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Clinical science
Original article
Risk factors for anxiety and depression in patients with glaucoma
  1. Fumihiko Mabuchi1,
  2. Kimio Yoshimura2,
  3. Kenji Kashiwagi1,
  4. Zentaro Yamagata3,
  5. Shigenobu Kanba4,
  6. Hiroyuki Iijima1,
  7. Shigeo Tsukahara1
  1. 1Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
  2. 2Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan
  3. 3Department of Health Sciences, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
  4. 4Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  1. Correspondence to Dr Fumihiko Mabuchi, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan; fmabuchi{at}yamanashi.ac.jp

Abstract

Aim To assess the risk factors for anxiety and depression in patients with glaucoma.

Methods Anxiety and depression in 408 patients with glaucoma were evaluated using the hospital anxiety and depression scale (HADS) questionnaire, which consists of two subscales, representing HADS-anxiety (HADS-A) and HADS-depression (HADS-D). To identify the risk factors for anxiety and depression, the stepwise and multiple linear regression analyses were carried out with the HADS-A and HADS-D subscores as dependent variables and demographic and clinical features as independent variables.

Results A stepwise linear regression analysis revealed the significantly related factors to be age for HADS-A (β=−0.046, p=0.0007) and HADS-D (β=0.035, p=0.011) and the mean deviation of the Humphrey Visual Field Analyzer 30-2 (HFA30-2) in the better eye for HADS-D (β=−0.095, p=0.0026). Based on multiple linear regression analyses, significant relationships were confirmed between age and the HADS-A subscore (β=−0.046, p=0.0008). Significant relationships were also confirmed between age (β=0.037, p=0.0077) or the mean deviation of HFA30-2 in the better eye (β=−0.094, p=0.0036) and the HADS-D subscore.

Conclusion A younger age was thus found to be a risk factor for anxiety, while an older age and increasing glaucoma severity were risk factors for depression in patients with glaucoma.

  • Glaucoma
  • anxiety
  • depression
  • hospital anxiety and depression scale
  • apotosis
  • telemedicine
  • pharmacology
  • public health
  • optic nerve
  • intraocular pressure
  • imaging
  • angle
  • experimental and laboratory
  • experimental and animal models
  • retina

https://doi.org/10.1136/bjophthalmol-2011-300910

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    Introduction

    Glaucoma is one of the most common chronic eye diseases that can potentially result in bilateral blindness, and glaucoma has previously been reported to associate with anxiety1–4 and depression,2 5–7 which are the two most common forms of psychological disturbances. We previously evaluated these psychological disturbances in patients with primary open angle glaucoma (POAG) and sex- and age-matched reference subjects using the hospital anxiety and depression scale (HADS), and also reported that the prevalence of POAG patients with anxiety or depression was higher than that in the reference subjects, which supports that glaucoma is related to anxiety and depression.8 These psychological disturbances affect the quality of life in patients with glaucoma.9 Additionally, it was also reported that the presence of depressive symptoms in patients led to poor glaucoma medication use.10 Providing glaucoma patients with appropriate psychological care is therefore essential to improving their quality of life and drug adherence. In order to detect, prevent and treat the emotional problems that develop in patients with glaucoma, it is important to understand the risk factors for these psychological disturbances. However, only a few studies about the risk factors for these conditions were reported previously, and further studies with a larger sample size, using different and reliable instruments for evaluating these psychological disturbances, are desirable to more fully elucidate their risk factors. In this study, we aimed to identify the predictors of anxiety and depression in patients with glaucoma.

    Participants and methods

    Glaucoma patients, including those with POAG, exfoliation glaucoma (XFG), primary angle closure glaucoma (PACG) and secondary glaucoma (SG), were enrolled from ophthalmology practices in University of Yamanashi and 14 general hospitals in Japan. A questionnaire including a checklist of systemic diseases and prescribed medications and a Japanese version of the HADS for psychiatric evaluation were distributed to the participants, and they submitted the questionnaire voluntarily. All participants had a complete fundus examination and a typical glaucomatous cupping of the optic disc with compatible visual field defects detected by automated static perimetry (Humphrey Visual Field Analyzer 30-2, Humphrey Instruments, San Leandro, California, USA; HFA30-2). Mean deviation (MD) in the last HFA30-2 taken within 3 years of enrolment in this study was used to evaluate the visual field loss. Only ‘reliable’ visual fields, defined by false-positive results, false-negative results or fixation losses not exceeding 33%, were used. The glaucoma patients with other ocular diseases that can cause visual field defect were not eligible to participate in this study. No patients with the following conditions were also eligible because of the high possibility that central nervous disorders may have caused psychological disturbances: patients with cerebrovascular disease,11 primary neurodegenerative diseases12 or schizophrenia.13 The patients prescribed β-blocker eye drops or oral carbonic anhydrase inhibitors were eligible to investigate whether these medicines cause depression. All participants gave a written informed consent prior to enrolment and our research protocol was approved by the Ethics Committee of University of Yamanashi. The study was conducted in accordance with the Declaration of Helsinki.

