The epidemiologyof cataractCataract is a major public health issue. In 1997, the World HealthOrganisation estimated that there are 38 million people blind in theworld, approximately half due to cataract.

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On current projections, there could be anestimated 50 million people blind due tocataract by 2020. Cataract affects everycountry: in the industrialised world, thereare 1.5 million cataract extractionsperformed each year in the USA at vastcost, and currently there is no treatmentother than surgery. Recently, the Britishgovernment has recognised the need toincrease the amount of cataract surgery inthe UK from 175,000 to 250,000 a year inits “Action on Cataract” initiative.(www.doh.gov.uk/cataracts)

DefinitionCataract is defined as an opacification ofthe crystalline lens of the eye (Figure 1).It has been suggested that a cataract isopacification with “severe” vision loss; theterm for cloudiness of the lens before thisloss of vision is lens opacity. However, thereis no clear cut-off point and the distinction,in terms of prevalence and aetiologicepidemiological research, is artificial.Therefore, for the purposes of this article,cataract will be defined as any opacificationwithin the lens. Before we try to answer thequestion “What causes cataract?”, we needto discuss how cataract is classified, as thevarious types of cataract each have differentrisk factors.

ClassificationCataract can be classified by anatomiclocation (“histological” classification), or byaetiology (its cause). An aetiologicalclassification, which consists of sevencategories (age-related, congenital,traumatic, and associated with intraoculardisease or systemic disease or noxiousagents), has obvious attractions. Table 1lists some classification systems. However,modern epidemiologic methods arediscovering an increasing number of riskfactors in “age-related” cataracts and it isdifficult to assign a person’s cataract,particularly in the elderly, to one specificaetiology. Cataract is likely to have amultifactorial aetiology. Therefore, a moreappropriate classification system is onebased on anatomical classification. It isrecognised that there are three main typesof cataract: cortical, nuclear and posteriorsubcapsular, each of which may carrydifferent risk factors, and this is the mostcommonly used classification system.

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Chris Hammond MD, MRCP, FRCOphth, Consultant in Ophthalmology, Farnborough Hospital, Bromley

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Figure 1:Photographs of cataracts taken from the twin study discussed in this article. The top pair of“Scheimpflug” images show a pair of discordant twins; the twin on the right has more nuclearcataract than the twin on the left. The middle retro-illumination images show the right eyes froma pair of twins, who revealed very similar amounts of early cortical cataract. The lower imagesare of an individual with a posterior subcapsular cataract: the left image shows a retro-illumination photograph of the opacity, and the image on the right shows its position at theposterior subcapsular portion of the lens.

www.optometry.co.uk 25

Table 2 Prevalence of cataract in recent population studies

Study Location Year Sample Cataract Prevalence for age (%)

Table 1 Classification systems of cataract

Classified by Types Examples

ANATOMIC LOCATION

CorticalNuclearPosterior subcapsularMixed

AETIOLOGYAge-relatedCongenitalGenetic/non-geneticTraumaticIntraocular disease uveitis, glaucoma, retinal detachment, association retinal degenerations, persistent

hyperplastic primary vitreous, aniridia, high myopia

Systemic disease association Metabolic disorders diabetes, galactosaemia, hypoparathyroidism, Wilson’s,Fabry’s, Refsum’s

Skin disease atopic dermatitis, congenitalectodermal dysplasia

Connective tissue Myotonic dystrophy,disorders Marfan’sRenal disease Alport’s, Lowe’sCentral nervous system Neurofibromatosis II, Sjogren’s

Noxious agent association Ionising radiation X-ray, ultravioletDrug-induced steroids, chlorpromazine

Grading of cataractsOne of the main factors limitingepidemiological research into cataract hasbeen the lack of an objective, reproducibleand standardised method for detectingand grading the lens opacity. As changesoccur with normal aging, it is importantto determine whether these areappropriate for a given subject’s age orwhether this represents cataract. Becauseof the slow pace of change, any methodused to detect progression of cataract inepidemiological research (whether it isstudying risk factors for progression or anintervention trial) must be sensitiveenough to detect that change. Methodsmust be reproducible and reliable,particularly when used by severalinvestigators in the same study. Severalmethods of grading cataract have beendeveloped, and these will be discussed ina future article in this series.

