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(Investigative Ophthalmology and Visual Science. 2001;42:1449-1454.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Refractive Errors and Incident Cataracts: The Beaver Dam Eye Study

Tien Yin Wong1,2,3, Barbara E. K. Klein1, Ronald Klein1, Sandra C. Tomany1 and Kristine E. Lee1

1 From the Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison; 2 Singapore National Eye Center and National University of Singapore; and the 3 Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
PURPOSE. To describe the relation between refractive errors and incident age-related cataracts in a predominantly white US population.

METHODS. All persons aged 43 to 84 years of age in Beaver Dam, Wisconsin, were invited for a baseline examination from 1988 through 1990 and a follow-up examination 5 years later from 1993 through 1995. At both examinations, participants had refraction and photographic assessment of cataract, according to a standardized protocol. Myopia was defined as a spherical equivalent of -1.0 diopters (D) or less, hyperopia as +1.0 D or more. The relations between refractive errors at baseline and cataract at baseline (prevalent cataract), 5-year incident cataract, and incident cataract surgery were analyzed by using generalized estimating equations.

RESULTS. When age and gender were controlled for, myopia was related to prevalent nuclear cataract (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.23–2.27), but not to cortical and posterior subcapsular cataracts. Myopia was not related to 5-year incident nuclear, cortical, and posterior subcapsular cataracts, but was related to incident cataract surgery (OR 1.89; CI 1.18–3.04). Hyperopia was related to incident nuclear (OR 1.56; CI 1.25–1.95) and possibly cortical (OR 1.25; CI 0.96–1.63) cataracts, but not to posterior subcapsular cataract or cataract surgery. After further adjustment for diabetes, smoking, and education, the association between myopia and incident cataract surgery was attenuated (OR 1.60; CI 0.96–2.64), but the associations between hyperopia and incident nuclear and cortical cataracts were unchanged.

CONCLUSIONS. These data support the cross-sectional association between myopia and nuclear cataract seen in other population-based studies, but provide no evidence of a relationship between myopia and 5-year incident cataract. Hyperopia may be related weakly to incident nuclear and cortical cataract.


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The relation between refractive errors and risk of age-related cataract is not clear. Earlier studies have suggested that high myopia may be associated with development of cataract,1 2 3 but less is known regarding the association with mild and moderate levels of myopia or hyperopia. Existing data have been derived largely from clinic-based studies, which are subject to selection biases.4 5 6 7 To our knowledge, only one population-based study has attempted to specifically evaluate the relation between refractive errors and cataract in detail. In the Blue Mountains Eye Study in Australia, current myopic refraction and early-onset myopia (defined as self-reported history of distance spectacle use before age 20 years) were related to prevalent posterior subcapsular cataract.8 However, the cross-sectional study design cannot adequately differentiate cause and effect, which is particularly problematic when dealing with whether refractive errors are risk factors for cataract, because cataract (e.g., nuclear sclerosis) is also known to affect refraction (e.g., myopia).2 9

The purpose of this study was to evaluate the relation between refractive errors and prevalent cataract, 5-year incident cataract, and incident cataract surgery, in the Beaver Dam Eye Study cohort.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Study Population
The Beaver Dam Eye Study is a population-based study of ocular diseases in adults. Its population, research methodology, and findings described in detail in other reports.10 11 Briefly, a private census of the population of Beaver Dam, Wisconsin, was performed from fall 1987 through spring 1988. All 5924 people who were 43 to 84 years of age were invited for baseline examinations from spring 1988 through fall 1990. The population was composed of predominantly white persons (99%). Of eligible persons, 4926 participated in the baseline examination. All subjects identified during the initial census were invited for a second examination 5 years after the first. Of the 4541 participants from the baseline examination surviving, 3684 (81.1%) returned for the follow-up examination from spring 1993 through summer 1995. Comparisons between participants and nonparticipants at baseline10 and follow-up11 have been presented elsewhere.

Procedures
The examination procedures for refraction and lens assessment at both baseline and follow-up were based on the same standardized protocol described in detail elsewhere.9 12 13 14 Tenets of the Declaration of Helsinki were followed. Refraction was obtained as follows: documentation of the refraction in the participant’s current prescription (if available) was followed by a standardized refraction using an automated refractor. The refraction was then refined according to a modification of the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol to obtain the best corrected visual acuity, when the automated refraction yielded visual acuity of 20/40 or worse.14 Interexaminer and intraexaminer comparisons showed no significant differences among examiners for the refractions obtained.

