1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
2 Department of Ophthalmology, Sundsvall Hospital, Sundsvall, Sweden
3 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
4 Stockholm Eye Clinic, H. M. Queen Sophia Hospital, Stockholm, Sweden
Correspondence to Dr. Birgitta Ejdervik Lindblad, Department of Ophthalmology, Sundsvall Hospital, SE-851 86 Sundsvall, Sweden (e-mail: birgitta.ejdervik.lindblad{at}swipnet.se).
Received for publication October 29, 2004. Accepted for publication March 9, 2005.
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
cataract; cohort studies; smoking; smoking cessation
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Epidemiologic studies have shown that the etiology of cataract is multifactorial and that incidence increases with advancing age (213
). Oxidative damage to lens proteins is suggested to be of importance (14
).
Cigarette smoking, which potentially increases oxidative stress in the lens, has been associated with an increased risk of cataract in the majority of cross-sectional (5, 10
, 11
), case-control (8
, 12
, 15
), and cohort studies (2
, 7
, 9
, 13
, 16
22
), although the findings are not entirely consistent (23
, 24
). The effect of smoking cessation on cataract development is not clear. Some studies (25
27
), but not all (21
), have shown that former smokers have a decreased risk of cataract in comparison with current smokers. However, to our knowledge, none of the previous studies evaluated the effect of smoking cessation and time since quitting smoking on the risk of cataract in comparison with never smokers.
To address further whether any benefit is obtained from quitting smoking, we examined prospectively the associations of smoking and time since quitting smoking with incidence of cataract extraction in a population-based cohort of 34,595 women aged 4983 years.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In September 1997, a follow-up questionnaire was mailed to 56,030 women who remained in the cohort after exclusion of those who had died or permanently moved out of the study area. The questionnaire included 350 items concerning cigarette smoking, diet, alcohol consumption, vitamin supplement use, physical activity, weight, height, reproductive factors, use of some medications, educational level, and diagnosis of hypertension and diabetes. Reminder letters were mailed to nonrespondents in November 1997 and February 1998. A total of 39,227 women (70 percent) returned the questionnaire (219 women were too sick to fill in the questionnaire, 548 refused to answer, and 16,036 did not respond at all). We excluded women whose questionnaires contained incorrect or missing personal identification numbers (n = 243); this yielded an identifiable cohort of 38,984 women. For this analysis, we excluded all women with a diagnosis of cancer (other than nonmelanoma skin cancer) (n = 1,738) and those who had undergone cataract extraction (n = 88) before the start of follow-up (September 15, 1997). Furthermore, we excluded women who moved into or out of the study area between 1987 and September 15, 1997 (n = 1,788), because information about cataract extraction during the period of living outside the study area was not available. Women with missing data on smoking status (n = 775) were also excluded from the analysis. The final study cohort included 34,595 women at the start of follow-up for cataract extractions in September 1997.
Assessment of smoking status
The women in the cohort were classified as never, past, or current smokers on the basis of self-report in the 1997 questionnaire. The number of cigarettes smoked per day was reported on the questionnaire for several periods in life: ages 1520 years, each decade thereafter, and the present.
Other exposures
The self-administered questionnaire collected information on possible risk factors for cataract, including diagnoses of diabetes and hypertension, use of steroid medication, alcohol consumption (frequencies and amounts of different beverages were converted into grams of alcohol and divided into quartiles), use of vitamin supplements, height and weight (body mass index was defined as weight in kilograms divided by the square of height in meters), and educational level.
