Illness uncertainty, anxiety, and depression in primary glaucoma and associated influencing factors

Abstract

BACKGROUND

Glaucoma, a condition frequently linked to severe depression, anxiety, and sleep disturbances, affects treatment adherence while potentially compromising effectiveness.

AIM

To explore illness uncertainty (IU), anxiety, and depressive symptoms in primary glaucoma and to discuss underlying triggers.

METHODS

We recruited 120 primary glaucoma cases between January 2022 and November 2023. The Mishel Uncertainty in Illness Scale (MUIS) and the Hospital Anxiety and Depression Scale (HADS) [include HADS-anxiety subscale (HADS-A) and HADS-depression subscale (HADS-D)] subscales, were used to assess IU and emotional distress (anxiety/depression), respectively. The MUIS-HADS subscale interrelationships were determined by Pearson correlation. IU-associated determinants were identified using univariate and binary logistic regression analyses.

RESULTS

The cohort showed a mean MUIS score of 79.73 ± 8.97, corresponding to a moderately high IU level. The HADS-A and HADS-D scores averaged 6.57 ± 3.89 and 7.08 ± 5.05 points, respectively, with 15.00% of participants showing anxiety symptoms and 24.17% exhibiting depressive signs. Significant positive connections were observed between MUIS and both HADS-A (r = 0.359, P < 0.001) and HADS-D (r = 0.426, P < 0.001). Univariate analysis revealed that disease duration, insomnia, monthly household income per capita, and the presence of comorbid chronic conditions were significantly associated with anxiety or depression. Multivariate analysis identified insomnia as a risk factor and higher monthly household income as a protective factor.

CONCLUSION

Patients with primary glaucoma experience moderate IU levels, generally low anxiety, and mild depression. Specifically, the anxiety and depression risks were 15.00% and 24.17%, respectively. A significant positive correlation existed between IU and anxiety/depression in these patients. Additionally, insomnia or lower monthly household income elevated anxiety/depression risks, enabling reliable anxiety/depression risk categorization among patients.

Key Words: Primary glaucoma; Illness uncertainty; Anxiety; Depression; Influencing factors

Core Tip: Patients with primary glaucoma experience moderate levels of illness uncertainty, overall minimal anxiety, yet mild-level depression. Specifically, the anxiety and depression risks were 15.00% and 24.17%, respectively. A significant positive correlation exists between illness uncertainty and both anxiety and depression in patients with primary glaucoma. Additionally, patients with insomnia or lower monthly household income were at a higher risk of developing anxiety and depression.

INTRODUCTION

Glaucoma is an optic neuropathy primarily characterized by progressive and irreversible damage to the optic nerve, leading to physical debilitation and visual impairment and, in severe cases, blindness[1]. Globally, it affects approximately 3.50% of individuals aged 40-80 years, with primary angle-closure glaucoma and primary open-angle glaucoma being the most common forms[2]. Glaucoma - multifactorial in pathogenesis - is influenced by dietary factors, tobacco use, myopia, intraocular pressure (IOP) elevation, senescence, family history, and central corneal thinning, among other factors[3,4]. Glaucomatous damage, mainly caused by raised IOP, manifests as retinal ganglion cell loss and retinal nerve fiber layer thinning. These changes cause optic nerve injury and a gradual deterioration of the peripheral and central visual fields, substantially affecting patients’ vision and daily living activities[5,6]. Beyond its physical impact, glaucoma imposes a significant psychological burden on patients[7]. Patients frequently experience progressive psychological distress as they become increasingly aware of the disease’s irreversible vision impairment and incurable characteristics[8]. Evidence also links individuals with glaucoma to an increased likelihood and severity of depression, anxiety, and sleep disorders compared to those without glaucoma[9]. Yin et al’s meta-analysis of 24334 individuals with glaucoma revealed markedly greater susceptibility to anxiety and depression, along with more severe symptoms, compared to those without the disease[10]. Hence, prioritizing mental health support for patients with glaucoma is critical. Moreover, depression and anxiety adversely impact glaucoma pathophysiology. Emotion-driven sleep disturbances may accelerate disease advancement by inducing visual field abnormalities and causing autonomic nervous system destabilization. Psychological stress, which correlates with IOP increases, can trigger or promote glaucoma progression[11,12]. In glaucoma, psychological characteristics show a close connection with treatment adherence and prognosis. A stronger ability to accept one’s condition, a more upbeat attitude, and greater satisfaction with life are linked to an increased likelihood of adhering to prescribed treatments. This highlights how addressing emotional barriers and cultivating a positive mindset can lead to enhanced compliance and thus superior treatment outcomes[13]. Individuals with chronic illnesses such as glaucoma frequently develop illness uncertainty (IU) - an inability to foresee outcomes and perceive disease complexity. When patients lack adequate education or clear explanations about their condition, IU often arises, adversely affecting their mental state[14].

