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com
1
Beijing Institute of
Ophthalmology, Beijing
Tongren Hospital, Capital
Medical University, Beijing,
China
2
Quinze-Vingts National
Ophthalmology Hospital, Paris
and Versailles Saint-Quentin-
en-Yvelines University,
Versailles, France
3
Clinical Investigation Center
(CIC) 503, Quinze-Vingts
National Ophthalmology
Hospital, Paris, France
4
Department of
Ophthalmology, Beijing
Tongren Eye Center, Beijing
Tongren Hospital, Capital
Medical University, Beijing,
China
5
Department of
Ophthalmology, Medical
Faculty Mannheim of the
Ruprecht-Karls-University
Heidelberg, Heidelberg,
Germany
Correspondence to
Dr Liang Xu, Beijing Institute
of Ophthalmology, Beijing
Tongren Hospital, Capital
Medical University, 17 Hougou
Lane, Chong Wen Men,
Beijing 100005, China;
xlbio1@163.com
Received 10 June 2013
Revised 24 July 2013
Accepted 17 August 2013
Published Online First
7 September 2013
To cite: Labbé A, Wang YX,
Jie Y, et al. Br J Ophthalmol
2013;97:1399–1403.
Labbé A, et al. Br J Ophthalmol 2013;97:1399–1403. doi:10.1136/bjophthalmol-2013-303838
Dry eye disease, dry eye symptoms and depression:
the Beijing Eye Study
Antoine Labbé,1,2,3 Ya Xing Wang,1 Ying Jie,4 Christophe Baudouin,2,3
Jost B Jonas,1,5 Liang Xu1
ABSTRACT
Aim To investigate the association between dry eye
symptoms and depression in an adult population.
Methods In this population-based cross-sectional
study, a random sample of 1957 subjects from the
Beijing Eye Study was examined for dry eye disease
(DED) in 2006. All patients completed an interviewer-
assisted questionnaire on dry eye symptoms and
underwent measurement of tear break-up time (TBUT),
slit-lamp evaluation of corneal staining and meibomian
gland dysfunction (MGD), and the Schirmer test. In
2011, 1456 subjects from this sample were evaluated
for depression using a depression scale. The association
between depression symptoms and dry eye clinical tests
was evaluated.
Results Definite depression was more prevalent in
patients with DED than in subjects without DED
(13.7±0.4% vs 8.6±0.3%, p=0.02). The depression
score was correlated with dry eye symptoms (correlation
coefficient r=0.07; p=0.013) but not with TBUT
( p=0.18), the Schirmer test ( p=0.37), corneal staining
( p=0.30) and MGD evaluation ( p=0.93). In multivariate
regression analysis, the risk of definite depression
remained significantly associated with dry eye symptoms
( p=0.028) after adjusting for lower cognitive status
( p=0.01), rural region of habitation ( p=0.023) and
lower body weight ( p=0.05).
Conclusions In an older population from Beijing,
depression was associated with DED and in particular
with dry eye symptoms.
INTRODUCTION
According to the 2007 Dry Eye Workshop, dry eye
disease (DED) is a multifactorial disease of the
tears and ocular surface that results in symptoms of
discomfort, visual disturbance and tear film instabil-
ity.1 Typical symptoms of dry eye include burning
or stinging, foreign body sensation, photophobia
and blurred vision. Although these symptoms are
rarely severe, the chronic ocular surface irritation
and visual disturbance observed in DED directly
decrease the quality of life of those with the condi-
tion,2–4 and interfere with the ability to carry out
daily functions.3
The chronic discomfort observed in DED may
also have a negative impact on other aspects of
patient health, such as cognitive processes, mood
and mental health.5 The association between DED
and psychiatric disorders has recently been investi-
gated in large retrospective epidemiological studies
analysing the comorbidities associated with dry
eye.6–8 These studies, based on medical record
diagnostic classification and treatments, found a
positive association between DED and depression.
Clinical science
Nevertheless, no detailed evaluation of this associ-
ation, in particular with regard to objective DED
parameters or symptoms and depression, has been
conducted. Additionally, few studies to date have
further analysed the relationship between DED
parameters and depression,2 9 10 and only one
population-based study evaluated an older popula-
tion.11 Thus, the aim of the present study was to
investigate the association between depression
symptoms and results from objective and subjective
tests for DED in an adult population-based study.
METHODS
The Beijing Eye Study is a population-based cross-
sectional study in Northern China. First conducted
in the year 2001, the study was repeated in 2006
and 2011. The only eligibility criterion for inclu-
sion in the study was age 40+years. The Medical
Ethics Committee of the Beijing Tongren Hospital
approved the study protocol and all participants
gave informed consent. At baseline and follow-up
examinations, all study participants underwent an
interview with standardised questions and a com-
plete ophthalmic examination. The study has been
described in detail previously.12
Of the 4439 subjects participating in the Beijing
Eye Study 2001, in 2006 a random sample of 1957
subjects underwent a complete evaluation of the
ocular surface in the following order: dry eye
symptom analysis, measurement of the tear-film
break-up time (TBUT), assessment of fluorescein
staining of the cornea, Schirmer test with anaesthe-
sia and evaluation of meibomian gland dysfunction
(MGD).13 The subjective symptoms of dry eye were
evaluated using a simple questionnaire composed of
three questions: ‘Do your eyes ever feel dry?’, ‘Do
you ever feel a gritty or sandy sensation in your
eyes?’ and ‘Do your eyes ever have a burning sensa-
tion?’. Possible answers to the questions were no (0),
less than once a month (1), once or twice a week
(2), at least once every day (3) or all the time (4).
The presence of dry eye symptoms was defined as
having one or more symptoms at least once every
day (score of 3 or 4 for any question). A quantitative
grading score of subjective dry eye symptoms was
obtained by summing the answers to the different
questions (score of 0–12). TBUT was measured by
instilling fluorescein into the inferior cul-de-sac and
calculating the average of three consecutive tear
breakup times. Fluorescein staining of the cornea
was graded 0 for no staining, 1 for mild staining
with a few disseminated stains and limited to less
than one-third of the cornea, 2 for moderate stain-
ing with a severity between grades 1 and 3, or 3 for
severe staining with confluent stains and occupying
1399
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Clinical science

