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Incidence of Dry Eye in an Older Population
Scot E. Moss, MA;
Ronald Klein, MD, MPH;
Barbara E. K. Klein, MD, MPH
Arch Ophthalmol. 2004;122:369-373.
ABSTRACT
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Objectives To estimate the 5-year incidence of dry eye and to examine its association with risk factors.
Methods The population of Beaver Dam, Wis, that was 43 to 84 years of age (n = 5924) was examined in the 1988-1990 (n = 4926), 1993-1995 (n = 3722), and 1998-2000 study phases (n = 2962). At the 1993-1995 examination, when dry eye data were first collected, and the 1998-2000 examination, 2783 subjects participated, and 44 were interviewed. Of these, 2802 provided dry eye history. The incidence cohort consisted of 2414 subjects not reporting dry eye in the 1993-1995 examination. Risk factor information was ascertained at the 1993-1995 examination and included demographics, medical history, cardiovascular disease risk factors, medications, and lifestyle factors.
Results During the 5-year interval between examinations, a history of dry eye developed in 322 of 2414 subjects, for an incidence of 13.3% (95% confidence interval [CI], 12.0%-14.7%). Incidence was significantly associated with age (P<.001). After adjusting for age, incidence was greater in subjects with a history of allergy or diabetes, who used antihistamines or diuretics, and with poorer self-rated health (P<.05). Age-adjusted incidence was less in subjects using angiotensin-converting enzyme inhibitors or consuming alcohol (P<.05). It was not significantly associated with sex, blood pressure, hypertension, serum total or high-density lipoprotein cholesterol level, body mass index, history of arthritis, gout, osteoporosis, cardiovascular disease, thyroid disease, or smoking, and use of caffeine, vitamins, antianxiety medications, antidepressants, calcium channel blockers, or anticholesterolemics.
Conclusions Incidence of dry eye is substantial. However, there are few associated risk factors. Some drugs (eg, diuretics and antihistamines) are associated with a greater risk, whereas others (angiotensin-converting enzyme inhibitors) are associated with lower risk.
INTRODUCTION
Dry eye syndrome is a common source of great discomfort in the elderly population, and it can seriously affect quality of life.1-3 Its management can be a frustrating experience for patients and their eye care providers. It has been shown to be associated with rheumatoid arthritis and other autoimmune diseases.4 Several studies have reported on the prevalence of dry eye and have examined these and other risk factors.5-10 However, because these studies are cross-sectional, they can demonstrate only that a factor is associated with dry eye and not whether the factor precedes the dry eye. This is important because people with dry eye may modify certain behaviors, such as diet and drug use, in response to the condition.
Therefore, longitudinal studies of dry eye are needed. We previously reported on the prevalence of dry eye in the Beaver Dam Eye Study.9 We are now able to examine the incidence of dry eye in the same cohort 5 years later. Thus, the purpose of this report is to estimate the 5-year incidence of dry eye in an elderly population and to examine its association with various risk factors.
METHODS
The methods and procedures used to identify and examine the Beaver Dam Eye Study population have been previously published.11-12 Briefly, a private census of Beaver Dam, Wis, was conducted to identify residents aged 43 to 84 years (n = 5924). Figure 1 presents the subsequent examination and follow-up history of this cohort through the 1988-1990, 1993-1995, and 1998-2000 study examination phases. At each phase, all attempts were made to examine the participants in the same order. Reasons for nonparticipation and comparisons between participants and nonparticipants at the 1988-1990 and 1993-1995 examinations have been reported elsewhere.11-12 Information on the presence of dry eye was first collected at the 1993-1995 examination, which is the starting point for incidence of dry eye. Thus, analysis is based on the 2827 participants in the 1993-1995 and 1998-2000 examinations. Comparisons of these subjects with the 513 who had died and the 382 who did not participate are presented in Table 1.
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Figure 1. Schematic showing participation in the Beaver Dam Eye Study.
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Table 1. Comparison of Characteristics of Participants and Nonparticipants in the 1998-2000 Examination of the Beaver Dam Eye Study*
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All examinations have followed similar protocols, which were approved by our institutional human subjects committee. Informed consent was obtained from each participant at each examination. The examination included a medical history questionnaire; measurement of height, weight, and blood pressure; determination of refractive error and visual acuity; dilation of the pupils; stereographic color fundus photography for evaluation of age-related maculopathy; slitlamp and retroillumination photography of the lenses for evaluation of cataract; and collection of urine and blood samples for a series of standard laboratory tests.
