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Article

Presence of Anxiety and Depression in Patients with Open-Angle Glaucoma of Different Degrees of Damage

by
Marija Olujić
1,2,
Dubravka Biuk
2,3,*,
Slaven Balog
1,2,
Ivana Kotromanović Šimić
2,
Darko Kotromanović
2,4 and
Katarina Dodig-Ćurković
2,5,6
1
Ophthalmology Polyclinic Dr. Balog, Ivana Gundulića 36 b, 31000 Osijek, Croatia
2
Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
3
Clinic for Eye Diseases, Clinical Hospital Centre Osijek, Europska Avenija 14, 31000 Osijek, Croatia
4
Oncology Clinic, Clinical Hospital Centre Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
5
Institute for Child and Adolescent Psychiatry, Clinical Hospital Centre Osijek, Europska Avenija 14, 31000 Osijek, Croatia
6
Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(11), 3954; https://doi.org/10.3390/jcm14113954
Submission received: 6 May 2025 / Revised: 29 May 2025 / Accepted: 31 May 2025 / Published: 3 June 2025
(This article belongs to the Section Ophthalmology)

Abstract

:
Background: Glaucoma is a group of eye conditions that damage the optic nerve, and it can be interconnected with psychoneurotic disorders due to the psychological and emotional stress that comes with such a chronic condition. The aim of this study was to examine the characteristics of the occurrence of anxiety, depression and open-angle glaucoma (OAG) in glaucoma patients from December 2023 to December 2024. Methods: This cross-sectional study was conducted on 200 patients with three different stages of OAG. Multiple questionnaires were used to determine the influence of different OAG stages on the severity of anxiety and depression. Results: While predicting the anxiety expression, in a multivariate logistic regression (stepwise method), there was a significant model in predicting the expression of anxiety: female gender (Odds ratio (OR) = 3.03), age of 66 and over (OR = 3.4) and the feeling of being under stress (OR = 7.07). In the prediction of a higher severity of depression, predictors are age 66 and older (OR = 2.03) and feeling stressed (OR = 9.47). Conclusions: While glaucoma and psychoneurotic disorders affect different systems in the body, the psychological toll of living with glaucoma can lead to exacerbation of glaucoma.

1. Introduction

Glaucoma is the second most common cause of blindness, but it is the leading cause of irreversible blindness worldwide. It is a multifactorial chronic and progressive optic neuropathy [1,2,3] with common characteristics that result in progressive and irreversible deterioration of the optic nerve and retinal nerve fibres, with corresponding deficits in the visual field (VF) [1,2,3,4].
Since glaucoma is a progressive chronic disease, it is essential to recognize the disease as early as possible so that the patient can be treated before irreversible structural changes occur [5]. Accordingly, early diagnosis is a priority. Antiglaucoma (ATG) treatment aims to slow down and/or prevent further progression of the disease. For now, ATG treatment with available medications and/or surgical therapy cannot reverse the prior glaucomatous damage to the optic nerve [3]. Glaucoma is most often a chronic disease that requires lifelong treatment and monitoring of possible disease progression [3]. Therefore, it is a significant socioeconomic problem, but also a psychological burden for the patient, since all forms of glaucoma can end in a complete loss of vision, i.e., blindness [2,6]. In patients with glaucoma, it is observed that even a slight loss of the peripheral part of the VF and the associated expected reduction in contrast sensitivity can have an impact on the patient’s functioning in everyday life, habits and quality of life, i.e., reduced opportunities for physical activity, impaired daily work habits and increased risk of injuries and falls [7].
Elevated intraocular pressure (IOP) is currently the only modifiable risk factor for controlling the progression of glaucoma [2]. Normal IOP is considered to be between 10 mm of mercury (mmHg) and 21 mmHg, with a mean of 15.7 mmHg [8] measured by Goldmann applanation tonometry (GAT), the gold standard for measuring IOP [9]. Only 2% of the world’s population has been shown to have normal values above 21 mmHg [10]. Traditional ATG treatment is based on lowering IOP with various ATG medications [8]. This is done to prevent the development of glaucomatous optic neuropathy. Although elevated IOP levels play a significant role in glaucoma, IOP alone is not always the determining factor.
Depending on the way in which the blockage of the aqueous humor drainage occurs, glaucoma is divided into open-angle glaucoma (OAG)—characterized by an open iridocorneal angle [11] and angle-closure glaucoma (ACG)—an anatomical configuration of the iridocorneal angle in which there is mechanical blockage of the trabecular meshwork by the peripheral part of the iris [12,13,14,15,16,17]. An additional division is into primary and secondary OAG and ACG [12,13,14,15,16].
Primary open-angle glaucoma (POAG) is a chronic, progressive disease of still unclear etiology, which can result in irreversible blindness [18]. It is usually encountered in patients older than 40 years of age and the likelihood of the disease increases with age. The following are at higher risk for developing the disease: older age, higher IOP values, people of black race, a positive family history of glaucoma in the first generation, people who are moderately to highly myopic (moderate to high myopia), low blood pressure—diastolic, thinner central corneal thickness [13,18].
OAG can be divided into three stages: early, moderate and advanced glaucomatous loss. In early glaucomatous loss, the target IOP range is between 15 mmHg and 17 mmHg, in intermediate glaucomatous loss the target IOP range is between 12 mmHg and 15 mmHg and in advanced glaucomatous loss the target IOP range is between 10 mmHg and 12 mmHg [18,19]. It is of utmost importance to maintain normal IOP values in patients with glaucoma. Patients with glaucoma are truly concerned about the health of their eyes—they fear blindness and increased financial costs due to long-term use of ATG therapy, but also a decrease in the ability to perform daily activities, including work. It has been shown so far that chronic diseases, such as glaucoma, are associated with psychological disorders, most often depression and anxiety, and therefore many studies have been conducted that have shown that the prevalence of anxiety or depression is high in patients with glaucoma [20].
Although studies have shown that the disease contributes to the development of anxiety and/or depression, few studies have so far indicated that negative emotions, such as anxiety or depression, are also a risk factor for the progression of physical diseases [21]. Anxiety and depression, as psychiatric disorders, account for an estimated 13% of the global burden of disease and are among the most difficult diseases to treat. These disorders typically present with a diverse range of symptoms, have complex genetic risk associations, and poorly understood aetiology [22]. Along with this, it has also been noted that patients with glaucoma often share common character traits, such as an irritable and excitable temperament associated with perfectionist efforts and signs of neuroticism, but also segments of the tendency to develop anxiety, irritability and hypochondria [21,23,24,25,26,27]. According to some studies conducted so far, these character traits have proven useful in the treatment of glaucoma because patients adhered to the correct application of ATG therapy in the treatment of glaucoma, while, on the other hand, these character traits have proven to be a risk factor for the development of glaucoma [24,28,29]. Poor adherence to prescribed ATG therapy was observed in patients with developed anxiety symptoms, due to previously known low bias towards ATG therapy [20].
The aim of this study was to examine the characteristics of the occurrence of anxiety, depression and open-angle glaucoma in glaucoma patients.