half or more of the cornea. The Schirmer test was performed
1 min after instillation of a drop of 0.5% proparacaine, and after
5 min the amount of wetting (mm) was recorded. MGD was
assessed by evaluating the presence of plugging and by expression
of the meibomian glands. MGD was graded 0 for no obstruction,
grade 1 for plugged with translucent serous secretion when the
lid margin was compressed, grade 2 for plugged with viscous or
waxy white secretion when the lid margin was compressed and
grade 3 for plugged with no secretion when the lid margin was
compressed.13 For each study participant, both eyes were tested
and the data of the worse eye, based on the clinical judgment of
the examiner, were used for analysis. DED was defined as the
presence of dry eye symptoms (one or more symptoms of dry eye
at least every day) associated with a Schirmer test <5 mm and/or
BUT<10 s.14 During the 2011 survey, a simple question aiming
to evaluate subjective symptoms of dry eye (‘Do your eyes ever
feel dry?’) was also asked, and graded as previously described.
Depressive symptoms were evaluated in the survey conducted
in 2011 using a Chinese depression scale adapted from the
Zung self-rated depression scale.12 The total score of depression
symptoms was converted to a 100-point scale. Definite depres-
sion was defined as having a depression score of 40 or higher.
Cognitive function was also assessed using the Mini Mental
Status Examination (MMSE) scale.12
Statistical analysis was performed using SPSS for Windows,
V.20.0 (SPSS, Chicago, Illinois, USA). The data were given as
mean values±SDs. The Gaussian distribution of the parameters
was tested using the Kolmogorov–Smirnov test. Continuous vari-
ables were compared using the Student t test and the χ2 test was
used to compare proportions. The association between variables
was examined applying the Pearson correlation test. Multivariate
logistic regression analysis was used to investigate the effects of
various parameters on depression. ORs and 95% CIs were pre-
sented. All p values were two-sided and were considered statistic-
ally significant when the values were less than 0.05.
RESULTS
From the 2006 random sample (1957) that had an evaluation of
the ocular surface, 1456 subjects (74.4%) underwent depressive
symptom evaluation in 2011. The subjects evaluated in 2011
and the 2006 sample did not differ significantly in terms of
gender ( p=0.49), frequency of DED ( p=0.58), best corrected
visual acuity (BCVA) (p=0.12), rural versus urban region of
habitation (p=0.66), level of education ( p=0.25) and gross
income ( p=0.55). Moreover, for the 1456 participants, the
individual scores of subjective dry eye symptoms obtained in
2006 were not different to the results obtained in 2011 ( paired-
samples t test, p=0.732).
Out of the 1456 participants examined in 2011, 241 (16.6%)
subjects had DED and 138 (9.5%) subjects had definite depres-
sion. The mean age of participants was 64.8±9.5 years (range:
50–91) and 867 were women (59.5%). Patients with DED were
older (p<0.001), more frequently women ( p=0.002), more
often living in an urban area (p<0.001), had a higher income
(p<0.001) and had a lower BCVA ( p<0.001) as compared to
patients without DED (table 1). Patients with depression were
more frequently women ( p=0.009) and living in a rural region
(p<0.001), had a lower level of education (p=0.005) and
income (p<0.001), and a lower cognitive function score
(p=0.007) as compared to patients without depression (table 1).

