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Current Eye Research, 36(1), 17, 2011 Copyright 2011 Informa Healthcare USA, Inc.

. ISSN: 0271-3683 print/ 1460-2202 online DOI: 10.3109/02713683.2010.519850


Anxiety and Depression in Patients with Dry Eye Syndrome

Meiyan Li1, Lan Gong1, Xinghuai Sun1, and William J. Chapin2

Department of Ophthalmology, EYE & ENT Hospital of Fudan University, Shanghai, China Department of Surgery, Division of OtolaryngologyHead and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

ABSTRACT Purpose: This study aimed to determine whether patients with dry eye syndrome [DES] have more symptoms of anxiety and depression than controls without DES. Methods: In this case-control study, the sample consisted of 89 DES subjects (13 diagnosed with Sjgrens syndrome [SS]) and 73 control subjects. Each subject was diagnosed as having DES or was chosen as a control subject by an ophthalmologist. The Zung Self Rating Anxiety Scales (SAS), Zung Self Rating Depression Scales (SDS), and Ocular Surface Disease Index (OSDI) were administered to all subjects. Scores of SAS and SDS, measuring level of anxiety and depression symptoms, were compared between the DES group and the control group. Correlations with other health status measures were conducted. Results: The SAS and SDS scores of the DES group were significantly higher than the control group (P<0.001, P<0.001). The prevalence of DES subjects with anxiety or depression symptoms was significantly higher than in the control group (P=0.003, P<0.001). In the DES group, SAS scores were found to be correlated with OSDI and educational level. SDS scores were found to be correlated with OSDI. Neither SAS nor SDS scores were correlated with age, sex, household income, tear break up time (BUT), Schirmer Test 1 (S1T), corneal fluorescein staining (FL), or visual acuity. Conclusion: Anxiety and depression are correlated with DES, demonstrating that DES is an important public health problem that merits increased attention and research.
KEYWORDS: Anxiety; Depression; Dry eye syndrome; Ocular Surface Disease Index; Sjgrens syndrome

Dry eye syndrome [DES] is one of the most frequently encountered ocular morbidities, with as many as 1.68 million American men 50 years and older having a reported clinical diagnosis or experiencing symptoms either constantly or often.1 DES is characterized by diminished production or increased evaporation of tears (non-Sjgrens syndrome keratoconjunctivitis sicca [non-SS KCS]) or by
Received 13 April 2010; accepted 26 August 2010 Correspondence: Lan Gong, Ph.D., Xinghuai Sun, Ph.D., Department of Ophthalmology, EYE & ENT Hospital of Fudan University, No. 83 Fenyang Road Shanghai 200031, China. E-mail:,

a systemic immunologic disorder (Sjgrens syndrome [SS]) that causes insufficient moisture production in the salivary and tear-producing glands.24 Typical symptoms of DES include watery eyes, burning or stinging, ocular grittiness, foreign body sensation, blurred vision, and photophobia,2,46 all of which greatly affect patient quality of life (QOL). Reports in the literature are emerging about DES and its significant impact on patient quality of life with various quality of life measurements,711 including general quality of life7,8 and vision-related daily life.9 However, psychological status, an essential part of QOL, has rarely been studied. Only a qualitative analysis of focus data was conducted in a meeting in 2002,12 pointing out that the experience of living with 1

2 M. Li etal. symptoms of DES elicited feelings, such as disappointment and frustration with self-esteem and emotional well-being also being affected. Anxiety and depression are two common forms of psychological disturbances that usually exist with physical disorders. To the best of our knowledge, there are few studies that investigate anxiety and depression in DES patients.12,13 Herein, we conducted a comparative study to investigate the psychological status of DES patients and the control subjects with the SAS and SDS survey tools. We also investigated whether Ocular Surface Disease Index (OSDI), tear break up time (BUT), Schirmer Test 1 (S1T), corneal fluorescein staining (FL), visual acuity, and demographic status including age, sex, household income, and educational level are correlated with anxiety or depression symptoms in DES patients. tear supplements on the day that they participated in the study. The 73 control subjects consisted of volunteer individuals who had applied to the Department of Ophthalmology with refraction-related complaints and met the following inclusion criteria. The inclusion criteria included no symptoms of DES, a S1T value greater than 10mm/5min, and a BUT greater than 10sec. Subjects with other ocular disease (other than age-related cataracts) were excluded from the control group. None of the control subjects enrolled was using tear supplements. All subjects had to be literate in Chinese, willing and able to finish a series of questionnaires without significant assistance, and willing to undergo clinical testing for DES as part of the study. Subjects with the following conditions were ineligible to participate in either group for this study: (1) current use of any medication due to a psychiatric disorder or cognitive impairment that might affect the psychological assessment; (2) subjects who had an uncontrolled systemic disease or disability that affected his or her daily activities (including ocular allergy, infection, or irritation that was not related to DES); (3) subjects who had external ocular disease or had undergone ocular surgery within the last 6 months; (4) subjects who were known to have allergy to any component of any of the agents used in the study (e.g., fluorescein); or (5) subjects who had undergone temporary or permanent lacrimal punctum occlusion.