Identification of cases and follow-up of the cohort
Between September 1997 and June 2002, 2,128 incident cases of extraction of age-related cataracts occurred among women in the cohort. These cases were identified through computerized registers of diagnoses of cataract extraction in the two counties. The registers were linked to the study population using personal identification numbers. We matched the cohort against the International Classification of Diseases, Tenth Revision, code for age-related cataract extraction (H25). Cataracts considered to be congenital or secondary to ocular trauma or intraocular inflammation and previous intraocular surgery were not included in the matching. According to the Swedish National Cataract Register, which covers more than 93 percent of all cataract extractions in Sweden (28), preoperative visual acuity in the operated-upon eye was less than 0.6 during the study period. Visual acuity less than 0.6 implies difficulty in driving. Mean visual acuity in the operated-upon eye was 0.3, which means difficulty in reading the newspaper, and more than one third of the patients were socially blind (visual acuity <0.1; difficulty in walking and eating) because of cataract.
The dates of deaths occurring in the cohort were ascertained through the Swedish Death Register, and information about dates of moving out of the study area was obtained by matching of the cohort with the Swedish Population Register. These registers are nearly 100 percent complete.
The study was approved by the ethical committee at the Karolinska Institutet (Stockholm, Sweden), and informed consent was obtained from the participants.
Statistical analysis
Follow-up ceased on the date of cataract extraction, death, migration out of the study area, or the end of follow-up (June 30, 2002), whichever came first. We examined risk of cataract extraction according to the mean number of cigarettes smoked per day during the period of smoking and according to age at starting smoking. The mean number of cigarettes smoked per day during the smoking period was calculated for both current and past smokers.
We used the Cox proportional hazards model to estimate relative risks as rate ratios, with 95 percent confidence intervals (29), using the PHREG procedure in SAS (version 8.2; SAS Institute, Inc., Cary, North Carolina). Relative risks were estimated for the average number of cigarettes smoked per day and the duration (years) of smoking. Risk estimates were also calculated for past smokers who had quit smoking less than 10 years, 1020 years, or more than 20 years before the start of follow-up in 1997. All relative risks were adjusted for potential risk factors, including age, diabetes, hypertension, use of steroid medication, alcohol consumption, use of vitamin supplements, body mass index, and educational level. We tested for trends by using the median value of each category to create a single continuous variable. All p values shown are two-sided.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
There was a positive association between intensity of cigarette smoking, measured as the average number of cigarettes smoked per day during one's smoking lifetime, and risk of cataract extraction. Table 2 presents risk estimates for smoking intensity among past and current smokers. Smoking more than 20 cigarettes/day was rare; only 283 women in the cohort had ever smoked more than 20 cigarettes/day, on average.
|
When we examined the association between age at starting smoking and risk of cataract extraction, we found no significant relation after adjusting for smoking intensity (data not shown).
To examine the association between time since quitting smoking and risk of cataract extraction, we stratified the data by smoking intensity, as measured by the mean number of cigarettes smoked per day during one's smoking lifetime (15
, 6
10
, 11
15
, or >15 cigarettes/day). There were too few women with cataract extraction who had smoked more than 15 cigarettes/day (n = 40) to analyze them separately; therefore, we present the results in three categories (table 3). Among women who had smoked 610 cigarettes/day, the relative risk of cataract extraction decreased with time since quitting smoking; compared with never smokers, past smokers who had quit smoking more than 10 years before baseline no longer had a significantly increased risk. Among women who had smoked more intensively (>10 cigarettes/day), after 20 years of nonsmoking the risk became small and no longer statistically significant; the trend analysis of risk estimates over time since quitting smoking was highly significant (p < 0.0001). In a small subgroup of women who had smoked even more intensively (>15 cigarettes/day), the multivariate risk estimate was 1.23 (95 percent CI: 0.66, 2.30) more than 20 years after quitting smoking (10 cases).
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The association of smoking with cataract has been considered in numerous previous epidemiologic studies (2, 5
, 7
13
, 15
24
). Although relative risk estimates vary across studies, most studies have reported a positive association between smoking and cataract (2
, 5
, 7
13
, 15
24
). Intensity of smoking, measured by the number of cigarettes smoked per day, and its association with cataract has been investigated in the Nurses' Health Study (16
) and the City Eye Study (21
). Both studies found a positive association with increasing intensity of smoking.