Table 1 Demographic characteristics of study subjects: depression and dry eye parameters
Subjects

DED evaluation Depression evaluation

Parameters All subjects Group without DED Group with DED Group without depression Group with depression

Number of subjects 1456 1215 241 (1) 1318 138 (2)

Age, years 64.82±9.47 64.33±9.38 67.26±9.60 p<0.001* 64.90±9.43 64.09±9.97 p=0.35
Gender
Male 40.5% 42.2% 31.5% p=0.002* 41.5% 30.4% p=0.009*
Female 59.5% 57.8% 68.5% 58.5% 69.6%
Residence
Rural 43.5% 46.7% 27.8% p<0.001* 42% 58% p<0.001*
Urban 56.5% 53.3% 72.2% 58% 42%
Level of education p=0.44 p=0.005*
Illiteracy or near illiteracy 7.2% 6.7% 9.5% 6.9% 10.3%
Primary school education 14.4% 15.3% 10% 14.3% 15.5%
Middle school education 42.7% 43.7% 37.8% 41.6% 52.9%
College education or more 35.7% 34.3% 42.7% 37.2% 21.3%
Income level 3.36±2.03 3.26±2.06 3.85±1.84 p<0.001* 3.43±2.04 2.69±1.88 p<0.001*
BCVA 0.94±0.21 0.95±0.21 0.90±0.23 p<0.001* 0.95±0.21 0.91±0.23 p=0.07
Cognitive function 26.50±3.41 26.52±3.39 26.44±3.54 p=0.76 26.61±3.26 25.51±4.49 p=0.007*
DS 31.12±7.25 30.99±7.20 31.79±7.51 p=0.12 29.32±3.84 48.35±9.33 p<0.001*
DES 1.52±2.32 0.72±1.36 5.51±1.98 p<0.001* 1.46±2.24 2.09±2.94 p=0.02*
Schirmer test, mm 11.77±7.00 12.00±7.07 10.63±6.59 p=0.005* 11.69±6.97 12.57±7.35 p=0.18
TBUT, s 7.76±5.43 8.13±5.71 5.90±3.13 p<0.001* 7.71±5.39 8.31±5.89 p=0.25
Corneal staining 0.67±0.54 0.66±0.54 0.69±0.54 p=0.45 0.67±0.53 0.68±0.58 p=0.68
MGD assessment 1.14±0.75 1.13±0.74 1.19±0.75 p=0.23 1.14±0.74 1.11±0.76 p=0.67
*p Values<0.05 were considered significant.
BCVA, best corrected visual acuity; DED, dry eye disease; DES, dry eye symptoms; DS, depression score; MGD, meibomian gland dysfunction; TBUT, tear film break-up time (1) as
compared to subjects without DED and (2) as compared to subjects without depression.

