age related cataract

ORIGINAL ARTICLE

Age-Related Cataract Is Associated with Type 2Diabetes and Statin Use

Carolyn M. Machan*, Patricia K. Hrynchak†, and Elizabeth L. Irving‡

ABSTRACTPurpose. Diabetes has been shown to be a risk factor for age-related (AR) cataract. As statins (HMG-CoA reductaseinhibitors) are now commonly prescribed for patients with type 2 diabetes, their impact on AR cataract prevalence shouldbe considered. This study determines associations between AR cataract, type 2 diabetes, and reported statin use in a largeoptometric clinic population.Methods. In all, 6397 patient files (ages �1–93 years) were reviewed. Overall prevalence of statin use was calculated forpatients with type 2 diabetes (n � 452) and without diabetes (n � 5884). Multivariable logistic regression analysis for ARcataract was performed controlling for patient sex, smoking, high blood pressure, type 2 diabetes, and statin use.Results. The prevalence of statin use (in patients aged �38 years) was 56% for those with type 2 diabetes and 16% forthose without diabetes. Type 2 diabetes was significantly associated with nuclear sclerosis (OR � 1.62, 1.14–2.29) andcortical cataract (OR � 1.37, 1.02–1.83). Statin use was associated with nuclear sclerosis (OR � 1.48, 1.09–2.00) and posteriorsubcapsular cataract (OR � 1.48, 1.07–2.04). The 50% probability of cataract in statin users occurred at age 51.7 and 54.9years in patients with type 2 diabetes and without diabetes, respectively. In non-statin users, it was significantly later at age 55.1and 57.3 years for patients with type 2 diabetes and without diabetes, respectively (p � 0.001).Conclusions. In this population, statin use was substantially higher in patients with type 2 diabetes and was associatedwith AR cataracts. Further long-term study is warranted to recommend monitoring of crystalline lenses in patients withtype 2 diabetes benefiting from statins.(Optom Vis Sci 2012;89:1165–1171)

Key Words: age-related cataract, type 2 diabetes, statins, epidemiology, prevalence

Several studies have identified diabetes as a risk factor forage-related (AR) cataracts.1–6 It has been predicted that bythe year 2025, �300 million people in the world will have

diabetes,7 and a corresponding global increase in AR cataract canbe expected. Studies have shown that taking statins (HMG-CoAreductase inhibitors) reduces cardiovascular risks in patients withdiabetes, even in those without high LDL-cholesterol.8,9 Conse-quently, statins are a class of pharmaceuticals commonly pre-scribed for patients with diabetes. Little work has been donespecifically on the wide use of statins in patients with diabetes andtheir combined impact on cataract development.10 Early clinicaltrials on patients without diabetes did not find significant lenticu-lar changes with statin use of �5 years.11–14 Subsequently, noadverse side effects on the human lens were listed in current drugcompendiums, and manufacturers did not recommend monitor-ing of the crystalline lens. Furthermore, statin use was generally not

controlled for in studies on diabetes and its associations to ARcataract. However, animal studies have clearly shown a correlationbetween cataract development and chronic statin treatment, al-though drug dosages have been generally higher than the clinicallevels given to humans.15–17 A few human population studies havesuggested a protective effect of statin use on cataract risk,18–20

hypothesizing an anti-inflammatory/antioxidant mechanism forthe effect.20 Recently, Hippilsley-Cox and Coupland21 looked atdata for �2 million patients (ages 30–84) in a prospective cohortstudy involving 368 general practices in the United Kingdom. Theeffects of statin type, dose, and duration of use were estimated byCox proportional hazard models. Refuting earlier findings, statinuse was associated with an increased risk of cataract, suggesting thatfurther study is warranted. The type of AR lens opacities [i.e.,nuclear sclerosis (NS), cortical cataract (CC), and/or posterior sub-capsular cataract (PSC)] involved has not been investigated forspecific association with statin use.

Type 2 diabetes accounts for 90% of all cases of diabetes inNorth America.7 Most studies on the risk factors for AR cataracthave included both type 1 and type 2 diabetes. This study com-

*OD†OD, FAAO‡OD, PhDSchool of Optometry, University of Waterloo, Waterloo, Ontario, Canada.

