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ORIGINAL CONTRIBUTION

Smoking Cessation and Risk


of Age-Related Cataract in Men
William G. Christen, ScD

Context Although cigarette smoking has been shown to be a risk factor for age-related
cataract, data are inconclusive on the risk of cataract in individuals who quit smoking.

Robert J. Glynn, ScD


Umed A. Ajani, MBBS
Debra A. Schaumberg, ScD
Julie E. Buring, ScD
Charles H. Hennekens, MD

Objective To examine the association between smoking cessation and incidence of


age-related cataract.
Design Prospective cohort study conducted from 1982 through 1997, with an average follow-up of 13.6 years.
Setting and Participants A total of 20 907 US male physicians participating in the
Physicians Health Study I who did not have a diagnosis of age-related cataract at baseline and had reported their level of smoking at baseline.

JoAnn E. Manson, MD

IGARETTE SMOKING HAS BEEN

shown to be an important
independent risk factor for
development of age-related
cataract.1-11 However, risk of cataract in
individuals who quit smoking is uncertain. Some studies have found that risk
of cataract remains elevated for many
yearsfollowingsmokingcessation.4,9 Othershavereportedthat the risk approaches
the level of never smokers several years
after quitting smoking, suggesting that
damage to the lens may be reversible.5,6,10
In a report from the Physicians Health
Study I, based on the first 5 years of follow-up, we showed that current smokers of 20 or more cigarettes per day, compared with never smokers, had a 2-fold
increased risk of cataract, while past
smokers had a 15% increased risk of cataract that was not statistically significant.8 In this article, we extend these findings by including cataracts diagnosed
during more than 13 years of follow-up
and by examining the relationship of time
since quitting smoking with risk of cataract following smoking cessation.
METHODS
The Physicians Health Study I was a randomized, double-blind, placebocontrolled trial of low-dosage aspirin
and b-carotene in the prevention of cardiovascular disease and cancer among

Main Outcome Measures Incident age-related cataract defined as self-report confirmed by medical record review, diagnosed after study randomization and responsible for vision loss to 20/30 or worse, and surgical extraction of incident age-related
cataract, in relation to smoking status and years since quitting smoking.
Results At baseline, 11% were current smokers, 39% were past smokers, and 50%
were never smokers. Average reported cumulative dose of smoking at baseline was
approximately 2-fold greater in current than in past smokers (35.8 vs 20.5 pack-years).
Two thousand seventy-four incident cases of age-related cataract and 1193 cataract
extractions were confirmed during follow-up. Compared with current smokers, multivariate relative risks (RRs) of cataract in past smokers who quit smoking fewer than
10 years, 10 to fewer than 20 years, and 20 or more years before the study were 0.79
(95% confidence interval [CI], 0.64-0.98), 0.73 (95% CI, 0.61-0.88), and 0.74 (95%
CI, 0.63-0.87), respectively, after adjustment for other risk factors for cataract and
age at smoking inception. The RR for never smokers was 0.64 (95% CI, 0.54-0.76).
The reduced risk in past smokers was principally due to a lower total cumulative dose
(RR of cataract for increase of 10 pack-years of smoking, 1.07; 95% CI, 1.04-1.10). A
benefit of stopping smoking independent of cumulative dose was suggested in some
analyses. Results for cataract extraction were similar.
Conclusion These prospective data indicate that while some smoking-related damage to the lens may be reversible, smoking cessation reduces the risk of cataract primarily by limiting total dose-related damage to the lens.
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JAMA. 2000;284:713-716

22071 US male physicians aged 40 to 84


years in 1982. At baseline, participants
completed mailed questionnaires that
included information on history of and
risk factors for cataract and whether
they had ever smoked cigarettes regularly (grouped as never, past, or current).

Current smokers were asked how many


cigarettes per day, on average, they
smoked. On the 60-month follow-up
questionnaire, subjects were asked to
give a detailed smoking history, including their age at starting and quitting
smoking. The 60-month questionnaire

Author Affiliations: Division of Preventive Medicine (Drs Christen, Glynn, Ajani, Schaumberg, Buring, and Manson) and Channing Laboratory (Dr
Manson), Department of Medicine, and Department of Ambulatory Care and Prevention (Dr Buring), Harvard Medical School and Brigham and
Womens Hospital, and Departments of Biostatistics

(Dr Glynn) and Epidemiology (Drs Buring and Manson), Harvard School of Public Health, Boston,
Mass; and Departments of Medicine, Epidemiology,
and Public Health, University of Miami School of
Medicine, Miami, Fla (Dr Hennekens).
Corresponding Author: William G. Christen, ScD, 900
Commonwealth Ave E, Boston, MA 02215-1204.