1400 Labbé A, et al. Br J Ophthalmol 2013;97:1399–1403. doi:10.1136/bjophthalmol-2013-303838

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Clinical science

Definite depression was more prevalent in patients diagnosed as Table 3 Univariate analysis of associations between definite
having DED than in subjects without DED (13.7±0.4% vs 8.6 depression, demographics and dry eye parameters
±0.3%, OR: 1.68; 95% CI 1.10 to 2.55; p=0.021) (table 1). The
proportion of subjects with a definite depression was also signifi- Parameters Pearson coefficient Significance
cantly higher in the group of patients experiencing dry eye symp- Age r=−0.02 p=0.34
toms as compared to patients without symptoms (13.8±0.4% vs Female gender r=0.07 p=0.012*
8.3±0.3%; OR: 1.77; 95% CI 1.19 to 2.63; p=0.006). These Rural residence r=−0.09 p<0.001*
results were similar when using the dry eye symptoms evaluated Marriage status r=−0.01 p=0.75
during the 2011 survey (13.5±0.3% vs 8.6±0.3% OR: 1.65; 95% Level of education r=−0.08 p=0.003*
CI 1.11 to 2.47; p=0.013). The mean depression score was also Gross income r=−0.11 p<0.001*
significantly higher in subjects with dry eye symptoms than in sub- Body height r=−0.07 p=0.004*
jects without symptoms (32.0±7.7 vs 30.9±7.1, p=0.016, using Body weight r=−0.06 p=0.024*
the 2006 survey data; 32.3±7.2 vs 30.8±7.3, p=0.004, using the Systolic blood pressure r=0.01 p=0.64
2011 survey data). Correspondingly, patients with depression Cognitive function r=−0.1 p<0.001*
experienced more dry eye symptoms than patients without depres- BCVA r=−0.05 p=0.046*
sion (p=0.02) (table 1) and the depression score was significantly DED r=0.06 p=0.014*
correlated to the dry eye symptoms (r=0.07; p=0.013) (table 2). DES r=0.08 p=0.003*
Nevertheless, the depression score was not significantly associated TBUT r=0.03 p=0.21
with the TBUT (p=0.18), the Schirmer test (p=0.37), corneal Schirmer test r=0.04 p=0.16
staining (p=0.30) or MGD evaluation (p=0.93). In a parallel Corneal staining r=0.01 p=0.65
manner, the dry eye symptoms were not correlated to any of the MGD assessment r=−0.01 p=0.66
ocular surface objective parameters (table 2).
Significant values are shown in bold.
In univariate analysis, definite depression was associated with *p Values <0.05 were considered significant.
dry eye symptoms (r=0.08; p=0.003), DED (r=0.06; BCVA, best corrected visual acuity; DED, dry eye disease; DES, dry eye symptoms;
p=0.014), BCVA (r=−0.07; p=0.046), female gender (r=0.07; MGD, meibomian gland disease; TBUT, tear film break-up time.
p=0.012), gross income (r=−0.11; p<0.001), level of educa-
tional background (r=−0.08; p=0.003), rural residence (r=
−0.09; p<0.001), cognitive evaluation (r=−0.1; p<0.001), epidemiological studies that showed a positive association
body height (r=−0.07; p=0.004) and weight (r=−0.06; between DED and depression.6–8 10 In a veterans population