1040-5488/12/8908-1165/0 VOL. 89, NO. 8, PP. 1165–1171OPTOMETRY AND VISION SCIENCECopyright © 2012 American Academy of Optometry

Optometry and Vision Science, Vol. 89, No. 8, August 2012

pared the prevalence of all clinically apparent AR lens opacities insubgroups with type 2 diabetes and without diabetes from a largeclinic population at the University of Waterloo, School of Optom-etry and Vision Science. The prevalence of statin use was alsocompared for these subgroups, and any associations determinedbetween statin use, type 2 diabetes, and AR cataract prevalence.

METHODS

Data Abstraction

The Waterloo Eye Study (WatES) database was developed froma retrospective file review of 6397 patient visits from January 2007to January 2008 at the University of Waterloo, School of Optom-etry and Vision Science. Data were abstracted for several variablesfor cross-sectional analysis. Abstraction methods, data qualityanalysis, study strengths and limitations, and population repre-sentation of the database have been detailed in an earlier arti-cle.22 Furthermore, overall cataract prevalence and the modelingtechnique using logistic regression have been reported previouslyfor this data set, including a comparison between male and femalepatients.23 The abstracted ocular health data in the current inves-tigation included the presence of any clinically apparent AR cata-ract (NS � grade I, LOCS II,2,24 any CC, any PSC, or any historyof related lens extraction [LE] and surgical dates of LE). A report oflens opacity in either eye was accepted as a diagnosis. The systemichealth information included a diagnosis of type 1 diabetes or type2 diabetes and any medication being taken. Patient age was elec-tronically calculated in the database from the date of assessmentand the patients’ birthday, and this information was available forall patient files.

Data Quality and Population Representation

As previously reported, the repeatability of data abstraction wasdetermined through interabstractor agreement rates of 425double-entered clinic files.22 The Cohen � was calculated for cat-egorical data and the intraclass correlation coefficient for continu-ous data. The age and sex distributions of WatES patients withdiabetes were compared with provincial diabetes rates available inthe Ontario diabetes database.25

Outcome Assessment and Statistical Analysis

Patients with type 1 diabetes (n � 61) were excluded, and theremaining patients (n � 6336) were separated into subgroups ofpatients having type 2 diabetes and those not having diabetes, andthen further sorted into patients having any or no AR lens opacity.The overall prevalence (%) of any AR cataract was determined forpatients with type 2 diabetes and without diabetes. Multivariablelogistic regression analysis, which controlled for age, was done todetermine prevalence probability functions for AR cataract in thetwo subgroups.

We have previously shown a sex difference in AR cataracts inthis population, with being female being associated with an in-creased risk of CC.23 Smoking is known to be associated withnuclear sclerosis.1–3,26 Recently, the Malay Study found that be-sides diabetes, the presence of high blood pressure (BP) was asso-ciated with increased odds of having cataract.27 Therefore, sex,

smoking, and high BP were controlled for, when the odds ratio(OR) for a diagnosis of type 2 diabetes and AR cataract prevalencewas calculated through multivariable logistic regression analysis.

Associations between each cataract type (NS, CC, and PSC) andtype 2 diabetes were determined independent of whether theyoccurred in a mixed-type presentation or as homogeneous opaci-ties. There were a significant number of patients with CC or PSCwho also had NS. For this reason, an insufficient number of pa-tients with only CC or PSC were available to consider patients witha single type of opacity in our analysis. Instead, we chose to do amultivariable logistic regression analysis controlling for the afore-mentioned variables as well as the other lens opacity types whenlooking at NS, CC, and then PSC. Patients with monocular LEwere categorized by the cataract type in the other eye. Patients whohad undergone bilateral LE (n � 312) were excluded, as it was notpossible to determine from the database which type of AR cataractexisted pre-surgically. For the remaining patients (n � 6024), ORswere calculated for any association between a diagnosis of type 2diabetes and cataract subtype presence.

Finally, the prevalence of reported statin use was determined forpatients with type 2 diabetes and those without diabetes. A multi-variable analysis was performed to control for age, sex, smoking,high BP, and type 2 diabetes status, to determine any associations(ORs) between statin use and overall AR cataract prevalence, andthen for each AR cataract subtype. Prevalence probability func-tions for AR cataract were determined for each of the followinggroups: (1) patients with type 2 diabetes not taking statins, (2)patients with type 2 diabetes taking statins, (3) patients withoutdiabetes not taking statins, and (4) patients without diabetes takingstatins. The ages at which there was a 50% probability of ARcataracts were determined for patients in each of these groups.

