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ORIGINAL CONTRIBUTION

Smoking Cessation and Riskof Age-Related Cataract in MenWilliam G. Christen, ScD

Robert J. Glynn, ScD

Umed A. Ajani, MBBS

Debra A. Schaumberg, ScD

Julie E. Buring, ScD

Charles H. Hennekens, MD

JoAnn E. Manson, MD

CIGARETTE SMOKING HAS BEEN

shown to be an importantindependent risk factor fordevelopment of age-related

cataract.1-11 However, risk of cataract inindividuals who quit smoking is uncer-tain. Some studies have found that riskof cataract remains elevated for manyyearsfollowingsmokingcessation.4,9Oth-ershavereportedthattheriskapproachesthe level of never smokers several yearsafter quitting smoking, suggesting that

damagetothelensmaybereversible.5,6,10

Ina reportfrom thePhysiciansHealthStudy I, based on the first 5 years of fol-low-up, we showed that current smok-ersof20or more cigarettesperday, com-pared with never smokers, had a 2-foldincreased risk of cataract, while pastsmokershad a 15% increased risk ofcata-ract that was not statistically signifi-cant.8 Inthis article, weextend thesefind-ings by including cataracts diagnosedduring more than 13 years of follow-upandbyexaminingtherelationshipoftime

since quitting smokingwith riskof cata-ract following smoking cessation.

METHODS

ThePhysicians HealthStudy I was a ran-domized, double-blind, placebo-controlled trial of low-dosage aspirinand-carotenein theprevention of car-diovascular disease and cancer among

22071 US male physicians aged 40 to 84years in 1982. At baseline, participantscompleted mailed questionnaires thatincluded information on history of and

risk factors for cataract and whetherthey had ever smoked cigarettes regu-larly (groupedas never,past, or current).

Current smokerswere askedhow manycigarettes per day, on average, theysmoked. On the 60-month follow-upquestionnaire, subjects were asked to

give a detailed smoking history, includ-ing their age at starting and quittingsmoking. The 60-month questionnaire

Author Affiliations: Division of Preventive Medi-cine (Drs Christen, Glynn, Ajani, Schaumberg, Bur-ing, and Manson) and Channing Laboratory (DrManson), Department of Medicine, and Depart-ment of Ambulatory Care and Prevention (Dr Bur-ing), Harvard Medical School and Brigham andWomens Hospital, and Departments of Biostatistics

(Dr Glynn) and Epidemiology (Drs Buring and Man-son), Harvard School of Public Health, Boston,Mass; and Departments of Medicine, Epidemiology,and Public Health, University of Miami School ofMedicine, Miami, Fla (Dr Hennekens).CorrespondingAuthor: WilliamG. Christen, ScD, 900Commonwealth Ave E, Boston, MA 02215-1204.

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

Objective To examine the association between smoking cessation and incidence ofage-related cataract.

Design Prospective cohort study conducted from 1982 through 1997, with an av-erage follow-up of 13.6 years.

Setting and Participants A total of 20907 US male physicians participating in thePhysicians Health Study I whodid not have a diagnosis of age-related cataract at base-line and had reported their level of smoking at baseline.

Main Outcome Measures Incident age-related cataract defined as self-report con-firmed by medical record review, diagnosed after study randomization and respon-sible for vision loss to 20/30 or worse, and surgical extraction of incident age-relatedcataract, 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 wasapproximately 2-foldgreater 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 cataractextractions were confirmed during follow-up. Compared with current smokers, mul-tivariate relative risks (RRs) of cataract in past smokers who quit smoking fewer than10 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 andage 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). Abenefit of stopping smoking independent of cumulative dose was suggested in someanalyses. Results for cataract extraction were similar.

Conclusion These prospective data indicate that while some smoking-related dam-age to the lens may be reversible, smoking cessation reduces the risk of cataract pri-marily by limiting total dose-related damage to the lens.