PrevalenceThere are few true population-basedprevalence studies for cataract, and asdifferent studies have used differentdefinitions, detection and gradingtechniques, they are difficult to compare.For example, early studies such as theFramingham Eye Study1 specified a visualacuity of less than 20/30 (6/9). However,there have been several studies usingphotographs to document the amount ofcataract which have not included visioncriterion in the definition of cataract, andthese are probably the most accurate recordof the prevalence of lens opacities in thepopulation. The most elderly subset of thepopulation is often under-represented inepidemiological studies, so it is not alwayseasy to project these figures to the generalpopulation. Cataract progressively increaseswith age such that it is estimated that somedegree of lens opacity is present in 50% of

those over 60 years and 100% in those over80 years of age worldwide. Threepopulation-based photodocumentationstudies are the Beaver Dam Eye Study2

(BDES) from the United States, the BlueMountains Eye Study3 (BMES) from Australia,and the Melton Eye Study4 (MES) from theUnited Kingdom. Table 2 lists the studies’details and some of the prevalence data;note that the BDES examined subjects, aged43-84 years old and the BMES, 49-96 yearsof age, so these are selected figures.

These three studies used slightlydifferent grading systems and so aredifficult to compare directly. Details andcomparison of the grading systems appearlater in the section on Cataract Grading. Thehigher prevalence of cortical and posteriorsubcapsular cataracts in the MES isattributable to different grading criteria: ifsimilar criteria to the Winconsin system areapplied, then the prevalence becomes 11%for cortical opacities and 2% for posteriorsubcapsular cataract.

These studies suggest that cataract iscommon in the community in theindustrialised countries, and is probablyeven more common in less developedcountries, where cataract may occur 10-15years earlier.

IncidenceIf exact prevalence is difficult to define,figures on incidence and progression areeven less certain. Recently three studieshave used more modern grading systems toexamine the question prospectively. TheItalian-American Cataract Study Group5

assessed a group of 1399 persons, agedbetween 45 and 79, the Longitudinal Studyof Cataract6 followed nuclear opacities in 764subjects with a median age of 65, and theBeaver Dam Eye Study recently published itsfive-year incidence data7. Figures from therecent studies are tabulated in Table 3.

Some of the differences can be explainedby different definitions of change, differentage structure of samples, or methodologicaldifficulties. Indeed, the Italian-AmericanStudy had considerable regression in grading(about 20%), suggesting either aninaccurate or a crude grading system hadbeen used as it is accepted that there islittle regression of lens opacities. TheBeaver Dam Study was more reliable, andshowed a 5 year incidence of 12% withsignificant nuclear cataract and 8% corticalcataract in their large study.

The studies show a steady incidence oflens opacities in the elderly age group, withprogression of lens opacities in thosealready with cataract in over two-thirds over5 years. The placebo arm of the antioxidanttrials underway (such as the Age-RelatedEye Disease Study (AREDS)) will alsocontribute to incidence and progressiondata.

BDES(3)

BMES(4)

MES(5)

USA

Australia

England

1988-90

1992-94

1992-95

4926

3654

1201(560*)

55-6465-7475-84

55-6465-7475-84

55-74

6.627.457.0

3.921.848.5

-

10.925.442.4

13.128.446.7

36

4.38.4

14.3

3.86.5

11.7

11

Age inyears

Nuclear Cortical PSC

Table 3 Comparison of incidence and progression data

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Twin and family studies ofage-related cataractFamily studies of disease are designed tostudy whether there is a shared familyeffect on the presence or absence ofdisease, which may suggest a geneticeffect. There was significant siblingcorrelation in both nuclear and corticalcataract in the Beaver Dam Eye Study,supporting the role of genes in age-relatedcataract. However, this could also representshared family environment.

Twin studies have been described as theperfect natural experiment to separatenature from nurture. Identical twins shareall the same genes, but non-identical twinsshare only half their genes on average. Anygreater similarity between the identicaltwins is, therefore, due to this additionalgene-sharing. I performed a twin study ofover 500 pairs of twins aged over 50 yearsto answer the question of the relativeimportance of genes and environment inage-related cataract (Figure 1). Theconclusion was a heritability of 48% fornuclear cataract: that is almost half thevariability of nuclear cataract is explainedby genetic factors. Age, as might beexpected for such an age-related trait,explained 38% of the variability, whileenvironment, only 14%8. This does notmean that environment is not important, asindividuals with a particular geneticsusceptibility may be predisposed tocataract if they encounter a specificenvironmental toxin, but overall in thepopulation genes are important in theaetiology of cataract. The same is true forcortical cataract also: a person’s genesinfluence the likelihood of cataractdeveloping later in life.