    Evaluation for psychological disturbance

    The HADS was used in this study. This questionnaire was developed by Zigmond and Snaith14 to identify and quantify the two most common forms of psychological disturbances (anxiety and depression) in physically ill patients. Data on the test–retest reliability and validity of HADS have been previously reported.15 Additionally, the original HADS was translated into Japanese and back-translated to English to ensure that the original meaning was retained. Factor analysis has provided reasonable confirmation of the Japanese version of the HADS scales.16 This scale contains 14 questions graded on a 4-point Likert scale (0–3) and consists of two subscales, thus representing HADS-anxiety (HADS-A) and HADS-depression (HADS-D). The minimum sum score of each of the seven item subscales is 0 and the maximum is 21, and higher scores are indicative of a higher level of depression and anxiety. In this study, scores higher than 10 on the HADS-A and HADS-D were defined as anxiety and depression respectively, as previously described.8

    Statistical analysis

    Data were analysed using SAS statistical software (V.9.1, SAS Institute Inc.). The mean subscores of the HADS-A and HADS-D were compared between the patients with POAG and non-POAG, and among the patients with POAG, XFG, PACG and SG, using Student t test. To identify the predictive factors for psychological disturbances (anxiety and depression) in patients with glaucoma, a stepwise linear regression analysis was carried out with HADS-A and HADS-D subscores as dependent variables and demographic and clinical features as independent variables. Age, gender, MD of the HFA30-2 in the better and worse eyes, the number of different types of eye drops used daily, and a history of glaucoma surgery (use of β-blocker eye drops or oral carbonic anhydrase inhibitors for the HADS-D subscore) were tested as independent variables. A multiple linear regression model was used to confirm the relationship between age and anxiety (HADS-A subscore), adjusted with or without demographic and clinical variables. The same model was also used to confirm the relationships between age or MD of the HFA30-2 in the better eye and depression (HADS-D subscore). We divided the samples into 10-year cohorts and 10 dB cohorts of the MD of the HFA30-2 in the better eye to graph the relationship between age or MD and these psychological disturbances. The mean subscores of the HADS-A and HADS-D were compared between the MD groups using an analysis of variance, and the prevalence of anxiety and depression was compared between the MD groups using the χ2 test. For statistical analysis, visual acuity was converted into a logarithm of minimum angular resolution (logMAR) visual acuity. For the eyes that could not be examined by HFA30-2 because of poor visual function, the vision level of these eyes was assigned an MD value of −34.0 dB. p Value <0.05 was considered to be statistically significant.

    Results

    Four hundred and eight glaucoma patients, including 318 POAG, 43 XFG, 32 PACG and 15 SG patients, participated in this study. The demographic data for the participants are shown in table 1. The mean age of the participants was 66.2±11.8 (mean ± SD) years, and ranged from 25 to 89 years. The participants consisted of 194 male and 214 female patients. The mean subscores of the HADS-A and HADS-D in the participants were 5.5±3.2 (ranged from 0 to 14) and 4.9±3.2 (ranged from 0 to 15), respectively. The mean subscores of the HADS-A in patients with POAG, XFG, PACG and SG were 5.5±3.3, 5.0±3.1, 5.5±2.8 and 6.6±3.7, respectively, and the mean subscores of the HADS-D in patients with POAG, XFG, PACG and SG were 4.9±3.2, 4.8±2.7, 4.8±3.3 and 5.1±4.0, respectively. There were no significant differences in the mean subscores of the HADS-A and HADS-D between the patients with POAG and non-POAG or among the patients with POAG, XFG, PACG and SG.