p=0.024), but not with age (r=−0.02; p=0.34), or marital study, Galor et al,7 evaluated the relationship between DED and
status (r=−0.01; p=0.75) (table 3). The multivariate logistic psychiatric disorders and observed that the presence of depres-
regression analysis included presence or absence of depression sion induced an approximately twofold increased risk of having
as dependent parameter and the variables that were significantly DED. Similarly, Fernandez et al,10 recently reported more dry
associated with depression in the univariate analysis as inde- eye symptoms in veterans with depression and post-traumatic
pendent parameters. After stepwise reduction of the list of inde- stress disorders. Nevertheless, these studies evaluated only
pendent parameters by dropping those parameters with a p veteran populations and did not use dimensional measures to
value>0.05, depression was eventually associated with dry eye evaluate depression symptoms and to categorise patients with
symptoms ( p=0.028), lower cognitive status ( p=0.01), rural depression. Kim et al11 evaluated DED and depression symp-
residence ( p=0.023) and lower body weight ( p=0.05) (table 4). toms and their relation to objective tests on DED in a
population-based cross-sectional study. As observed in the
present study, these authors found a positive correlation
DISCUSSION
between depression and dry eye symptoms. Similarly, there was
In an adult population from Beijing, depression was associated
with DED and in particular with dry eye symptoms. These
results are in accordance with previous retrospective
Table 4 Multivariate logistic regression analysis between definite
depression, demographics and dry eye parameters
Table 2 Results of correlation between dry eye parameters and 95% CI
depression symptoms Parameters OR Significance Lower Upper
Schirmer Corneal MGD
Variables DES test TBUT staining assessment Age 0.99 p=0.57 0.96 1.02
Female gender 1.19 p=0.55 0.67 2.12
Schirmer test r=−0.04 Rural residence 0.45 p=0.023* 0.22 0.89
p=0.10 Level of education 1.28 p=0.09 0.96 1.7
TBUT r=−0.04 r=0.06 Gross income 1 p=0.35 0.99 1
p=0.16 p=0.017*
Body height 0.99 p=0.89 0.96 1.03
Corneal r=−0.001 r=0.16 r=−0.15
Body weight 0.98 p=0.05* 0.96 1
staining p=0.96 p<0.001* p<0.001*
Cognitive evaluation 0.93 p=0.01* 0.87 0.98
MGD r=0.03 r=−0.02 r=0.03 r=0.03
assessment p=0.30 p=0.40 p=0.24 p=0.23 BCVA 0.64 p=0.42 0.22 1.87
DS r=0.07 r=0.02 r=0.03 r=0.03 r=0.002 DED 1.11 p=0.77 0.55 2.25
p=0.013* p=0.37 p=0.18 p=0.30 p=0.93 DES 1.14 p=0.028* 1.01 1.27
Significant values are shown in bold. The dependent variable was the presence of definite depression. Significant values are
*p Values <0.05 were considered significant. shown in bold.
DES, dry eye symptoms; DS, depression score; MGD, meibomian gland dysfunction; *p Values <0.05 were considered significant.
TBUT, tear film break-up time. BCVA, best corrected visual acuity; DED, dry eye disease; DES, dry eye symptoms.

