am. j. epidemiol. 2000 delcourt 497 504

7/28/2019 Am. J. Epidemiol. 2000 Delcourt 497 504

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American Journal of EpidemiologyCopyright O 2000 by The Johns H opkins University School of Hygiene and Public HealthAll rights reserved

vo l . 151 , No. 5Printed in USA.

Risk Factors for Cortical, Nuclear, and Posterior Subcapsular CataractsThe POLA Study

Cecils Delcourt,1 Jean-Paul Cristol,2 Fr6deric Tessier,3 Claude L. Leger,2 Francoise Michel,2 Laure Papoz,1 an dthe POLA Study Group4

The POLA (Pathologies Oculaires Li6es a i'Age) Study is a population-based study of cataract and age-related macular degeneration and their risk factors being carried out among 2,584 residents of Sete, southernFrance, aged 60-95 years. Recruitment took place between June 1995 and July 1997. Cataract classificationwas based on a standardized lens examination by slit lamp, according to Lens Opacities Classification SystemIII. This paper presents results obtained from cross-sectional analysis of the first phase of the study. Inpolytomous logistic regression analyses, an increased risk of cataract was found for female sex (cataractsurgery: odds ratio (OR) = 3.03; cortical cataract: OR = 1.67), brown irises (cortical, nuclear, and mixedcataracts: OR = 1.61), smoking (cataract surgery: OR = 2.34 for current smokers and OR = 3.75 for formersmokers), known diabetes of 10 or more years' duration (posterior subcapsular, cortical, and mixed cataractsand cataract surgery: OR = 2.72), use of oral corticosteroids for at least 5 years (posterior subcapsular cataract:OR = 3.25), asthma or chronic b ronchitis (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 withhigher 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 1-standard-deviation increase). Most of the risk factors identified in this study confirm the findings of other s tudies.The association of cataract with plasma retinol level requires further investigation. Am J Ep/cfem/o/2000;151:497-504 .cataract; cortisone; cross-sectional studies; diabetes mellitus; eye diseases ; risk factors; smoking; vitamin A

Cataract is the leading cause of blindness, account-ing for 50 percent of blindness w orldwide (1). With theglobal aging of populations, particularly in industrial-ized countries, the prevalence of this condition isincreasing rapidly. The only therapy currently avail-able is lens extraction. The growing need for surgicalresources is particularly critical in developing coun-tries, but it also affects industrialized countries. Forinstance, cataract surgery has become the most com-mon surgical procedure among people aged 65 yearsor more in the United States, with an estimated $3.4billion cost to Medicare in 1991 (2). An increasedunderstanding of cataract etiology may lead to the

Received for publication December 30, 1998, and accepted forpublication May 18, 1999.Abbreviations: LOCS III , Lens Opacities Classification System III;OR, od ds ratio; POLA, Pathologies Oculaires Liees a I'Age.11nstitut National de la Sante et de la Recherche Medicate(INSERM ), Unite 500 , Montpellier, France.2Laboratoire de Biologie et Biochimie des LJpides, UniversityHospital of Montpellier, Montpellier, France.3 InstHut National Agronomique, Paris, France.4 Members of the POLA Study Group are listed in the Acknowl-edgmentReprint requests to Dr. Cecile Delcourt, INSERM Unite 500, 39Avenue Charles Flahault, 34093 Montpellier, Cedex 5, France.

development of nonsurgical strategies for delaying orpreventing cataract. In the United States, the NationalEye Institute estimates that a 10-year delay in the onsetof cataract would result in a 50 percent reduction in theprevalence of cataract (1).The POLA (Pathologies Oculaires Liees a I'Age)Study is an epidemiologic study being conducted insouthern France that is designed to identify risk factorsfor cataract and age-related macular degeneration.Most of the epidemiologic studies on this subject havebeen conducted in the United States; our study is oneof the few European studies on this subject (3-7) andis , to our knowledge, the first to be carried out inFrance. We present here the associations of ag e-relatedposterior subcapsular, cortical, nuclear, and mixedcataracts with demographic, medical, and nutritionalrisk factors.MATERIALS AND METHODSStudy population

The POLA Study is a prospective study taking placein Sete, a town of 40,000 inhabitants located on the

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Mediterranean Sea in southern France. The objectiveof this survey is to study age-related eye diseases(cataract and macular degeneration) and their risk fac-tors. Inclusion criteria were 1) being a resident of thetown of Sete and 2) being aged 60 years or over on theday of the baseline examination. According to the1990 population census, there were almost 12,000 res-idents eligible for participation; the objective was torecruit 3,000. The population was informed of thestudy through the local media (television, radio, andnewspapers). We also contacted 4,543 residents indi-vidually by mail and by telephone, using the electoralroll. Between June 1995 and July 1997, we recruited2,584 participants, including 1,133 men and 1,451women, with an average age of 70.4 years. This paperpresents results obtained from cross-sectional analysisof the first phase of the study. We are currently under-taking a follow-up examination, 3 years after baseline.

