Place-based exposure and cataract risk in the Beaver Dam cohort.
Cataracts are common concomitants of aging, and restoration of vision after the effects of cataracts usually requires surgery The cost of cataract surgery and related doctor visits to Medicare in 2010 was budgeted at $3.2 billion (Lane & Aggarwala, 2010). While cataract surgery is effective, complications of such surgery exist. As longevity increases, the number of persons having cataract surgery is likely to rise. Thus, diagnosis of cataracts imposes a health burden to the individuals involved and to health care costs for society.
Three types of age-related cataracts include nuclear, cortical, and posterior subcapsular. While the most important risk factor for each type of cataract is age, evidence suggests different factors may increase risk, and those factors appear to differ among the three types. For example, smoking is associated with increased risk of nuclear cataract, diabetes with cortical cataract, and steroid medications with posterior subcapsular cataract (PSC). Conversely, statin medications appear to decrease the risk of nuclear cataract (Klein, Klein, Lee, & Grady, 2006).
Several environmental exposures have been associated with eye diseases. For example, high-dose whole body radiation exposure is associated with cataracts (Blakely et al., 2010; Little, 2009), occupational exposure to ionizing radiation is associated with posterior lens changes (Ciraj-Bjelac et al., 2010), and the more conventional exposure to environmental UV-B in ambient light is associated with cortical cataracts (Cruickshanks, Klein, & Klein, 1992). Other environmental exposures, such as lead, gold, copper, and heavy metals have been hypothesized to increase the risk of developing cataracts (Ernst, Baltzan, Deschenes, & Suissa, 2006; Schaumberg et al., 2004).
Efforts to identify modifiable risk factors continue. In the Beaver Dam cohort, data were available for the established risk factors for cataracts as well as geocoded residential locations, which allowed us to characterize the cohort by location. In addition, exploratory spatial analyses utilized environmental monitoring data of rural well water to evaluate cataract risk. We hypothesized that rural living may be associated with the development of specific cataract types in older adults.
Methods used to identify and describe the population have appeared in detail in previous reports (Klein, Klein, & Lee, 1996; Klein, Klein, Lee, Cruickshanks, & Chappell, 2001; Klein, Klein, Lee, Cruickshanks, & Gangnon, 2006; Klein, Klein, Linton, & De Mets, 1991; Linton, Klein, & Klein, 1991). In brief, a private census of the population of Beaver Dam, Wisconsin (99% white), was performed from fall 1987 to spring 1988 (Linton et al., 1991). Of the 5,924 enumerated persons 43-84 years of age, 4,926 participated in the baseline examination in 1988 to 1990. In the three follow-up examinations, 3,722, 2,962, and 2,375 persons participated in the 5, 10, and 15-year follow-up examinations, respectively (Klein et al., 1996; Klein et al., 2001; Klein et al., 2006; Klein et al., 1991). Tenets of the Declaration of Hel sinki were followed, institutional human experimentation committee approval from the University of Wisconsin was granted, and informed consent was obtained from all subjects in the form of a signature verifying they had read an explanation of procedures and policies and agreed to them. During the study visit, standard measurements were made and a codified questionnaire was administered.
Photographs of the lenses were taken with two different cameras: a slit-lamp camera and a retroillumination camera (Klein, Klein, Linton, Magli, & Neider, 1990). The pupil diameter at the time of the baseline photographs was recorded on the examination form for each of the two subsequent examinations. The grading procedures for the lens were based on detailed codified decision rules (Klein et al., 1990). Graders were masked to subject identity and personal characteristics. Scores for nuclear sclerosis were based on comparisons with standard photographs. The scale has five levels of severity based on opacity of the nucleus, with 1 indicating no opacity and 5 indicating a great amount of opacity. Levels 4 and 5 were considered to be cases of nuclear cataract in this and previous publications of prevalence data (Klein, Klein, & Linton, 1992). Scores for cortical cataract and PSC were based on weighted estimates of the degree of opacity of the lens area, as defined by a circular grid, divided into eight pie-wedge shaped peripheral areas and a central circular area overlaid on the photograph (Klein et al., 1990). Cases of cortical cataract were those with opacity of 5% or more of the lens surface. PSC opacity was defined as 5% or more of a grid segment. The classification of cataract types corresponded to a lens opacity of sufficient severity that a clinical ophthalmologist would label it as a cataract (Klein et al., 1990). The estimates of incidence were based on all persons having corresponding gradable subfields at all visits.
