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. 2022 Apr 19;14:25158414221090100. doi: 10.1177/25158414221090100

The prevalence of anxiety symptoms and disorders among ophthalmic disease patients

Zulvikar Syambani Ulhaq 1,2,✉, Gita Vita Soraya 3, Nadia Artha Dewi 4, Lely Retno Wulandari 5
PMCID: PMC9021519  PMID: 35464342

Abstract

Background:

Progressive and irreversible vision loss has been shown to place a patient at risk of mental health problems such as anxiety. However, the reported prevalence of anxiety symptoms and disorders among eye disease patients vary across studies. Thus, this study aims to clarify the estimated prevalence of anxiety symptoms and disorders among ophthalmic disease patients.

Methods:

Relevant studies on the prevalence of anxiety symptoms and disorders among eye disease patients were collected through international databases, PubMed, Scopus, and Web of Science. A random-effects model was used to determine the pooled prevalence of anxiety symptoms and disorders among ophthalmic disease patients.

Results:

The 95 included studies yielded a pooled prevalence of 31.2% patients with anxiety symptoms and 19.0% with anxiety disorders among subjects with ophthalmic disease. Pediatric patients were more anxious (58.6%) than adults (29%). Anxiety symptoms were most prevalent in uveitis (53.5%), followed by dry eye disease (DED, 37.2%), retinitis pigmentosa (RP, 36.5%), diabetic retinopathy (DR, 31.3%), glaucoma (30.7%), myopia (24.7%), age-related macular degeneration (AMD, 21.6%), and cataract (21.2%) patients. Anxiety disorders were most prevalent in thyroid eye disease (TED, 28.9%), followed by glaucoma (22.2%) and DED (11.4%). When compared with healthy controls, there was a twofold increase on the prevalence of anxiety symptoms (OR = 1.912, 95% CI 1.463–2.5, p < 0.001) and anxiety disorders (OR = 2.281, 95% CI 1.168–4.454, p = 0.016).

Conclusion:

Anxiety symptoms and disorders are common problems associated with ophthalmic disease patients. Thus, comprehensive and appropriate treatments are necessary for treating anxiety symptoms and disorders among ophthalmic disease patients.

Keywords: anxiety symptoms and disorders, ophthalmic disease, prevalence

Introduction

Anxiety disorders are highly prevalent, affecting about 7.3% (4.8%–10.9%) of the population, 1 with higher incidence among females relative to males. 2 Among them, specific phobias are the most common type of anxiety disorder, followed by panic disorder, social anxiety disorder, and generalized anxiety disorder.2,3 Anxiety disorders are also highly comorbid with other mental disorders, especially depressive disorders.2,4 These implicate that patients with anxiety and depressive disorders may often have poorer outcomes and require specific psychopharmacological adjustments.

Chronically ill patients are at high risk of experiencing anxiety disorders as a result of the psychoemotional disturbances implicated by physical deterioration or limitations. As an example, vision loss is considered to be progressive and irreversible, placing the patient at increased risk of mental health problems which may negatively influence the individual’s quality of life. 5 Several studies have shown the association between anxiety symptoms and ocular diseases.6–8 However, the reported prevalence of anxiety symptoms and disorders in patients with ocular diseases remains highly varied, ranging from 2.4% to 78%6,9 and 6.3% to 73%, respectively.10,11

Meanwhile, early identification and management of anxiety is crucial in eye disease cases, as acute emotional stress can result in sudden intraocular pressure (IOP) elevation in the glaucomatous eye and has been associated with severe ocular hypertension. 12 Due to the potential negative impact of poor mental health status on both the ophthalmic condition and general well-being of the patient, prompt identification and management of emotional and social factors correlated with anxiety should be taken into account in order to achieve optimal treatment. Indeed, patients with anxiety symptoms and disorders often experience significant impairment in functioning in global, social, occupational, and physical domains. 13 Thus, identification of the impairment profile for those suffering from anxiety is essential to understand the hurdles that treatment may need to overcome. Altogether, in order to quickly identify and manage anxiety issues in ophthalmic disease subjects, decision-makers require a representative estimate on the prevalence of said condition. Hence, this study aims to systematically review the reported prevalence of both anxiety disorders and symptoms in ophthalmic disease patients, and to provide a pooled prevalence of anxiety among the eye disease patients.