The baseline examination took place in a mobileunit equipped with ophthalmologic devices (a projec-tor 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 cam-era (TRC 50 XF; Topcon)). We moved the mobile unitfrom one area to another to be in the proximity of thecontacted participants.Participants gave written consent for participation inthe study. The study's design was approved by theEthical Committee of Montpellier University Hospital(Montpellier, France).Cataract classification

Four ophthalmologists performed the ophthalmo-logic examinations. The examination included arecording of the participant's ophthalmologic history(particularly lens extraction and the year of extrac-tion); a measure of the best corrected far visual acuityin the right and left eyes; after pupil dilation, a quanti-tative assessment of nuclear, cortical, and posteriorsubcapsular lens opacities by slit lamp, according tothe Lens Opacities Classification System EQ (LOCSIJT) (8); and one 50 color photograph of each eye, cen-tered on the macular area.The type and degree of lens opacification weregraded by slit lamp following LOCS HI procedures(8). The LOCS in system, which is based on standardphotographs, provides decimal, nearly continuousgrades separately for nuclear opalescence (NO) (rang-ing 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 pos-terior subcapsular opacities (P) (ranging from 0 to 5.9,using five standards).

Severe cataract. We chose to classify as severecataracts lens opacifications which led to significantvisual impairment in most participants (grades of NO 4 or NC > 4 for nuclear cataract, C > 4 for corticalcataract, and P > 2 for posterior subcapsular cataract).Participants were classified as having a single type ofcataract (nuclear, cortical, or posterior subcapsular)when only one type of opacity was present. Thenuclear group, for instance, consisted of participantswith nuclear cataract only in both eyes, or nuclearcataract only in one eye and moderate or no cataract inthe other eye. The mixed cataract group consisted ofparticipants with various combinations of nuclear, cor-tical, and posterior subcapsular opacities in one or botheyes.

Moderate cataract. We chose to classify partici-pants as having moderate cataract if they were free ofsevere cataract and had moderate opacities (2 < NO 160mmHg 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 fastingblood samples taken at the participant's home on themorning of the examination. They included measure-ments of plasma (cholesterol, triglycerides, and vita-mins A, E, and C) and red blood cells (reduced glu-tathione). Plasma triglyceride and total cholesterollevels were measured by routine enzymatic methodswith a reagent purchased from B oehringer Lab oratories(Norristown, Pennsylvania). Plasma high densitylipoprotein cholesterol was assayed in the supernatantafter precipitation of apolipoprotein B-containinglipoproteins by magnesium phosphotungstate kit(bioM6rieux S.A., M arcy-1'Etoile, France). Retinol anda-tocopherol were measured by high performance liq-uid chromatography according to the method previ-ously described by Catignani and Bieri (9). In eachseries of measurements, one sample of the liotrol mix-ture was measured as an internal standard, to preventany shift during the study. Ascorbic acid was measuredby high performance liquid chromatography accordingto the method described by Tessier and Birlouez-Aragon (10). Red blood cell reduced glutathione wasmeasured by colorimetric assay (Bioxytech GSH-400;OXIS International, Inc., Paris, France).Missing data

Among the 2,558 participants for whom cataract sta-tus was available, 46 subjects (1.8 percent) refusedblood sam pling. For an additional 44 subjects (1.7 per-cent), some data were missing in the standardizedinterview. Therefore, the analyses discussed belowwere performed in 2,468 subjects. Concerning red

blood cell glutathione, 356 (14.4 percent) measure-ments could not be made because of technical failure;this left 2,112 subjects for the analysis. Ascorbic acidwas measured only in subjects recruited after N ovember20 , 1995 (n = 2,020).Statistical analysis