2. Materials and Methods

2.1. Participants (Respondents)

This cross-sectional study included 200 patients diagnosed with three different stages of POAG who were treated at the Glaucoma Infirmary of the Clinical Hospital Centre Osijek in a one-year period from December 2023 to December 2024. Patients who were included were those who came for a check-up due to POAG and had treated for more than two years, as well as those who were diagnosed with POAG within the past two years. Inclusion criteria were patients with POAG with ATG therapy, adults aged 18 to 70 years, while the exclusion criteria were underage people or those over 70 years of age, those with a history of glaucoma surgery or a history of iridotomy, as well as people not being treated for POAG.
All patients included in this study underwent a complete ophthalmological examination, which consisted of taking a detailed medical history, examining the anterior and posterior segment of the eye with a slit-lamp biomicroscope, measuring IOP with a GAT, and additionally completing the questionnaires.
POAG staging was based both on the severity of VF damage and structural metrics of the optic nerve head. A staging system was thus based on the mean deviation (MD) parameter of the VF, i.e., early glaucomatous loss MD ≤ 6 decibel (dB), moderate glaucomatous loss 6 > MD ≤ 12 dB and advanced glaucomatous loss MD > 12 dB [18].

2.2. Questionnaires

The research was conducted with the Crown–Crisp Experiential Index (CCEI), which is intended to identify and measure common symptoms and personality traits within the conventional categories of psychoneurotic diseases and personality disorders. It is used to determine psychoneurotic disorders, and consists of 48 questions, which include six subscales: free-floating anxiety (FFA), phobic anxiety (PHOA), obsessiveness, somatic manifestations of anxiety, depression and hysteria. The total score provides a measure of general emotional instability or neuroticism with a profile of six subscale scores [30,31,32]. The CCEI questionnaire was translated into Croatian, and published by “Naklada Slap”, which gave written permission for the use of 200 copies of the CCEI questionnaire for the purpose of this research. CCEI has undergone all appropriate linguistic and cultural validation processes to ensure its reliability and validity in the Croatian population.
The General Anxiety Disorder 7 Scale (GAD-7) is a validated instrument for identifying generalized anxiety disorder [33]. It consists of seven questions that are answered on a Likert scale from 0 (“not at all”) to 3 (“almost every day”), depending on how often one of the listed disorders has occurred during the past two weeks. The total score can range from 0 to 21 and indicates the severity of the anxiety disorder. The results can be divided into four categories of anxiety: mild (0–4), moderate (5–9), moderately severe (10–14) and severe anxiety (15–21) [33,34]. The third questionnaire was the Patient Health Questionnaire 9 (PHQ-9), which is used for detecting depressive disorders [35]. It consists of nine items that address symptoms of depression (e.g., decreased interest in doing usual activities, feeling down, depressed, or hopeless, trouble sleeping, feeling tired or lacking energy, problems with appetite, feeling dissatisfied with oneself, difficulty concentrating, being slow or moving excessively, and thoughts of death and self-harm). Respondents indicated the frequency of occurrence of the listed symptoms during the past two weeks on a Likert scale from 0 (“not at all”) to 3 (“almost every day”). The total score of the PHQ-9 questionnaire ranges from 0 to 27. Based on the total score, the results can be classified into five categories depending on the degree of depression: minimal (0–4), mild (5–9), moderate (10–14), moderately severe (15–19) and severe depression (20–27). The GAD-7 and PHQ-9 questionnaires have been translated into Croatian, are publicly available, and their use does not require permission [33]. A schematic comparison of CCEI, GAD-7 and PHQ-9 questionnaires by function, usability and clinical validation is shown in Table 1. Before administering the CCEI, GAD-7 and PHQ-9 questionnaires, the respondents were familiar with their content and purpose, and they signed an informed consent and consent for their administration and data collection. In addition to using the questionnaire, the following information was examined and recorded on the questionnaire: gender of the participants, age of the participants, POAG stage, length of treatment for POAG, number of application of ATG therapy per day, whether the patient achieved the target IOP with ATG treatment, whether they suffered from other ophthalmological conditions before the diagnosis of POAG and whether they felt stressed.
This study has observed the associations between the observed variables without interfering the treatment; accordingly, the patients did not receive mental health referral whether or not significant anxiety and/or depression scores were detected.