This study addresses the lack of comprehensive analyses on IU, anxiety, depressive symptoms, and related factors in individuals with primary glaucoma. By thoroughly examining patients’ psychological states and identifying potential determinants, this study provides evidence to support improved adherence, clinical outcomes, psychological well-being, and overall quality of life. The originality of this research is reflected in three aspects: (1) It quantifies IU and emotional disorders (anxiety/depression) in 120 patients with primary glaucoma to provide comprehensive psychological profiling; (2) Our analysis demonstrates the connection between IU and such mood disturbances; and (3) We identified psychological distress-associated determinants, facilitating anxiety/depression risk stratification in patients with primary glaucoma.

MATERIALS AND METHODS

Study population

The inclusion criteria including: (1) Diagnosis of primary glaucoma based on established diagnostic criteria[15]; (2) Age ≥ 18 years; (3) Bilateral eye involvement of the disease; (4) Availability of complete clinical records; and (5) Normal cognitive and communication skills. Exclusion criteria including: (1) Pregnant or breastfeeding women; (2) Presence of other ocular comorbidities; (3) Conditions or factors associated with elevated IOP; (4) Concurrent infections or inflammatory diseases; (5) Psychiatric conditions or antidepressant use (e.g., antidepressants or anti-anxiety agents); (6) Secondary glaucoma; and (7) Cognitive impairments. Adhering strictly to the abovementioned inclusion and exclusion criteria, we recruited 120 primary glaucoma cases from January 2022 to November 2023.

Sample size calculation

According to empirical guidelines, logistic regression requires approximately 10-20 samples per independent variable. This study examined eight variables, requiring at least 80 cases. The final sample of 120 subjects satisfied this criterion.

Survey methods

The survey team comprised healthcare professionals with intermediate or higher qualifications, all of whom received standardized training to ensure consistency in survey administration. On the visitation day, two trained investigators conducted Hospital Anxiety and Depression Scale (HADS) assessments[10], during which interviews and observational methods were merged. Upon completion, the two investigators independently scored the responses, and the average score was calculated as the final anxiety score for each patient. Additionally, each participant independently completed a general information questionnaire. For patients with significant visual impairment or limited literacy who struggled to understand the questionnaire, the investigators provided face-to-face explanations to ensure clarity. These patients were then asked to complete the questionnaire independently within 20 minutes. All questionnaires were collected upon completion. All 120 distributed questionnaires were returned valid, yielding a 100% valid response rate.

Outcome measurements

IU: This evaluation utilized the Mishel Uncertainty in Illness Scale (MUIS)[16] from unpredictability (15 items) and complexity (10 items) dimensions. Each item is rated on a 5-point Likert scale, where 1 represents “strongly disagree” and 5 indicates “strongly agree”, yielding a total possible score of 125. Higher scores reflect a greater IU degree. Scores are classified into three levels: 25-58 (low), 59-92 (moderate), and 93-125 (high).

Anxiety and depression: The 14-item (7 items each for anxiety and depression subscales) HADS was utilized for anxiety and depression measurements[17]. Each subscale has a maximum score of 21. A cutoff score of 8 is used to interpret the results: Scores of 0-7 indicate normal levels, 8-10 suggest mild anxiety or depressive symptoms, and 11-21 confirm the presence of clinically significant anxiety or depression.

Statistical analysis

This study used the mean ± SEM to present continuous variables and independent samples t-tests for between-group comparisons. Frequency counts and percentages were used to summarize categorical variables; intergroup differences were assessed through χ² tests. SPSS 21.0 executed all data processing procedures. Univariate and binary logistic regression analyses were employed to identify the factors influencing IU in patients with primary glaucoma. Statistical analyses employed a significance cutoff of P value < 0.05.

RESULTS

IU in 120 patients with primary glaucoma

In the present study, the complexity dimension score of IU among primary glaucoma patients was measured as 36.73 ± 6.26 points, and the unpredictability dimension score was 42.99 ± 5.45 points. The cumulative total MUIS score was calculated to be 79.73 ± 8.97 points. Among the participants, 0.83% exhibited low IU levels, 92.50% demonstrated moderate levels, and 6.67% showed high levels (Table 1).