Genetics ofage-related cataractThe twin study leads us toward thepossibility that genetic influences may beinvolved in the development of age-related

cataract. This aspect has until now beenlargely ignored in age-related cataractresearch, although mutations are known tobe important in congenital cataract, andcan cause cataract in mouse models.Differentially expressed genes from lensepithelia dissected from age-relatedcataractous and noncataractous humanlenses have recently been described, andother differential expression of genes inold rather than young eyes. A mutationhas been implicated in adult onsetcataract associated with myotonicdystrophy. It is very likely therefore thatover the next10 years further genetic abnormalities inage-related cataract will be identified,which will help our understanding of themechanisms of cataract formation and,maybe, allow development of treatmentsto delay onset or progression of cataract.

Risk factorsA wide range of risk factors have beenreported for cataract, though for many ofthese the evidence is not conclusive as towhether the observed associations arecausative. Studying risk factors for cataractis difficult, as lifetime measures may berequired, as it is not known if there is a“critical period” for exposure. Measurementof ocular exposure can be difficult

(eg ultraviolet light: exposure depends onnot only the amount of sunshine, but otherfactors such as brow prominence, and hatand sunglasses wear). In addition,confounding needs to be considered (forexample, older people are more likely to goto church, and as cataract is age-related, astudy might conclude that going to churchis a risk factor for cataract if age was notaccounted for), and there may beinteractions between different exposures.

Different conclusions can be drawn fromthe same data; some authors conclude thatdiabetes, glaucoma and myopia are majorcauses in Western countries, with severediarrhoeal disease being more important inthe developing world, but others believethat heat, oxygen and light are the majorcauses. I will attempt to examine some ofthe most important factors identified inlarge-scale epidemiological studies in thisreview. Figure 2 illustrates some of themore important known associations withcataract.

AgeThe strongest risk factor for cataract is age:the Beaver Dam Eye Study demonstratedrates of 1.5%, 1.5% and 1.6% for nuclearcataract, cortical opacities and posteriorsubcapsular cataracts respectively in thoseaged 43-54, rising to 57%, 42.4% and14.3% in subjects over the age of 75 years.Although this cannot exclude cohort effects(that is, the risk changes over thegeneration), every study shows similarfindings.

Female genderThere seems to be an excess risk indevelopment of cataract in women,particularly cortical lens opacities, whichhas been verified by several cross-sectionaland case-control studies. For example, theBMES demonstrated nuclear opacities in53.3% of women compared to 49.7% ofmen, cortical cataract in 25.9% of womencompared to 21.1% in men, while PSCopacities were no different.

Hormones may be involved; the BDEShas reported that use of hormonereplacement therapy seems to be protective

Cataracttype

Nuclear

Cortical

PSC

Years

252525

Incidence %

5.111.511.528.24.49.6

Progression %

53.580.437.166.942.565.5

Incidence %

5.97.7

Progression %

10.312.0

Beaver Dam(43-84yr)

Incidence %

12.0

8.0

3.0

Longitudinal Study(>65yr)

Italian-American(65-74yr)

Figure 2:Diagrammatic representation of some of the more important causes of cataract

CORTICAL• Age• Female• Ultraviolet Light• Afro-Caribbean

POSTERIORSUBCAPSULAR• Age• Diabetes• Steroid Treatment

NUCLEAR• Age• Smoking• Diet/antioxidants?

Cataract: some risk factors

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for severe nuclear opacities, and previouspregnancy may also protect againstcataracts, as well as late onset menopause.This potential role of oestrogen needs to bevalidated by other cohort studies.

Sunlight(ultraviolet irradiation)Sunlight has been associated with cataracts,although the evidence is conflicting, withmany studies not examining individualexposure. The Chesapeake Bay watermenstudy9 specifically calculated individuallifetime dose of UV-B in 838 subjects anddetermined that doubling exposure toUV-light increased the risk of corticalcataract by 60%, but found no associationwith nuclear cataract. Animal experimentalevidence shows a link between cataract andUV-B, and the epidemiological evidencesuggests that cortical cataract is related toUV-light, nuclear cataract is NOT related,and evidence for an association withposterior subcapsular cataract is uncertain.