The associations of the different types of cataractwith the potential risk factors w ere estimated by polyt-omous logistic regression. Patients without any severeopacities constituted the reference group in all analy-ses. We used a strategy similar to that of other studiesof cataract (4,11 ), as follows. 1) Age- and sex-adjustedodds ratios were calculated for all potential risk fac-tors. All variables w ith an odds ratio that differed from1 (p < 0.10) for at least one type of cataract wereretained for the next phase of an alysis. 2) A full mu lti-variate analysis was carried out. 3) A reduced multi-variate analysis was conducted, and those variableswhich did not show any significant (p < 0.05) associa-tion with any of the cataract types were excluded.4) Coefficients for a given variable were constrained tobe equal across selected cataract types when their esti-mates in the reduced m odel were not significantly dif-ferent. 5) Coefficients for certain variables for selectedcataract types were constrained to be 0 when their esti-ma tes in the reduced m odel were not significantly dif-ferent from 0. The comp arisons between the full m odeland the reduced model and between the reduced modeland the final model were made with a %2 test of theimprovement in the log-likelihood.Concerning diabetes, because of a known effect ofduration for any physiologic change, we chose to cre-ate two duration groups (10 years, a10-year duration being about the median) before per-forming any statistical analysis. By contrast, educa-tional level and iris color were recorded as three-classvariables: primary, secondary, and superior for educa-tion and blue, green/light brown, and dark brown foriris color. Since primary and secondary educational

levels on the one hand and light brown and dark browniris color on the other hand did not show any differ-ence for any type of cataract in step 2, we ch ose to poolthese 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 con-strained polytomous logistic regression).

RESULTSAs table 1 shows, among men the prevalence of

cataract increased from 10.1 percent below age 70Am J Epidemiol Vol. 15 1, No. 5, 2000


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50 0 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 inthe POLA* Study, southern France, 1995-1997

Age group (years) Total60 -69 70-79Men n = 554 n = 411 n= 1 17 n= 1,082PSC* only 5.2 9.5 6.8 7.0

Cortical only 1.4 3.4 6.8 2.8Nuclear only 1.3 6.1 17.9 4.9Mixed 1.3 6.1 17.1 4.8Cataract surgery 0.9 7.0 13.7 4.6Total 10.1 32.1 62.4 24.1

Women n=673 n=5 61 n=152 n= 1,386PSC only 4.7 8.9 6.6 6.6Cortical only 2.8 4.8 9.2 4.3Nuclear only 1.5 8.9 13.8 5.8Mixed 1.6 8.5 20.4 6.5Cataract surgery 1.6 5.7 23.7 5.7Total 12.3 36.9 73.7 29.0

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

years to 62.4 percent at age 80 years or more. Theprevalence of cataract was slightly higher in women,and it increased from 12.3 percent below age 70 yearsto 73.7 percent at age 80 years or more. While poste-rior subcapsular cataract was the most frequent type ofcataract below age 70 years (5.2 percent in men and4.7 percent in women), nuclear and mixed cataractswere the most frequent types at and above age 80 years(17.9 percent and 17.1 percent, respectively, in menand 13.8 percent and 20.4 percent in women).Overall, 43.1 percent of posterior subcapsular opac-ities were associated with other opacities, and there-fore were classified under "mixed cataracts." This pro-portion increased to 71.0 percent among participantsaged 80 years or more. This explains the decrease inthe prevalence of posterior subcapsular cataract aloneover age 80 years, the vast majority of posterior sub-capsular opacities being classified as mixed cataracts.Similarly, 45.9 percent and 46.6 percent of cortical andnuclear opacities, respectively, were classified asmixed cataracts.Table 2 presents the distribution of the studied riskfactors in the POLA Study. In this Mediterranean pop-ulation, the majority of the participants had brownirises. Three fourths of the men had smoked duringtheir lives, versus only 15 percent of the women.Known diabetes, cardiovascular disease, and asthmawere more frequent in men, while cancer, knee or hiposteoarthritis, and treatment with oral corticosteroidswere more frequent in women. Levels of total and highdensity lipoprotein cholesterol, apolipoprotein A l, anda-tocopherol were higher in women.