2.3. Statistical Methods

Before we have started this research, we used G*Power (ver. 3.1.2.) to determine the minimum required sample size for three independent groups, with a significance level of 0.05 and a power of 0.80. The minimum required sample size was 159 subjects. For regression analysis, the minimum required sample size with a power of 0.85 is 129 subjects. In conclusion, the minimum causal size is 159 subjects (58 per group).
Categorical data are presented as absolute and relative frequencies. Differences in categorical variables were tested with the χ2 test and, if necessary, with Fisher’s exact test. Normality of distribution of continuous variables was tested with the Shapiro–Wilk test. Continuous data were described by the median and interquartile range (IQR) limits. Differences in continuous variables between two independent groups were tested with the Mann–Whitney U test (the Hodges Lehmann difference in median with the corresponding 95% confidence interval for the difference is expressed). Differences in continuous variables between three independent groups were tested with the Kruskal Wallis test (with the Conover post hoc test). The correlation score is given by the Spearman correlation coefficient ρ (Rho). Logistic regression, bivariate and multivariate (Stepwise method), evaluated the influence of several factors (stages of glaucoma and other general and clinical characteristics) on the probability of given outcomes: expression of anxiety and depression [38,39]. All values are two-sided. The significance level was set at alpha = 0.05. The statistical package MedCalc® Statistical Software version 23.1.1 was used for statistical analysis [40]. The report on the conducted research was prepared according to the guidelines for reporting research results in biomedicine and healthcare [41].

2.4. Study Approval

The study was approved by the Ethics Committee of the Clinical Hospital Centre Osijek (approval date: 11 November 2022, Number: R1-14554/2022) and the Ethics Committee of the Faculty of Medicine Osijek (approval date: 23 February 2023, Class: 602-04/23-08/03, Reg. Number: 2158-61-46-23-17). Informed consent for voluntary participation in the study was obtained from all eligible patients who met the appropriate inclusion criteria.

3. Results

3.1. Basic Characteristics of the Participants

This study was conducted on 200 subjects, patients treated for POAG, of whom 68 (34%) were men and 132 (66%) were women. Most subjects were aged 56 to 65. The response rate of the participants was 100%. Previous ophthalmological diseases were recorded in 36 (18%) subjects. The number of subjects was equal for all three stages of POAG. A total of 93 (46.5%) subjects had a subjective feeling of stress. A total of 150 (75%) subjects achieved the target values of IOP (Table 2).
The median age of the subjects was 65 years, ranging from 37 to a maximum of 70 years, and the median duration of treatment was 96 months (8 years), ranging from one month to 564 months (47 years). Subjects received ATG therapy one to four times per day, with a median of two times (Table 2).
The median total score of the GAD-7 scale is 8, ranging from 0 to 20. According to the achieved values, it is observed that 55 (27.5%) respondents have a mild level of anxiety, and moderately severe or severe anxiety is recorded in 81 (40.5%) respondents (Table 2).
The median total score of the PHQ-9 scale is 7, ranging from 0 to 22. According to the achieved values, it can be seen that 69 (34.5%) respondents have a minimal level of depression, 38 (19%) have a moderate level and moderately severe or severe depression is recorded in 31 (15.5%) respondents (Table 2).

3.2. Correlations Between Glaucoma Stages and Anxiety (GAD-7) Correlation of Respondents’ Anxiety (GAD-7 Questionnaire) with Respondents’ Characteristics

The anxiety score is significantly higher in respondents who report feeling stressed than in those who do not feel this way (Mann–Whitney U test, p < 0.001), while there is no significant differences in the anxiety score according to the GAD-7, which assesses other characteristics of the respondents (Table 3).
By examining the correlation, it was observed that the age of the subjects is significantly, positively and weakly correlated with the GAD-7 questionnaire score in the group of subjects who achieved target IOP values (Rho = 0.215), while there is no significant correlation between the GAD-7 score and the length of treatment and the degree of glaucoma (Table 4).
In the correlation of anxiety levels according to the GAD-7 questionnaire, it is observed that moderately severe and severe anxiety is significantly more pronounced in subjects aged 66 and over compared to younger subjects (χ2 test, p = 0.04) (Figure 1). Also, out of a total of 93 (47%) subjects who feel stressed, there are significantly more subjects, 16 of them (84.2%) with moderate or severe depression (χ2 test, p < 0.001) (Figure 2).

3.3. Correlations Between Glaucoma Stages and Depression (PHQ-9) Association of Depression (PHQ-9 Questionnaire) with Characteristics of the Subjects

The lowest depression score (according to PHQ-9) was significantly observed in subjects aged up to 55 years compared to subjects aged 66 and over (Kruskal Wallis test, p = 0.03) (Figure 3). Also, the depression score was significantly higher in subjects who reported feeling stressed than in those who did not (Mann–Whitney U test, p < 0.001), while there were no significant differences in depression scores according to other characteristics of the subjects (Figure 4, Table 5).
Spearman’s correlation coefficient was used to assess the relationship between the depression score according to the PHQ-9 questionnaire and the age of the subjects and the duration of the disease (months). It was noticed that the age of the subjects is significantly, positively and weakly related to the result of the PHQ-9 questionnaire, in the entire group of subjects (Rho = 0.182), as well as in the group of subjects in whom the target IOP values were achieved (Rho = 0.269).
The same significant relationships are also found in the case of the length of treatment. The longer the treatment, the more pronounced the depression in the group of all subjects (Rho = 0.199), and in the group of subjects in whom the target IOP values were achieved (Rho = 0.221). The degree of glaucoma is not significantly related to the depression score (PHQ-9 scale) (Table 6).
In the correlation of the level of depression according to the PHQ-9 questionnaire, it is observed that out of a total of 93 (47%) respondents who feel stressed, there are significantly more respondents, 29 of them (93.5%) with moderate or severe depression (χ2 test, p < 0.001).

3.4. Correlations Between Glaucoma Stages and Psychoneurotic Disorders (CCEI)

With regard to the results of the CCEI questionnaire, it can be seen that the highest score was given to obsessiveness and somatic manifestations of anxiety and depression, and the lowest to the hysteria subscale (Table 7).
Considering the obtained values, 98 (49%) of the respondents had pronounced depression, 81 (40.5%) had pronounced FFA, while the least of them, 42 (21%) had pronounced obsessiveness (Table 8).