SmokingThere is now fairly consistent evidence thatsmoking is related to nuclear and posteriorsubcapsular cataracts. The London City EyeStudy10 reported that smokers of more than25 cigarettes a day were three times aslikely to develop cataracts thannon-smokers, and ex-smokers had anintermediate risk, lending support to acausal relationship. It has also been shownthat cigarette smoking increases the risk ofprogression of nuclear opacities. However,smoking is not related to cortical cataract.

DiabetesAlthough clinic-based case-control studieshave reported diabetes as a risk factor, theymay be susceptible to selection anddefinition biases. However, population basedstudies have confirmed that diabetes is arisk factor for cataract. An example is theFramingham Eye Study1, which foundcataract in 19% of diabetics compared to12% in non-diabetics, and found the riskonly in those under the age of 65. There isalso in vitro and in vivo evidence of thecausation of cataract by elevated glucoselevels and osmotic changes. All forms ofcataract, particularly posterior subcapsularcataract, seem to be increased in diabetics.

SteroidsThe cataractogenic nature of steroid drugshas been well described, both inepidemiological surveys as well as in clinicand case series. The hallmark of the steroidinduced cataract is the posterior subcapsularcataract, which has been linked to dose andduration of treatment. Posterior subcapsularcataracts are uncommon (less than 10% ofcataract), but because of their position inthe lens and their sometimes rapid

development, they have a large impact onvision and constitute a greater proportion ofthe surgical case-load.

Socio-economic factorsLow education in terms of years at schoolhas been associated with cataract in diversepopulations, even attempting to correct foroccupational, nutritional and environmentalfactors. An excess of cataract has beenfound in rural populations, after correctingfor ultraviolet exposure. Non-professionalshad a higher rate of cataract thanprofessionals in the Lens Opacities Case-Control Study11. These factors are difficult todisentangle from other factors such as diet,alcohol consumption and smoking, and atpresent, there is no obvious biochemical orphysiological explanation, and so should betreated with some caution.

Height, weight and body massAlthough some studies have demonstratedlow height as a risk factor for cataract aswell as low body mass index, this has notbeen confirmed in other studies. Low heightmay reflect short stature as a marker ofchronic malnutrition at an early age. Theinteresting finding that weight at one yearof age is inversely related to nuclearcataract 60-70 years later may support thehypothesis that early nutrition is importantin age-related nuclear cataract.

AlcoholThere is conflicting evidence as to whetheralcohol consumption is a significant riskfactor for cataract. An Oxfordshire case-control12 study found that people drinkingmore than four units a day had twice therisk of cataract, and other researchers havesuggested an effect, similar to alcohol’scardiovascular effects, where a little alcoholis good for you, but not too much. However,evidence is not consistent.

Diarrhoea and severe dehydrationCase-control studies in India showed thatsevere diarrhoea and dehydration, resultingin confinement to bed for at least threedays, carried a three to four-fold risk fordeveloping cataract in later life. This hasnot been confirmed in other studies inIndia, although they did not use such astringent definition. Further research in thisarea is required, as it may be an importantmodifiable risk factor.

HypertensionHypertension is another risk factor withconflicting evidence as to its significance.Recently, allowing subtypes to be graded,the Beaver Dam Eye Study7 concluded thatpeople with hypertension were more likelyto have posterior subcapsular lens opacitieswith an odds ratio of 1.39 (95% confidence

interval 1.05,1.84) (for further explanation,see Armstrong and Eperjesi - The use ofdata analysis methods in Optometry: Basicmethods, OT June 16, 2000), but nuclearand cortical cataract seemed to be unrelatedto blood pressure. The mechanism by whichthis may operate is unclear.

AntioxidantsOxidation of lens proteins is associated withcataract formation, and it follows that highlevels of antioxidants, such as vitamins, maybe protective. The evidence is varied and noclear consensus emerges. The Lens Opacitiescase-control study in Boston11 found regularintake of multivitamins protective of alltypes of cataract, while prospective data of50,000 nurses in the United Statesdetermined the risk of cataract extraction tobe 45% lower in women taking vitamin Csupplements for at least 10 years. However,other studies have not supported thisfinding. Vitamin E, again found to have aprotective effect in the Boston series and inanimal experiments, had no significanteffect in the Nurses Health Study13, whichdid show a protective effect for carotenoidlevels, but not β-carotene, in particular.