Systolic and diastolic blood pressures were recorded as the average of 2 measurements. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension with use of antihypertensives. Body mass index was defined as weight in kilograms divided by the square of height in meters. Subjects were considered to have diabetes if they reported a history of diabetes mellitus; treatment with insulin, oral hypoglycemic agents, or diet; or receiving a new diagnosis during participation in the study. The criterion for diagnosis was a glycosylated hemoglobin value of greater than 2 SDs above the mean for a given age-sex group and a random blood glucose level of greater than 200 mg/dL (>11.1 mmol/L). Arthritis, fractures, osteoporosis, gout, thyroid disorder, and stroke were determined by history. A history of cardiovascular disease was defined as a history of angina, heart attack, or stroke. Participants were asked to bring to the examination all prescription and over-the-counter medications that they were regularly taking. The examiner asked whether there were other medications being taken that were not brought. If there were, the participant was asked to contact the examiner later with the medication name. Participants, their physicians, and their pharmacies were contacted when necessary to verify medication use. The name of each drug was entered into the database and assigned a code reflecting that of the American Hospital Formulary Service for each active ingredient.13 Heavy drinking was defined as current or past consumption of 4 or more servings of alcoholic beverages daily. The average weekly consumption of alcohol in grams was computed as the sum of alcohol from each 0.355-L (12-oz) serving of beer, 0.118-L (4-oz) serving of wine, and 0.044-L (1.5-oz) serving of liquor or distilled spirits. Each serving of beer, wine, and liquor was considered to contain 12.96, 11.48, and 14.00 g of alcohol, respectively. A current or ex-smoker was an individual who had smoked at least 100 cigarettes in his life. Pack-years smoked was computed as the number of packs (20 cigarettes) smoked each day times the number of years smoked. The average daily consumption of caffeine in milligrams was computed as the sum of caffeine from each 0.237-L (8-oz) serving of brewed coffee (103 mg), instant coffee (57 mg), hot or iced tea (36 mg), hot chocolate (6 mg), and caffeine-containing soda (46 mg).
History of dry eye was not determined at baseline. At the 5- and 10-year follow-up examinations, the presence of dry eye was determined by means of subject self-report. Dry eye was defined as a positive response to the question, "For the past 3 months or longer, have you had dry eyes?" For subjects needing further prompting, this was described as a "foreign-body sensation with itching and burning, sandy feeling, not related to allergy." Because history of dry eye was not obtained until the 1993-1995 examination, that juncture is regarded as the baseline for these analyses. All covariate information pertains to that point. Incidence of dry eye was defined as a positive report of dry eye at the 10-year examination or interview in persons who did not report having dry eye at the 5-year examination. Differences in rates of incidence were tested for statistical significance by means of Mantel-Haenszel procedures.14 Age-adjusted incidence rates were computed by the direct method.15 Proportions of 0.426, 0.306, 0.208, and 0.060 for the groups aged 48 to 59, 60 to 69, 70 to 79, and 80 to 91 years, respectively, were used for the standard population. These proportions reflect the age distribution of the set of participants at risk for incidence of dry eye. Logistic regression was used to examine the association of several variables with the incidence of dry eye.
RESULTS
Among the 2827 subjects who participated in the 1993-1995 and 1998-2000 examinations, 388 had reported having dry eye in the 1993-1995 examination, and 25 were missing dry eye information at 1 or both examinations (Figure 1). This left 2414 subjects at risk for incidence of dry eye. Among the 3722 subjects participating in the 1993-1995 examination, the presence of dry eye (n = 534) at that time had no effect on the age- and sex-adjusted odds of dying before the 1998-2000 examination (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.77-1.32).
Among the 2414 subjects at risk for incidence of dry eye, age varied from 48 to 91 years with a mean ± SD of 63 ± 10 years. Men constituted 44% of the cohort, and 99% were white. Dry eye was reported in 322 of 2414 subjects at risk, for a 5-year incidence of 13.3% (95% CI, 12.0%-14.7%). Incidence of dry eye increased significantly with age (P<.001), from 10.7% in subjects aged 48 to 59 years to 17.9% in those 80 years or older (Figure 2). The incidence of dry eye was also higher overall in women (14.7%) compared with men (11.7%) (P = .04; Figure 2). However, after adjusting for age, the difference was no longer statistically significant (P = .06).
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Figure 2. The 5-year incidence of dry eye by age and sex in the Beaver Dam Eye Study. Numbers constitute the sample sizes.