RESULTS

As previously reported, Cohen � statistic values were high forabstraction repeatability of patient sex and the presence of NS, CC,PSC, and LE, as was the intra-class coefficient value for patientage.23 The Kappa value for the presence of diabetes was high at0.99 with �1% disagreement rate between abstractors. The Kappavalue was somewhat lower for overall medications (� � 0.84);however, when considered on its own, the interabstractor agree-ment for statin use was high at � � 0.95, with a disagreement rateof �1%.

Table 1 details patient characteristics for this study. There were61(�1%) patients with type 1 diabetes who were not included inthe remaining analysis. The mean age for the type 2 diabetes sub-group was approximately 14 years older than that for the patientswithout diabetes. Patients without diabetes had a slightly higherproportion of female patients compared with male patients. How-ever, there were fewer female patients compared with male patientswith type 2 diabetes.

The Canadian Diabetes Association used algorithms applied tohealth care administrative data from 1995 to 1999 to create theOntario Diabetes Database (ODD).25 Fig. 1 compares the agedistribution of WatES patients with diabetes (type 1 and type 2diabetes) with the 1999 ODD numbers using their age groupings.The overall rate of diabetes in people �19 years of age was 10.5%for the WatES database in 2007 and 6.2% for the ODD in 1999.

1166 Age-related Cataract, Type 2 Diabetes and Statin Use—Machan et al.


For both databases, women in the 20- to 34-year age-group had aslightly higher prevalence of diabetes than men, but a lower prev-alence in all remaining age-groups. WatES has a lower proportionof patients with diabetes who are �64 years of age, and a slightlyhigher proportion of patients with diabetes in the 35- to 64-yearage range.

The relatively older WatES type 2 diabetes subgroup had 77.0%of its patients with some clinically apparent AR cataract, whereasthe proportionately younger no diabetes subgroup only had 32%.Fig. 2 shows the prevalence of AR cataract in the subgroups inyearly age-groups. Prevalence probability functions determinedwith logistic regression are also shown, and, as expected, AR cata-racts occurred significantly earlier in patients with type 2 diabetescompared with those without diabetes. For this population, a di-agnosis of type 2 diabetes was associated with increased odds ofhaving AR cataracts (OR � 1.86, 95% CI: 1.34–2.59) across thelife span when controlling for age, being female, smoking, and highBP. After multivariable analysis, a diagnosis of type 2 diabetes inthis study group was associated with increased odds of having NS

(OR � 1.84, 1.32–2.56), CC (OR � 1.38, 1.04–1.82), and PSC(OR � 1.52, 1.04–2.19) compared with patients with no diabetes.

The mean age of patients taking statins was 68.5 years (�11.1).Statin use increased with age such that 0.4% of WatES patients�39 years of age, 9.2% of patients between 39 and 59 years, and30.5% of patients �60 years were taking statins. In patients �38years, statin use was reported in 56% of patients with type 2 dia-betes, but only 16% of patients without diabetes. Table 2 showsthe result of multivariable regression analysis that included statinuse. After controlling for age, sex, smoking, high BP, and type 2diabetes, statin use was significantly associated with AR cataract(OR � 1.57, 1.15–2.13), NS (OR � 1.48, 1.09–2.00), and PSC(OR � 1.48, 1.07–2.04), but not CC (OR � 1.02, 0.80–1.30).PSC was no longer significantly associated with type 2 diabeteswhen statin use was considered. CC was still associated with beingfemale (OR � 1.59, 1.30–1.94), and in this analysis, with high BP(OR � 1.24, 1.00–1.53). NS was associated with smoking (OR �1.62, 1.08–2.42).

Table 3 shows the prevalence of cataract in patients (�30 years),sorted by a diagnosis of type 2 diabetes and statin use, in 10-yearintervals. The prevalence of cataract increased at a faster rate inpatients with diabetes who used statins. Similar prevalence levelswere seen in patients with diabetes who did not use statins and inpatients without diabetes who did use statins. The prevalence ofcataract increased at the slowest rate in patients without diabeteswho did not use statins. Fig. 3 demonstrates the result of logisticregression for each of the four groups. The probability of ARcataract in patients who used statins reached 50% at age 51.7 yearsfor patients with type 2 diabetes and at age 54.9 years for patientswithout diabetes. In patients who did not use statins, it was later at55.1 and 57.3 years for patients with type 2 diabetes and withoutdiabetes, respectively.