Study Overview
Eligible subjects completed several questionnaires between June 2009 and December 2009 to assess their psychological status and ocular symptoms with SAS, SDS, and OSDI survey tools. Socio-demographic data were obtained by chart review. Questionnaires were completed before the examination to ensure that the clinical encounter would not influence subject responses. All surveys were completed by self-administration. Written informed consent was obtained from all participants after a complete description of the study and subjects were compensated for their time.

Assessment of Psychological Status

Subjects completed two standardized assessments measuring anxiety and depression symptoms. The SAS is a 20-item, four-point Likert scale self-report assessment for the presence and severity of affective symptoms and somatic components of anxiety.14 Fifteen of the items express negative experience or symptoms (e.g., I am afraid for no reason at all) and 5 express positive experience and are reversed (e.g., I feel that everything is all right and nothing bad will happen). The SDS is a 20-item four-point Likert scale self-report assessment for depression.15 Ten of the items express negative experience or symptoms (e.g., I have crying spells or feel like it) and ten express positive experiences and are reversed (e.g., My life is pretty full). The Chinese versions of both scales have been validated and have been widely used to assess anxiety and depression associated with a wide range of diseases.16 Item responses of both SAS and SDS are ranked from 1 to 4, with higher scores corresponding to more frequent symptoms. For each item, subjects are asked to provide a score corresponding to the frequency with
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Study Population
Eighty-nine consecutive DES patients referred to the Eye and ENT Hospital (Fudan University, Shanghai, PR China) were recruited if they were at least 18 years of age and had symptoms of DES for at least 3 months. The diagnostic criteria for DES were as follows: (1) a frequent or sustained occurrence of any one of the following seven symptoms: burning sensation, gargalesthesia, foreign body sensation, sensation of stabbing pain, dryness, photophobia, or asthenopia; (2) a S1T value of less than 10mm/5min and a BUT of less than 10sec; or (3) corneal fluorescein staining (+) and/or rose-bengal staining were noted. In the case that any two of the above three conditions were present, the subject was diagnosed with DES. Of the 89 DES patients, 13 were diagnosed with SS. None of the subjects enrolled were using

Anxiety and Depression in Dry Eye Syndrome 3 which each event in question occurs. The following scale was used: 1=A little of the time/very rarely/rarely; 2=Once in a while/some of the time/occasionally; 3=Good part of the time/very often /often; 4=Most of the time/always/almost always. The raw total scores were converted to a 100-point scale by multiplying by 1.25.16 Subjects receiving converted scores of more than 50 on the SAS and SDS were considered to have symptoms of anxiety and depression, respectively.16 association of the dependent variable and the independent variable. Associations between clinical variables were examined by Spearmans rank correlation test and expressed as the Spearman correlation coefficient. Statistical s ignificance level was set at 0.05.