Methods

Study criteria and search strategy

This study was performed according to the instructions of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. 14 Criteria of studies included in this meta-analysis were: (1) observational studies that reported either anxiety symptoms or disorders among patients with eye disease; (2) anxiety symptoms/states and disorders examined based on a validated methods/tools and clinical diagnosis, respectively; (3) ophthalmic diseases diagnosed based on the judgment of qualified ophthalmologists or medical records according to the International Classification of Disease and Codes (ICD-11); and (4) both adult and pediatric age were included. Relevant studies were searched from electronic databases such as PubMed, Scopus, and Web of Science, utilizing the following keywords: anxiety, prevalence/incidence, and eye/ocular disease/ophthalmology until January 2022.

Data extraction and quality assessment

Data were extracted as follows: author, year of publication, study design, country, sample size, mean age of participants or otherwise indicated, type of disease, diagnostic method with its corresponding cutoff value, and the prevalence of anxiety disorders or symptoms. To assess the quality of the observational study, the Newcastle-Ottawa Scale (NOS) was applied. 15 The maximum score for each study is 9. Studies scoring less than 5 were judged to be at a high risk of bias. 16

Statistical analysis

Prevalence estimates of anxiety symptoms and disorders were calculated from 95 studies. Heterogeneity was evaluated with the I2 statistic, wherein I2 values more than 50% indicated substantial heterogeneity. If heterogeneity existed, the random-effects model was then used; otherwise, the fixed-effects model was applied. Secondary analysis was used to evaluate the prevalence of anxiety symptoms and disorders among patients with ophthalmic disease relative to healthy subjects. A funnel plot and Begg’s test were used to investigate the publication bias if the pooled effect size consisted of 10 or more studies.17–22 Meta-analysis was performed utilizing Open Meta-Analyst software package. 23 The value of 0.05 was indicative of statistical significance.

Results

Ninety-five studies were included in this meta-analysis,6–11,24–98 among which 81 evaluated anxiety symptoms while 14 evaluated anxiety disorders among patients with ophthalmic disease (Figure 1). The characteristics of the included studies are shown in Table 1. The prevalence of anxiety symptoms and disorders among ophthalmic disease patients ranged from 2.4% to 95.87% and 6.5% to 77.5%, respectively. The random-effect model was used because heterogeneity existed (I2 > 50%). The overall pooled prevalences of anxiety symptoms and disorders among patients with ophthalmic disease were 31.2% (6507/23,415 subjects, 95% CI 25.8%–36.7%, p < 0.001, Figure 2) and 19.0% (6502/60,174 subjects, 95% CI 16.1%–22%, p < 0.001, Figure 3), respectively. When the study was classified based on age, the pooled prevalence of anxiety symptoms in adult and pediatric patients were 29% (7726/33,981 subjects, 95% CI 25.8%–32.3%, p < 0.001) and 58.6% (649/945 subjects, 95% CI 18.6%–98.5%, p = 0.004), respectively (Figure 2).

Figure 1.

Figure 1.

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Flow diagram of the study selection process.

Table 1.

Characteristics of the included studies.