2000 American Medical Association. All rights reserved.

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713

SMOKING CESSATION AND RISK OF CATARACT

Table 1. Age-Adjusted Prevalence of Baseline Characteristics That Are Possible Risk Factors
for Cataract by Smoking Status at Baseline, Physicians Health Study I*
Never Smokers
(n = 10 444)

Past Smokers
(n = 8190)

Current Smokers
(n = 2273)

48.0
32.1

36.4
37.0

41.7
37.4

60-69

15.5

20.5

17.2

70-84

4.4

6.1

3.7

Diabetes, %
Hypertension, %

2.1
12.7

2.2
14.1

2.7
13.9

BMI, mean, kg/m2

24.8

25.1

25.1

Alcohol use, %
Daily
Weekly

17.6
49.3

29.5
51.8

34.5
43.8

Monthly

Age range, %, y
40-49
50-59

12.6

9.5

11.1

Physical activity, %
Parental history of MI, %

73.4
13.3

73.2
13.1

64.2
14.3

Multivitamin use, %

18.5

20.3

21.3

Smoking history
Pack-years, mean (SD)

...

Age at starting smoking,


mean (5th-95th percentile), y
Age at quitting smoking,
mean (5th-95th percentile), y

20.5 (17.4)

35.8 (21.0)

...

19 (14-26)

19 (14-29)

...

38 (23-56)

...

*BMI indicates body mass index; MI, myocardial infarction; and ellipses, data not applicable.
Reported systolic blood pressure of 160 mm Hg or higher, diastolic blood pressure of 95 mm Hg or higher, or history
of treatment for hypertension.
Reported vigorous exercise once per week or more.
Reported MI in either parent before age 60 years.

also requested information on amount


of cigarettes smoked for both current and
past smokers. Subjects were asked,
When you smoke (or smoked), on average how many cigarettes per day do
(did) you smoke (,1 pack per day, 1
pack per day, 1-2 packs per day, or $2
packs per day)? Information on new occurrence of cataract and cataract extraction was ascertained on yearly follow-up questionnaires.
This investigation includes the 20907
participants who had no diagnosis of
cataract and provided information
about cigarette smoking at baseline.
Following a report of a cataract
diagnosis or extraction and receipt of
written consent to obtain medical
records pertaining to cataract, treating
ophthalmologists or optometrists
were contacted by mail to obtain
information about presence of lens
opacities, date of diagnosis, visual
acuity loss, cataract extraction, other
ocular abnormalities that could
explain visual acuity loss, cataract
type, and etiology.
714

End points were incident cataract and


extraction of incident cataract. Cataract
was defined as a self-report confirmed by
medical record review initially diagnosed after randomization, age-related in
origin, with best-corrected visual acuity of 20/30 or worse attributable to cataract. This article includes all available
data through December 1997.
Cox proportional hazards models were
used to assess the effect of smoking cessation on risk of cataract while simultaneously controlling for other cataract risk
factors. Models were fit using current
smokers as the reference category, as recommended in the 1990 surgeon generals report on smoking cessation.12 In initial analyses, subjects were classified as
never, past, or current smokers, based on
data reported at baseline. We then examined the risk of cataract in past smokers
who quit less than 10 years, 10 to less
than 20 years, or 20 or more years before
study entry in models that controlled for
other cataract risk factors and for age at
starting smoking or number of cigarettes consumed per day. Finally, we

