EPIDEMIOLOGY

Incidence of Dry Eye in an Older Population

Scot E. Moss, MA; Ronald Klein, MD, MPH; Barbara E. K. Klein, MD, MPH

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 report-
ing dry eye in the 1993-1995 examination. Risk factor
information was ascertained at the 1993-1995 examina-
tion and included demographics, medical history, car-
diovascular disease risk factors, medications, and life-
style factors.
Results: During the 5-year interval between examina-
tions, a history of dry eye developed in 322 of 2414 sub-
jects, for an incidence of 13.3% (95% confidence inter-
val [CI], 12.0%-14.7%). Incidence was significantly
associated with age (P⬍.001). After adjusting for age, in-
cidence 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 in-
cidence 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 li-
poprotein cholesterol level, body mass index, history of
arthritis, gout, osteoporosis, cardiovascular disease, thy-
roid disease, or smoking, and use of caffeine, vitamins,
antianxiety medications, antidepressants, calcium chan-
nel blockers, or anticholesterolemics.
Conclusions: Incidence of dry eye is substantial. How-
ever, there are few associated risk factors. Some drugs
(eg, diuretics and antihistamines) are associated with a
greater risk, whereas others (angiotensin-converting en-
zyme inhibitors) are associated with lower risk.
Arch Ophthalmol. 2004;122:369-373

From the Department of
Ophthalmology and Visual
Sciences, University of
Wisconsin Medical School,
Madison. The authors have no
relevant financial interest in
this article.
D
RY EYE SYNDROME IS A
common source of great
discomfort in the elderly
population, and it can se-
riously affect quality of
life.1-3 Its management can be a frustrat-
ing experience for patients and their eye
care providers. It has been shown to be as-
sociated with rheumatoid arthritis and
other autoimmune diseases.4 Several stud-
ies have reported on the prevalence of dry
eye and have examined these and other risk
factors.5-10 However, because these stud-
ies are cross-sectional, they can demon-
strate only that a factor is associated with
dry eye and not whether the factor pre-
cedes the dry eye. This is important be-
cause people with dry eye may modify cer-
tain 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 ex-
amine the incidence of dry eye in the same
cohort 5 years later. Thus, the purpose of
this report is to estimate the 5-year inci-
dence of dry eye in an elderly population
and to examine its association with vari-
ous risk factors.
METHODS
The methods and procedures used to identify
and examine the Beaver Dam Eye Study popu-
lation 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 sub-
sequent 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 compari-
sons between participants and nonpartici-
pants at the 1988-1990 and 1993-1995 exami-
nations have been reported elsewhere. 11,12

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5924
Eligible Residents
4926
Examined
1988-1990
38 3684
Examined Examined
684 558
Not Examined Died
1993-1995 1993-1995
2783 Examined,
44 Interviewed
382 513
Not Examined Died
1998-2000
2414 at Risk 388 Not at 25 Missing
for Dry Eye Risk Information
Figure 1. Schematic showing participation in the Beaver Dam Eye Study.
Information on the presence of dry eye was first collected at
the 1993-1995 examination, which is the starting point for in-
cidence of dry eye. Thus, analysis is based on the 2827 partici-
pants in the 1993-1995 and 1998-2000 examinations. Com-
parisons of these subjects with the 513 who had died and the
382 who did not participate are presented in Table 1.
All examinations have followed similar protocols, which were
approved by our institutional human subjects committee. In-
formed consent was obtained from each participant at each ex-
amination. The examination included a medical history ques-
tionnaire; 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 photog-
raphy 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 sys-
tolic 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 his-
tory of diabetes mellitus; treatment with insulin, oral hypogly-
cemic agents, or diet; or receiving a new diagnosis during par-
ticipation 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, frac-
tures, osteoporosis, gout, thyroid disorder, and stroke were de-
termined by history. A history of cardiovascular disease was
defined as a history of angina, heart attack, or stroke. Partici-
pants were asked to bring to the examination all prescription
and over-the-counter medications that they were regularly tak-
ing. The examiner asked whether there were other medica-
tions being taken that were not brought. If there were, the par-
ticipant was asked to contact the examiner later with the
medication name. Participants, their physicians, and their phar-
macies were contacted when necessary to verify medication use.
The name of each drug was entered into the database and as-
signed a code reflecting that of the American Hospital Formu-
lary 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
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of wine, and 0.044-L (1.5-oz) serving of liquor or distilled spir-
its. 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 caf-
feine in milligrams was computed as the sum of caffeine from
each 0.237-L (8-oz) serving of brewed coffee (103 mg), in-
stant 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 de-
fined 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.” Be-
cause 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. Inci-
dence of dry eye was defined as a positive report of dry eye at
the 10-year examination or interview in persons who did not re-
port 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 re-
gression was used to examine the association of several vari-
ables with the incidence of dry eye.
RESULTS
Among the 2827 subjects who participated in the 1993-
1995 and 1998-2000 examinations, 388 had reported hav-
ing 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 sub-
jects at risk, for a 5-year incidence of 13.3% (95% CI,
12.0%-14.7%). Incidence of dry eye increased signifi-
cantly 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).
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 pre-
sents the results of this analysis. Persons with diabetes
or a history of allergy reported a higher 5-year inci-
dence of dry eye than those without. The use of certain
medications was also associated with incidence of dry eye.
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 Table 1. Comparison of Characteristics of Participants and Nonparticipants
in the 1998-2000 Examination of the Beaver Dam Eye Study*