Geocoding Participants' Location
Participants' street mailing addresses at the baseline examination were assigned latitude and longitude coordinates (i.e., geocodes) to the address point location with an 80% spelling and 80% overall sensitivity score using ArcView GIS 3.2. For unmatched addresses using street address, the nine digit ZIP code line segment centroid was used as the geocode. For the remaining unmatched addresses, the 1990 ZIP code centroid was used.
To examine location as a risk factor, the authors assigned participants who lived in the ZIP code of 53916 (Beaver Dam, Wisconsin) at baseline an edge, urban, or rural classification. "Edge" was defined as living within a buffer zone, i.e., within a quarter mile of either side of the Beaver Dam incorporated boundary in 1990 (U.S. Census Bureau, 2005). "Urban" was defined as living within the Beaver Dam incorporated area in 1990 but not within the buffer zone. "Rural" was defined as not living in either the Beaver Dam incorporated area or the buffer zone in 1990 but within the ZIP code of 53916 (Figure 1). For exploratory analysis of rural participants' exposure to nitrate-nitrogen exposure from drinking private well water, the authors reclassified the geocoded locations as living outside of the incorporated area of Beaver Dam (rural) or not.
Nitrate-Nitrogen Well Water Data
We obtained publicly available data on nitrate-nitrogen contamination of groundwater from the Wisconsin Department of Agriculture, Trade and Consumer Protection (WDATCP). As part of the Atrazine Rule Evaluation Study, WDATCP randomly sampled 289 private wells using a stratified random sampling procedure to analyze the groundwater for various herbicides and nitrate-nitrogen in 1994 (Baldock, 1993; LeMasters & Baldock, 1997; Vanden Brook et al., 2002). These samples were analyzed using gas chromatography for nitrate-nitrogen by the WDATCP's Bureau of Laboratory Science. Wisconsin residents living outside of incorporated city or village boundaries rely on private wells located near their residences for their drinking water.
Natural neighbor interpolation (Sibson, 1981) was used to estimate nitrate-nitrogen levels in groundwater across the entire state. Natural neighbor interpolation uses a weighted moving average of concentrations of nitrate-nitrogen residues in residential drinking water in surrounding or neighboring observed wells. Neighboring points and the corresponding weights are based on the Voronoi diagram of the data points (Okabe, 2000). The Voronoi diagram of a set of points is a partitioning of the plane into regions associated with each point such that every point in a given partition is closer to the generating point than any other point. This interpolation was performed using ArcGIS 9.3.
Variables used in the analyses were age at examination; educational status (four categories: less than high school graduate, high school graduate or GED, some college or baccalaureate degree, and graduate or professional school [e.g., law, medicine]); income (dichotomous, defined as reported annual household income of [less than or equal to] $29,000 or [greater than or equal to] $30,000); history of comorbitidities (cardiovascular disease, cancer, and diabetes; all were dichotomous); reported drinking alcohol at least one time in the previous year (dichotomous); steroid use (dichotomous; defined as currently taking any steroid medication); and smoking status (three categories: current, former, and never). A never smoker was defined as someone who had smoked less than 100 cigarettes in his or her lifetime; a former smoker had smoked at least 100 cigarettes in his or her lifetime but was not currently smoking every day or some days; a current smoker was defined as smoking at least 100 cigarettes in his or her lifetime and currently smoking every day or some days. Level of physical activity was also included in the analyses; a sedentary lifestyle was defined as engaging in physical activity that caused sweating fewer than three times per week, and an active lifestyle was defined as engaging in physical activity that caused sweating three or more times per week.
Incidence of cataract was calculated separately for each eye for each type of age-related cataract, taking into account the competing risk of death and cataract surgery. For the incidence of a particular cataract type, the population at risk included all eyes free of that cataract type and cataract surgery at baseline. The 15-year cumulative incidence was calculated for each eye separately, and was reported for the right eye only (Table 2) (Kaplan, 1958). Odds ratios (OR), confidence intervals (CI), and p-values were modeled by incorporating data from both eyes, using general estimating equation (GEE) techniques to account for correlation between the eyes (Table 2) (Hosmer & Lemeshow, 1989). SAS version 9 was used for all analyses (Klein, Klein, & Moss, 1997).
Those eyes whose lenses were removed due to trauma or in conjunction with ocular surgery unrelated to cataract were excluded. Other specific characteristics caused an eye to be excluded from the calculation of incidence of an age-related cataract; these included intraocular surgery, invasive intraocular trauma, confounding lens lesions in the photographs, absence of a photograph, or ungradable photograph at the baseline or follow-up examination. Analyses are based on those persons who lived within the ZIP code of 53916 (Beaver Dam) at the time of the baseline examination and had a geocode match to the address or nine-digit ZIP code.