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also requested information on amountofcigarettessmokedforbothcurrent andpast smokers. Subjects were asked,When you smoke (or smoked), on av-erage how many cigarettes per day do

(did) you smoke (1 pack per day, 1pack per day, 1-2 packs per day, or2packsperday)? Informationonnewoc-currence of cataract and cataract extrac-tion was ascertained on yearly fol-low-up questionnaires.

This investigation includes the20907participants who had no diagnosis ofcataract and provided informationabout cigarette smoking at baseline.

Following a report of a cataractdiagnosis or extraction and receipt ofwritten consent to obtain medical

records pertaining to cataract, treatingophthalmologists or optometristswere contacted by mail to obtaininformation about presence of lensopacities, date of diagnosis, visualacuity loss, cataract extraction, otherocular abnormalities that couldexplain visual acuity loss, cataracttype, and etiology.

Endpoints were incident cataractandextraction of incident cataract. Cataractwasdefined as a self-report confirmedbymedical record review initially diag-nosed after randomization, age-relatedin

origin, with best-corrected visual acu-ityof 20/30 or worse attributable to cata-ract. This article includes all availabledata through December 1997.

Coxproportionalhazardsmodelswereused to assess the effect of smoking ces-sation on risk of cataract while simulta-neouslycontrollingforother cataractriskfactors. Models were fit using currentsmokers asthereferencecategory, asrec-ommended in the 1990 surgeon gener-als report onsmoking cessation.12 In ini-tial analyses, subjects were classified as

never,past,or current smokers,basedondatareportedatbaseline.Wethen exam-ined the risk of cataract in past smokerswho quit less than 10 years, 10 to lessthan 20years, or 20or moreyearsbeforestudy entryin modelsthatcontrolledforother cataract risk factors and for age atstarting smoking or number of ciga-rettes consumed per day. Finally, we

examined the independent contribu-tions oftotal cumulativedoseandsmok-ingstatus (past vscurrent) torisk ofcata-ract inever smokers.The significanceofvariables was tested using the likeli-hood ratio test. To calculatetotalcumu-

lative dose, subjects were classified bypack-years of smoking. We used base-line data on amountsmoked for currentsmokersand60-monthfollow-up ques-tionnairedataonamountsmokedforpastsmokers (since information on amountsmoked was collected only for currentsmokers at baseline) to calculate pack-years ofsmoking at baseline.Wedefinedpack-years as the number of years ofsmoking times the number of packs ofcigarettes smoked per day.

Cigarettesmoking is associated withan increased risk of age-related macu-

lar degeneration (AMD) in this popu-lation,13 andsubjectswith cataractmayhavebeenidentifiedbecauseofpresenceof AMD. Therefore, we also conductedanalyses in which we included diagno-sisof AMDas a time-varyingcovariate.Relativerisk(RR)estimatesderivedfromthesemodels, however,werenot mate-rially different from estimates derivedfrom models that were unadjusted fordiagnosis of AMD (data not shown).

RESULTS

At baseline, 11% of the study partici-pants were current smokers, 39% werepast smokers, and 50% werenever smok-ers. Compared with current smokers,past smokers were older and, after ad-justing for age, tended to report less al-cohol use, diabetes, parental history ofmyocardial infarction, and multivita-min use, but more physical activity(TABLE1). Mean age at starting smok-ingwas similar inpast andcurrentsmok-ers, but total pack-years of smoking atbaseline 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 age-related cataract diagnoses and 1193cataract extractions confirmed by medi-cal record review. Risk of cataract inpast smokers was intermediate be-tween current and never smokers.