Participants Living Nonparticipants Dead Nonparticipants

Characteristic in
1993-1995 Examination No. Mean (SD) No. Mean (SD) P Value No. Mean (SD) P Value
Age, y 2827 63.6 (9.8) 382 66.1 (10.5) ⬍.001 513 74.1 (9.6) ⬍.001
Systolic BP, mm Hg 2768 129 (19) 372 133 (21) ⬍.001 499 133 (22) ⬍.001
Diastolic BP, mm Hg 2768 77 (10) 372 77 (10) .95 498 73 (12) ⬍.001
BMI 2727 29.6 (5.5) 362 30.0 (5.3) .28 456 28.8 (5.9) .006
Total cholesterol level, mg/dL 2756 240 (44) 360 243 (48) .30 499 227 (51) ⬍.001
HDL cholesterol level, mg/dL 2749 53 (17) 360 53 (16) .93 499 48 (16) ⬍.001
Living Dead Nonparticipants,
Participants, No. (%) Nonparticipants, No. (%) P Value No. (%) P Value
Male 2827 (42.3) 382 (40.3) .47 513 (51.1) ⬍.001
Hypertension 2774 (38.9) 373 (40.2) .65 494 (54.7) ⬍.001
Cardiovascular disease 2812 (11.9) 380 (10.8) .61 504 (33.3) ⬍.001
Diabetes mellitus 2750 (8.6) 364 (9.6) .55 495 (20.4) ⬍.001

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); BP, blood pressure.
SI conversion factor: To covert cholesterol to millimoles per liter, multiply by 0.0259.
*Sample sizes may vary owing to missing information.

Persons using antihistamines, diuretics, or steroids had

25
a higher incidence, whereas those using angiotensin-
converting enzyme (ACE) inhibitors had a lower inci- 20
dence. The differences in incidence between subjects not Incidence, %
taking or taking antianxiety drugs, antidepressants, cal- 15
cium channel blockers, anticholesterolemics, multivita-
mins, and hormone replacement (women only) were not 10 Women
Men
statistically significant (data not shown). There were no Total
5
significant differences between subjects with (n=388) and
without (n=2414) dry eye in the 1993-1995 examina- 0
tion with respect to discontinuing use of a drug if they 48-59 60-69 70-79 ≥80
Age, y
were using it or beginning to use it if they were not, with
1 exception. People with dry eye in the 1993-1995 ex- Women 543 394 305 102
amination were more likely to begin using antidepres- Men 485 344 198 43

