effects
of estrogen use on lens transmittance in postmenopausal
women. Ophthalmology 1997;104:970-3.
20. Hiller R, Sperduto RD, Ederer F. Epidemiologic associations
with cataract in the 1971-1972 National Health and Nutrition
Examination Survey. Am J Epidemiol 1983,118:239^9.
21. Mohan M, Sperduto RD, Angra SK, et al. India-US casecontrol study of age-related cataracts. India-US Case-Control
Study Group. Arch Ophthalmol 1989;107:670-6.
22. Leske MC, Chylack LT Jr, He Q, et al. Risk factors for nuclear
opalescence in a longitudinal study. Am J Epidemiol 1998;
147:36^1.
23. West S, Munoz B, Emmett EA, et al. Cigarette smoking and
risk of nuclear cataracts. Arch Ophthalmol 1989;107:1166-9.
24. Hiller R, Sperduto RD, Podgor MJ, et al. Cigarette smoking
and the risk of development of lens opacities: the Framingham
studies. Arch Ophthalmol 1997,115:1113-18.
25. Cumming RG, Mitchell P. Alcohol, smoking, and cataracts:
The Blue Mountains Eye Study. Arch Ophthalmol 1997;115:
1296-303.
26. West S, Munoz B, Schein OD, et al. Cigarette smoking and
risk for progression of nuclear opacities. Arch Ophthalmol
1995;113:1377-80.
27. Klein BE, Klein R, Linton KL, et al. Cigarette smoking and
lens opacities: The Beaver Dam Eye Study. Am J Prev Med
1993;9:27-30.
28. Ross MA, Crosley LK, Brown KM, et al. Plasma concentrations of carotenoids and antioxidant vitamins in Scottish
males: influences of smoking. Eur J Clin Nutr 1995;49:861-5.
29. Pocock SJ, Delves HT, Ashby D, et al. Blood cadmium concentrations in the general population of British middle-aged
men. Hum Toxicol 1988;7:95-103.
30. Ramakrishnan S, Sulochana KN, Selvaraj T, et al. Smoking of
beedies and cataract: cadmium and vitamin C in the lens and
blood. Br J Ophthalmol 1995;79:202-6.
31. Cekic O. Effect of cigarette smoking on copper, lead, and cadmium accumulation in human lens. Br J Ophthalmol 1998;82:
186-8.
32. Klein BE, Klein R, Wang Q, et al. Older-onset diabetes and
lens opacities: The Beaver Dam Eye Study. Ophthalmic
Epidemiol 1995;2:49-55.
33. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14.
34. Garbe E, Suissa S, Lelorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA
1998;280:539-43.
35. Klein BE, Klein R, Lee KE. Cardiovascular disease, selected
cardiovascular disease risk factors, and age-related cataracts:
The Beaver Dam Eye Study. Am J Ophthalmol 1997; 123:
338-16.
36. Glynn RJ, Christen WG, Manson JE, et al. Body mass index:
an independent predictor of cataract Arch Ophthalmol 1995;
113:1131-7.
37. Klein BE, Klein R, Jensen SC, et al. Hypertension and lens
opacities from the Beaver Dam Eye Study. Am J Ophthalmol
1995; 119:640-6.
38. Mares Perlman JA, Brady WE, Klein BE, et al. Diet and
nuclear lens opacities. Am J Epidemiol 1995;141:322-34.
39. Mitchell P, Cumming RG, Smith W, et al. Diet and cataract:
The Blue Mountains Eye Study. (Abstract). (Presented at the
ARVO annual meeting, Fort Lauderdale, Florida, May 1999).
Invest Ophthalmol Vis Sci 1999;4O(suppl):S194.
40. Tavani A, Negri E, La Vecchia C. Food and nutrient intake and
risk of cataract. Ann Epidemiol 1996;6:41-6.
41. Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake
and cataract extraction in women: a prospective study. BMJ
1992;305:335-9.
42. Vitale S, West S, Hallfrisch J, et al. Plasma antioxidants and
risk of cortical and nuclear cataract. Epidemiology 1993;4:
195-203.
43. Knekt P, Heliovaara M, Rissanen A, et al. Serum antioxidant
vitamins and risk of cataract. BMJ 1992;305:1392-4.
44. Leske MC, Wu SY, Hyman L, et al. Biochemical factors in the
lens opacities: case-control study. The Lens Opacities CaseControl Study Group. Arch Ophthalmol 1995; 113:1113-19.
Am J Epidemiol Vol. 151, No. 5, 2000