Of the 3,684 people seen at baseline and then at follow-up, 48 were excluded for residing outside of the 53916 ZIP code and six more were excluded because they had geocodes of their ZIP code centroid. In other words, for these six participants, their specific location within Beaver Dam ZIP code could not be ascertained; they could have lived within the city limits, in the edge, or in the rural part of the ZIP code. Of the remaining 3,630 eligible participants, 268 people were excluded from all analyses for right eye cataract and 254 were excluded from all analyses for left eye cataract due to surgery or trauma. An additional 217 were excluded from right eye analyses and 204 were excluded from left eye analyses due to missing or ungradable photos (including those with confounding lesions). Overall, a total of 377 participants were excluded from all analyses for both eyes, and 3,253 participants contributed to GEE modeling for at least one outcome.
Characteristics of all participants in the Beaver Dam Eye Study cohort were similar to the participants contributing to these study analyses (data not shown). Rural residents tended to be statistically younger, male, less educated, more sedentary, and never smokers compared to urban residents, and edge residents tended to be less educated than urban residents (Table 1).
The cumulative incidence of each cataract endpoint by urban/rural/edge home location indicates slight differences in cumulative incidence among the three cataract types (Table 2). Within each type of cataract, compared to those living in urban areas, the lowest incidences were for those living in rural areas and then those living in the edge areas. Compared to urban residents, the OR (95% CI) for rural participants' risk of cortical cataract, nuclear cataract, and PSC were 0.92 (0.73, 1.16), 0.85 (0.69, 1.06), and 0.71 (0.48, 1.05), respectively, controlling for age, sex, smoking status, and educational status (Table 2). Adding other important covariates listed in Table 1 as well as duration of residence from baseline by location did not alter the results. Little change occurred in ORs when we included the number of years living in the same location.
To further examine potential effects of place of residence on cataract risk, we evaluated rural residents (n = 640) who lived outside of the Beaver Dam city limits but within the Beaver Dam Zip code of 53916 and their relative exposure to nitrate-nitrogen in their drinking water. Compared to rural residents with nitrate-nitrogen exposure of less than 5 parts per million (ppm), rural residents whose well water had concentrations of nitrate-nitrogen of 10 ppm (OR; 95% CI) had higher odds of developing cortical cataract (1.37; 0.81, 2.31), nuclear cataract (0.97; 0.58, 1.61), and PSC (1.23; 0.50, 3.05), although the relationships were not statistically significant after adjusting for age, gender, educational status, and smoking (Table 3). No apparent effect occurred of quantity of water consumed or of use of a water filter in the home water system on these relationships (data not shown).
In our study, the Beaver Dam cohort did not have an increased risk of cataracts if they lived in a rural environment, after adjusting for age, sex, educational status, and smoking status. Rather, they seem to have been at a reduced risk, though not statistically significant. A strength of our study is presence and type of cataract determined by objective grading of standard images from their cohort. Furthermore, data were prospectively collected on established risk factors for cataracts and adjusted for those that vary by urban, edge, or rural status.
Before we began these analyses, we hypothesized that differences might exist in cataract incidence related to location. Historically, the known disparity in health of individuals living in a rural environment compared to those living in an urban environment have documented differences in health care access and utilization, cost, and geographic variations in providers, specialists, and services (Hartley, 2004). With an increased use of multilevel modeling, environment-specific factors are also being studied to understand the differences in health outcomes between urban and rural residents (Verheij, 1996). Although virtually all support the concept that life in the country is different from life in town, the specifics related to these differences particularly as they pertain to environmental exposures have yet to be fully characterized. We could not find any literature that addressed variations in cataract risk within a small geographic area that related to rural and small city residents. In comparing cataract risk for those living in a rural setting to those living in a small city, we found a nonstatistically significant reduced risk for rural residents. We were unable to identify the factor or factors that led to this finding from data collected in our longitudinal study.