Men(n = 1,082) Women(n= 1,386)Personal characteristics

Mean age (years)High educational level (%)Brown irises (%)

Medical historySmoking (%)

Current smokerFormer smoker

Body mass indexfKnown diabetes mellitus (%)

Duration of


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Risk Factors for Cataract 501TABLE 3. Odds ratios for cataract estimated by multlvariate polytomous logistic regression (final model) among adults aged60-95 years, POLA* Study, southern I

Personal characteristicsAge (per 1-year Increase)Female sexHigh educational levelBrown irises

Medical historySmokingCurrent smokerFormer smokerKnown diabetes mellltusDuration of


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50 2 Delcourt et al.potential risk factors. To assess possible bias in recruit-ment, we previously compared our sample with theentire eligible population according to age, sex, andsocial class. Although the sex distribution was similarin both populations, our sample underrepresentedolder persons and overrepresented the middle andupper social classes (15). Bias from self-selection maytherefore have affected cataract prevalence rates.Personal characteristics

After adjustment for other risk factors, women hadthreefold 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 stud-ies (4, 11, 16). These sex differences were alreadypresent before adjustment and were increased by theadjustments for smoking and diabetes, both of whichwere much more prevalent in men. The factorsexplaining the excess risk of cataract, particularly cor-tical cataract, in women remain to be identified. Theymay relate to sex differences, particularly to hormonelevels (17-19), or to differences in lifestyle or otherenvironmental exposures.Participants with a high level of education had a 40percent lower risk of all types of cataract. The associ-ation of lower socioeconomic status with cataract is ageneral finding that has been seen in studies with var-ious settings (4, 11, 16, 20-22). This very consistentfinding suggests, in particular, an influence of lifestyleon the etiology of cataracts.Participants with brown irises were at higher risk forcortical, nuclear, and mixed cataracts, which is consis-tent with the findings of two case-control studies (4,11). However, in a prospective study, iris color was notassociated with nuclear cataract (22). The mechanismby which iris color is linked to cataract remainsunclear. The same mechanism may explain the excessprevalence of cortical cataract found in Black popula-tions (1 1, 16).Medical history

Consistent with the findings of a number of studies,smoking was a strong risk factor for cataract, the riskbeing mostly confined to nuclear cataract (and cataractextraction) (3, 11, 22 -27 ). In observational studies, thepossible existence of a confounding factor responsiblefor the relation cannot be completely dismissed.However, the strength of the relation, the specificity ofits association with nuclear cataract, and the consis-tency of the relation across populations with differentlifestyles and exposures all favor a causal association.The mechanism by which smoking is related tocataract is unclear. Smoking may cause damage to the

lens by increasing oxidative stress, by lowering levelsof circulating antioxidants, or by increasing lens cad-mium levels (28-31).Diabetes was strongly associated with the risk of alltypes of cataract, except nuclear cataracts. Again, thisfinding is very consistent with the literature (5-7, 11,16, 20, 32). As w e found in our study, the four studieswhich have distinguished between the different types ofcataract (5 , 11, 16, 32) found associations with subcap-sular posterior and/or cortical cataract, but none founda significant relation with nuclear cataract. Finally, asexpected, our study showed that the risk of cataractincreases strongly with the duration of diabetes.The use of oral corticosteroids was a strong risk factorfor subcapsular posterior cataract, confirming the resultsof three other studies (4, 5, 11). Recently, an associationhas also been reported between use of inhaled cortico-steroids and subcapsular posterior cataract (33) andcataract extraction (34). This may explain our findingthat asthma and chronic bronchitis were associated withincreased risk of cataract extraction.We also found an association of subcapsular poste-rior cataract with a history of cancer. To our knowl-edge, this is the first report on this association, sincehistory of cancer was not recorded in the other studies.This association of subcapsular posterior cataract withcancer may be mediated by an adverse effect of radio-therapy or chemotherapy on the lens. In our study, wedid not have enough cases of cancer to distinguishbetween radiotherapy and chemotherapy. Furtherresearch is needed to confirm this finding.Finally, cardiovascular disease was associated withan increased risk of cortical cataract, while hyperten-sion was associated with a reduced risk of lens extrac-tion. These results conflict with those of the other stud-ies on the subject: N one of the four existing studies (4,11, 22, 35) have found a relation between history ofcardiovascular disease and any type of cataract. Fourstudies (4, 11, 22, 36) did not find significant relationsof hypertension with cataract, w hile two studies (7, 37)found a significant increased risk of cataract in casesof hypertension. Globally, these results do not favorthe possibility of a major effect of cardiovascular dis-ease and hypertension in the etiology of cataract.Given the number of comparisons made in this analy-sis, it is possible that the associations of cataract withcardiovascular disease and hypertension are chancefindings.Biochemical variables

The only significant association among biochemicalvariables and cataract in this study concerned plasmaretinol. A strong, highly significant inverse relationwas found between plasma retinol level and nuclearAm J Epidemiol Vol. 151, No. 5, 2000