Two nutrition intervention trials, theLinxian Cataract Studies in the Far East13,demonstrated a 36% reduction in theincidence of nuclear cataract in those aged65-74 taking multivitamins, and a 44%reduction in this age group in thosereceiving riboflavin/niacin supplementation.There are several multicentre prospectiverandomised trials underway to answer thequestion whether vitamin supplementationmay be protective against cataract, but theeffects may be small in the relatively well-nourished western world.

Myopia and glaucomaAlthough myopia and glaucoma have beenreported as strong risk factors in Oxfordshirecase-control studies15 these have not beenduplicated elsewhere and further research isnecessary before any conclusions can bedrawn.

TreatmentCurrently, the only proven treatment ofcataract is surgical extraction and there arean estimated 8 million operations per year.It has been estimated that by 2020 over 30million operations per year will be requiredto reduce cataract blindness to less than amillion. Good epidemiological research isrequired to look at risk factors andtreatments which might delay onset ofcataract: back in 1984 it was estimated thatif cataract could be delayed by 10 years, theamount of surgery could be reduced by 45%with huge cost savings. There is currently alarge deficit in cataract surgery across theUK, particularly with the ageing population,and it has been estimated that the cataract

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surgical rate must double over the next20 years in order to maintain waiting listsas they are. With its initiative of “Action onCataract”, the Government seems to bestarting to address this. Further articles inthis series will discuss referrals and surgicalmethods to improve efficiency within theNational Health Service.

As stated earlier, there are currentlytrials of antioxidant vitamins underway tosee whether cataract can be prevented orprogression slowed. Although aspirin mighttheoretically prevent cataract, evidence fromlarge randomised trials of aspirin has beendisappointing and has shown no benefit, sothis cannot be recommended at present.

ConclusionGenes and environmentin age-related cataractCataract is a multifactorial disease, in whichage, female gender, diabetes, smoking,steroids and (probably) sunlight have beenshown to be definite risk factors. There arenumerous other possible risk factors forwhich there is conflicting evidence, andfurther epidemiological studies, such as,large randomised prospective studies, arerequired to find out if there is any way ofpreventing or slowing progression ofcataract. In particular, the role of diet andantioxidants is controversial, and it may bethat in relatively well-nourished populationssuch as ours, vitamin supplements may nothave much of a role. The twin studysuggests there is a significant genetic riskin age related cataract, so susceptibilitygenes require identification. Identificationof these genes will result in greaterknowledge of the mechanisms of cataractformation which may, in future, lead totreatments to delay development orprogression of cataract.

Reference List

1. Sperduto, R.D. and Hiller, R. (1984).The prevalence of nuclear, cortical andposterior sub-capsular lens opacities ina general population sample.Ophthalmology 91:815-818

2. Klein BE, Klein R, Linton KL. Prevalenceof age-related lens opacities in apopulation. The Beaver Dam Eye Study.Ophthalmology. 1992;99:546-52.

3. Mitchell P, Cumming RG, Attebo K,Panchapakesan J. Prevalence of cataractin Australia: the Blue Mountains eyestudy. Ophthalmology. 1997;104:581-8.

4. Deane JS, Hall AB, Thompson JR,Rosenthal AR. Prevalence of lenticularabnormalities in a population-basedstudy: Oxford clinical cataract grading inthe Melton Eye Study. OphthalmicEpidemiology. 1997;4:195-206.

5. Anonymous. Incidence and progressionof cortical, nuclear, and posteriorsubcapsular cataracts. The Italian-American Cataract Study Group.American Journal of Ophthalmology.1994;118:623-31.

6. Leske MC, Chylack LTJ, Wu SY, et al.Incidence and progression of nuclearopacities in the Longitudinal Study ofCataract. Ophthalmology. 1996;103:705-12.

7. Klein BEK, Klein R, Lee KE. Incidentcataract after a five-year interval andlifestyle factors: the Beaver Dam EyeStudy. Ophthalmic Epidemiology.1999;6:247-55.