For the evaluation of cataracts, after pupil dilation, photographs were taken of the lens, by using slit lamp and retroillumination cameras.15 The photographs were subsequently graded for the presence and severity of cataract. The grading procedure was based on detailed codified decision rules, by graders masked to subjects’ identities and characteristics (and presence or severity of lens opacities at baseline when grading photographs from the follow-up examination). Scores for nuclear sclerosis were based on comparisons with standard photographs that included a five-step level of severity based on opacity of the nucleus.15 Scores for cortical and posterior subcapsular cataracts were based on weighted estimates of degree of opacity of lens area as defined by a circular grid, divided into eight pie-wedged peripheral areas and a central circular area.15 In general, overall reproducibility was good and was similar for inter- and intragrader comparisons.12 13

During the course of the standardized interview, questions were asked about education, diabetes status, and cigarette smoking, among other variables.

Definitions
Refraction status was defined according to refraction at the baseline examination.9 The results of the automated refraction were used in the analyses for 96% of eyes at baseline, the results of ETDRS refraction were used in 4% of eyes, and refraction from the current prescription was used in the remaining subjects (<1% of eyes). Eyes without a lens, with an intraocular lens, or with best corrected visual acuity of 20/40 and worse were excluded. For this analysis, myopia was defined as a spherical equivalent of -1.00 diopters (D) or less, hyperopia as a spherical equivalent of +1.00 D or more, and emmetropia as a spherical equivalent of between -0.75 and +0.75 D.

Definitions for lens opacity at the baseline (referred to as prevalent cataract) and follow-up examinations (5-year incident cataract, and 5-year progression of lens opacity) have been described in other publications.12 13 In summary, prevalent or incident cataract was defined according to the following specific criteria: nuclear sclerosis of level 4 or more, cortical opacities involving 5% or more of the lens surface, and posterior subcapsular opacities involving 5% or more of a grid segment. A prevalent cataract was a specific lens opacity of this severity at the baseline examination, whereas an incident cataract was based on the development of that opacity at the follow-up examination in eyes free of the specific lesion at baseline. Progression referred to an increase in the severity or involvement by that specific opacity, according to the following criteria: nuclear sclerosis as a change of one level and cortical and posterior subcapsular opacities as a change of 0.75 units or more after the square-root transformation of the data (to account for the increase in variability of estimated area of involvement as the base amount increased). The rationale and interpretation of the criteria for progression are described in more detail in other reports.13

Incident cataract surgery was defined as the absence of the lens in the follow-up examination, if the lens was present at baseline.16 Exceptions were lenses removed for a reason other than cataract.

All other characteristics in this analysis were defined from baseline data. Age was defined as the age at the time of the baseline examination. Diabetes mellitus was defined as a history of known diabetes (treated with insulin or oral hypoglycemic drugs and/or diet) or elevated glucose and glycosylated hemoglobin, based on specific criteria.17 Cigarette smoking was defined as having ever smoked (100 cigarettes or more in a lifetime) or having never smoked (fewer than 100 cigarettes). Education level was categorized into four levels (fewer than 12 years, 12 years, 13–15 years, and >15 years).

Statistical Analysis
Of the 4926 persons examined at the baseline examination, 4533 had phakic eyes and had best corrected visual acuity of 20/40 in at least one eye. Of these, 63 had evidence of direct trauma, ungradable lens, or missing lens data in both eyes, leaving 4470 persons available for the analysis of prevalent cataract. Analyses of 5-year incidence of cataract were based on the 3684 persons who participated in both baseline and follow-up examinations. Persons were excluded if both eyes (1) had no lens, had an intraocular lens, had best corrected visual acuity of worse than 20/40 at baseline, or were missing refraction data (n = 209) or (2) had prevalent cataract at baseline, had an ungradable lens, or had missing lens data either at baseline or at follow-up (n = 422). This left 3053 persons for incident cataract analyses.

Initially, data from left and right eyes were analyzed separately. For regression models, we used data from both eyes, based on the generalized estimating equation method described by Zeger et al.18 and Liang and Zeger.19 This method allows use of data from both eyes, adjusting for the correlation between the two eyes in a single person. Age- and gender-adjusted odds ratio (OR) and its 95% confidence interval (CI) were calculated for a specific cataract type, in the presence of different severities of refractive errors compared with emmetropia. In multivariate models, we controlled for diabetes, smoking, and education—variables that were associated with the presence or development of cataract in our population. For models with cortical and posterior subcapsular cataract, we further adjusted for presence of nuclear cataract at baseline, because nuclear sclerosis increases the refractive index of the lens and lens power.9 All statistical analyses were performed by computer (SAS software; SAS Institute, Inc., Cary, NC).