No Study Year Country Disease Age
[Mean (SD)]		 Study design Assessment tools Cutoff Prevalence (case/participants) NOS
Anxiety states
1 Agorastos et al. 2013 Germany Glaucoma 70.8 (8.4) Cross-sectional study STAI >44 21% (18/86) 6
2 Ayaki et al. (a) 2015 Japan Glaucoma 59.5 (19.9) Cross-sectional study HADS ⩾10 38.8% (42/109) 6
3 Cumurcu et al. 2006 Turkey Glaucoma (PXG + POAG) 53.26 (13.22)
49.65 (11.11)		 Case-control, Cross-sectional study HARS >17 9.6% (7/73) 7
4 Eramudugolla et al. (a) 2013 Australia Glaucoma 76.22 (2.89) Population-based cross-sectional study GADS ⩾4 8.7% (2/23) 7
5 Fasih et al. 2010 Pakistan Glaucoma (POAG) 56.21 (13.37) Cross-sectional study HADS-A ⩾11 33% (33/100) 6
6 Hwang and Kim 2015 Korea Glaucoma 49.2 ( 10.6) Cross-sectional study HADS-A >10 51.4% (37/72) 6
7 Kong et al. 2015 China Glaucoma (PACG + POAG) 58.16 (14.42)
52.86 (12.64)		 Cross-sectional study SAS ⩾45 55% (55/100) 7
8 Lim et al. 2016 Singapore Glaucoma
(PACG + POAG)		 67.1 (12.0) Cross-sectional study HAM-A >17 63% (61/97) 6
9 Mabuchi et al. 2008 Japan Glaucoma (POAG) 66.9 (11.9) Case-control study HADS-A >10 13% (30/230) 7
10 Otori et al. 2017 Japan Glaucoma 62.4 (13.1) Cross-sectional study STAI ⩾45 78.0% (351/450) 6
11 Pei et al. 2012 China Glaucoma (PACG) NA Cross-sectional study HADS-A >10 26.7% (16/60) 6
12 Rezapour et al. (a) 2018 Germany Glaucoma 55 Population-based cohort study GAD-7 ⩾3 5.3% (18/333) 7
13 Siguan-Bell and Florcruz 2019 Philippine Glaucoma 61.6 (13.9) Cross-sectional study HADS-P ⩾11 15% (12/82) 6
14 Tastan et al. 2010 Turkey Glaucoma 64.23 (13.15) Case-control study HADS ⩾8 40% (49/121) 7
15 Wu et al. (a) 2019 China Glaucoma 57.59 (15.89) Cross-sectional study HADS-A >10 12.2% (52/428) 6
16 Yochim et al. 2012 USA Glaucoma 70 (9.2) Cross-sectional study GAI ⩾11 2.4% (1/41) 6
17 Zhang et al. (a) 2018 China Glaucoma 57.20 (13.94) Cross-sectional study HADS-A ⩾8 29.66% (78/263) 6
18 Zhan and Zhilan 2013 China Glaucoma (POAG) NA Cross-sectional study HAM-A >17 59% (49/83) 6
19 Zhou et al. 2013 China Glaucoma 55.40 (15.26) Cross-sectional study HADS-A >10 22.92% (116/506) 6
20 Dayal et al. 2022 India Glaucoma 59.2 (12.6) Cross-sectional study HADS-A ⩾8 6.5% (13/200) 6
Anxiety states
21 Abe et al. 2021 Brazil Glaucoma 70.14 (15.8) Cross-sectional study HADS >12 4.65% (6/129) 6
22 Onwubiko et al. 2020 Nigeria Glaucoma 18–72 a Cross-sectional study HADS ⩾11 44% (80/182) 6
23 Shin et al. 2021 China Glaucoma (POAG) 54.14 (16.87) Cross-sectional study BAI >10 16.7% (44/251) 6
24 Zhang et al. (b) 2021 China Glaucoma (POAG) 56.6 (15.7) Cross-sectional study HADS-A >8 28.1% (18/64) 6
25 Au Eong et al. 2012 Singapore AMD 68.1 (9.4) Cross-sectional study EQ-5D (EQ_5) >1 20.7% (70/338) 6
26 Augustin et al. 2007 France/ Germany/ Italy Wet AMD NA Cross-sectional study HADS ⩾8 50% (168/336) 6
27 Rezapour et al. (b) 2020 Germany AMD 54.4 (11.0) Cross-sectional study GAD-7 ⩾3 4.2% (46/1089) 6
28 Fernández-Vigo et al. 2021 Spain Wet AMD 80.9 (6.6) Cross-sectional study HADS >10 25.5% (14/55) 6
29 Senra et al. 2017 UK Wet AMD 80 (7.4) Cross-sectional study HADS-A ⩾8 17.3% (52/300) 6
30 Eramudugolla et al. (b) 2013 Australia AMD 75.63 (4.25) Population-based cross-sectional study GADS ⩾4 10.5% (2/19) 7
31 Evans et al. 2007 UK AMD 85.7 (5.2) Population-based cross-sectional study GHQ-28 NA 9.6% (50/516) 7
32 Mathew et al. 2011 Australia AMD 78.0 (7.7) Cross-sectional study GADS ⩾2 29.4% (43/145) 8
33 Ryu et al. 2017 Korea AMD 69.41 (7.74) Population-based cross-sectional study EQ-5D (EQ_5) >1 17.6% (58/326) 7
34 Hernández-Moreno et al. 2021 Portugal AMD + DR 68.8 (11.96) Cross-sectional study HADS-A NA 18% (13/71) 6
35 Ayaki et al. (b) 2019 Japan DED 59.5 (19.9) Cross-sectional study HADS ⩾10 43.5% (107/247) 6