Table 1.Age-Adjusted Prevalence of Baseline Characteristics That Are Possible Risk Factorsfor Cataract by Smoking Status at Baseline, Physicians Health Study I*

Never Smokers(n = 10 444)

Past Smokers(n = 8190)

Current Smokers(n = 2273)

Age range, %, y40-49 48.0 36.4 41.7

50-59 32.1 37.0 37.4

60-69 15.5 20.5 17.2

70-84 4.4 6.1 3.7

Diabetes, % 2.1 2.2 2.7

Hypertension, % 12.7 14.1 13.9

BMI, mean, kg/m2 24.8 25.1 25.1

Alcohol use, %Daily 17.6 29.5 34.5

Weekly 49.3 51.8 43.8

Monthly 12.6 9.5 11.1

Physical activity, % 73.4 73.2 64.2

Parental history of MI, % 13.3 13.1 14.3

Multivitamin use, % 18.5 20.3 21.3

Smoking historyPack-years, mean (SD) . . . 20.5 (17.4) 35.8 (21.0)

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

. . . 19 (14-26) 19 (14-29)

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

. . . 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.

SMOKING CESSATION AND RISK OF CATARACT

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Compared with men who continuedto smoke, past smokers had a statisti-cally significant 23% reduced risk ofcataract diagnosis (RR, 0.77; 95% con-fidence interval [CI], 0.66-0.88) and28% reduced risk of cataract extrac-

tion (RR, 0.72; 95% CI, 0.60-0.86), af-ter adjustment for other risk factors forcataract.TheRR in never smokers com-pared with men who continued tosmoke was 0.64 (95% CI, 0.54-0.76) forcataract diagnosis and 0.65 (95% CI,0.53-0.79) for cataract extraction.

Compared with men who continuedto smoke, men who had quit less than10 years before study entry had an ap-proximately 20% reduced risk of cata-ract diagnosis after adjustment for othercataract risk factors and average num-ber of cigarettes smoked per day or age

at starting smoking (TABLE 2). Therewas little additional reduction in risk inmen who had quit 10 or more years be-fore study entry. For cataract extrac-tion, there was an approximately 25%reduced risk in men who had quit lessthan 10years before study entryvs thosewhocontinued to smoke.Similarly,thereappeared to be little additional reduc-tionin riskin men who quitsmoking 10or more years before study entry. Forboth endpoints, risk of cataract in long-term quitters appeared to remainslightly

(but not significantly) elevated com-pared with risk in never smokers.

When we examined the indepen-dent contributions of total cumulativedose andsmoking status to risk of cata-ract among ever smokers, the best-fitting multivariate model included onlya term for total cumulative dose (RR,

1.07; 95% CI, 1.04-1.10). Thus, therewas a 7% increased risk of cataract as-sociated with a 10-pack-year increasein smoking exposure. Addition of a2-level categorical termfor smoking sta-tus (past vs current, RR, 0.85; 95% CI,0.73-1.00) was suggestive of an inde-pendent benefit associated with beinga past smoker, but did not signifi-cantly improve the fit of the modelbased on the likelihood ratio test(P=.08). For cataract extraction, thebest-fittingmodel didincludea term forsmoking status (past vs current, RR,

0.80; 95% CI, 0.65-0.97) in addition toa continuous term for total pack-yearsof smoking (for a 10-pack-year in-crease, RR, 1.05; 95% CI, 1.01-1.09),suggesting a benefit for past smokersthat was independent of total cumula-tive dose. There were no significant in-teractions between smoking status andcumulative dose for either end point.

COMMENT

In this cohort of US male physicians,the risk of cataract in past smokers ap-

peared to be intermediate between therisks in continuing smokers and never

smokers. Compared with those whocontinued to smoke, a lower risk ofcataract in past smokers was apparentin men who had quit smoking less than10 years before study entry, with littleadditional reduction in risk associated

with longer time since quitting smok-ing. Thelower risk in past smokers wasdue primarily to their lower total cu-mulative dose of smoking, althoughthere was evidence of a benefit of quit-ting smoking that was independent ofcumulative dose, suggesting that somesmoking-relateddamagein the lens maybe reversible on smoking cessation.