3.5. Association of Psychoneurotic Disorders (CCEI Questionnaire) with the Age of the Subjects, the Duration of Treatment and the Stage of Glaucoma

Spearman’s correlation coefficient was used to assess the correlation between the age of the subjects, the duration of treatment and the stage of glaucoma with the subscales of the CCEI questionnaire. It is observed that the significant correlations are somewhat weaker (Rho < 0.5).
In the group of all subjects, older subjects have a more pronounced somatic manifestation of anxiety (Rho = 0.190) and depression (Rho = 0.183). The longer the treatment, the more pronounced the somatic manifestation of anxiety (Rho = 0.164), and the lower the stage of glaucoma, the more pronounced obsessiveness (Rho = −0.147).
In subjects who did not achieve the target IOP, older subjects have a less pronounced FFA (Rho = −0.344), and subjects with a higher stage of glaucoma have a more pronounced hysteria subscale (Rho = −0.323).
Respondents with achieved target IOP and older respondents have lower values of FFA (Rho = 0.174), less pronounced somatic manifestations of anxiety (Rho = 0.222) and less pronounced depression (Rho = 0.251). The longer the duration of treatment, the more pronounced the somatic manifestation of anxiety (Rho = 0.197) (Table 9).

3.6. The Influence of Glaucoma Stage and Other Characteristics of the Subjects on the Severity of Anxiety and Depression

To check the influence of glaucoma stages and other characteristics on the severity of anxiety and depression, bivariate and multivariate logistic regression were performed.
In the prediction of a higher severity of depression according to the PHQ-9, in the bivariate logistic regression, it is observed that older patients (odds ratio (OR) = 1.08) and those who feel stressed (OR = 9.61) increase the probability of a more pronounced depression (PHQ-9). Multivariate logistic regression (stepwise method) shows that there is a significant model in the prediction of the severity of depression according to the PHQ-9, and it consists of two predictors: age 66 and older (OR = 2.03) and feeling stressed (OR = 9.47). The model is fully significant (χ2 test = 53.1, p < 0.001) and explains from 23% (according to Cox&Snell R2) to 32% (according to Negelkerke R2) of the variance in the severity of depression and correctly classifies 74% of cases (Table 10).
In predicting higher levels of anxiety according to GAD-7, in bivariate logistic regression, it is observed that the feeling of being exposed to stress (OR = 6.02) and age in the range of 56 to 65 years (OR = 2.82) increase the probability of higher levels of anxiety (GAD-7). Multivariate logistic regression (stepwise method) shows that there is a significant model in predicting the level of depression according to GAD-7, and one predictor is the feeling of being under stress (OR = 6.02). The model is completely significant (χ2 test = 26.2, p < 0.001) and explains from 12% (by Cox&Snell R2) to 18% (by Negelkerke R2) of the variance in the level of anxiety and correctly classifies 73% of cases (Table 10).
In the prediction of the expression of FFA according to CCEI, in bivariate logistic regression, it is observed that women compared to men (OR = 1.98), subjects of older age (OR = 1.05) and those subjects who feel that they are under stress (OR = 6.05) increase the probability of more pronounced FFA. Multivariate logistic regression (stepwise method) shows that there is a significant model in predicting the expression of FFA, and it consists of the following predictors: female gender (OR = 3.03), age of 66 years and over (OR = 3.4) and the feeling of being under stress (OR = 7.07). The model is entirely significant (χ2 test = 43.5, p < 0.001) and explains from 22% (according to Cox&Snell R2) to 30% (according to Negelkerke R2) of the variance in expression of FFA and correctly classifies 70% of cases (Table 10).
In the prediction of the severity of PHOA according to CCEI, in bivariate logistic regression, it is observed that women compared to men (OR = 3.31), older respondents (OR = 1.07), and those respondents who feel stressed (OR = 2.45) increase the probability of more pronounced PHOA. Multivariate logistic regression (stepwise method) shows that there is a significant model in the prediction of the severity of PHOA, and it consists of three predictors: female gender (OR = 6.12), older age (OR = 1.08) and feeling stressed (OR = 3.33). The model is entirely significant (χ2 test = 35.9, p < 0.001) and explains from 19% (according to Cox&Snell R2) to 26% (according to Negelkerke R2) of the variance in the severity of PHOA and correctly classifies 71% of cases (Table 10).

3.7. Correlation of the Depression Subscale with the Characteristics of the Subjects

In the depression subscale, there is a significantly higher score in women than in men (Mann–Whitney U test, p = 0.006), and in subjects who state that they feel stressed than in those who do not (Mann–Whitney U test, p < 0.001). Respondents under the age of 55 have a significantly lower score than older respondents (Kruskal Wallis test, p = 0.007), while there are no significant differences in the scores of the somatic manifestation of anxiety subscale in terms of other characteristics of the respondents (Table 11).
Significantly more respondents aged 66 and over (χ2 test, p = 0.001) and those who feel stressed (χ2 test, p < 0.001) have pronounced depression, while in other characteristics there are no significant differences in the distribution of respondents according to the severity of depression (Table 12).