Table 1 Illness uncertainty in 120 patients with primary glaucoma, mean ± SEM/n (%).

Indicators	Score (points)
Complexity	36.73 ± 6.26
Unpredictability	42.99 ± 5.45
MUIS	79.73 ± 8.97
Low level	1 (0.83)
Moderate level	111 (92.50)
High level	8 (6.67)

MUIS: Mishel Uncertainty in Illness Scale.

Anxiety/depression status in 120 patients with primary glaucoma

Among the 120 patients, 18 (15.00%) exhibited anxiety, with an overall score of 6.57 ± 3.89 points, whereas 29 patients (24.17%) showed depressive signs, with an overall score of 7.08 ± 5.05 points (Table 2).

Table 2 Anxiety and depression status in 120 patients with primary glaucoma, mean ± SEM/n (%).

Indicators	< 8 points		≥ 8 points		Total
HADS-A	102 (85.00)	5.21 ± 1.62	18 (15.00)	14.28 ± 4.06	6.57 ± 3.89
HADS-D	91 (75.83)	5.45 ± 1.90	29 (24.17)	14.93 ± 3.60	7.08 ± 5.05

HADS-A: Hospital Anxiety and Depression Scale-anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-depression subscale.

Correlation of IU with anxiety/depression in primary glaucoma

We employed the Pearson correlation to examine the association of IU with anxiety/depression in the study patients. A significant positive correlation between MUIS and HADS-anxiety subscale (HADS-A) (r = 0.359, P < 0.001) and between MUIS and HADS-depression subscale (HADS-D) (r = 0.426, P < 0.001) was identified (Table 3).

Table 3 Correlation between illness uncertainty and anxiety/depression in primary glaucoma patients.

Indicators	r, P value
MUIS and HADS-A	0.359, P < 0.001
MUIS and HADS-D	0.426, P < 0.001

MUIS: Mishel Uncertainty in Illness Scale; HADS-A: Hospital Anxiety and Depression Scale-anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-depression subscale.

Univariate analysis of factors influencing anxiety or depression in patients with primary glaucoma

Among the 120 patients, 34.17% exhibited anxiety (HADS-A ≥ 8) or depression (HADS-D ≥ 8). The cohort was sub-grouped based on anxiety/depression status: The anxiety/depression group (41 cases) and the non-anxiety/depression group (79 cases). Univariate analysis indicated that factors such as gender, age, disease type, and educational level were not significantly linked to anxiety/depression in primary glaucoma (P > 0.05). In contrast, disease duration, insomnia, monthly household income per capita, and the presence of comorbid chronic conditions were significant triggers (P < 0.05; Table 4).

Table 4 Univariate analysis of factors influencing anxiety/depression in primary glaucoma patients, n (%).

Indicators	Anxiety/depression (n = 41)	Non-anxiety/depression (n = 79)	χ2	P value
Gender			0.243	0.622
Male (n = 49)	18 (43.90)	31 (39.24)
Female (n = 71)	23 (56.10)	48 (60.76)
Age (years old)			1.163	0.281
< 60 (n = 55)	16 (39.02)	39 (49.37)
≥ 60 (n = 65)	25 (60.98)	40 (50.63)
Disease duration (months)			8.167	0.017
< 1 (n = 58)	16 (39.02)	42 (53.16)
1-12 (n = 36)	10 (24.39)	26 (32.91)
> 12 (n = 26)	15 (36.59)	11 (13.92)
Disease type			1.536	0.464
Acute angle-closure glaucoma (n = 36)	13 (31.71)	23 (29.11)
Chronic angle-closure glaucoma (n = 61)	18 (43.90)	43 (54.43)
Open-angle glaucoma (n = 23)	10 (24.39)	13 (16.46)
Educational level			0.443	0.506
Below senior high school (n = 42)	16 (39.02)	26 (32.91)
Senior high school or above (n = 78)	25 (60.98)	53 (67.09)
Insomnia			9.461	0.002
No (n = 88)	23 (56.10)	65 (82.28)
Yes (n = 32)	18 (43.90)	14 (17.72)
Monthly household income per capita (yuan)			9.213	0.010
< 2500 (n = 56)	27 (65.85)	29 (36.71)
2500-5000 (n = 46)	10 (24.39)	36 (45.57)
> 5000 (n = 18)	4 (9.76)	14 (17.72)
Comorbid chronic conditions			4.102	0.043
No (n = 97)	29 (70.73)	68 (86.08)
Yes (n = 23)	12 (29.27)	11 (13.92)

Insomnia in this case is a complication of glaucoma rather than a primary condition.