36 Li et al. (a) 2011 China DED 42 Descriptive study SAS ⩾45 30.3% (27/89) 7
37 Li et al. (b) 2018 China DED 19.7 (2.7) Cross-sectional study SAS ⩾35 92.6% (87/94) 7
38 Liyue et al. 2015 Singapore DED 54.49 (10.76) Cross-sectional study HADS ⩾8 26.1% (24/96) 6
39 Na et al. 2015 Korea DED 44.9 (0.8) Population-based cross-sectional study EQ-5D (EQ_5) >1 17.5% (142/816) 7
40 Wen et al. 2012 China DED 41 (15) Cross-sectional study SAS >52 61.8%% (175/283) 6
41 Yilmaz et al. 2015 Turkey DED 41 a Case-control study DASS >7 63.3% (77/121) 7
Anxiety states
42 Wu et al. (b) 2019 China DED 45.52 (12.8) Case-control study GAD-7 ⩾5 39% (41/106) 7
43 Kitazawa et al. 2018 Japan DED 61.3 (18.1) Observational prospective study HAM-A ⩾14 14.7% (5/34) 6
44 Bitar et al. 2019 USA DED 65.5 (13.3) Prospective study GAD-7 >10 22.2% (10/45) 6
45 Zhang et al. (c) 2016 China SSDE 46.8 (11.1) Case-control study SAS >50 43.33% (13/30) 7
46 Ayaki et al. (c) 2018 Japan Cataract 59.5 (19.9) Cross-sectional study HADS ⩾10 36.9% (59/159) 6
47 Eramudugolla et al. (c) 2013 Australia Cataract 77.57 (4.5) Population-based cross-sectional study GADS ⩾4 10.8% (21/94) 7
48 Evans et al. 2007 UK Cataract 84.7 (5.3) Population-based cross-sectional study GHQ-28 NA 8.2% (29/350) 7
49 Zhang et al. (d) 2018 China Catracat 70.23 (9.78) Cross-sectional study HADS-A ⩾8 18% (18/100) 6
50 Onal et al. 2017 Turkey Uveitis 36.09 (12.49) Cross-sectional study STAI-I ⩾40 52.5% (52/99) 6
51 Sittivarakul and Wongkot 2018 Thailand Uveitis 43.5 a Descriptive study HADS-A ⩾8 12.8% (11/86) 6
52 Eser-Öztürk et al. (a) 2021 Turkey Behçet Uveitis 34.76 (11.14) Cross-sectional study STAI-I ⩾40 58.6% (34/58) 6
53 Eser-Öztürk et al. (b) 2021 Turkey Behçet Uveitis 34.76 (11.14) Cross-sectional study STAI-II ⩾40 79.3% (46/58) 6
54 Silva et al. 2017 Brazil Uveitis 42.8 (14.5) Cross-sectional study HADS ⩾8 65.1% (52/80) 6
55 Heindl et al. 2021 Germanuy Unilateral anophthalmic 62.54 (16.77) Cross-sectional study GAD-7 ⩾5 44.7% (132/295) 7
56 Ayaki et al. (d) 2016 Japan Retinal disease 59.5 (19.9) Cross-sectional study HADS ⩾10 42.3% (51/120) 6
57 Ayaki et al. (e) 2017 Japan IOL 59.5 (19.9) Cross-sectional study HADS ⩾10 28.4% (28/99) 6
58 Ayaki et al. (f) 2019 Japan Lid/Conjungtiva 59.5 (19.9) Cross-sectional study HADS ⩾10 41.8% (121/289) 6
59 Chaumet-Riffaud et al. 2017 France RP 38.2 (7.1) Cross-sectional study HADS ⩾8 36.5% (54/148) 6
60 Eramudugolla et al. (d) 2014 Australia Co-morbid eye diseases 79.94 (4.91) Population-based cross-sectional study GADS ⩾4 11.8% (6/51) 7
61 Evans et al. 2007 UK Eye disease (a) 83.4 (5.1) Population-based cross-sectional study GHQ-28 NA 9.7% (25/259) 7
62 Evans et al. 2007 UK Refractive Error 83.1 (5.0) Population-based cross-sectional study GHQ-28 NA 9.8% (44/450) 7
Anxiety states
63 Evans et al. 2007 UK Eye disease (b) 85.5 (5.9) Population-based cross-sectional study GHQ-28 NA 9.4% (30/316) 7
64 Kempen and Zijlstra 2014 The Netherlands Low vision 77.4 (8.8) Cross-sectional study HADS ⩾8 14.9% (22/148) 7
65 Kleinschmidt et al. 1995 USA Visual impairment 76.85 Cross-sectional study STAI ⩾45 25% (20/80) 6
66 Łazarczyk et al. 2016 Poland Myopia 13-17 a Cross-sectional study STAIC ⩾7 22.8% (26/114) 7
67 Rees et al. 2016 Australia DR, DME 64.9 (11.6) Cross-sectional study HADS ⩾8 22.7% (118/519) 6
68 Zhang et al. (e) 2021 China DR 56.7 (11.6) Cross-sectional study HADS-A ⩾9 41.1% (43/105) 7
69 Richards et al. 2014 UK Ptosis 61.6 (15.3) Cross-sectional study HADS ⩾11 27.9% (17/61) 7
70 Sianohara et al. 2017 Japan RP 60.7 (15.4) Cross-sectional study HADS-A >8 37% (41/112) 6
71 van der Aa et al. (a) 2015 The Netherlands Eye disease 73.7 (12.3) Cross-sectional study HADS-A ⩾8 18% (45/246) 6
72 van der Aa et al. (b) 2015 The Netherlands Eye disease 77.6 (9.27) Cross-sectional study HADS-A ⩾8 7.48% (46/615) 7