4. Discussion

Glaucoma is a group of eye conditions that damage the optic nerve, which leads to optic neuropathy [4]. It is often associated with IOP, although it can also occur with normal IOP [2]. There is some evidence that chronic stress can have a negative effect on eye health [42]. Stress may potentially raise IOP, which is a key factor in glaucoma development or progression. If left untreated, it can lead to vision loss and even blindness. Many types of glaucoma, particularly OAG, develop slowly and painlessly, with no obvious symptoms in the early stages [11]. Over time, it can cause peripheral vision loss that could be tested on VF. On the other hand, ACG can have sudden, severe symptoms like eye pain, nausea and vision impairment.
Psychoneurotic disorders are a group of psychological conditions that involve anxiety, depression, stress and emotional disturbances that can affect a person’s mental and emotional well-being. These conditions are often linked to stress and conflict and are less severe than psychotic disorders. The diagnosis of a chronic condition like glaucoma can lead to emotional and psychological challenges [43,44]. The fear of losing vision can lead to anxiety, depression or even panic attacks, which may be classified as psychoneurotic disorders [43]. People with glaucoma may develop a heightened sense of worry about their future quality of life, leading to generalized anxiety or depression which has been shown by numerous studies [44,45,46].
Both glaucoma and psychoneurotic disorders do sometimes require intensive management, often involving a combination of medical treatments and lifestyle adjustments. In glaucoma it is necessary to achieve target IOP, whether with the ATG eye drops or glaucoma surgery. In the case of psychoneurotic disorders, psychotherapy (e.g., cognitive–behavioural therapy) along with the proper medications (e.g., antidepressants or anxiolytics) could be useful to alleviate symptoms. Numerous population-based studies have shown that there is a vital connection between glaucoma and psychiatric disorders, depression and anxiety being the most common [47].
The fundamental mechanisms underlying the connection between glaucoma and psychoneurotic disorders are still unclear, i.e., complicated. However, based on the studies conducted so far, several clear directions can be found as to how this happened. Usually, patients react to a decrease in visual acuity and a decrease, i.e., a loss in the width of the visual field. This gradually leads to the inability to carry out everyday activities, and it is also impossible for some patients to continue their previous occupation. Because of the above, the possibility of earning money is reduced, and all this leads to an increase or worsening of already existing anxiety and depressive disorders. However, the worst consequence that everyone fears is still permanent blindness. Likewise, some psychiatric medications can have an effect on the existing eye condition, but on the other hand, medications used in the treatment of glaucoma can have neuropsychiatric effects [44].
Glaucoma and depression can be closely linked, with the challenges of living with glaucoma contributing to feelings of sadness, hopelessness and despair. Depression is common among individuals with chronic health conditions, and glaucoma is no exception. Previous studies have tested the level of depression using different depression scales. In their systematic review and meta-analysis, Groff et al. concluded that the presence of depression in glaucoma patients has been determined through various studies using different questionnaires [43]. However, based on an insight into the previously published and available studies, they did not pay additional attention to the severity of anxiety and depression depending on the level of progression of glaucomatous damage, nor on the achieved target IOP, which we have clearly highlighted in our study.
Moreover, Yin et al. conducted a meta-analysis comparing numerous cross-sectional studies on the prevalence and severity of depression and anxiety in glaucoma patients. This information is very valuable for ophthalmologists as well as psychiatrists. Their results showed that glaucoma patients are easily depressed and tend to have more pronounced symptoms of depression as well as anxiety symptoms. This is fully consistent with our survey. Therefore, ophthalmologists and psychiatrists should pay more attention to the increased emotional problems of patients and try to help patients stay focused on their treatment and try to improve their quality of life [46].
A similar study was conducted by Dayal et al., where they noticed the prevalence of depression from 13% to 30% and anxiety prevalence from 6% to 25%, which supports our study. They have also mentioned that there is a strong correlation between the severity of vision loss in patients with glaucoma and the appearance of symptoms of anxiety and depression [48].
Groff et al. also attempted to determine the prevalence and severity of anxiety with a variety of questionnaires, as we did. The figures showed that about 25% of glaucoma patients have anxiety, but they also have more pronounced anxiety-related symptoms. Statistically significant levels of anxiety were noted in POAG and in ACG. Nevertheless, when they tried to determine the depression prevalence, it was about 19%, and glaucoma patients had more pronounced depression-related symptoms. In this case, the depression was more pronounced in ACG glaucoma than in other glaucoma types [43].
In a study conducted by Onwubiko et al., the authors came to similar conclusions as in our study. Looking at the participants, their study also had a predominantly female population, and most participants had advanced glaucoma, of which 44% had signs of anxiety, and approximately 76% had signs of depression [49]. Due to the advanced nature of the disease, accompanied by fear of losing visual acuity, it was significant to associate it with the presence of anxiety and depression, as well as IOP values < 21 mmHg.
In our study, we have also observed the intensity of anxiety present. Our study has shown, according to the GAD-7 that, out of 200 participants, 55 (27.5%) respondents do have a mild level of anxiety, and moderately severe or severe anxiety is recorded as present in 81 (40.5%) respondents. According to the PHQ-9 questionnaire that has been used in our survey, it can be seen that 69 (34.5%) respondents have a minimal level of depression, 38 (19%) have a moderate level and, sadly, moderately severe or severe depression was registered in 31 (15.5%) respondents. Accordingly, it is evident that the psychological burden of glaucoma patients is more pronounced in those patients with more pronounced glaucoma symptoms, i.e., in those patients who have a more advanced stage of glaucoma, although we did not find statistically significant difference in anxiety and depression presence depending on the glaucoma stage.
The prevalence of anxiety and depression among glaucoma patients is generally high. In the case of patients with advanced glaucoma, the most important factor that can lead to the development of anxiety and/or depression is the fear of a decrease and possible loss of visual acuity [49]. If better attention were paid to the psychological burdens faced by glaucoma patients, especially those with the most severe stages of glaucoma, this would ensure better patient adherence to prescribed therapy [43] and greater confidence in the course of the disease, as well as a better understanding of the disease itself.
While glaucoma is primarily an eye condition, the psychological impact that it has on individuals can lead to significant anxiety. The fear of vision loss, uncertainty about the future and the stress of managing a chronic disease can all contribute to heightened anxiety as well as depression. Managing both the physical aspects of glaucoma and the emotional toll it takes is important for overall well-being. Long-term glaucoma can also lead to the presence of depression. Healthcare providers should be aware of the mental health challenges that individuals with chronic conditions like glaucoma face and should screen for anxiety and depression regularly [48].
This study has some limitations that may impact the validity of the obtained results. Since it was designed as a cross-sectional study, it is not possible to establish causality, therefore only associations between the observed variables could be observed. Other limitations of this study would also be a rather small number of participants. Therefore, future research should increase the number of participants, i.e., have a larger sample. Although the gender distribution in this study reflects the actual patient flow in our institution during the observed period, future studies could benefit from a more balanced distribution or a gender-stratified analysis to increase the credibility of the findings. It would also be advisable to have more participants with more pronounced stages of glaucoma as well as to monitor the development of psychoneurotic disorders. With the more pronounced monitoring process, we could be able to prevent the progression of psychoneurotic disorders as well as to try to slow down the speed of glaucoma progression. Regular monitoring could also prevent the patients from premature discontinuation of regular taking the prescribed therapy.