Several previous studies have exam-ined therisk of cataract in former smok-er s. A po pul ati o n- based, cr o ss-sectional survey of 838 Marylandwatermen indicated that therisk of pure

nuclear opacities decreased during thefirst 10 years following smoking ces-sation and continued to decrease withlonger time since quitting.5 A more re-cent analysis of prospective data fromthat cohort showed that past smokersandnever smokers hadsimilar progres-sion rates of nuclear sclerosis during 5years of follow-up.10 In theLens Opaci-ties Case-Control Study, there was anincreased risk of nuclear sclerosisamong current smokers (RR, 1.7; 95%CI, 1.0-2.8), but none was reported for

past smokers.6

The results of 2 otherstudies suggest that the risk of cata-

Table 2.Relative Risks of Cataract Diagnosis and Extraction by Years Since Quitting Smoking*

Current Smokers(n = 2272)

Never Smokers(n = 10 450)

Past Smokers, Years Since Quitting Smoking

10(n = 1640)

10 to 20(n = 2795)

20(n = 2541)

Cataract Diagnosis

No. of cases 250 868 149 261 450

Age- and treatment-adjusted RR (95% CI) 1.00 0.66 (0.57-0.76) 0.83 (0.68-1.02) 0.77 (0.65-0.92) 0.79 (0.67-0.92)

Multivariate RR (95% CI) 1.00 0.67 (0.58-0.77) 0.81 (0.66-1.00) 0.75 (0.63-0.90) 0.79 (0.67-0.92)


Cataract Extraction

No. of cases 155 507 85 152 243

Age- and treatment-adjusted RR (95% CI) 1.00 0.64 (0.54-0.77) 0.78 (0.60-1.02) 0.74 (0.59-0.93) 0.73 (0.59-0.89)



*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 -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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ract, especially among heavy smokers,decreases little, if at all,following smok-ing cessation. In the City Eye Study, across-sectional analysis of baseline datashowed that past heavy smokers (25cigarettes per day) had a risk of nuclear

sclerosis (RR, 2.6; 95% CI, 1.4-5.0)comparable in magnitude with the riskin current heavy smokers (RR, 2.9; 95%CI, 1.4-5.9).4 There was no increasedrisk of nuclear sclerosis in past mod-erate (15-24 cigarettes per day) or pastlight (1-14 cigarettes per day) smok-ers in that study. In the Nurses HealthStudy, the overall RR for past smokersvs never smokers was 1.0 (95% CI,0.8-1.2). However, the risk of cataractin past smokers who had smoked atleast 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 remainedcomparable after 10 or more years fol-lowing smoking cessation.9

Our findings in thePhysicians HealthStudyI arein broad agreement with pre-vious studies that indicate a reduced riskof cataract in past smokers comparedwith current smokers, due primarily tolower total cumulative dose in pastsmokers. We found no evidence to in-dicate that even the most heavily ex-posed men in our population did not

benefit from smoking cessation. How-

ever, our data show that compared withmen who have never smoked, pastsmokers appear to have a slightly el-evated risk of cataract that may persistfor years following smoking cessation.

Several possible limitations of the

study should be considered. The pro-spective study design reduces the pos-sibility of bias in reports of cigarettesmoking or other potential risk factorsaccording to disease outcome. Randommisclassificationof cigarette exposure isa possibility, but would tend to under-estimate any true association betweencigarette smoking and cataract. Ran-dom misclassification of cataract wouldalso underestimate any true effect ofsmoking, but wasminimized by the useof medical records to confirm the self-reports. Nonrandom misclassification of

cataract is unlikely since medical re-cords were reviewed without knowl-edge of participants exposure status.Morbidityfollow-up wasmore than 99%complete(through December 1997) andmedical records were obtained for 92%to 94% ofcurrent, past,and never smok-erswho reported cataract.Thus, bias dueto incomplete follow-up is not likely todistort these results.