73 Wong and Yu 2013 China GO 54 a Cross-sectional study HADS ⩾8 19% (23/122) 7
74 Ye et al. 2015 China Eye enucleation 36.3 (12.6) Cross-sectional study HADS ⩾8 40% (78/195) 6
75 Yokoi et al. 2013 Japan Myopia 60 a Cross-sectional study HADS-A ⩾8 25.9% (53/205) 7
76 Mao et al. 2021 China Intermittent Exotropia 8.17 (2.81) Cross-sectional study HADS-A ⩾8 95.87% (373/389) 7
77 Magdalene et al. 2021 India Severe visual impairment and blindness <18 a Cross-sectional study DASS >7 56.56% (250/442) 7
78 Canamary et al. 2019 Brazil Ocular toxoplasmosis 41.5 (14.5) Cross-sectional study HADS-A ⩾8 38.3% (31/81) 6
79 Gollrad et al. 2021 Germany Uveal melanoma 59.12 (13.6) Prospective study GAD-7 ⩾5 57.2% (75/131) 6
80 Kabedi et al. 2020 Congo PCV 66.1 (6.9) Prospective case–control study HADS-A ⩾8 73.3% (11/15) 6
81 Frank et al. 2019 USA Visual impairment ⩾65 a Cohort PHQ-4-A >3 27.2% (2063/7584) 7
Anxiety disorders
1 Bernabei et al. 2011 Italy Visual impairment 71.9 (7.7) Cross-sectional study Clinical diagnosis NA 10.6% (11/104) 7
2 Bunevicius et al. 2005 Lithuania GO 45 (14) Cross-sectional study MINI NA 73% (22/30) 7
3 Chiang et al. 2013 Taiwan Blepharitis 54.8 (18) Cross-sectional study Clinical diagnosis NA 9.5% (932/9764) 7
4 Hassan et al. 2015 USA Strabismus NA Cross-sectional study Clinical diagnosis NA 21.9% (65/297) 6
5 Jacob et al. 2017 Germany AMD 75.7 (10.1) Retrospective cohort study Clinical diagnosis NA 11.7% (887/7580) 6
6 Li et al. (c) 2011 USA Eye disease 75.8 (0.1) Cross-sectional study Clinical diagnosis NA 6.5% (1461/22,482) 7
7 van der vaart et al. 2015 The Netherlands DED NA Cross-sectional study Clinical diagnosis NA 11.4% (823/7207) 7
8 Zhang et al. (f) 2017 USA Glaucoma NA Retrospective case-control study. Clinical diagnosis NA 17% (1916/11,234) 8
9 Berchuck et al. 2020 USA Glaucoma 60.0 (14.2) Cohort Clinical diagnosis NA 28% (113/408) 8
10 Steven et al. 2016 Germany DED NA Retrospective cohort study Clinical diagnosis NA 7.7% (4/52) 6
11 Abdel-aty and Kombo 2021 USA Non-Infectious Scleritis NA Cross-sectional study Clinical diagnosis NA 9.3% (15/162) 6
12 Cockerham et al. 2021 USA TED 45.2 (7.6) Cross-sectional study Clinical diagnosis NA 34% (34/100) 7
13 Wang et al. 2021 USA TED 49.4 (13.6) Retrospective cohort study Clinical diagnosis NA 26% (188/714) 7
14 Dudani et al. 2021 India Central serous chorioretinopathy 39.55 (8.33) Prospective study Clinical diagnosis NA 77.5% (31/40) 6
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AMD, age-related macular degeneration; BAI, Beck’s Anxiety Inventory; DASS, Depression Anxiety Stress Scales; DED, dry eye disease; DME, diabetic macular edema; DR, diabetic retinopathy; EQ-5D; EuroQol-5D health-status descriptive system; GAD-7, Generalized Anxiety Disorder-7 Scale; GAD, Goldberg Anxiety and Depression; GAI, Geriatric Anxiety Inventory; GHQ-28, Anxiety subscale of the General Health Questionnaire; GO, Graves ophthalmopathy; HADS, Hospital Anxiety and Depression Scale; HADS-A, HDSA-Anxiety, HADS-P, Hospital Anxiety and Depression Scale (The Filipino version); HAM-A, Hamilton Anxiety Rating Scale; HARS, Hamilton Anxiety Rating Scale; NA, not available; NOS, the Newcastle-Ottawa Scale; MINI, Mini-International Neuropsychiatric Interview; PXG, pseudoexfoliative glaucoma; PACG, primary angle-closure glaucoma; POAG, primary open-angle glaucoma; PCV, polypoidal choroidal vasculopathy; PHQ-4, The Patient Health Questionnaire for Depression and Anxiety; RP, retinitis pigmentosa; SAS, The Zung Self-rating Anxiety Scale; SD, standard deviation; SSDE, Sjögren syndrome dry eye; STAI, The State-Trait Anxiety Inventory; STAIC, The State-Trait Anxiety Inventory for Children; TED, Thyroid Eye Disease. Gray shading indicates children group.