5. Conclusions

In conclusion, our study enhances understanding of the correlation between glaucoma and psychoneurotic disorders. According to the bivariate logistic regression of the GAD-7, results have shown that, in predicting the higher anxiety level, the subjective feeling of being exposed to stress and being in the age in the range of 56–65 years increases the probability of higher levels of anxiety. According to the CCEI, female gender, an age of 66 years and over and the feeling of being under stress have a statistically significant correlation with prediction of the expression of FFA in glaucoma patients. Prediction of the severity of depression with bivariate logistic regression and multivariate logistic regression (stepwise method), according to the PHQ-9, suggests that there are only two predictors, which are age 66 years and older and a subjective feeling of being under stress. Moreover, according to the results of this study, glaucoma severity did not show significant association with anxiety or depression levels, which has important clinical implications for screening practices. Coordinating glaucoma care between ophthalmologists and mental health professionals can ensure comprehensive care and improve quality of life. A multidisciplinary approach to glaucoma is necessary to help reduce anxiety and depression, while ongoing medical management of glaucoma is essential to maintaining eye health.

Author Contributions

Conceptualization, M.O., K.D.-Ć. and D.B.; Data curation, M.O., I.K.Š., D.K. and S.B.; Formal analysis, S.B., I.K.Š., M.O. and D.K.; Funding acquisition, D.K. and I.K.Š.; Investigation, M.O., K.D.-Ć., D.B. and S.B.; Methodology, M.O., D.B. and K.D.-Ć.; Project administration, I.K.Š. and D.K.; Resources, D.K. and I.K.Š.; Software, S.B.; Supervision, K.D.-Ć., D.B. and M.O.; Validation, M.O. and S.B.; Writing—original draft, M.O., K.D.-Ć. and D.B.; Writing—review and editing, M.O., K.D.-Ć., D.B., S.B., I.K.Š. and D.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Clinical Hospital Centre Osijek (approval date: 11 November 2022, Number: R1-14554/2022) and by the Ethics Committee of the Faculty of Medicine in Osijek (approval date: 23 February 2023, Class: 602-04/23-08/03, Reg. Number: 2158-61-46-23-17).

Informed Consent Statement

Informed consent was obtained from all subjects involved in this study.

Data Availability Statement

All data are available and can be delivered to anyone upon request.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ACGAngle-closure glaucoma
ATGAntiglaucoma
CCEICrown-Crisp Experiential Index
dBDecibel
FFAFree-floating anxiety
GAD-7General Anxiety Disorder 7
GATGoldmann applanation tonometry
GCLGanglion cell layer
IOPIntraocular pressure
IQRInterquartile range
MDMean deviation
mmHgMillimeters of mercury
NTGNormal tension glaucoma
OAGOpen-angle glaucoma
OROdds ratio
PHOAPhobic anxiety
PHQ-9Patient Health Questionnaire 9
POAGPrimary open-angle glaucoma
RNFLRetinal nerve fibre layer
VFVisual field