The demographic and ophthalmologic data are presented in Tables 1 and 2. The population included 162 adult subjects with 89 having DES (76 with non-SS KCS, 13 with SS) and 73 being control subjects. The two groups were comparable with regards to sex, household income, and marital status showing no statistically significant difference except with age and educational level (P<0.05 for each). After statistical correction of baseline covariates (age and educational level), both the SAS and SDS scores of the DES group were higher than those of the control group (t=4.35, P<0.001 and t=4.57, P<0.001, respectively). With regards to comparisons between the two groups of prevalence of anxiety and depression symptoms, the prevalence in the DES group was significantly
TABLE 1 Demographic characteristics of study population Baseline Dry eye syndrome Control group characteristics group (n=89) (n=73) P value Age (years)a 42 (32.551) 36 (28.542) 0.0015 Range of age 1859 2359 (years) Gender, n (%) 0.149 Male 17 (19.1) 21 (28.8) Female 72 (80.9) 52 (71.2) Marital status, 0.679 n (%) Married 73 (82.0) 58 (79.5) Single 16 (18.0) 15 (20.5) Household 0.8589 income, n (%) Low (< RMB3000) 54 (60.7) 42 (57.5) 13 (14.6) 20 (27.4) Moderate ( RMB30005000) 22 (24.7) 11 (15.1) High (> RMB5000) Education level, 0.0432 n (%) 36 (40.5) 18 (24.7) Junior high school or less 18 (20.2) 17 (23.3) Senior high school University or 35 (39.3) 38 (52.0) higher 89 (100) 0 In use of tear supplements, n (%) a Median (P25P75).

Additional Measures
Ocular Surface Disease Index Questionnaire The OSDI, developed by Allergan, Inc., is a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to DES. Subjects were questioned with three different subscales: ocular symptoms (e.g., Eyes that feel gritty?), vision-related functions and limitations (e.g., Have problems with your eyes limited you in reading?), and environmental triggers (e.g., Have your eyes felt uncomfortable in windy conditions?) during a 1-week recall period. Each answer was scored based on frequency of symptoms using a 5-point scale from 0 (indicating no problem) to 5 (indicating a significant problem). Responses to all questions were combined for a composite OSDI score ranging from 0 to 100, with higher scores indicating more severe symptoms.17 Clinical and Socio-Demographic Measures Clinical measures included visual acuity, FL, BUT, and S1T. Socio-demographic data collected included age, sex, career, educational level, marital status, household income, use of tear supplements, and duration of disease. All ophthalmologic examinations were done by the same ophthalmologist.

Statistical Analysis
Data were analyzed using Stata9.0 software package (Statacorp, Texas, USA) and reported as means standard deviation (SD) or medians. Comparison of continuous variables was done by a KruskalWallis test and Mann-Whitney U test. In addition, a Bonferronicorrected post hoc test was conducted to adjust the observed significant level for multiple comparisons. Statistical analysis of categorical variables was performed using the chi-square test. Multiple linear regression and logistic regression were used to adjust for selected covariates (age and educational level) to control for potentially confounding factors, by holding the selected covariates constant and then observing the
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4 M. Li etal.
TABLE 2 Ophthalmologic data of dry eye syndrome and control group Dry eye syndrome Control group P value Duration of 3.053.32 0 disease (years) BUT (second) Right eyea 4 (36) 11 (1012) 0.000 4 (36) 11 (1012) 0.000 Left eyea S1T (mm/5min) 4 (26) 12 (1015) 0.000 Right eyea 4 (17) 13 (1115) 0.000 Left eyea FL (+), n Right eye 18 0 Left eye 22 0 39.6 (22.957.5) 10.4 (2.318.1) 0.000 OSDIa a Median (P25P75). BUT: break up time; S1T: Schirmer Test 1; FL: corneal fluorescein staining; OSDI: ocular surface disease index. TABLE 3 Comparison of the psychological disturbances between DES group and control group DES group Control (n=89) group (n=73) t z P value SAS, 46.29.2 39.97.5 4.35 0.000 mean SDa SDS, 48.911.5 41.39.1 4.57 0.000 mean SDa Anxiety 27 (30.3) 6 (8.2) 2.96 0.003 disorder, n (%)b 37 (41.6) 10 (13.7) 3.68 0.000 Depression disorder, n (%)b a Adjusted age, educational level by multiple linear regression model. bAdjusted age, educational level by logistic regression model. SAS: Zung Self Rating Anxiety Scales; SDS: Zung Self Rating Depression Scales; DES: dry eye syndrome. TABLE 4 Correlation of SAS and SDS scores with sociodemographic status and clinical parameters for DES group SAS scores SDS scores r P value r P value Age -0.0658 0.5400 -0.0902 0.4006 Gender 0.0608 0.5717 -0.0462 0.6672 Educational -0.2507 0.0178 -0.1621 0.1291 level Household -0.0806 0.4525 -0.1156 0.2806 income OSDI 0.3060 0.0035 0.2670 0.0114 Duration of 0.0637 0.5532 -0.1020 0.3416 disease BUT Right eye 0.0934 0.3842 0.1355 0.2053 Left eye 0.0112 0.9168 0.0435 0.6855 S1T Right eye 0.0384 0.7209 0.0841 0.4333 Left eye -0.0819 0.4454 0.0445 0.6785 FL Right eye -0.0320 0.7661 -0.0274 0.7990 Left eye 0.0416 0.6987 -0.0376 0.7264 Visual Acuity Right eye -0.0220 0.8380 0.0290 0.7875 Left eye 0.0659 0.5395 0.0960 0.3709 DES: dry eye syndrome; SAS: Zung Self Rating Anxiety Scales; SDS: Zung Self Rating Depression Scales; OSDI: Ocular Surface Disease Index; BUT: tear break up time; S1T: Schirmer Test 1; FL: corneal fluorescein staining.