8. Hammond CJ, Snieder H, Spector TD,Gilbert CE. Genetic and environmentalfactors in age-related nuclear cataractsin monozygotic and dizygotic twins.New England Journal of Medicine.2000;342:1786-90.

9. Taylor HR, West SK, Rosenthal FS, Munoz B,Newland HS, Abbey H. Effect of ultravioletradiation on cataract formation. NewEngland Journal of Medicine 1988; 319:1429-1433.

10. Flaye DE, Sullivan KN, Cullinan TR, Silver JH,Whitelocke RA. Cataracts and cigarettesmoking. The City Eye Study. Eye 1989; 3:379-384.

11. Leske MC, Chylack LTJ, Wu SY. The LensOpacities Case-Control Study. Risk factorsfor cataract. Archives of Ophthalmology1991; 109: 244-251.

12. Harding JJ, van Heyningen R. Beer,Cigarettes and military work as risk factorsfor cataract. Developments inOphthalmology 1989; 17: 13-16.

13. Nurses study: Hankinson SE, Stampfer MJ,Seddon JM, et al. Nutrient intake andcataract extraction in women: aprospective study. BMJ 1992; 305: 335-339.

14. Sperduto RD, Hu T-S, Milton RC, et al. TheLinxian Cataract Studies. Two nutritionintervention trials. Archives ofOphthalmology 1993; 111: 1246-1253.

15. Harding JJ, Egerton M, van Heyningen R,Harding R. Diabetes, glaucoma, sex, andcataract: analysis of combined data fromtwo case control studies. British Journalof Ophthalmology 1993; 77: 2-6.

About the authorChris Hammond trained as a senior registrar at St Thomas’ Hospital. He was a Fellow at Moorfields Eye Hospital and is now a Consultant at Farnborough Hospital, Bromley NHS Trust.

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Module 3 Part 2

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1 The UK government is aiming for howmany cataract operations per year in its“Action on Cataract” initiative?

a 175 000b 250 000c 1 500 000d 30 million

2 Which one of the following statementsis correct?

a studies investigating cataract are easy tocompare

b cataract grading methods should not besensitive to change

c photographic grading systems are mostreproducible and reliable

d lens opacities usually regress inepidemiological studies

3 Which one of the following statementsis correct?

a genes are important in congenitalcataract

b the genes responsible for age-relatedcataract have been identified

c environmental factors have been shownto be more important than genetic make-up

d genes are unlikely to be important in age-related cataract

4 The heritability of nuclear cataract hasbeen reported as:

a 12%b 38%c 48%d 66%

5 The prevalence of nuclear cataract:a is greater in women than menb is greater in men than womenc is the same in the two sexesd is greatest in the 65-74 age group

6 In patients over the age of 75 years:a posterior subcapsular cataract is the

commonest cataract typeb cortical cataract is present in over 40%c nuclear cataract is rared diabetes is the commonest cause of lens

opacities

7 Which one of the following has NOTbeen shown to be associated withcataract formation?

a high myopiab Marfan’s syndromec myotonic dystrophyd myasthenia gravis

8 Which one of the following isassociated with cortical cataract?

a steroid intakeb smoking c vitamin Dd ultraviolet light

9 The London City Eye Studydemonstrated that:

a alcohol may be related to cataractb ultraviolet light exposure is related to

posterior subcapsular cataractc smoking is associated with cataractd vitamin C is protective in cataract

10 Which one of the following statementsis incorrect regarding cigarettesmoking?

a it is related to the development ofnuclear cataract

b it is related to the development ofposterior subcapsular cataract

c ex-smokers have an increased risk ofdeveloping cataract compared to non-smokers

d it is related to the development ofcortical cataract

11 Hypertension may be related to whichtype of cataract:

a nuclearb corticalc posterior subcapsulard congenital

12 Which one of the following statementsis correct regarding cataract?

a 20 million people will be blind due tocataract by 2020

b cataract is more common in mencompared to women

c tall height may be associated withcataract

d diarrhoea may be associated withcataract

Multiple choice questions -CPD Cataract Epidemiology MCQs

An answer return form is included in this issue.

It should be completed and returned to:

CPD Initiatives (c2983b),

OT, Victoria House, 178–180 Fleet Road, Fleet,

Hampshire, GU13 8DA by March 7, 2001.

Please note there is only ONE correct answer