JAMA, August 9, 2000Vol 284, No. 6 (Reprinted)

examined the independent contributions of total cumulative dose and smoking status (past vs current) to risk of cataract in ever smokers. The significance of
variables was tested using the likelihood ratio test. To calculate total cumulative dose, subjects were classified by
pack-years of smoking. We used baseline data on amount smoked for current
smokers and 60-month follow-up questionnaire data on amount smoked for past
smokers (since information on amount
smoked was collected only for current
smokers at baseline) to calculate packyears of smoking at baseline. We defined
pack-years as the number of years of
smoking times the number of packs of
cigarettes smoked per day.
Cigarette smoking is associated with
an increased risk of age-related macular degeneration (AMD) in this population,13 and subjects with cataract may
have been identified because of presence
of AMD. Therefore, we also conducted
analyses in which we included diagnosis of AMD as a time-varying covariate.
Relative risk (RR) estimates derived from
these models, however, were not materially different from estimates derived
from models that were unadjusted for
diagnosis of AMD (data not shown).
RESULTS
At baseline, 11% of the study participants were current smokers, 39% were
past smokers, and 50% were never smokers. Compared with current smokers,
past smokers were older and, after adjusting for age, tended to report less alcohol use, diabetes, parental history of
myocardial infarction, and multivitamin use, but more physical activity
(TABLE 1). Mean age at starting smoking was similar in past and current smokers, but total pack-years of smoking at
baseline were almost 2-fold greater in
current smokers than in past smokers
(35.8 vs 20.5 pack-years) (Table 1).
During an average of 13.6 years of
follow-up, there were 2074 agerelated cataract diagnoses and 1193
cataract extractions confirmed by medical record review. Risk of cataract in
past smokers was intermediate between current and never smokers.

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SMOKING CESSATION AND RISK OF CATARACT

Compared with men who continued


to smoke, past smokers had a statistically significant 23% reduced risk of
cataract diagnosis (RR, 0.77; 95% confidence interval [CI], 0.66-0.88) and
28% reduced risk of cataract extraction (RR, 0.72; 95% CI, 0.60-0.86), after adjustment for other risk factors for
cataract. The RR in never smokers compared with men who continued to
smoke was 0.64 (95% CI, 0.54-0.76) for
cataract diagnosis and 0.65 (95% CI,
0.53-0.79) for cataract extraction.
Compared with men who continued
to smoke, men who had quit less than
10 years before study entry had an approximately 20% reduced risk of cataract diagnosis after adjustment for other
cataract risk factors and average number of cigarettes smoked per day or age
at starting smoking (TABLE 2). There
was little additional reduction in risk in
men who had quit 10 or more years before study entry. For cataract extraction, there was an approximately 25%
reduced risk in men who had quit less
than 10 years before study entry vs those
who continued to smoke. Similarly, there
appeared to be little additional reduction in risk in men who quit smoking 10
or more years before study entry. For
both end points, risk of cataract in longterm quitters appeared to remain slightly
(but not significantly) elevated compared with risk in never smokers.

When we examined the independent contributions of total cumulative


dose and smoking status to risk of cataract among ever smokers, the bestfitting multivariate model included only
a term for total cumulative dose (RR,
1.07; 95% CI, 1.04-1.10). Thus, there
was a 7% increased risk of cataract associated with a 10-pack-year increase
in smoking exposure. Addition of a
2-level categorical term for smoking status (past vs current, RR, 0.85; 95% CI,
0.73-1.00) was suggestive of an independent benefit associated with being
a past smoker, but did not significantly improve the fit of the model
based on the likelihood ratio test
(P = .08). For cataract extraction, the
best-fitting model did include a term for
smoking status (past vs current, RR,
0.80; 95% CI, 0.65-0.97) in addition to
a continuous term for total pack-years
of smoking (for a 10-pack-year increase, RR, 1.05; 95% CI, 1.01-1.09),
suggesting a benefit for past smokers
that was independent of total cumulative dose. There were no significant interactions between smoking status and
cumulative dose for either end point.
COMMENT
In this cohort of US male physicians,
the risk of cataract in past smokers appeared to be intermediate between the
risks in continuing smokers and never

smokers. Compared with those who


continued to smoke, a lower risk of
cataract in past smokers was apparent
in men who had quit smoking less than
10 years before study entry, with little
additional reduction in risk associated
with longer time since quitting smoking. The lower risk in past smokers was
due primarily to their lower total cumulative dose of smoking, although
there was evidence of a benefit of quitting smoking that was independent of
cumulative dose, suggesting that some
smoking-related damage in the lens may
be reversible on smoking cessation.
Several previous studies have examined the risk of cataract in former smokers. A population-based, crosssectional survey of 838 Maryland
watermen indicated that the risk of pure
nuclear opacities decreased during the
first 10 years following smoking cessation and continued to decrease with
longer time since quitting.5 A more recent analysis of prospective data from
that cohort showed that past smokers
and never smokers had similar progression rates of nuclear sclerosis during 5
years of follow-up.10 In the Lens Opacities Case-Control Study, there was an
increased risk of nuclear sclerosis
among current smokers (RR, 1.7; 95%
CI, 1.0-2.8), but none was reported for
past smokers.6 The results of 2 other
studies suggest that the risk of cata-