a

Age presented as mean/median/range.

Figure 2.

Figure 2.

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Forest plot of the 81 studies estimating the pooled prevalence of anxiety symptoms among patients with ophthalmic disease, of which 3 studies were conducted in pediatric patients.

Figure 3.

Figure 3.

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Forest plot of the 14 studies estimating the pooled prevalence of anxiety disorders among patients with ophthalmic disease.

Subgroup analysis was performed for studies evaluating anxiety symptoms and disorders among patients with the ophthalmic disease yielded similar findings. The highest prevalence of anxiety symptoms was observed in patients with uveitis [53.5%, 95% CI, 27.4%–79.6%, p < 0.001; patients with Behçet uveitis had a higher prevalence of anxiety symptoms (69.3%, 95% CI, 49%–89.6%, p < 0.001) than those with any type of uveitis (43.3%, 95% CI, 9.9%–76.6%, p = 0.011, Figure 4(a))], followed by patients with dry eye disease (DED) (37.2%, 95% CI, 17.4%–40.5%, p < 0.001, Figure 4(b)), retinitis pigmentosa (RP) (36.5%, 95% CI, 19.8%–54.6%, p < 0.001, Figure 4(c)), diabetic retinopathy (DR) (31.3%, 95% CI, 13.5%–49.1%, p < 0.001, Figure 4(d)), glaucoma [30.7%, 95% CI, 22.3%–39%, p < 0.001; patients with primary-angle closure glaucoma (PACG) had a higher prevalence of anxiety symptoms (52.5%, 95% CI, 24.9%–80%, p < 0.001) than those with primary-open angle glaucoma (POAG, 33.1%, 95% CI, 21%–45.2%, p < 0.001) or any type of glaucoma (25.6%, 95% CI, 14.3%–36.9%, p < 0.001, Figure 5(a))], myopia (24.7%, 95% CI, 20%–29.4%, p < 0.001, Figure 5(b)), age-related macular degeneration [AMD, 21.6%, 95% CI, 12.5%–30.7%, p < 0.001, Figure 5(c); patients with wet AMD had a higher prevalence of anxiety symptoms (34.3%, 95% CI, 16.6%–52%, p < 0.001) than those with any type of AMD (15.3%, 95% CI, 8.3%–22.3%, p < 0.001, Figure 5(c))], and cataract (21.2%, 95% CI, 7.8– 34.6%, p = 0.002, Figure 5(d)). For anxiety disorders, the highest prevalence was detected in patients with thyroid eye disease (TED) (28.9%, 95% CI, 21.8%–36%, p < 0.001, Figure 6(a)), followed by patients with glaucoma (22.2%. 95% CI, 11.7%–32.6%, p < 0.001, Figure 6(b)) and DED (11.4%. 95% CI, 10.5%–12.2%, p < 0.001, Figure 6(b)).