sants by the 1998-2000 examination than those without

dry eye (11.8% vs 5.3%; P⬍.001).
Additional significant factors in the age-adjusted
analysis (Table 2) included alcohol consumption. Per-
sons consuming alcohol in any amount were less likely
to report dry eye incidence than nonusers. Also, sub-
jects reporting themselves to be in poorer health com-
pared with others their age had a higher incidence. Per-
sons 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 inci-
dence of dry eye (Table 2).
Several additional characteristics were examined for
associations with incidence of dry eye that were not sta-
tistically significant. These included body mass index; sys-
tolic and diastolic blood pressure; high-density lipopro-
tein 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 preva-
lence of dry eye were not found to be associated with in-
cidence. These included arthritis and thyroid disease (Table
2). When we examined the effect of dry eye on the inci-
Figure 2. The 5-year incidence of dry eye by age and sex in the Beaver Dam
Eye Study. Numbers constitute the sample sizes.
dence 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) com-
pared 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 as-
sociated with incidence of dry eye, logistic regression mod-
els were developed. Age was included in every model.
Other variables were selected in stepwise fashion. Sub-
jects who were missing information for any of the vari-
ables 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 his-
tory 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 cor-
ticosteroids is added to the model, the association of

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 dinal or incidence studies have the advantage compared
Table 2. Age-Adjusted Incidence of Dry Eye with cross-sectional studies in that the risk factors were
at the 10-Year Examination by Subject Characteristics observed before the occurrence of dry eye. Therefore, any
at the 5-Year Examination
risk factors discovered are more (although not necessar-
Incidence, P
ily) likely to be in the causal pathway. This report is, to
Characteristic, Value Total No.* (%) Value our knowledge, the first to examine the incidence of dry
Hypertension
eye. We found the overall 5-year incidence of dry eye to
Absent 1475 (14.2) be 13.3%.
.20† However, as a consequence, few studies are avail-
Present 894 (12.4)
Total cholesterol level, mg/dL able for direct comparison with ours. Some report an in-
58-209 520 (11.7) crease in prevalence of dry eye with age,6,10 but this is not
210-236 643 (12.8) consistent.5 Our incidence results agree with those of the
.06‡
237-265 588 (14.1)
former studies. However, as seen in the multivariable
266-600 600 (15.3)
Diabetes mellitus analysis, the effect of age may be attenuated when other
Absent 2164 (13.1) confounding factors such as general health or medica-
.05†
Present 181 (18.9) tion use are considered. Also, some prevalence studies
Arthritis history report more dry eye in women,6,9 but, again, this finding
Absent 1439 (13.0) is not universal.5,10 We noted a somewhat greater inci-
.32†
Present 957 (14.5)
dence in women, but after controlling for age, the dif-
Thyroid disease history
Absent 2109 (13.1)
ference between women and men was not statistically sig-
.43† nificant. The higher prevalence of dry eye in women may
Present 289 (14.9)
Allergy history be a result of men with dry eye not being observed be-
Absent 1747 (12.1)
.01†
cause they have died.
Present 572 (16.0) There are a number of inconsistencies between re-
ACE inhibitor use sults for incidence of dry eye and prevalence results we
No 2145 (13.9)
Yes 269 (9.2)
.03† presented earlier9 and other prevalence studies. For in-
Antihistamine use stance, prevalence studies, including the prevalence phase
No 2201 (12.8) of this study, have noted an association of arthritis and thy-
.01†
Yes 213 (18.7) roid disease with dry eye.6,9 However, we failed to find a
Diuretic use relationship between a history of arthritis or thyroid dis-
No 1966 (12.5) ease and the incidence of dry eye. We can only speculate
.02†
Yes 448 (16.4)
as to why this is so. First, it may be that dry eye precedes
Steroid use
No 2309 (12.9) arthritis and thyroid disease or that they occur more or
.01† less together. We observe this in the case of arthritis, but
Yes 105 (22.2)
Smoking history not thyroid disease. Also, we are not able to distinguish
Nonsmoker 1148 (12.6) the type of arthritis present. We might observe a stronger
Ex-smoker 937 (13.7) .50† relationship if we could focus on rheumatoid arthritis.
Current 325 (15.4)
It is generally believed that certain drugs are asso-
Alcohol consumption, g/wk
0 1298 (14.9)
ciated with prevalence of dry eye.16-18 These include di-
ⱕ37 359 (11.0) uretics, antihistamines, and psychotropics. Except for di-
.03‡ uretics and to a lesser extent antihistamines, we found
⬎37-98 393 (11.9)
⬎98 355 (11.0) no associations of these drugs or other commonly used
Self-rated health drugs such as calcium channel blockers and anticholes-
Excellent 598 (10.7) terolemics with the incidence of dry eye. Also, except for
Good 1503 (13.2)
⬍.001‡ the antidepressants, we found no predilections to change
Fair 283 (18.7)
Poor 27 (22.4) medications as a function of earlier dry eye status. In the
case of antidepressants, people with dry eye at the 1993-
Abbreviation: ACE, angiotensin-converting enzyme. 1995 examination were more likely to be taking an an-
SI conversion factor: To convert cholesterol to millimoles per liter, multiply tidepressant 5 years later than people without dry eye.
by 0.0259. In a cross-sectional study, this would result in the ap-
*Totals may vary owing to missing information.
†Calculated by means of the Mantel-Haenszel test of general association. pearance of a relationship with prevalence, even if there
‡Calculated by means of the Mantel-Haenszel test of trend. was no relationship with incidence. However, this ex-
planation would not apply to antianxiety agents.
history of allergy became weaker (OR, 1.30; 95% CI, 0.98- We found a protective effect for the use of ACE in-
1.72), suggesting that the medications taken for allergy hibitors. To our knowledge, this is the first report of any
may be the material factor. relationship between these drugs and dry eye. Other stud-
ies have suggested that ACE inhibitors have anti-
COMMENT inflammatory effects.19,20 We can only speculate as to
whether this is the basis for the connection. Further study
Large epidemiological studies of dry eye are few. In ad- may be worth pursuing.
dition, all previous observational studies of dry eye have There are some limitations to this study. First, we
been cross-sectional or prevalence studies.5-10 Longitu- relied on self-reports of the study subjects to determine