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Figure 1. Distribution of respondents according to age groups in relation to the severity of anxiety determined by the GAD-7.
Figure 1. Distribution of respondents according to age groups in relation to the severity of anxiety determined by the GAD-7.
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Figure 2. Distribution of respondents according to the feeling of stress in relation to the severity of anxiety determined by the GAD-7.
Figure 2. Distribution of respondents according to the feeling of stress in relation to the severity of anxiety determined by the GAD-7.
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Figure 3. Distribution of respondents according to age groups in relation to the depression scores determined by the PHQ-9.
Figure 3. Distribution of respondents according to age groups in relation to the depression scores determined by the PHQ-9.
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Figure 4. Distribution of respondents according to the feeling of stress in relation to the depression scores determined by the PHQ-9.
Figure 4. Distribution of respondents according to the feeling of stress in relation to the depression scores determined by the PHQ-9.
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Table 1. Comparison of assessment tools used in the study by function, usability and clinical validation.
Table 1. Comparison of assessment tools used in the study by function, usability and clinical validation.
InstrumentPurpose/Primary FocusNumber of ItemsClinical ValidationUsability for Patients
CCEI (Crown–Crisp Experiential Index)Assesses six domains of neurotic disorders: free-floating anxiety, phobic anxiety, obsessiveness, somatic symptoms, depression, and hysteria48Validated in multiple clinical populations; commonly used in psychoneurotic assessments [32]Moderate—requires more time and cognitive effort
GAD-7 (Generalized Anxiety Disorder-7)Screens for and measures severity of generalized anxiety disorder7Widely validated and recommended for clinical use [36]High—short, simple, and user-friendly
PHQ-9
(Patient Health Questionnaire-9)
Screens for and evaluates severity of depressive symptoms9High clinical validity and reliability [37]High—brief and easy to administer
Table 2. General and clinical characteristics of the subjects; GAD-7 and PHQ-9 scale scores and distribution of respondents according to level of anxiety/depression.
Table 2. General and clinical characteristics of the subjects; GAD-7 and PHQ-9 scale scores and distribution of respondents according to level of anxiety/depression.
Sex [n (%)]
    Male68 (34)
    Female132 (66)
Age groups [n (%)]
    Up to 55 22 (11.0)
    56–65 years92 (46.0)
    66 and over86 (43.0)
OAG stage [n (%)]
    Stage I68 (34.0)
    Stage II 65 (32.5)
    Stage III 67 (33.5)
Earlier ophthalmological state [n (%)]36 (18.0)
Subjective feeling under stress [n (%)]93 (46.5)
Achieved IOP goal [n (%)]150 (75)
Age (years) [Median (IQR)]65 (60–68)
Length of treatment (months) [Median (IQR)]96 (39–156)
Number of application of ATG therapy per day [Median (IQR)]2 (1–2)
OAG stage [n (%)]
    Stage I68 (34.0)
    Stage II 65 (32.5)
    Stage III 67 (33.5)
GAD-7 Total Score [Median (IQR)]8 (4–12)
Level of anxiety [n (%)]
    Mild (0–4)55 (27.5)
    Moderate (5–9)64 (32.0)
    Moderately Severe (10–14)62 (31.0)
    Severe anxiety (15–21)19 (9.5)
PHQ-9 Total Score [Median (IQR)]7 (3–11)
Level of depression [n (%)]
    Minor (0–4)69 (34.5)
    Mild (5–9)62 (31.0)
    Moderate (10–14)38 (19.0)
    Moderately Severe (15–19)28 (14.0)
    Severe depression (20–27)3 (1.5)
IQR—interquartile range.
Table 3. Differences in anxiety scores (GAD-7) in relation to respondent characteristics.
Table 3. Differences in anxiety scores (GAD-7) in relation to respondent characteristics.
Median
(IQR)
GAD-7
Difference95% Confidence Intervalp
Gender
Men8 (4–12)0−1–20.99 *
Women8 (4–12)
Age groups
Up to 55 years5 (3–9) 0.06
56–65 years8 (5–12)--
66 and over9 (4–13)
OAG stage
Stage I7 (5–12) 0.91
Stage II8 (4–12)--
Stage III8 (4–12)
Feeling stressed
No5 (3–9)53–6<0.001 *
Yes11 (7–14)
Achieved IOP target values
No7 (4–11)10–30.13 *
Yes8 (4–13)
* Mann–Whitney U test; Kruskal Wallis test.
Table 4. Correlation of GAD-7 scale results with age of subjects, length of treatment and degree of glaucoma.
Table 4. Correlation of GAD-7 scale results with age of subjects, length of treatment and degree of glaucoma.
Spearman’s Rho Correlation Coefficient
(p Value)
Age
of the Respondent
Length of TreatmentGlaucoma Stage
GAD-7 scale—all respondents0.133
(0.06)
0.124
(0.08)
0.001
(0.99)
GAD-7 scale
IOP target values not achieved−0.157
(0.28)
0.209
(0.15)
0.110
(0.45)
IOP target values achieved0.215
(0.008)
0.120
(0.14)
0.036
(0.66)
Table 5. Differences in depression scores (PHQ-9) in relation to respondent characteristics.
Table 5. Differences in depression scores (PHQ-9) in relation to respondent characteristics.
Median
(IQR)
Difference95% Confidence Intervalp
Sex
    Male7 (4–11)0−1–20.76 *
    Female7 (3–12)
Age groups
    Up to 55 6 (3–7)--0.03 †§
    56–65 years6 (3–11)
    66 and over8 (4–13)
OAG stage
    Stage I6 (4–11) 0.95 
    Stage II 7 (3–11)--
    Stage III 7 (3–12)
Feeling stressed
No4 (3–7)64–7<0.001 *
Yes11 (7–15)
Achieved IOP target values
Not6 (3–9)1−1–20.31 *
That7 (4–12)
* Mann–Whitney U test; Kruskal Wallis test (post hoc Conover test). §. At the p < 0.05 level, the differences are significant (up to 55 years) vs. (66 and older).
Table 6. Correlation of PHQ-9 scale results with the age of the subjects, length of treatment and degree of glaucoma.
Table 6. Correlation of PHQ-9 scale results with the age of the subjects, length of treatment and degree of glaucoma.
Spearman’s Rho Correlation Coefficient
(p Value)
Age of Subjects Length of TreatmentDegree of Glaucoma
PHQ-9 scale—all respondents0.182 (0.01)0.199 (0.005)0.020 (0.78)
PHQ-9 scale
IOP target values not achieved−0.152 (0.29)0.144 (0.32)0.154 (0.29)
IOP target values achieved0.269 (0.001)0.221 (0.006)0.035 (0.67)
Table 7. Mean and dispersion measures of individual subscales of the CCEI questionnaire.
Table 7. Mean and dispersion measures of individual subscales of the CCEI questionnaire.
Median
(IQR)
Range from Minimum to Maximum Value
Free floating anxiety (FFA)5 (2–10)0–16
Phobic anxiety (PHOA)5 (4–7)0–16
Obsessiveness8 (6–10)0–14
Somatic manifestations of anxiety7 (4–10)0–16
Depression7 (4–9)0–14
Hysteria4 (2–5)0–12
Table 8. Distribution of respondents according to the severity of each subscale of the CCEI questionnaire.
Table 8. Distribution of respondents according to the severity of each subscale of the CCEI questionnaire.
Number (%) of Respondents in Relation to the Severity of Each Subscale
Not ExpressedExpressed
Free floating anxiety (FFA)119 (59.5)81 (40.5)
Phobic anxiety (PHOA)133 (66.5)67 (33.5)
Obsessiveness158 (79.0)42 (21.0)
Somatic manifestations of anxiety133 (66.5)67 (33.5)
Depression102 (51.0)98 (49.0)
Hysteria146 (73.0)54 (27.0)
Table 9. Correlation of the age of the subjects, duration of treatment and stage of glaucoma with the subscales of the CCEI questionnaire in all subjects, and in groups according to the achieved target IOP values.
Table 9. Correlation of the age of the subjects, duration of treatment and stage of glaucoma with the subscales of the CCEI questionnaire in all subjects, and in groups according to the achieved target IOP values.
Spearman’s Correlation Coefficient Rho
(p Value)
Age of the RespondentDuration of TreatmentGlaucoma Stage
All respondents
Free floating anxiety (FFA)0.068 (0.34)0.109 (0.12)−0.006 (0.94)
Phobic anxiety (PHOA)0.042 (0.56)0.051 (0.48)0.049 (0.49)
Obsessiveness0.050 (0.48)0.050 (0.48)−0.147 (0.04)
Somatic manifestations of anxiety0.190 (0.01)0.164 (0.02)0.022 (0.76)
Depression0.183 (0.01)0.082 (0.25)0.023 (0.75)
Hysteria−0.021 (0.77)0.051 (0.48)−0.134 (0.06)
Target IOP not reached
Free floating anxiety (FFA)−0.344 (0.01)0.022 (0.88)−0.053 (0.71)
Phobic anxiety (PHOA)−0.062 (0.67)0.011 (0.94)0.154 (0.29)
Obsessiveness−0.057 (0.69)0.013 (0.93)−0.104 (0.47)
Somatic manifestations of anxiety0.034 (0.81)0.042 (0.77)−0.053 (0.71)
Depression−0.040 (0.78)0.090 (0.54)−0.084 (0.56)
Hysteria−0.125 (0.39)−0.086 (0.55)−0.323 (0.02)
Target IOP achieved
Free floating anxiety (FFA)0.174 (0.03)0.143 (0.08)0.043 (0.60)
Phobic anxiety (PHOA)0.077 (0.35)0.067 (0.42)0.052 (0.53)
Obsessiveness0.096 (0.24)0.068 (0.41)−0.094 (0.26)
Somatic manifestations of anxiety0.222 (0.01)0.197 (0.02)0.073 (0.37)
Depression0.251 (<0.001)0.100 (0.23)0.100 (0.23)
Hysteria0.016 (0.84)0.100 (0.22)−0.028 (0.74)
Table 10. Prediction of the probability of severe depression according to the PHQ-9, pronounced anxiety according to the GAD-7 questionnaire, pronounced FFA according to the CCEI and expressed PHOA according to the CCEI questionnaire (multivariate logistic regression).
Table 10. Prediction of the probability of severe depression according to the PHQ-9, pronounced anxiety according to the GAD-7 questionnaire, pronounced FFA according to the CCEI and expressed PHOA according to the CCEI questionnaire (multivariate logistic regression).
βWaldpOdds Ratio (OR) 95% Confidence Interval
PHQ-9
    Age (66 and over)0.065.500.022.031.03–3.99
    Feeling stressed2.2739.3<0.0019.474.75–19.59
    Constant−6.2710.70.001
GAD-7
    Feeling stressed1.7921.4<0.0016.022.82–12.9
    Constant0.322.680.04
FFA (CCEI)
    Sex (Female)1.117.970.0053.031.40–6.52
    Feeling stressed2.0428.9<0.0017.703.66–16.21
    Constant−2.0330.6<0.001
PHOA (CCEI)
    Sex (Female)1.8121.3<0.0016.122.84–13.2
    Age0.086.050.011.081.02–1.15
    Feeling stressed1.209.880.0023.331.57–7.05
    Constant−6.92.10.001
β—regression coefficient.
Table 11. Depression subscale score in relation to respondent characteristics.
Table 11. Depression subscale score in relation to respondent characteristics.
Median
(IQR)
Depression Subscales
Difference95% Confidence Intervalp *
Sex
Male5 (4–8)10–20.006
Female7 (5–9)
Age groups
Under 55 years5 (4–6) 0.007 †§
56–65 years6 (4–9)--
66 and over7 (4–9)
Stage of OAG
Stage I7 (4–9) 0.94
Stage II6 (4–9)--
Stage III7 (4–9)
Feeling stressed
No5 (3–7)32–3<0.001
Yes8 (6–10)
Achieved IOP target values
No6 (4–8)10–20.15
Yes7 (4–9)
* Mann–Whitney U test; Kruskal Wallis test (post hoc Conover test). §. At the p < 0.05 level, there are significant differences (up to 55 years) vs. (all other groups).
Table 12. Severity of depression in relation to characteristics of the subjects.
Table 12. Severity of depression in relation to characteristics of the subjects.
Number (%) of Respondents According to Severity of
Depression
p *
No
(n = 102)
Yes
(n = 98)
Total
(n = 200)
Sex
Male37 (36.3)31 (31.6)68 (34)0.49
Female65 (63.7)67 (68.4)132 (66)
Age groups
Up to 55 years18 (17.6)4 (4.1)22 (11)0.001
56–65 years51 (50)41 (41.8)92 (46)
66 and over33 (32.4)53 (54.1)86 (43)
Stage of OAG
Stage I34 (33.3)34 (34.7)68 (34)0.46
Stage II37 (36.3)28 (28.6)65 (32.5)
Stage III31 (30.4)36 (36.7)67 (33.5)
Target IOP achieved73 (71.6)77 (78.6)150 (75)0.25
Feeling stressed34 (33.3)59 (60.2)93 (46.5)<0.001
* χ2 test.
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MDPI and ACS Style