DISCUSSION

In WatES patients �38 years of age, reported statin use wasalmost 3.5 times higher in patients with type 2 diabetes than inthose without diabetes. Statin use was significantly associated withAR cataract such that the probability of cataract for patients with

TABLE 1.Characteristics of the patients with type 2 diabetes and without diabetes, and a subset of those �38 years of age foreach group

Type 2 Diabetes Without Diabetes

Alln � 452

�38 yearsn � 438

Alln � 5884

�38 yearsn � 3135

Mean age � SD (yr) 64.3 � 12.4 65.3 � 11.1 40.8 � 25.4 61.8 � 13.2Females 194 (42.9) 183 (41.8) 3236 (55.0) 1755 (56.0)Smoking 33 (7.3) 30 (6.8) 273 (4.6) 196 (6.3)High blood pressure 270 (59.7) 268 (61.2) 894 (15.2) 880 (28.1)Statin use 248 (54.9) 246 (56.2) 490 (8.3) 486 (15.5)AR cataracts 348 (77.0) 348 (79.5) 1885 (32.0) 1874 (59.8)Bilateral lens extraction 57 (12.6) 57 (13.0) 256 (4.4) 255 (8.1)Nuclear sclerosis 282 (62.4) 282 (64.4) 1546 (26.3) 1543 (49.2)Cortical cataract 104 (23.0) 104 (23.7) 525 (8.9) 519 (16.6)Posterior subcapsular cataract 44 (9.7) 44 (10.0) 194 (3.3) 192 (6.1)

Presented as the number of patients (%), unless otherwise specified.

FIGURE 1.Prevalence of diabetes (%) as a function of age group for males (M) andfemales (F), in the WatES 2007 and the ODD 1999.

Age-related Cataract, Type 2 Diabetes and Statin Use—Machan et al. 1167


type 2 diabetes who did not use statins was similar to patientswithout diabetes who did use statins. Furthermore, a clinicallymeaningful difference (5.6 years) was found for the age of 50%probability of AR cataract between WatES patients without diabe-tes who did not use statins and those with type 2 diabetes who didtake statins. Specifically, statin use was associated with NS andPSC types of AR cataracts.

The bio-plausibility of these results lies in the fact that the crys-talline lens membrane requires high cholesterol for proper epithe-lial cell development and lens transparency.28 Increased cataractformation has been seen in both animals and humans with hered-itary cholesterol deficiency,28,29 and the risk exists that statins caninhibit cholesterol biosynthesis in the human lens.

Another important finding was that PSC, long associated withdiabetes, was no longer significantly associated with type 2 diabeteswhen statin use was considered. This can be the result of statin usebeing directly associated with PSC in people with diabetes ratherthan diabetes itself. But it may also be the result of too few patients

with type 2 diabetes who are not using statins to reach statisticalsignificance. Also, only a few studies have found diabetes to be arisk factor for NS.4,6,30 However, most studies looked at muchhigher grades of NS than WatES, resulting in weak associationsbetween diabetes and NS. It is possible that NS at these levels tendsto occur at fairly advanced ages where the prevalence of severediabetes diminishes because of increased mortality.31

It is likely that some of the associations found in this study, butnot in previous investigations, reflect the potential additional yearsof statin use compared with earlier studies. Statins are intended forlong-term use and Neutel et al.,32 in their report on statin use inCanada, found that approximately 75% of users continue to takestatins for at least 2 years once they have started. Cenedella28 sug-gests that the long-term impact of statin use requires study periodsof between10 to 20 years.

This study had several strengths. More than 6000 patient visitscontributed to the information in the WatES database providingsignificant statistical power throughout analyses. Age-related cata-

FIGURE 2.The prevalence of AR cataract in WatES patients with type 2 diabetes (n � 452) and patients that do not have diabetes (n � 5884) over the entire lifespan in yearly age-groups. The probability function of AR cataract using logistic regression has been included with 95% confidence intervals.

TABLE 2.Odds ratio (95% CI) for AR cataracts and cataract subtypes: NS, CC, and PSC, in WatES patients using multivariablelogistic regression analysis

Age Female Smoking High BP Type 2 diabetes Statin use

AR cataract 1.22 1.01 1.52 1.21 1.60 1.57(1.20–1.23) (0.82–1.24) (1.03–2.24) (0.95–1.55) (1.13–2.27) (1.15–2.13)

NS 1.21 0.97 1.62 1.21 1.62 1.48(1.19–1.23) (0.79–1.19) (1.08–2.42) (0.95–1.55) (1.14–2.29) (1.09–2.00)

CC 1.08 1.59 0.99 1.24 1.37 1.02(1.07–1.10) (1.30–1.94) (0.63–1.55) (1.00–1.53) (1.02–1.83) (0.80–1.30)