Mechanisms linking cigarette smok-ing and cataract have been described,includinga direct effect on the lens,14,15

as well as indirect effects on antioxi-

dant levels16-20 and levels of endoge-nous proteolytic enzymes, thought tobe important for removal of damagedprotein from the lens.21 Stopping smok-ing may alleviate further direct dam-age to lens proteins and, perhaps, al-

low reversal of some of the earlydeleterious effects of smoking.Cataract is a leading cause of visual

impairment in the United States andrepresents a major drain on health careresources.22 Approximately 1.35 mil-lion cataract operations are performedyearly in the United States at an esti-matedcost of $3.5 billion.22 Given theseconsiderations, recognition that smok-ing is an important, avoidable cause ofage-related cataract can be expected tohave major public health implica-tions. The data presented extend pre-

vious findings by demonstrating thatsmoking cessation reduces the risk ofcataract primarily by limiting totalsmoking-related damage to the lens.The data also indicate that some dam-age in the lens may not be reversed withsmoking cessation, underscoring theimportance of early cessation of smok-ing and, preferably, the avoidance ofsmoking altogether.

Funding/Support: This study was supported by re-search grants HL 26490, HL 34595, CA 34944, CA40360, and EY 06633 from the National Institutes of

Health.

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6. Leske MC, Chylack LT, Wu SY. The Lens Opaci-ties Case-Control Study: risk factors for cataract. ArchOphthalmol. 1991;109:244-251.7. Klein BEK, Klein R, Linton KLP, Franke T. Ciga-rette smoking andlensopacities: theBeaver DamEyeStudy.Am J Prev Med. 1993;9:27-30.8. ChristenWG, MansonJE, SeddonJM, et al.A pro-spective study of cigarette smoking and risk of cata-ract in men.JAMA. 1992;268:989-993.

9. HankinsonSE,Willett WC,ColditzGA, etal. A pro-spective study of cigarette smoking and risk of cata-ract surgery in women. JAMA. 1992;268:994-998.10. West S, Munoz B, Schein OD, et al. Cigarettesmoking andrisk forprogressionof nuclear opacities.Arch Ophthalmol.1995;113:1377-1380.11. Hiller R, Sperduto RD, Podgor MJ, et al. Ciga-rette smoking and risk of development of lens opaci-ties.Arch Ophthalmol.1997;115:1113-1118.12. Department of Health and Human Services. TheHealth Benefits of Smoking Cessation: A Report ofthe Surgeon General, 1990.Rockville, Md: Dept ofHealth and Human Services; 1990. DHHS publica-tion (CDC)90-8416.

13. ChristenWG, Glynn RJ,MansonJE, Ajani UA,Bur-ing JE. A prospective study of cigarette smoking andrisk 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 re-action.Exp Eye Res. 2000;70:73-80.

16. Mohan M, Sperduto RD, Angra SK, et al. In-dia-US case-control studyof age-related cataracts.ArchOphthalmol. 1989;107:670-676.17. BunceGE, Kinoshita J, HorwitzJ. Nutritional fac-tors in cataract.Ann Rev Nutr. 1990;10:233-254.18. Jacques PF, Chylack LT, McGandy RB, Hartz SC.Antioxidant statusin persons withand without senilecataract.Arch Ophthalmol.1988;106:337-340.19. Chow CK, Thacker RR, Changchit C, et al.Lower levels of vitamin C and carotenes in plasmaof cigarette smokers. J Am Coll Nutr. 1986;5:305-312.20. Stryker WS, Kaplan LA, Stein EA, et al. The rela-tion of diet,cigarettesmoking,and alcohol consump-tionto plasma beta-carotene andalpha-tocopherol lev-

els.Am J Epidemiol.1988;127:283-296.21. Taylor A, Davies KJA. Protein oxidation and lossof protease activity may lead to cataract formation inthe aged lens. Free Radic Biol Med. 1987;3:371-377.22. National Advisory Eye Council. Vision Research:A National Plan, 1999-2003. Rockville, Md: Dept ofHealth and Human Services; 1998. NIH publication98-4120.


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