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Because many of the risk factors examined for their associations with incidence of dry eye are correlated with age, further analysis was age adjusted. Table 2 presents the results of this analysis. Persons with diabetes or a history of allergy reported a higher 5-year incidence of dry eye than those without. The use of certain medications was also associated with incidence of dry eye. Persons using antihistamines, diuretics, or steroids had a higher incidence, whereas those using angiotensin-converting enzyme (ACE) inhibitors had a lower incidence. The differences in incidence between subjects not taking or taking antianxiety drugs, antidepressants, calcium channel blockers, anticholesterolemics, multivitamins, and hormone replacement (women only) were not statistically significant (data not shown). There were no significant differences between subjects with (n = 388) and without (n = 2414) dry eye in the 1993-1995 examination with respect to discontinuing use of a drug if they were using it or beginning to use it if they were not, with 1 exception. People with dry eye in the 1993-1995 examination were more likely to begin using antidepressants by the 1998-2000 examination than those without dry eye (11.8% vs 5.3%; P<.001).
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Table 2. Age-Adjusted Incidence of Dry Eye at the 10-Year Examination by Subject Characteristics at the 5-Year Examination
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Additional significant factors in the age-adjusted analysis (Table 2) included alcohol consumption. Persons consuming alcohol in any amount were less likely to report dry eye incidence than nonusers. Also, subjects reporting themselves to be in poorer health compared with others their age had a higher incidence. Persons with a higher total cholesterol level had a higher age-adjusted incidence of dry eye, but this association did not reach statistical significance (P = .06). Hypertension and smoking history were also not associated with incidence of dry eye (Table 2).
Several additional characteristics were examined for associations with incidence of dry eye that were not statistically significant. These included body mass index; systolic and diastolic blood pressure; high-density lipoprotein cholesterol level; ratio of total to high-density lipoprotein cholesterol; leukocyte count; hematocrit level; a history of gout, fractures, or osteoporosis; pack-years smoked; caffeine consumption; and a history of heavy drinking (data not shown).
Some factors known to be associated with prevalence of dry eye were not found to be associated with incidence. These included arthritis and thyroid disease (Table 2). When we examined the effect of dry eye on the incidence of a history of arthritis and thyroid disease, we found that those with dry eye in the 1993-1995 examination (n = 388) did not have a significantly different incidence of arthritis compared with people without (n = 2414) (27.5% vs 21.3%; P = .08). The corresponding incidences of thyroid disease were also not significantly different (3.9% vs 4.9%; P = .47). However, in people with (n = 322) compared with people without (n = 2092) incidence of dry eye, arthritis was more likely to develop (28.3% vs 20.3%; P = .01), but not thyroid disease (5.2% vs 4.8%; P = .76).
To determine which factors were independently associated with incidence of dry eye, logistic regression models were developed. Age was included in every model. Other variables were selected in stepwise fashion. Subjects who were missing information for any of the variables are excluded from the analysis. The results of this procedure are presented in Table 3. In addition to older age, subjects with poorer self-rated health, with a history of allergy, or who used diuretics were at higher risk for incident dry eye. Those using ACE inhibitors were at lower risk. When the use of antihistamines and corticosteroids is added to the model, the association of history of allergy became weaker (OR, 1.30; 95% CI, 0.98-1.72), suggesting that the medications taken for allergy may be the material factor.
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Table 3. Odds for 5-Year Incidence of Dry Eye for a Specified Increment in Subject Characteristics*
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COMMENT
Large epidemiological studies of dry eye are few. In addition, all previous observational studies of dry eye have been cross-sectional or prevalence studies.5-10 Longitudinal or incidence studies have the advantage compared with cross-sectional studies in that the risk factors were observed before the occurrence of dry eye. Therefore, any risk factors discovered are more (although not necessarily) likely to be in the causal pathway. This report is, to our knowledge, the first to examine the incidence of dry eye. We found the overall 5-year incidence of dry eye to be 13.3%.
However, as a consequence, few studies are available for direct comparison with ours. Some report an increase in prevalence of dry eye with age,6, 10 but this is not consistent.5 Our incidence results agree with those of the former studies. However, as seen in the multivariable analysis, the effect of age may be attenuated when other confounding factors such as general health or medication use are considered. Also, some prevalence studies report more dry eye in women,6, 9 but, again, this finding is not universal.5, 10 We noted a somewhat greater incidence in women, but after controlling for age, the difference between women and men was not statistically significant. The higher prevalence of dry eye in women may be a result of men with dry eye not being observed because they have died.