PSC 1.06 0.93 1.06 0.95 1.33 1.48(1.05–1.08) (0.71–1.23) (0.57–1.98) (0.70–1.28) (0.90–1.96) (1.07–2.04)

Note: Patients with type 1 diabetes were excluded.



racts, type 2 diabetes, and statin use were found to be prevalentconditions in this population, especially after 38 years of age, mak-ing them appropriate factors for cross-sectional analysis. The studybenefited from using the criterion of any clinically apparent ARcataract, as opposed to the more commonly chosen advanced levelsof lens opacity. Thus, yearly prevalence levels for overall AR cata-ract approached 100% by the late 70s. Also, the WatES database

included data for all yearly age-groups so that a probability of ARcataract function for the entire human age range could be gener-ated through logistic regression analysis.

Study limitations include the fact that cross-sectional studiescannot determine causation. Because WatES is a clinic population,the results may not be generalizable to the entire population. Forexample, patients with diabetes are encouraged to get routine eye

TABLE 3.Raw data for age-groups �30 years (n � 3985): number of patients in each of the four subgroups, number in eachsubgroup that have AR cataract, and the percentage of the total number in each age-group that have AR cataract

Age-group

30–39 40–49 50–59 60–69 70–79 80�

Type 2 diabetes (N � 447)Statin use

N 4 17 49 77 76 25N with AR cataract 1 5 32 72 75 25% with AR cataract 25.0 29.4 65.3 93.5 98.7 100

No statin useN 7 25 50 51 49 17N with AR cataract 0 3 28 41 49 17% with AR cataract 0.0 12.0 56.0 80.4 100 100

No diabetes (N � 3538)Statin use

N 4 24 64 141 164 93N with AR cataract 0 4 36 123 161 92% with AR cataract 0.0 16.7 56.3 87.2 98.2 98.9

No statin useN 451 692 618 598 476 213N with AR cataract 8 76 214 486 468 213% with AR cataract 1.8 11.0 34.6 81.3 98.3 100

FIGURE 3.Comparison of the probability of AR cataract using logistic regression analysis in four patient groups: having type 2 diabetes and using statins, type 2diabetes and not using statins, no diabetes and using statins, and no diabetes and not using statins. The age of 50% probability of AR cataract is indicatedby a dash line for each of the four groups.



assessments because of their increased risk of ocular disease, andtherefore, we could expect a clinical eye care population to have asomewhat higher percentage of patients with diabetes than thegeneral population.26 Selection bias in clinic-based populationstudies can occur, as patients with symptoms from maturing cata-racts are more likely to seek out vision care than those without.31

Our inclusion of pre-symptomatic levels of cataract should helpoffset this bias. Limitations in available file information did notallow for analysis of type, dosage, or duration of statin use orpatient blood cholesterol levels and their relationships to lens opac-ity. However, the strong association found between statin use andAR cataract in this study indicates a need for additional study toinvestigate these more specific aspects of statin use. Given the highcost of LE to the health care system, further work on the impact ofstatin use on cataract surgery rates is also recommended.

Regardless of the outcome of further study, the benefits of statinuse in people with type 2 diabetes are anticipated to continue tooutweigh any associated increased risk of AR cataract. However,given the known financial and functional burdens, both in terms ofsurgical costs and visual impairment when surgery is inaccessible orpending,26,33–36 it is important to identify and minimize factorsthat accelerate cataract development. Information provided herecan serve public health efforts to educate people on the risks oftreatments associated with type 2 diabetes. It also supports currentefforts to curtail type 2 diabetes prevalence trends. Finally, resultsfrom further investigation into these associations may encouragethe development of alternative medications for lowering cho-lesterol that are not associated with an increased risk of cataractdevelopment.37

ACKNOWLEDGMENTS

We thank Linda Lillakas of the University of Waterloo, School of Optometryand Vision Science for help with the preparation of the manuscript. This workwas supported by NSERC (Canada) and CRC (Canada) to ELI and presentedin part at the American Academy of Optometry, Boston MA, October 12–15,2011.

Received: February 8, 2012; accepted May 10, 2012.

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Elizabeth L. IrvingSchool of Optometry

University of Waterloo200 University Ave W.

Waterloo, OntarioCanada N2L3G1

e-mail:[email protected]



http://one.aao.org/CE/PracticeGuidelines/PPP.aspx

http://one.aao.org/CE/PracticeGuidelines/PPP.aspx

http://www.aoa.org/documents/CPG-8.pdf

age related cataract

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