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Table 3. Odds for 5-Year Incidence of Dry Eye
for a Specified Increment in Subject Characteristics*
Characteristic Increment P Value OR (95% CI)
Age, y 10 .04 1.14 (1.01-1.30)
Self-rated health 1 Level ⬍.001 1.49 (1.23-1.81)
ACE inhibitors Using .006 0.53 (0.34-0.84)
History of allergy Present .01 1.40 (1.07-1.84)
Diuretics Using .04 1.38 (1.02-1.86)
Abbreviations: ACE, angiotensin-converting enzyme; CI, confidence
interval; OR, odds ratio.
*Data are missing for 1 or more characteristics in 98 subjects.
the presence of dry eye with no objective testing. How-
ever, the tests commonly performed are notoriously lack-
ing in sensitivity and specificity.6,21 Thus, we believe al-
lowing 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 How-
ever, we consequently are not able to differentiate be-
tween tear-deficient and evaporative dry eye. Risk fac-
tors 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 com-
parisons 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 occur-
rences of dry eye between examinations that had re-
solved would not be detected. In addition, the 5-year in-
terval 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. Further-
more, as an older population, the cohort has experi-
enced attrition due to death before and after the deter-
mination 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 so-
cioeconomic 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 re-
sults may be due to chance. Thus, it is important to con-
sider the reported results not in isolation, but in a con-
text 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
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aged 48 to 91 years. There are few independently asso-
ciated risk factors, especially those subject to interven-
tion. However, some drugs, such as diuretics and anti-
histamines, are associated with increased risk for dry eye,
whereas ACE inhibitors are associated with decreased risk.
This latter association deserves further research. Per-
haps 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.
Submitted for publication June 12, 2003; final revision re-
ceived 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).
Corresponding author: Scot E. Moss, MA, Depart-
ment of Ophthalmology and Visual Sciences, University of
Wisconsin–Madison, 610 N Walnut St, 454 WARF, Madi-
son, WI 53726-2336 (e-mail: moss@epi.ophth.wisc.edu).
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