To evaluate location beyond categorizing residential location as urban, edge, or rural, we also explored the potential relationship of nitrate-nitrogen exposure from drinking water and cataract risk. The source of nitrate-nitrogen in drinking water is from applications of it along with other agricultural chemicals to agricultural fields (Vanden Brook et al., 2002). The Safe Water Drinking Act of 1996 sets the maximum allowable level of nitrate-nitrogen in public drinking water at 10 ppm. This level is based on an association of incidence of methemoglobinemia (blue baby syndrome) and exposure to nitrate-nitrogen in drinking water (Johnson & Kross, 1990). Unlike public drinking water, no regulations exist on private drinking water regarding testing or remediation of contaminants. In Wisconsin, the percentage of private wells with nitrate-nitrogen levels [greater than or equal to] 10 ppm has remained steady at approximately 9% (Brandt et al., 2008). In the segment of the population that might have had significant exposure to agricultural chemicals (i.e., rural persons who use well water), measured by 10 ppm nitrate-nitrogen exposure in drinking water, the authors did not see a difference in relative risk of cataracts compared to those with low levels of nitratenitrogen exposure (<5 ppm). This finding provides some evidence that exposure to agricultural chemicals in drinking water may not influence cataract risk.
Inferences from our study should be drawn cautiously due to several limitations. Our study was performed in a relatively small city in the Midwestern U.S. Urban-rural differences in exposures in this setting are likely to differ from urban-rural differences in and around larger cities, so these data may not reflect differences elsewhere. The Beaver Dam cohort is virtually entirely of northern European ancestry; differences in ethnicity and genetic background may affect susceptibility to cataract risk factors and this may differ in urban and rural environments. We were not able to evaluate gene-environment interaction. Another limitation of our study was the relatively small sample size in which a small or modest effect size may not have been able to be detected. The nitrate-nitrogen exposure assessment used interpolated values from a relatively small number of randomly selected wells, which could not take into consideration any geological variation in water distribution. Finally, no data were collected on complete water consumption habits, including source of water. Therefore, only exposure to residential drinking water was evaluated.
These results suggest that further research of differences associated with environmental exposures in cataract incidence is necessary, as cataract is a common condition responsible for functional disability. In evaluating nitrate-nitrogen exposure through drinking water, results suggest that exposure to agricultural chemicals in rural drinking water was not a likely source of cataract risk. We were unable to identify any specific factor or factor(s) associated with a reduced cataract risk for rural residents compared to small city residents. Identifying modifiable risk factors may result in decreased incidence of this condition. This would provide a benefit to quality of life and to reduced medical costs.
Acknowledgements: We thank Stan Senger, environmental quality section supervisor at WDATCP for the private well water data. We also thank Michael Hardy, GIS specialist at the University of Missouri Center for Applied Research and Environmental Systems for his assistance with the orthophotograph of Beaver Dam and GIS. This work was supported by a grant from the National Eye Institute, National Institutes of Health (EY05694); and, in part, by Research to Prevent Blindness (R. Klein and B.E.K. Klein, Senior Scientific Investigator Awards). The content of this article is solely the responsibility of the authors and does not necessarily reflect the official views of the National Eye Institute or the National Institutes of Health.
Corresponding Author: Jane A McElroy, Assistant Professor, University of Missouri, Family and Community Medicine Department, MA306, Medical Science Building, 1 Hospital Drive, Columbia, MO 65212. E-mail: firstname.lastname@example.org.
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Jane A. McElroy, PhD
University of Missouri-Columbia
Barbara E.K. Klein, PhD, Kristine E. Lee, MS, Kerri P. Howard, MS, Ronald Klein, PhD