Figure 4.

Figure 4.

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Forest plot of the pooled prevalence of anxiety symptoms in the different types of patients with ophthalmic disease: (a) uveitis; (b) dry eye disease (DED); (c) retinitis pigmentosa (RP); (d) Diabetic retinopathy (DR).

Figure 5.

Figure 5.

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Forest plot of the pooled prevalence of anxiety symptoms in the different types of patients with ophthalmic disease: (a) glaucoma; (b) myopia; (c) age-related macular degeneration (AMD); (d) cataract.

Figure 6.

Figure 6.

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Forest plot of the pooled prevalence of anxiety disorders in the different types of patients with ophthalmic disease: (a) thyroid eye disease (TED); (b) glaucoma; (c) dry eye disease (DED).

For the secondary analysis, 22 and 8 studies evaluating anxiety symptoms and disorders among patients with the ophthalmic disease were analyzed. The overall results indicated that relative to healthy controls, patients with ocular disease exhibit nearly a twofold increase of experiencing anxiety symptoms (OR = 1.912, 95% CI 1.463–2.5, p < 0.001, Figure 7(a)), of which patients with DED had slightly higher anxiety symptoms (OR = 2.19, 95% CI 1.411–3.399, p < 0.001, Figure 7(b)) than those with glaucoma (OR = 1.822, 95% CI 1.058–3.135, p = 0.03, Figure 7(c)), but these findings were not observed in patients with myopia nor AMD (Supplemental Figure 1A and B). In line, the risk of developing anxiety disorders among ophthalmic disease patients was two times higher than in control subjects (OR = 2.281, 95% CI 1.168–4.454, p = 0.016, Figure 8). The funnel plot generated from 22 studies was symmetrical (Supplemental Figure 1 C) with the Begg’s test (p = 0.108), indicating no evidence of publication bias.

Figure 7.

Figure 7.

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Forest plot of the pooled prevalence of anxiety symptoms in patients with ophthalmic disease and control subjects: (a) overall; (b) dry eye disease (DED) group; (c) glaucoma.

Figure 8.

Figure 8.

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Forest plot of the pooled prevalence of anxiety disorders in patients with ophthalmic disease and control subjects.

Discussion

This study showed that the prevalence of anxiety symptoms and disorders among patients with ophthalmic disease were relatively higher than that reported in the general population.1,99 We also found that anxiety symptoms and disorders were two times more prevalent among patients with ophthalmic disease than control subjects. Based on the type of eye disease, the highest prevalence of anxiety symptoms was found in patients with uveitis, followed by DED, RP, DR, glaucoma, myopia, AMD, and cataract. Similarly, anxiety disorders were also commonly occurred in patients with glaucoma and DED in addition to TED. It is interesting to note that pediatric patients with ocular disease tended to have a higher prevalence of anxiety symptoms than adults. This is because children may have low coping strategies against potentially stressful situations or alternatively, both primary and secondary control coping may not fully develop in early childhood due to a lack of concrete operational cognitive capacities. 100 Although most of the studies showed low-risk of bias, heterogeneity was observed across the studies. This is possibly due to a variety of detection methods/assessment tools and its cutoff value.

Our study suggests that a higher prevalence of anxiety symptoms was frequently occurred in patients with chronic eye disease (in our study, we reported such as Behçet uveitis, TED, glaucoma, RP, DR, macular degeneration, uncorrected refractive error, and cataract). More than 50% of patients with Behçet uveitis had experience anxiety symptoms. Indeed, depression and anxiety are consistently observed disorders in Behçet’s disease (BD) individuals across studies. 101 It is notable that in 2017, a meta-analysis performed by Wan et al. 68 indicates that DED is associated with nearly a three times increase in the prevalence of anxiety. Recently, Basilious et al. 102 indicated possible interrelationships between DED severity with anxiety symptoms. In agreement with this finding, Zhang et al. 42 demonstrated that glaucoma patients exhibit a 10-fold increase in the risk of developing anxiety disorders. In addition, for the first time, we have shown a higher prevalence of anxiety symptoms in PACG than POAG subjects. This is possibly because relative to POAG, PACG carries a threefold increased risk of severe bilateral visual impairment. 103 In parallel, Dawson et al. 104 showed that the prevalence estimate of anxiety symptoms in people with AMD ranges from 9.6% to 30.1%, and interestingly, we found that patients with wet AMD had slightly higher anxiety symptoms than previously reported. 104 Although both glaucoma and AMD are considered slow-progressing eye diseases, acute onset of vision loss often occurs in wet AMD. Therefore, patients usually seek a rapid referral and treatment. On the other hand, the lives of people with glaucoma are largely unaffected while the disease progresses silently, which may have a long-term negative impact on their quality of life. 105 Thus, according to our findings, it is possible to hypothesize that the chronicity of glaucoma may be closely associated with the development of anxiety symptoms and disorders.