The effect of smoking cessation on the risk of cataract has been considered in a few studies (21, 25
27
). Risk estimates differ between studies, depending on whether the reference group is current smokers or never smokers. In a cross-sectional study of 838 Maryland watermen, West et al. (27
) found a 33 percent decreased risk of nuclear opacity in past smokers as compared with current smokers 10 years after quitting smoking. In the City Eye Study, no reduction in risk was noted among past heavy smokers (>25 cigarettes/day) compared with never smokers; however, time since quitting smoking was not taken into account. There was no increased risk for past light smoking (<15 cigarettes/day) (21
). In a prospective study of 19,698 men, Christen et al. (26
) found a 25 percent decreased risk of cataract surgery within 10 years after quitting smoking in comparison with current smokers, with no additional reduction being observed more than 20 years after quitting smoking. In a recent analysis of women in the Nurses' Health Study and men in the Health Professionals Follow-up Study, past smokers who had quit smoking 25 or more years previously had a 20 percent decreased risk of cataract extraction in comparison with current smokers after adjustment for intensity of smoking, but the risk did not decrease to the level of never smokers (25
).
The main strengths of our study are the population-based design and the high response rate. The prospective design excluded the risk of recall bias in the self-reports of cigarette smoking and other potential risk factors, because information on presumed risk factors was recorded before cataract extraction. Furthermore, follow-up of the cohort through computerized registers of cataract extraction that contained data collected from eye clinics in the study area, without knowledge of exposure status, reduced the likelihood of nonrandom misclassification. The large number of women with cataract extractions allowed us to examine associations within subgroups with reasonable statistical power.
However, our study also had some potential limitations. No international standard exists for the definition of cataract. In our study, we focused on cataract severe enough to cause visual impairment and require lens extraction, thus being of the greatest clinical and public health importance. Use of cataract surgery as the endpoint decreased the risk of misclassification of disease diagnosis. There might be random misclassification if female smokers with cataract were less likely to undergo cataract extraction, which would lead to underestimation of the true association between cigarette smoking and cataract extraction. Standardized eye examination of all women in this large population-based cohort was not possible. Information on cataract type was not assessed in a standardized manner at different eye clinics, and documentation of subtypes in the medical records was too incomplete for us to obtain sufficient data for analysis.
The estimates of lifetime cigarette smoking were based on retrospective recall. Because data on smoking status were collected only at baseline, random misclassification of current and past smoking could occur because of women underestimating their smoking habits. This would lead to underestimation of the true association between cigarette smoking and cataract extraction. Improper inclusion of failed quitters as past smokers would lead to a reduced estimate of the benefit of smoking cessation. The suggestion of higher risk estimates among past smokers than among current smokers in our study may be due to a different smoking pattern among past smokers, as indicated by a greater proportion of women with a higher smoking intensity, or residual confounding, which we were not able to adjust for.
Smoking increases oxidative stress in the lens by generating free radicals and reduces plasma concentrations of several antioxidants and proteolysis enzymes important for the removal of damaged proteins from the lens (14). Cadmium is also found to be accumulated in the cataractous lenses of smokers. Cadmium may hasten cataractogenesis by affecting lens enzymes such as superoxide dismutase and glutathione peroxides, thereby weakening defense against oxidative damage (30
, 31
).
Our findings confirm those of previous studies showing that cigarette smoking increases the risk of cataract requiring surgical extraction in women. The effect of smoking cessation on the decreased risk of cataract extraction was observed earlier among women smoking less intensively than among women smoking more heavily. It seems that in the latter group, a much longer period of time is needed. However, even in the latter group, smoking cessation lowered the risk over time, indicating that the lens has an ability to repair protein damage with time.
The increasing proportion of smokers among young women in some populations may lead to a potentially growing number of women at risk of developing cataract in the future. Increased risk of cataract is yet one more reason to encourage women to never start smoking or to quit smoking early, since so many serious diseases are related to smoking.
![]() |
ACKNOWLEDGMENTS |
---|
Confllict of interest: none declared.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|