Labbé A, et al. Br J Ophthalmol 2013;97:1399–1403. doi:10.1136/bjophthalmol-2013-303838 1401

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Clinical science
no association between objective dry eye parameters (TBUT and
Schirmer test) and the depression score.11 These results were
also in agreement with two smaller-scale case-control studies
showing that depression and anxiety scores were correlated to
the Ocular Surface Disease Index (OSDI).2 9 In contrast,
another study evaluating the burden of DED in daily life
reported that mental health was unaffected by dry eye symptoms
regardless of the severity level or diagnosis.4 A reason for the
discrepancy between the studies may have been that the general
health status questionnaire (Short Form 36 (SF-36)) used in that
study was not specific for measuring the psychological status of
the subjects.
Although an association has been detected between depres-
sion and DED, it may be more likely that the symptoms of DED
and not DED itself were associated with depression or depres-
sion symptoms. There may be several possible explanations for
this relationship. First, dry eye symptoms may induce or increase
anxiety and depression symptoms. Despite complex pathophysi-
ology, chronic pain negatively impacts multiple aspects of
patient health including cognitive processes and mental health.5
Moreover, DED negatively affects the patient’s everyday living
and quality of life, as a result of chronic pain and also through
visual performance alteration and the perception of visual func-
tion.2–4 15 The need for frequent instillations of eye drops can
also affect social interactions.16 In a recent study, Pouyeh et al17
showed that the presence of ocular surface symptoms was nega-
tively correlated to the performance of daily activities, the cap-
acity to work as well as emotional well-being. These chronic
impacts of dry eye symptoms on many components of daily life
might contribute to the development of depression in patients
with DED. Second, depression and its medications might induce
or aggravate DED. Although antidepressant medications are
known risk factors for DED,7 18 it has been shown that depres-
sion itself is involved in the pathophysiology of DED and not
just its treatments .7 Despite common risk factors such as female
gender or age, biological studies showed a dysregulation of
neuropeptides and an increased production of inflammatory
cytokines in patients with depression,19–21 which are also
mechanisms involved in DED.7 11 If depression itself is involved
in the pathophysiology of DED, one can argue that other clin-
ical parameters evaluating the tear film such as tear film
break-up time, Schirmer test and corneal staining will be asso-
ciated with depression scores. However, results from the present
and previous studies found no significant correlation between
depression and the results of clinical objective parameters of
DED.9–11 In a parallel manner, the results of dry eye symptoms
evaluation were not significantly associated with DED objective
parameters in our study and in previous other investigations.16
One may also take into account that perception of dry eye
symptoms can be influenced by many factors including depres-
sion and anxiety.22 23 A depressive mood may aggravate dry eye
symptoms or lower the threshold for perceiving ocular surface
discomfort.24 Moreover, changes in the psychological status of
patients could also modify the reported intensity of symptoms.
Our study has limitations that need to be considered when
interpreting the results. First, the DED and depression evalua-
tions were performed with a 5-year interval (DED evaluation in
2006 and depression evaluation in 2011). Although DED is a
chronic disease, some patients may have experienced relief from
their dry eye symptoms and others may have newly developed
DED or its symptoms may have worsened over time. The indi-
vidual dry eye symptoms evaluated in 2011 were however not
different than those evaluated in 2011, so that this limitation of
the study may not have markedly influenced the results and
1402 Labbé A, et al. Br J Ophthalmol 2013;97:1399–1403. doi:10.1136/bjophthalmol-2013-303838
conclusions of our study. Second, dry eye symptoms were evalu-
ated using a simple scoring system made up of three questions.
Questionnaires such as the OSDI (with 12 questions) or the Dry
Eye Questionnaire (with 21 questions) would have delivered a
more detailed analysis of dry eye symptoms.14 Nevertheless,
questionnaires using only three questions have also been used in
previous large epidemiological studies such as the Women’s
Health Study.25 Third, the questionnaire used to evaluate
depression symptoms was adapted from the Zung self-rating
depression scale, but was not self-administered. Since some
study participants could not answer the different questions
alone; consequently, these questions were asked by trained tech-
nicians for all subjects. This may explain the relatively low value
of depressions score observed in the present study.9 26 Finally,
several parameters that may influence the relationship between
dry eye and depression, such as the presence of concomitant
ocular surface disorders or other systemic diseases, the use of
systemic (in particular antidepressant medications) or topical
medications were not systematically evaluated in our study.
In conclusion, our study found an association between dry
eye symptoms and depression. Due to the study design, this
investigation could not address whether depression increased
dry eye symptoms or vice versa or whether both conditions
influenced each other. Clinicians should be aware of the fre-
quent association between depression and DED in order to
better understand and better evaluate patient issues in DED.
Contributors All authors included in the paper fulfil the criteria of authorship. No
one else who fulfils the criteria has been excluded as an author.
Competing interests AL has received an unrestricted grant from ‘La Fondation de
France’.
Ethics approval The protocol of the study was approved by the Medical Ethics
Committee of the Beijing Tongren Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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Dry eye disease, dry eye symptoms and

depression: the Beijing Eye Study
Antoine Labbé, Ya Xing Wang, Ying Jie, Christophe Baudouin, Jost B
Jonas and Liang Xu

Br J Ophthalmol 2013 97: 1399-1403 originally published online

September 7, 2013
doi: 10.1136/bjophthalmol-2013-303838

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http://bjo.bmj.com/content/97/11/1399

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