higher than in the control group (z=2.96, P=0.003 and z=3.68, P < 0.001, respectively) (Table 3). SAS scores were found to be correlated with OSDI and educational level (r=0.3060, P=0.0035 and r=-0.2507, P=0.0178) while SDS scores were found to be correlated with OSDI (r=0.2670, P=0.0114). Neither SAS nor SDS scores were correlated with the age, sex, household income, duration of disease, BUT, S1T, FL, or visual acuity (all P>0.05) as seen in Table 4. Considering the psychological status of SS might differ from that of non-SS KCS due to different prognosis18 or co-existing auto-immune disease(s), we made a subgroup analysis to investigate the psychological status difference between non-SS KCS group (n=76), SS group (n=13), and control group (n=73). After statistical correction of baseline covariates (age and educational level) a statistically significant difference was found

among the three groups (P<0.05). Both the non-SS KCS group and SS group had higher SAS/ SDS score than the control group (P<0.05, for each). However, there was no statistically significant difference between SAS/ SDS scores for the non-SS KCS group and SS group (P=0.384, P=0.186). With regards to comparisons of prevalence of anxiety and depression among the three groups, both the non-SS KCS group and SS group had higher prevalence than the control group (P<0.05, for each), while no statistically significant difference was found between the prevalence of anxiety and depression in the non-SS KCS group and SS group (P=0.460, P=0.549, respectively) (Table 5).

Our results provide insight into the psychological status of DES subjects, indicating DES subjects were more anxious and depressed than those without DES. These results are in agreement with Erb etal.s19 study, which also found that primary keratoconjunctivitis (pKCS) subjects were more depressed than control subjects without pKCS with Beck Depression Inventory. However, a separate study8 reported that the mental health of DES patients was consistently
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Anxiety and Depression in Dry Eye Syndrome 5

TABLE 5 Comparison of the psychological disturbances between non-SS KCS group, SS group, and control group Comparison of the three groups Bilateral comparison Non-SS KCS(n=76) SS (n=13) Controls (n=73) P value P value SAS, mean SDa 46.39.5 45.77.6 39.97.5 0.000 a 0.001 b 0.000 c 0.384 49.311.9 46.98.9 41.39.1 0.000 a 0.001 SDS, mean SDa b 0.000 c 0.186 23 (30.3) 4 (30.8) 6 (8.2) 0.001 a 0.019 Anxiety, n (%)b b 0.003 c 0.460 34 (44.7) 3 (23.1) 10 (13.7) 0.000 a 0.001 Depression, n (%)b b 0.016 c 0.549 a Adjusted age, educational level by multiple linear regression model. bAdjusted age, educational level by logistic regression model. SAS: Zung Self Rating Anxiety Scales; SDS: Zung Self Rating Depression Scales; Non-SS KCS: non-Sjgrens syndrome keratoconjunctivitis sicca; SS: Sjgrens Syndrome. a: Non-SS KCS vs. control; b: SS vs. control; c: Non-SS KCS vs. SS.