Multivariate analysis of factors influencing anxiety or depression in patients with primary glaucoma

Factors identified as significant in the univariate analysis, along with MUIS scores, were included as independent variables, while anxiety/depression was designated as the dependent variable. Binary logistic regression analysis demonstrated that insomnia significantly contributed to anxiety/depression in the study patients, whereas a higher monthly household income per capita acted as a protective factor. Tables 5 and 6 present the variable assignments and regression analysis results.

Table 5 Variable assignments.

Indicators	Variables	Assignments
Disease duration (months)	X1	< 1 = 0, 1-12 = 1, > 12 = 2
Insomnia	X2	No = 0, yes = 1
Monthly household income per capita (yuan)	X3	< 2500 = 0, 2500-5000 = 1, > 5000 = 2
Comorbid chronic conditions	X4	No = 0, yes = 1
MUIS (points)	X5	Continuous variable
HADS-A ≥ 8 or HADS-D ≥ 8	Y	No = 0, yes = 1

MUIS: Mishel Uncertainty in Illness Scale; HADS-A: Hospital Anxiety and Depression Scale-anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-depression subscale.

Table 6 Multivariate analysis of factors influencing anxiety or depression in primary glaucoma patients.

Factors	β	SE	Wald	P value	Exp (β)	95%CI
Disease duration (months)	0.398	0.271	2.161	0.142	1.489	0.876-2.530
Insomnia	1.074	0.473	5.166	0.023	2.927	1.159-7.391
Monthly household income per capita (yuan)	-0.830	0.321	6.690	0.010	0.436	0.232-0.818
Comorbid chronic conditions	0.806	0.524	2.361	0.124	2.238	0.801-6.257
MUIS (points)	0.004	0.024	0.024	0.878	1.004	0.958-1.052

MUIS: Mishel Uncertainty in Illness Scale; CI: Confidence interval.

DISCUSSION

Addressing IU, anxiety, and depression in individuals with primary glaucoma can promote a more positive outlook toward their condition. This positive mindset, in turn, facilitates smoother recovery by enhancing treatment adherence and optimizing therapeutic responses[18]. However, the role played by IU and anxiety/depression in primary glaucoma remains underexplored. Therefore, this study addresses this gap by examining these relationships and identifying key anxiety/depression triggers. We retrospectively enrolled 120 primary glaucoma cases, whose mean MUIS score was 79.73 ± 8.97 points with the majority (92.50%) demonstrating intermediate IU. Xia et al[19] reported a comparable MUIS score of 79.83 ± 14.0 points in heart disease patients undergoing coronary stent implantation, supporting our data. The observed moderate IU likely stems from contributors such as the condition’s chronic progression, information accessibility issues, treatment complexity, and ongoing visual impairment[20]. Additionally, our cohort demonstrated an overall non-anxious state, as evidenced by a 15.00% prevalence of anxiety and a score of 6.57 ± 3.89 on HADS-A. However, mild depressive symptoms were present (depression prevalence: 24.17%, HADS-D score: 7.08 ± 5.05). Giacometti et al[21] similarly reported depression in 26.9% and anxiety in 25.71% of cases among patients with glaucoma, with the depression prevalence showing remarkable consistency with our findings. The difference in anxiety rates may result from regional sample diversity and variations in assessment methods. In a cohort study of 446 Chinese individuals with glaucoma, Wu et al[22] documented anxiety prevalence at 12.11% and depression at 25.78%, highly consistent with our observations. The subsequent analysis revealed that IU correlated positively with anxiety and depression in patients with primary glaucoma. Similar patterns have been observed across various patient populations. In their investigation of female systemic lupus erythematosus patients, Cui et al[23] identified a strong positive correlation between IU and depression/anxiety. Moreover, Cheng et al[24] demonstrated significant positive correlations between IU and anxiety (r = 0.416) and depression (r = 0.434) in patients undergoing maintenance hemodialysis, further validating our results. Glaucoma diagnosis may trigger varying uncertain processes such as unfamiliarity, ambiguity, suspicion, and unpredictability due to a lack of communication and information, resulting in psychological distress, which explains the significant positive correlation between IU and anxiety-depression[25]. The pathological-psychological mechanism may involve fear of disease progression driven by IU - a primary stressor that can trigger varying degrees of negative emotional responses in patients. Autonomic nervous system disorders may mediate glaucoma-induced IOP fluctuations, resulting in abnormal IOP and disrupted ocular hemodynamics. The resulting physical discomfort can, in turn, further exacerbate negative emotions like anxiety or depression[26,27].