    View this table:
    Table 1

    Demographic and clinical characteristics of participants

    To identify the variables that were independently associated with the HADS-A or HADS-D subscores, we conducted a stepwise linear regression analysis. This analysis revealed age to be significantly associated with the HADS-A (β=−0.046, p=0.0007, table 2) and HADS-D (β=0.035, p=0.011, table 3), and MD of the HFA30-2 in the better eye was related to the HADS-D (β=−0.095, p=0.0026, table 3). To confirm the association between the HADS subscores and these identified risk factors, multiple linear regression analyses were performed. Significant relationships were found between age and the HADS-A subscore both with and without adjusting for demographic and clinical variables (β=−0.046, p=0.0008 and β=−0.043, p=0.0022, respectively, table 4). Significant relationships were also found, both with and without adjusting for demographic and clinical variables, between the age (β=0.037, p=0.0077 and β=0.036, p=0.0076 respectively) or MD of the HFA30-2 in the better eye (β=−0.094, p=0.0036 and β=−0.065, p=0.0033 respectively) and the HADS-D subscore (table 5). These relationships were graphically illustrated in figures 1–4. The HADS-D subscores and the prevalence of depression were still significantly different between the MD groups (p=0.012, analysis of variance and p=0.0019, χ2 test respectively), even when the patients were limited to those aged 70–80 years to exclude the influence of age.

    View this table:
    Table 2

    Factors predicting anxiety (HADS-A subscore) in patients with glaucoma as determined by a stepwise linear regression analysis

    View this table:
    Table 3

    Factors predicting depression (HADS-D subscore) in patients with glaucoma as determined by a stepwise linear regression analysis

    View this table:
    Table 4

    Results of a multiple regression analysis using the HADS-A subscale as the dependent variable in patients with glaucoma

    View this table:
    Table 5

    Results of a multiple regression analysis using the HADS-D subscale as the dependent variable in patients with glaucoma

    Figure 1
    Figure 1

    The association between age and the hospital anxiety and depression score (HADS) in patients with glaucoma. The HADS-anxiety (HADS-A) subscores in younger glaucoma patients tended to be higher compared with those in older patients. On the other hand, the HADS-depression (HADS-D) subscores in older glaucoma patients tended to be higher compared with those in younger patients.

    Figure 2
    Figure 2

    The association between age and the prevalence of anxiety (a score higher than 10 on the hospital anxiety and depression score-anxiety) or depression (a score higher than 10 on the hospital anxiety and depression score-depression) in patients with glaucoma. The prevalence of anxiety in younger glaucoma patients tended to be higher compared with that in older patients. On the other hand, the prevalence of depression in older glaucoma patients tended to be higher compared with that in younger patients. The prevalence of anxiety was higher than that of depression in glaucoma patients younger than 70 years of age.

    Figure 3
    Figure 3

    The association between the MD of the HFA30-2 in the better eye and the HADS-D subscore in patients with glaucoma. There was a significant difference (p=0.0040, analysis of variance) in the HADS-D subscores between the MD groups. The HADS-D subscores in patients with an MD ranging from −10 to −20 dB or an MD −20 dB were significantly higher than those in patients with an MD −10 dB. HADS-D, hospital anxiety and depression score-depression; HFA30-2, Humphrey Visual Field Analyzer 30-2; MD, mean deviation.

    Figure 4
    Figure 4

    The association between the MD of the HFA30-2 in the better eye and depression (a score higher than 10 on the hospital anxiety and depression score-depression) in patients with glaucoma. There was a significant difference (p=0.0006, χ2 test) in the prevalence of depression between the MD groups. The prevalence of depression in patients with an MD ranging from −10 to −20 dB or an MD −20 dB was significantly higher than that in patients with an MD −10 dB. HFA30-2, Humphrey Visual Field Analyzer 30-2; MD, mean deviation.

    Discussion

    In this study, age had a negative correlation with the HADS-A subscore in patients with glaucoma. To our knowledge, this is the first report to show that younger glaucoma patients tend to be more anxious compared with older patients. A younger age as a predictor for anxiety has also been reported for other chronic physical diseases, such as cardiovascular diseases17 and cancer.18 Ramsawh et al19 described that the severity of anxiety disorders declined over time by a naturalistic, longitudinal, short-interval follow-up performed to elucidate the course of anxiety disorders over 14 years in a population of 453 largely middle-aged patients recruited from outpatient psychiatry and primary care facilities. Orgeta20 reported that younger adults had greater emotional regulation difficulties compared with older ones, which may support the fact that younger age is a risk factor for anxiety in patients with glaucoma. As glaucoma can potentially result in bilateral blindness, younger glaucoma patients may have been more anxious about maintaining their visual function, because of their longer remaining lifespan. Bechetoille et al4 described that anxiety scores in a glaucoma-specific health-related quality of life questionnaire dropped noticeably when patients were first diagnosed with glaucoma. It has also been reported that most glaucoma patients showed an anxious reaction to their announcement of the diagnosis, and that they were dissatisfied with the information provided by their doctor and sought other sources of information.3 Patients with little information about their disease also have higher HADS scores,15 and so it is important for ophthalmologists to provide accurate and appropriate information about glaucoma to prevent patients, especially younger patients, from developing anxiety.