Olujić, M.; Biuk, D.; Balog, S.; Kotromanović Šimić, I.; Kotromanović, D.; Dodig-Ćurković, K. Presence of Anxiety and Depression in Patients with Open-Angle Glaucoma of Different Degrees of Damage. J. Clin. Med. 2025, 14, 3954. https://doi.org/10.3390/jcm14113954

AMA Style

Olujić M, Biuk D, Balog S, Kotromanović Šimić I, Kotromanović D, Dodig-Ćurković K. Presence of Anxiety and Depression in Patients with Open-Angle Glaucoma of Different Degrees of Damage. Journal of Clinical Medicine. 2025; 14(11):3954. https://doi.org/10.3390/jcm14113954

Chicago/Turabian Style

Olujić, Marija, Dubravka Biuk, Slaven Balog, Ivana Kotromanović Šimić, Darko Kotromanović, and Katarina Dodig-Ćurković. 2025. "Presence of Anxiety and Depression in Patients with Open-Angle Glaucoma of Different Degrees of Damage" Journal of Clinical Medicine 14, no. 11: 3954. https://doi.org/10.3390/jcm14113954

APA Style

Olujić, M., Biuk, D., Balog, S., Kotromanović Šimić, I., Kotromanović, D., & Dodig-Ćurković, K. (2025). Presence of Anxiety and Depression in Patients with Open-Angle Glaucoma of Different Degrees of Damage. Journal of Clinical Medicine, 14(11), 3954. https://doi.org/10.3390/jcm14113954

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