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Risk Factors for Cataract 50 3

and mixed cataracts, as well as cataract surgery (for a1-standard-deviation increase, OR = 0.75; 95 percentconfidence interval: 0.66, 0.86). Three studies havefound a significant inv erse relation between total vitaminA intake and nuclear cataract (11, 38, 39). Relationswith other types of cataract or with all cataracts wereless clear (11, 38-41).The relation of nuclear cataracts with dietary pre-formed vitamin A (i.e., retinol) w as less strong than therelation with total dietary vitamin A (4, 38, 41). Thissuggests that carotenoids may be more important in therisk of nuclear cataract than retinol.To our knowledge, only two previous studies haveassessed the association of plasma retinol with nuclearcataract (42, 43). These studies did not find any signifi-cant association. However, one study had little statisti-cal power and used a crude evaluation of lens status(43). The other found a nonsignificant negative associa-tion of plasma retinol with nuclear cataract and a signif-icant positive association with cortical cataract (42).The results of this study strongly suggest that vita-min A may be protective for cataract. Our findings aresupported by those of previous dietary studies (11, 38,39), while the two available studies on plasma retinol(42, 43) gave inconsistent results. Possible confound-ing of the cataract-retinol association by carotenoidsmust be evaluated. Measurement of plasma carotenoidlevels is currently being performed in our study.Alternatively, the nucleus of the lens may be sensitiveto nutrient deficiencies. Indeed, apart from low levelsof vitamin A, low levels of protein and amino acids,riboflavin, niacin, thiamine, and folate have beenfound to be associated with higher risk of nuclearcataract in other studies (38, 39, 44).Methodology

Our study had several methodological limitations.Our method of selecting participants led to underrep-resentation of older persons and overrepresentation ofthe middle and upper social classes in comparison withthe entire eligible population (15). Bias from self-selection may therefore have occurred. However, mostof our findings concerning the identified risk factors(eye color, smoking, diabetes, corticosteroids) andtheir relations with each type of cataract are in com-plete consistency with those of other studies in the lit-erature. It is therefore unlikely that less consistentfindings, particularly associations of cataract withplasma retinol, are only a result of selection bias.Since this analysis was cross-sectional, we cannotassume that the presence of the risk factors identifiedpreceded the development of cataract. It is possiblethat the development of cataract caused changes inlifestyle, inducing changes in some of the risk factors.

Since information on many of the studied risk factorswas obtained by interview, recall bias might also haveproduced these results. However, since most of ourfindings are specific to each type of cataract and con-sistent with the literature, the effect of such biases wasprobably limited. Because the majority of the studiesconducted to date have been case-control or cross-sectional in design, prospective studies will be neededto confirm these results.Summary

Our study confirmed most of the risk factors forcataract identified in other studies, including lowereconomic status, smoking, use of corticosteroids, dia-betes, and brown irises. We also found a strong associ-ation of nuclear and mixed cataracts with low plasmaretinol levels, which requires further evaluation.

ACKNOWLEDGMENTSFinancial support for this study was provided by theInstitut National de la Sant6 et de la Recherche M&licale(Paris, France), die Fondation de France, Department of theEpidemiology of Aging (Paris), the Region Languedoc-Roussillon (Montpellier, France), the Fondation pour laRecherche M6dicaJe (Paris), the Association Retina-France(Toulouse, France), Rh6ne Poulenc S.A. (Paris), EssilorInternational (Paris), and the Centre de Recherche etd'Information Nutritionnelle (Paris).The POLA Study Group: CoordinationDr. CecileDelcourt, Annie Lacroux, Sylvie Fourrey, Marie-Jose'Covacho, Pierre Paillard, Alice Ponton-Sanchez, Dr.Roselyne Defay, Dr. Alain Colvez, and Dr. Laure Papoz(Principal Coordinator); OphthalmologyDrs. LouisBalmelle, Jacques Costeau, Jean-Luc Diaz, FabienneRobert, and Bernard Arnaud; BiologyLaboratoire deBiologie et Biochimie des Lipides, Montpellier: Dr. Jean-Paul Cristol, Dr. Martine Delage, Dr. Marie-Heiene Vernet,Gilles Fouret, Dr. Francoise Michel, Dr. Claude Leger,and Dr. Bernard Descomps; Laboratoire de ToxicologieBiophysique, Montpellier: Drs. Pierre Mathieu-Daude andJean-Claude Mathieu-Daude"; Institut National Agrono-

mique, Paris: Drs. Fr6d6ric Tessier and Ines Birlouez-Aragon.

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