Table 2. Relative Risks of Cataract Diagnosis and Extraction by Years Since Quitting Smoking*
Past Smokers, Years Since Quitting Smoking
Current Smokers
(n = 2272)
No. of cases
Age- and treatment-adjusted RR (95% CI)
Multivariate RR (95% CI)
Multivariate RR (95% CI)

250
1.00
1.00
1.00

Never Smokers
(n = 10 450)
Cataract Diagnosis
868
0.66 (0.57-0.76)
0.67 (0.58-0.77)
0.64 (0.54-0.76)

No. of cases
Age- and treatment-adjusted RR (95% CI)
Multivariate RR (95% CI)
Multivariate RR (95% CI)

155
1.00
1.00
1.00

Cataract Extraction
507
0.64 (0.54-0.77)
0.66 (0.54-0.79)
0.65 (0.53-0.79)

,10
(n = 1640)

10 to ,20
(n = 2795)

$20
(n = 2541)

149
0.83 (0.68-1.02)
0.81 (0.66-1.00)
0.79 (0.64-0.98)

261
0.77 (0.65-0.92)
0.75 (0.63-0.90)
0.73 (0.61-0.88)

450
0.79 (0.67-0.92)
0.79 (0.67-0.92)
0.74 (0.63-0.87)

85
0.78 (0.60-1.02)
0.76 (0.58-0.99)
0.75 (0.57-0.98)

152
0.74 (0.59-0.93)
0.72 (0.57-0.91)
0.70 (0.56-0.88)

243
0.73 (0.59-0.89)
0.73 (0.59-0.90)
0.69 (0.56-0.85)

*RR indicates relative risk; CI, confidence interval.


Ninety-six cases of cataract diagnosis and 51 cases of cataract extraction were excluded because of missing information on age at starting smoking, age at quitting smoking, or
number of cigarettes smoked.
Cox regression models adjusted for age, aspirin and b-carotene treatment assignment, diabetes, hypertension, body mass index, alcohol use, physical activity, parental history of
myocardial infarction, current multivitamin use, and number of cigarettes smoked (,20/d, 20/d, .20/d to 40/d, or .40/d).
Cox regression models adjusted for covariates in the above footnote, with age at starting smoking in place of number of cigarettes smoked.

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715

SMOKING CESSATION AND RISK OF CATARACT

ract, especially among heavy smokers,


decreases little, if at all, following smoking cessation. In the City Eye Study, a
cross-sectional analysis of baseline data
showed that past heavy smokers ($25
cigarettes per day) had a risk of nuclear
sclerosis (RR, 2.6; 95% CI, 1.4-5.0)
comparable in magnitude with the risk
in current heavy smokers (RR, 2.9; 95%
CI, 1.4-5.9).4 There was no increased
risk of nuclear sclerosis in past moderate (15-24 cigarettes per day) or past
light (1-14 cigarettes per day) smokers in that study. In the Nurses Health
Study, the overall RR for past smokers
vs never smokers was 1.0 (95% CI,
0.8-1.2). However, the risk of cataract
in past smokers who had smoked at
least 35 cigarettes per day (RR, 1.8; 95%
CI, 1.1-2.9) was similar to the risk in
current heavy smokers (RR, 1.6; 95%
CI, 1.0-2.7), and these risks remained
comparable after 10 or more years following smoking cessation.9
Our findings in the Physicians Health
Study I are in broad agreement with previous studies that indicate a reduced risk
of cataract in past smokers compared
with current smokers, due primarily to
lower total cumulative dose in past
smokers. We found no evidence to indicate that even the most heavily exposed men in our population did not
benefit from smoking cessation. How-