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Comparison of persons included (n = 4470) and excluded (n = 456) in the prevalent cataract analyses is presented in Table 1 . In general, persons excluded were older, more likely to be women, and less likely to be smokers; had higher systolic and diastolic blood pressure and lower education and income; and had higher prevalence of diabetes at baseline. A similar comparison is shown for the 3053 persons included in the incident cataract analyses (Table 1) . Persons excluded were also older and more likely to be women; had higher blood pressures and lower education and income; and had higher prevalence of diabetes at baseline.


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Table 1. Comparison of Persons Included and Excluded from Analyses, by Baseline Characteristics

 
Among persons included in the prevalent cataract analyses, the frequency of myopia and hyperopia (either eye meeting the definition at baseline) was 25.5% and 45.8%, respectively. In comparison, the corresponding frequencies were 26.9% and 42.5% among persons included in the incident cataract analyses. The prevalence of cataract (either eye meeting the definition at baseline) was 14.3% for nuclear, 14.4% for cortical, and 4.4% for posterior subcapsular.

The crude rates of nuclear, cortical, and posterior subcapsular cataracts, by refractive errors are shown in Table 2 (results shown on right eyes; results for left eyes were similar and are not presented). For these analyses, myopia and hyperopia were also divided into three categories, based on approximately equal frequency in each category. In general, hyperopia was associated with a higher prevalence and 5-year incidence and progression of cataracts. Increasing severities of hyperopia were also associated with increasing frequencies of nuclear and cortical, but not posterior subcapsular, cataracts.


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Table 2. Prevalence and 5-Year Incidence and Progression of Nuclear, Cortical, and Posterior Subcapsular Cataract, by Refractive Status

 
The age- and gender-adjusted ORs for nuclear, cortical, and posterior subcapsular cataracts, by refractive error, are shown in Table 3 . Myopia was related to prevalent nuclear (OR 1.67; CI 1.23–2.27), but not cortical and posterior, subcapsular cataracts. Myopia was not related to 5-year incidence or progression of nuclear, cortical, or posterior subcapsular cataracts.


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Table 3. Age- and Gender-Adjusted Odds Ratios of Nuclear, Cortical, and Posterior Subcapsular Cataract, by Refractive Errors

 
Hyperopia was related to prevalence (OR 1.25; CI 0.99–1.57), 5-year incidence (OR 1.56; CI 1.25–1.95), and 5-year progression (OR 1.22; CI 1.07–1.39) of nuclear cataract. Hyperopia was also weakly related to incidence (OR 1.25; CI 0.96–1.63) and progression (OR 1.18; CI 0.99–1.41) of cortical cataract, but not of posterior subcapsular cataract. The age- and gender-adjusted relation between refractive errors and 5-year incident cataract surgery is shown in Table 4 . Myopia, but not hyperopia, was related to incident cataract surgery.


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Table 4. Age- and Gender-Adjusted Odds Ratios of Incident Cataract Surgery, by Refractive Errors

 
When diabetes, smoking, and education were controlled for, most associations were similar to the age- and gender-adjusted ORs (Table 5) . Myopia was significantly related to prevalent nuclear cataract and possibly incident cataract surgery. Hyperopia was related to incidence and progression of nuclear, and possibly cortical, cataracts.


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Table 5. Multivariate-Adjusted Odds Ratios of Nuclear, Cortical, and Posterior Subcapsular Cataract, by Refractive Errors

 
Finally, analyses with refraction treated as a continuous independent variable (0.25-D increments) showed no consistent patterns of association (data not shown).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Both refractive errors and age-related cataracts are common ocular conditions. In the United States, three quarters of adults have refractive errors,14 20 whereas one quarter have age-related cataracts.21 A number of population-based studies in different ethnic groups have demonstrated a strong and consistent cross-sectional association between myopia and age-related nuclear cataract.8 22 23 24 25 26 The association between myopia and prevalent nuclear cataract in our study is consistent with these data. However, this association is difficult to explain and has been attributed in part to increasing lens power due to increasing density of lens nucleus with age.27 In support of this hypothesis is the observation in Beaver Dam that persons with severe nuclear sclerosis at baseline were more likely to have a myopic change in refraction after 5 years, compared with no change or a hyperopic change in persons with only mild nuclear sclerosis.9