unaffected by the disease, regardless of severity level or diagnosis. There are two potential reasons for this difference. First, the Short Form-36 used in a study by Mertzanis et al.8 was a health questionnaire aiming to measure general quality of life. This questionnaire was not used specially to identify and quantify the psychological status of subjects. Second, the study population and the normative data included people with comorbidities that may have influenced the result. In our study, SAS and SDS scores were found to be correlated with OSDI scores, but were not correlated with clinical parameters BUT, S1T, and FL. These results could potentially be explained by several possibilities. One possibility is that symptoms of DES, such as pain, could induce the occurrence of anxiety and depression symptoms. It is well known that pain or disabilities in chronic disease can induce anxiety and depression.20 This explanation may help us understand the lack of correlation between SAS/SDS scores and clinical parameters. Some studies have found that symptoms of DES typically deviate from signs,2123 just as OSDI scores were not correlated with clinical parameters (BUT, S1T, and FL) in our study (data not shown). Another possibility is that those who scored higher on the SAS and SDS scales (the more anxious or depressed) tended to report more severe symptoms of DES. We also found no correlation between psychological disturbance (anxiety and depression) and duration of disease. One explanation for this phenomenon might be that on the first stage of disease, patients were anxious and depressed because of the unpleasant symptoms, unsatisfying palliative treatments and
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reduced quality of life. However, as time went on they gradually accepted the living conditions associated with DES. Another explanation for this lack of correlation might be the relatively short disease duration in our DES group (mean + S.D, 3.053.32 years). In accordance with Meijer etal.s24 study, we found a negative significant correlation between anxiety symptoms and educational level. One possible explanation is that highly educated subjects got information through various channels and had a better understanding of the disease, which led to better psychological status. However, no correlation was noted between depression and educational level. With regard to SS, many studies2528 have reported that SS patients experienced increased clinical anxiety or depression. In accordance with our study, a study by Valtysdottir et al.27, using the Hospital Anxiety and Depression Scale, reported that the prevalence of anxiety and depression in SS patients was 48% and 32%, respectively, significantly higher than the control group. This prevalence was higher than in our study, in which we found prevalence to be 30.8% and 23.1%, respectively. This difference may have been a result of the different instruments used for measuring psychological disturbances and the small sample size of our study. But recently, Stevenson etal.26 reported that SS patients had significantly higher scores than controls for depression but a significant difference between the same two groups for anxiety was not found. To date, the results of this study elicit discussion and further studies are needed. There are several important limitations to this study. First, a statistically significant difference of age and educational level were found between the DES group and

6 M. Li etal. the control group. The control group was significantly younger and more highly-educated than the DES group. When recruiting control subjects, we noted that those of a younger demographic and the highly-educated tended to be more willing to participate in our study. For this reason, there existed a selection bias in our study. To account for this, we used a multiple linear regression or logistic regression to control the two confounding factors of age and educational level. Second, we did not exclude the subjects with age-related cataracts in our study. Considering the influences of cataracts on visual acuity, the measured scores of SAS, SDS, and OSDI could potentially be significantly altered. We observed that visual acuity was comparable between the DES group and control group. However, not excluding patients with cataracts is an important limitation to our study and patients with cataracts should be excluded from future studies. Third, when comparing the psychological status among the non-SS KCS group, the SS group, and control group, the sample size of the SS group was small, consisting of only 13 subjects limiting the statistical power of the test. Evaluating the psychological status of DES patients, while planning their treatment, is essential to providing optimal treatment. To most ophthalmologists, DES is a frustrating problem for which treatment options are usually limited to palliative techniques, such as pharmacologic therapy, punctal occlusion, and acupuncture.29 Although patients with a mild condition generally receive adequate relief from such treatment, most patients with chronic and moderate-to-severe DES continue to experience symptoms despite maximum use of palliative treatments.30 Patients with chronic disease tend to be anxious and depressed, which could lead them to be suspicious of their doctors and treatments20 greatly inhibiting the efficacy of treatment. For this reason, observing patient psychological status will help doctors to offer the best customized treatment for each DES patient. In conclusion, further studies with a larger sample size using different methods for identifying psychological disturbances are desirable to understand more fully the relationship between dry eye and these psychological disturbances.

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The authors gratefully acknowledge Naiqing Zhao and Yongfu Yu of the Department of Biostatistics, School of Public Health, Fudan University, for their help with the statistical analyses. Declaration of interest: The authors report no conflicts of interest.

Anxiety and Depression in Dry Eye Syndrome 7

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