    It was previously reported that anxious personality traits and anxiety disorders were more prevalent in a severe POAG group (n=48) than control (n=37) or early POAG (n=48) groups using the Vocabulaire Binois Pichot, Cattel's 16 Personality Factors, Thematic Apperception Test and the Rorschach Test,1 and that the risk of anxiety in female patients with glaucoma (n=68) was found to be higher than in male subjects (n=53) using the HADS.9 However, there were no relationships between anxiety and the severity of glaucoma or gender in this study, although the severity of the visual field defect in the better eye was associated with depression. Further studies using other instruments should be performed to elucidate whether the severity of glaucoma and gender are associated with anxiety.

    With regard to depression, older age and a decreasing MD of the HFA30-2 in the better eye were associated with depression in this study. Skalicky and Goldberg6 reported that depression was more prevalent with increasing glaucoma severity in patients aged 70–79 years using the Nelson Glaucoma Severity Scale and the Geriatric Depression Scale-15 questionnaire, and that older age was a risk factor for depression. Our results supported their report, and this finding was confirmed in patients with a wider range of ages (ranging from 25 to 89 years) by a multiple linear regression analysis. Erb et al2 reported that the POAG inpatients (n=21), not outpatients, had higher scores for depression compared with the cataract patients (n=18) using the Beck Depression Inventory. This might have been because the POAG inpatients might suffer from more severe glaucoma compared with the POAG outpatients. Cumurcu et al21 reported that the scores of the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale of the XFG group (n=41) were significantly higher than those of the control (n=40) and POAG (n=32) groups, although there were no differences between the control and POAG groups regarding depression. In this study, there were no differences between the patients with POAG and XFG regarding depression. Tastan et al9 reported that the risk of anxiety and depression was higher in unmarried compared with married participants, including 121 patients with glaucoma and 64 control subjects. Unfortunately, we did not investigate whether the participants were married or unmarried, and so this factor was not tested as an independent variable in our stepwise linear regression model.

    It remains controversial with regard to whether the clinical use of a β-blocker is responsible for depression.22 23 We previously reported that the prevalence of patients with depression was not different between the POAG patients being treated with and without β-blocker eye drops.8 This study also did not find any relationship between the use of β-blocker eye drops and depression, although a stepwise linear regression analysis was performed with a larger number of glaucoma patients. The use of β-blocker eye drops does not seem to be the principal cause of depression in patients with glaucoma. However, it has been reported that depression in patients with glaucoma while using timolol maleate (non-selective β-blocker) eye drops was improved by withdrawal or switching to betaxolol hydrochloride (β-1 selective β-blocker) eye drops.24 Thus, patients with suspected depression should be evaluated by using survey instruments for depression or by consulting a psychiatrist before the prescription of β-blocker eye drops. Depression has also been reported as one of the side-effects of oral carbonic anhydrase inhibitors,25 although there have been no studies that have performed a statistical analysis to evaluate the relationship between the use of oral carbonic anhydrase inhibitors and depression. In this study, as was the case with the β-blocker eye drops, there was no statistically significant relationship found between oral carbonic anhydrase inhibitor use and depression. However, further studies in a larger number of patients should be performed to more fully evaluate the relationship between them, because the number of patients who used oral carbonic anhydrase inhibitors in this study was small (18 patients).

    As potential limitations of this study, the population sample was based on voluntary participation, and both anxiety and depression might affect an individual's participation in filling out a questionnaire. This selection bias might have had some influence on the investigated outcomes. In addition, these psychological disturbances might affect an individual's ability to perform a visual field test. Although the HADS is easy and convenient for trial purposes, a questionnaire is not comparable with a formal psychiatric diagnosis of depression or anxiety. Moreover, other ethnic populations may have different psychological reactions to glaucoma.

    In conclusion, a younger age was found to be a risk factor for anxiety, while an older age and increasing glaucoma severity were risk factors for depression in patients with glaucoma. It is therefore essential for physicians and co-medical staff to be aware of the risk factors for anxiety and depression in patients with glaucoma, and to provide glaucoma patients with appropriate psychological care as well as ophthalmological care to prevent them from developing anxiety and depression.

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    Footnotes

    • Competing interests None.

    • Ethics approval Ethics approval was provided by Ethics Committee of University of Yamanashi.

    • Provenance and peer review Not commissioned; externally peer reviewed.