A more relevant and important issue is whether refractive errors are risk factors for age-related cataract. Anecdotal evidence and clinic-based studies have suggested that myopia, particularly severe and pathologic myopia, may increase the risk of cataract.1 2 3 4 5 6 7 Few data are available from population-based studies regarding risk of cataract in persons with mild to moderate myopia or hyperopia. The Blue Mountains Eye Study recently looked at refractive errors and risk of age-related cataract in an Australian population.8 Early-onset myopia, defined as a self-reported history of distance spectacle use before 20 years of age and excluding eyes with hyperopia, was associated with a four times higher odds of posterior subcapsular cataract detected during the survey, when participants were 49 to 98 years of age. Further, a graded cross-sectional association was shown between increasing levels of myopia and odds of prevalent posterior subcapsular cataract. The authors therefore suggested that myopia could be a risk factor for the development of posterior subcapsular cataract. However, the study was cross-sectional in design, and the definition of early-onset myopia may be unreliable, because it was based on self-reported data, which are dependent on memory and interpretation of the interview question. In the Beaver Dam study, the relations between a history of wearing distance spectacles, age of first use of distance spectacles, and prevalent age-related cataracts were inconsistent.28

This analysis provides objective documentation of the 5-year risk of age-related cataract in adults with mild and moderate severities of refractive errors. We could not find a clear association between myopia and 5-year incidence or progression of nuclear, cortical, and posterior subcapsular cataracts. Hyperopia may be related weakly to incidence (OR 1.55) and progression (OR 1.24) of nuclear cataract and possibly to incidence (OR 1.27) and progression (OR 1.20) of cortical cataract.

We are unable to explain the relation between hyperopia and incident nuclear or cortical cataract. In a previous analysis, we observed an association between thinner lens and incident cortical cataract.29 A cross-sectional association between hyperopia and nuclear cataract has also been noted in the Blue Mountains Eye Study.8 Oxidative lens damage appears to occur early in myopic eyes, but it is not known whether similar changes take place in hyperopic eyes.30 31 Further research in this area is warranted. In any case, the associations we observed were weak, and it is possible that these results were related to chance.

We also found an association between myopia and 5-year risk of cataract surgery. The underlying reason is likely to be complex, because many factors are related to incident cataract surgery in our population.16 Because posterior subcapsular cataract was the most important lens opacity predicting the need for cataract surgery,16 it is possible that the higher risk of cataract surgery may be related to the development of posterior subcapsular cataract in myopic eyes during the 5-year interval. However, we cannot verify this. Another possible explanation is that persons with myopia may have had more frequent interactions with ophthalmologists and other eye-care providers, and may have been more likely to have cataract surgery during the 5-year interval between baseline and follow-up.

Significant strengths of this study include a large sample size and use of data from both eyes, high response rate at both baseline and follow-up examinations, standardized protocol for refraction and masked photographic grading of cataract, and ability to control for other known cataract risk factors. However, there are several important limitations that warrant consideration. First, our definitions of myopia and hyperopia were based on refraction data obtained in adults 43 to 84 years of age at the time of the baseline examination. As a result, it is difficult to estimate the effects of axial and early- or childhood-onset myopia and risk of cataract. Studies with precise refractive data collected early in life or with axial length and keratometry data would be useful in evaluating these associations. Second, the population is composed mainly of white persons with a relatively low prevalence of myopia. We did not have a sufficient number of high myopes to examine its relation to incident cataract (number of persons with less than -6.0 D in their right eyes; n = 20). Our data may therefore not be applicable to other groups (e.g., Chinese) with a higher prevalence of severe myopia.25 Third, selection biases may have masked some association and accentuated others. For example, the failure to observe an association between myopia and cataract may be due to the excluded persons’ having a higher prevalence of both hyperopia and cataract. Finally, as in any observational studies, we may be unable to control for unmeasured cataract risk factors or other confounders.

In summary, our study supports the cross-sectional association between myopia and nuclear cataract seen in other population surveys, but provides no evidence of an association between mild and moderate levels of myopia and 5-year risk of cataract. Hyperopia may be related to incident nuclear and cortical cataract. Other prospective studies in populations with a higher prevalence of severe refractive errors, perhaps supplemented with ocular biometry data, may yield further information regarding these associations.


    Footnotes
 
Supported by an American Diabetes Association Mentor Fellowship Award and the National University of Singapore (TYW); and National Institutes of Health Grant EYO6594 (RK, BEKK). RK is the recipient of a Senior Scientific Investigator Award from Research to Prevent Blindness.

Submitted for publication November 14, 2000; revised January 30, 2001; accepted February 16, 2001.

Commercial relationships policy: N.

The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Corresponding author: Tien Yin Wong, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 610 North Walnut Street, 460 WARF, Madison, WI 53705-2397. wong{at}epi.ophth.wisc.edu


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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