ever, our data show that compared with


men who have never smoked, past
smokers appear to have a slightly elevated risk of cataract that may persist
for years following smoking cessation.
Several possible limitations of the
study should be considered. The prospective study design reduces the possibility of bias in reports of cigarette
smoking or other potential risk factors
according to disease outcome. Random
misclassification of cigarette exposure is
a possibility, but would tend to underestimate any true association between
cigarette smoking and cataract. Random misclassification of cataract would
also underestimate any true effect of
smoking, but was minimized by the use
of medical records to confirm the selfreports. Nonrandom misclassification of
cataract is unlikely since medical records were reviewed without knowledge of participants exposure status.
Morbidity follow-up was more than 99%
complete (through December 1997) and
medical records were obtained for 92%
to 94% of current, past, and never smokers who reported cataract. Thus, bias due
to incomplete follow-up is not likely to
distort these results.
Mechanisms linking cigarette smoking and cataract have been described,
including a direct effect on the lens,14,15
as well as indirect effects on antioxi-

dant levels16-20 and levels of endogenous proteolytic enzymes, thought to


be important for removal of damaged
protein from the lens.21 Stopping smoking may alleviate further direct damage to lens proteins and, perhaps, allow reversal of some of the early
deleterious effects of smoking.
Cataract is a leading cause of visual
impairment in the United States and
represents a major drain on health care
resources.22 Approximately 1.35 million cataract operations are performed
yearly in the United States at an estimated cost of $3.5 billion.22 Given these
considerations, recognition that smoking is an important, avoidable cause of
age-related cataract can be expected to
have major public health implications. The data presented extend previous findings by demonstrating that
smoking cessation reduces the risk of
cataract primarily by limiting total
smoking-related damage to the lens.
The data also indicate that some damage in the lens may not be reversed with
smoking cessation, underscoring the
importance of early cessation of smoking and, preferably, the avoidance of
smoking altogether.

9. Hankinson SE, Willett WC, Colditz GA, et al. A prospective study of cigarette smoking and risk of cataract surgery in women. JAMA. 1992;268:994998.
10. West S, Munoz B, Schein OD, et al. Cigarette
smoking and risk for progression of nuclear opacities.
Arch Ophthalmol. 1995;113:1377-1380.
11. Hiller R, Sperduto RD, Podgor MJ, et al. Cigarette smoking and risk of development of lens opacities. Arch Ophthalmol. 1997;115:1113-1118.
12. Department of Health and Human Services. The
Health Benefits of Smoking Cessation: A Report of
the Surgeon General, 1990. Rockville, Md: Dept of
Health and Human Services; 1990. DHHS publication (CDC)90-8416.
13. Christen WG, Glynn RJ, Manson JE, Ajani UA, Buring JE. A prospective study of cigarette smoking and
risk of age-related macular degeneration in men.
JAMA. 1996;276:1147-1151.
14. Ramakrishnan S, Sulochana KN, Selvaraj T, et al.
Smoking of beedies and cataract. Br J Ophthalmol.
1995;79:202-206.
15. Paik DC, Dillon J. The nitrite/alpha crystallin reaction. Exp Eye Res. 2000;70:73-80.

16. Mohan M, Sperduto RD, Angra SK, et al. India-US case-control study of age-related cataracts. Arch
Ophthalmol. 1989;107:670-676.
17. Bunce GE, Kinoshita J, Horwitz J. Nutritional factors in cataract. Ann Rev Nutr. 1990;10:233-254.
18. Jacques PF, Chylack LT, McGandy RB, Hartz SC.
Antioxidant status in persons with and without senile
cataract. Arch Ophthalmol. 1988;106:337-340.
19. Chow CK, Thacker RR, Changchit C, et al.
Lower levels of vitamin C and carotenes in plasma
of cigarette smokers. J Am Coll Nutr. 1986;5:305312.
20. Stryker WS, Kaplan LA, Stein EA, et al. The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol. 1988;127:283-296.
21. Taylor A, Davies KJA. Protein oxidation and loss
of protease activity may lead to cataract formation in
the aged lens. Free Radic Biol Med. 1987;3:371377.
22. National Advisory Eye Council. Vision Research:
A National Plan, 1999-2003. Rockville, Md: Dept of
Health and Human Services; 1998. NIH publication
98-4120.

Funding/Support: This study was supported by research grants HL 26490, HL 34595, CA 34944, CA
40360, and EY 06633 from the National Institutes of
Health.

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