University of Wisconsin-Madison
TABLE 1 Participant Characteristics by Urban/Edge/Rural Residential Status in the Beaver Dam Eye Study Characteristics Urban Edge p-Value p-Value (a) (n = 2263) (n = 540) Crude % Crude % Age (years) 43-54 35.7 32.41 .42 .43 55-64 29.21 31.67 65-74 26.38 27.59 >75 8.71 8.33 Alcohol use No 12.46 12.41 .97 .9 Yes 87.54 87.59 Comorbidities (b) No 71.91 71.7 .92 .97 Yes 28.09 28.3 Hypertension (c) No 51.37 54.63 .17 .12 Yes 48.63 45.37 Income ($/year) [less than or 60.4 57.5 .22 .13 equal to] 29,000 >30,000 39.6 42.5 Education <High school 20.88 31.3 <.001 <.001 High school 46.84 44.63 College 15.57 12.96 >College 16.72 11.11 Sex Female 56.12 57.04 .7 .74 Male 43.88 42.96 Smoking status Never 43.94 44.81 .73 .88 Past 36.78 36.3 Current 19.27 18.89 Steroid use No 95.75 95.42 .74 .76 Yes 4.25 4.58 Visual acuity (d) Better than 20/40 98.13 97.59 .47 .55 20/40-20/160 1.69 2.22 20/200 and worse 0.18 0.19 Sedentary lifestyle No 27.93 24.44 .1 .11 Yes 72.07 75.56 Sunlight exposure Unexposed 74.46 75.93 .48 .48 Exposed 25.54 24.07 Characteristics Rural p-Value p-Value (a) (n= 450) Crude % Age (years) 43-54 46.89 <.001 <.001 55-64 30.89 65-74 17.78 >75 4.44 Alcohol use No 11.78 .69 .9 Yes 88.22 Comorbidities (b) No 76.92 .03 .38 Yes 23.08 Hypertension (c) No 56.89 .03 .33 Yes 43.11 Income ($/year) [less than or 53.69 .009 .67 equal to] 29,000 >30,000 46.31 Education <High school 25.33 .003 <.001 High school 47.78 College 15.33 >College 11.56 Sex Female 51.11 .05 .09 Male 48.89 Smoking status Never 50.22 .08 .002 Past 31.11 Current 18.67 Steroid use No 96.56 .44 .53 Yes 3.44 Visual acuity (d) Better than 20/40 99.55 .03 .2 20/40-20/160 0.45 20/200 and worse 0.00 Sedentary lifestyle No 18.44 <.001 <.001 Yes 81.56 Sunlight exposure Unexposed 79.15 .036 .036 Exposed 20.85 (a) Adjusted for age and gender. (b) Includes cancer, diabetes, and cardiovascular disease. (c) Defined as systolic blood pressure [greater than or equal to] 140 mmHg and/or diastolic blood pressure [greater than or equal to] 90 mmHg or use of antihypertensive medication. (d) Best corrected visual acuity in the better eye. TABLE 2 Cumulative Incidence in Right Eyes and Multivariable-Adjusted Odds Ratio of All Eyes for Cataract Type by Residential Location Right Eye Only All Eligible Eyes Cataract At Risk (n) Cumulative Adjusted (b) Type Incidence OR (c) (%) (a) Cortical cataract Urban 1985 20.8 Ref Edge 472 20 0.94 Rural 414 16.3 0.92 Nuclear cataract Urban 2000 26.9 Ref Edge 462 27.1 0.97 Rural 409 19.1 0.85 PSC (c) Urban 2162 7.3 Ref Edge 514 7.6 1.05 Rural 432 4.6 0.71 All Eligible Eyes Cataract Adjusted (b) Adjusted (b) Type 95% CI (c) p-Value Cortical cataract Urban Edge 0.77, 1.16 .59 Rural 0.73, 1.16 .47 Nuclear cataract Urban Edge 0.80, 1.17 .74 Rural 0.69, 1.06 .16 PSC (c) Urban Edge 0.78, 1.42 .74 Rural 0.48, 1.05 .09 (a) Accounts for competing risk of death. (b) Adjusted for age, gender, education, and smoking status. (c) OR = odds ratio; CI = confidence interval; PSC = posterior subcapsular cataract. TABLE 3 Cumulative Incidence in Right Eyes and Multivariable-Adjusted Odds Ratio of All Eyes for Cataract Type by Nitrate Levels (a) in Water Supply of Rural Residents Right Eye Only Cataract Type At Cumulative Risk (n) Incidence (%) (b) Cortical cataract Low nitrate 261 15.3 Mid nitrate 257 17.4 High nitrate 74 18.5 Nuclear cataract Low nitrate 256 20.7 Mid nitrate 256 17.2 High nitrate 68 28.4 PSC (c) Low nitrate 271 3.7 Mid nitrate 268 5.9 High nitrate 77 2.9 All Eligible Eyes Cataract Type Adjusted (b) Adjusted (b) Adjusted (b) OR (c) 95% CI (d) p-Value Cortical cataract Low nitrate Ref Mid nitrate 1.03 0.70, 1.51 .88 High nitrate 1.37 0.81, 2.31 .24 Nuclear cataract Low nitrate Ref Mid nitrate 0.8 0.56, 1.15 .23 High nitrate 0.97 0.58,1.61 .9 PSC (c) Low nitrate Ref Mid nitrate 1.07 0.55, 2.08 .85 High nitrate 1.23 0.50, 3.05 .65 (a) Low nitrate level <4 parts per million (ppm); mid = 5-9 ppm; high >10 ppm. (b) Accounts for competing risk of death. (c) Adjusted for age, gender, education, and smoking status. (d) OR = odds ratio; CI = confidence interval; PSC = posterior subcapsular cataract.
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|Title Annotation:||ADVANCEMENT OF THE SCIENCE|
|Author:||McElroy, Jane A.; Klein, Barbara E.K.; Lee, Kristine E.; Howard, Kerri P.; Klein, Ronald|
|Publication:||Journal of Environmental Health|
|Date:||Jan 1, 2014|
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