There are a number of inconsistencies between results for incidence of dry eye and prevalence results we presented earlier9 and other prevalence studies. For instance, prevalence studies, including the prevalence phase of this study, have noted an association of arthritis and thyroid disease with dry eye.6, 9 However, we failed to find a relationship between a history of arthritis or thyroid disease and the incidence of dry eye. We can only speculate as to why this is so. First, it may be that dry eye precedes arthritis and thyroid disease or that they occur more or less together. We observe this in the case of arthritis, but not thyroid disease. Also, we are not able to distinguish the type of arthritis present. We might observe a stronger relationship if we could focus on rheumatoid arthritis.
It is generally believed that certain drugs are associated with prevalence of dry eye.16-18 These include diuretics, antihistamines, and psychotropics. Except for diuretics and to a lesser extent antihistamines, we found no associations of these drugs or other commonly used drugs such as calcium channel blockers and anticholesterolemics with the incidence of dry eye. Also, except for the antidepressants, we found no predilections to change medications as a function of earlier dry eye status. In the case of antidepressants, people with dry eye at the 1993-1995 examination were more likely to be taking an antidepressant 5 years later than people without dry eye. In a cross-sectional study, this would result in the appearance of a relationship with prevalence, even if there was no relationship with incidence. However, this explanation would not apply to antianxiety agents.
We found a protective effect for the use of ACE inhibitors. To our knowledge, this is the first report of any relationship between these drugs and dry eye. Other studies have suggested that ACE inhibitors have anti-inflammatory effects.19-20 We can only speculate as to whether this is the basis for the connection. Further study may be worth pursuing.
There are some limitations to this study. First, we relied on self-reports of the study subjects to determine the presence of dry eye with no objective testing. However, the tests commonly performed are notoriously lacking in sensitivity and specificity.6, 21 Thus, we believe allowing the subjects to be the arbiters of their own signs and symptoms to be valid for this somewhat nebulous condition. In addition, in the prevalence results, several well-known risk factor associations with dry eye were found, supporting the validity of this approach.9 However, we consequently are not able to differentiate between tear-deficient and evaporative dry eye. Risk factors for these 2 entities may differ. This might weaken any associations that are present. Differences between this study and others in how dry eye is defined also make it difficult to contrast findings among them. However, this would affect quantitative comparisons more than comparisons of general associations between risk factors and dry eye. The 5-year interval between examinations may also be a limitation. The 5-year incidence reported herein may not be a true cumulative incidence because occurrences of dry eye between examinations that had resolved would not be detected. In addition, the 5-year interval may be too long a period to attempt to associate some risk factors with the outcome. The result of these circumstances would most likely be a bias toward the null hypothesis and underestimation of incidence. Furthermore, as an older population, the cohort has experienced attrition due to death before and after the determination of dry eye. This has the potential to introduce bias if the risk factors and dry eye are both associated with mortality. However, this is not likely, as we do not find dry eye to be associated with mortality. Again, the effect would at most be a diminution of relationships. In addition, as the study cohort is a middle-class, white population, the results of this investigation may not be applicable to other groups of differing ethnicity or socioeconomic class. However, because it is population based, our study is more likely to be representative than a clinic-based cohort. Finally, because of the number of associations examined, some statistically significant results may be due to chance. Thus, it is important to consider the reported results not in isolation, but in a context that includes other available evidence and biological plausibility or mechanisms.
CONCLUSIONS
Incidence of dry eye is common in the older population, occurring at a rate of 13.3% during 5 years in persons aged 48 to 91 years. There are few independently associated risk factors, especially those subject to intervention. However, some drugs, such as diuretics and antihistamines, are associated with increased risk for dry eye, whereas ACE inhibitors are associated with decreased risk. This latter association deserves further research. Perhaps of equal significance are the relationships that were not found. Factors such as arthritis and thyroid disease, which are generally regarded as being associated with dry eye and have been confirmed by prevalence studies, were not found to predict incidence. Nevertheless, this in no way invalidates the cross-sectional results, for these may simply be contemporaneous events.
AUTHOR INFORMATION
Corresponding author: Scot E. Moss, MA, Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison, 610 N Walnut St, 454 WARF, Madison, WI 53726-2336 (e-mail: moss{at}epi.ophth.wisc.edu).
Submitted for publication June 12, 2003; final revision received October 6, 2003; accepted November 17, 2003.
This study was supported by grant EY06594 from the National Institutes of Health, Bethesda, Md (Drs R. Klein and B. E. K. Klein).
From the Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison. The authors have no relevant financial interest in this article.
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