In this study, anxiety or depression was observed in 34.17% of patients with primary glaucoma. Univariate analysis revealed that disease duration, insomnia, monthly household income per capita, and comorbid chronic conditions were intimately associated with anxiety or depression in these patients. Mabuchi et al[28] identified younger age as a predictor of anxiety in such patients, while older age and greater disease severity were linked to an increased depression risk. Abe et al[29] reported that female patients with glaucoma exhibited a higher likelihood of developing anxiety and/or depression, and those with multiple comorbidities also faced an elevated risk of these mental health disorders, which corroborates our findings. Diabetes-related anxiety or depression may worsen with glycemic fluctuations, possibly tied to chronic glycemic instability and higher complication rates[30]. Binary logistic regression analysis further identified insomnia as a contributor to anxiety/depression in primary glaucoma, whereas higher monthly household income per capita emerged as a protective factor. This association may stem from insomnia-related daytime fatigue and impaired concentration in individuals with glaucoma, both of which can exacerbate negative emotional states[31]. In contrast, patients with higher household incomes are likely to experience less financial stress, enabling them to approach treatment and recovery with greater ease. Additionally, higher income levels facilitate access to superior medical resources, thereby contributing to the amelioration of negative emotions[32]. Nonetheless, caution is warranted when interpreting the protective association with low-income status, as it could signal healthcare accessibility variations, like reduced routine follow-up visits in this group. These findings corroborate those of Chen et al[33], who reported that shorter disease duration and better subjective sleep quality were notably related to mitigated symptoms of depression/anxiety in dry eye disease. Improved educational attainment helps reduce anxiety and depressive symptoms in patients with glaucoma. While best-corrected visual acuity in both eyes was linked to adjusted anxiety, further analysis revealed that vision-related quality of life (rather than objective visual function measures) was the primary contributor to psychological distress in these patients. Additionally, IOP fluctuations might worsen anxiety through a dysfunctional autonomic nervous system[22].

Based on the above findings, the key drivers of emotional distress in glaucoma sufferers include insomnia and monthly household income per capita. Focusing on these factors through tailored interventions can effectively reduce mental health risks among this patient population. Nondrug therapies like light exposure, Baduanjin with ear pressure techniques, scent-based relaxation, cognitive behavior therapy, and mindfulness exercises may improve sleep and mood in patients experiencing insomnia secondary to primary glaucoma[34]. Low-income patients with glaucoma may benefit from social support, including free vocational training programs and reimbursable eye care services (e.g., eye exercises and mydriatic examination). By enhancing the financial situation while reducing healthcare expenses, such interventions could potentially mitigate psychological distress[35]. Meanwhile, targeted psychological interventions and health education can be considered. For example, 30-60 minutes daily meditation can hinder disease progression, reduce stress, and regulate emotions to alleviate disease-related psychological burden; providing patients with targeted, personalized, and comprehensive self-management interventions contributes to enhanced disease-related cognition and gradually eliminates IU, further controlling negative emotions[36,37].

This study has certain limitations. First, the cross-sectional methodology results in the inability to establish causal relationships, necessitating future longitudinal analysis to further determine the temporal relationships among IU, anxiety, and depression in primary glaucoma. Second, as a single-center study with a limited sample size, result generalizability may be limited; future multicenter studies are warranted to strengthen research rigor. Third, potential confounding factors, such as best-corrected visual acuity, visual impairment staging, and education level, were excluded. Incorporating these parameters can help determine their impact on patient anxiety or depression. Fourth, information on medical visit frequency remains unexplored, which, if supplemented, could possibly elucidate the observed protective effect of low-income status.

CONCLUSION

IU in patients with primary glaucoma correlates positively with anxiety and depression. Furthermore, patients suffering from insomnia and those with lower monthly household incomes are at an increased risk of experiencing anxiety and depression. Implementing targeted psychological interventions and health education for these individuals could prove effective in mitigating their negative emotional states.