Patients with TED often have a problem with the disfigurement of the eye. This can change the appearance of the eyes and lead to affected individuals looking tired all the time. 106 These cosmetic issues can have a significant impact on emotional well-being and may be correlated with the development of anxiety disorders, because patients may face exclusion more often due to their facial appearance. Together, our study suggests that anxiety symptoms and disorders are common problems associated in patients with ophthalmic disease.

Anxiety symptoms and disorders that occur in ophthalmic disease patients may be due to several factors, such as a feeling of hopelessness and failing to cope, as a consequence of the untreatable and unpredictable losses of the visual field 107 and losing of the driving license. 108 The anxiety may also be elicited by socioeconomic aspects, including increased costs from doctor and hospital visits, medications, and health care.109,110 From a biochemical standpoint, low serotonin levels (5-HT) have been associated with anxious behavior. 111 Indeed, the reduction of serum 5-HT levels is observed in patients with glaucoma and chronic central serous chorioretinopathy.112,113 Interestingly, the administration of selective serotonin reuptake inhibitors (SSRIs) as well as anti-anxiety has been shown to not only improve anxiety symptoms but also suppressed the intraocular pressure (IOP) in glaucomatous patients, 114 thereby implying that 5-HT may involve in glaucoma pathogenesis. Nevertheless, comprehensive and appropriate treatments are necessary for treating anxiety disorders among ophthalmic disease patients, which may help to reduce the cost of treatment. Moreover, cooperation between ophthalmologists and psychiatrists is essential to support complete eye treatment and to improve mental health conditions.

One of the strengths of this study is that it represents a comprehensive and updated evaluation on the prevalence of anxiety symptoms and disorders in all patients with ocular disease, while a previous study by Zheng et al. 115 only specifically evaluated depression and depressive symptoms. Moreover, in the previous studies,68,115 they combine both symptoms and disorders as a single entity, but in fact, anxiety symptoms and disorders are two different entities. In addition, the strengths of the study included the in-depth analysis of anxiety symptoms in the pediatric group, which was not previously examined.

Some limitations should be noted when interpreting these findings. (1) Because anxiety is often comorbid with depression, the inclusion of studies that report a mixed prevalence of anxiety and depression may have influenced the prevalence estimate in this study. (2) Because the instruments for examining the anxiety symptoms or states are not uniform, this possibly contributes to the observed heterogeneity in this meta-analysis. (3) The uneven number of studies on glaucoma, DED, and AMD could be the other possible source of bias. (4) Because most of the included studies were designed as cross-sectional studies, the causal relationship between anxiety symptoms/disorders and ocular diseases can not be determined. (5) Included studies in the pediatric population are limited, thus the current finding may not be precise and further studies are still required.

In conclusion, our study implies that anxiety symptoms and disorders are common among ophthalmic disease patients. Therefore, a comprehensive and collaborative approach is essential116,117 to quickly identify and effectively care for ophthalmic disease patients with anxiety symptoms or disorders. Since more studies are expected to be available, additional accurate estimations can be performed to verify this conclusion.

Supplemental Material

sj-tif-1-oed-10.1177_25158414221090100 – Supplemental material for The prevalence of anxiety symptoms and disorders among ophthalmic disease patients
Click here for additional data file. (8.9MB, tif)

Supplemental material, sj-tif-1-oed-10.1177_25158414221090100 for The prevalence of anxiety symptoms and disorders among ophthalmic disease patients by Zulvikar Syambani Ulhaq, Gita Vita Soraya, Nadia Artha Dewi and Lely Retno Wulandari in Therapeutic Advances in Ophthalmology

Footnotes

Author contributions: Zulvikar Syambani Ulhaq: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Validation; Writing – original draft; Writing – review & editing.

Gita Vita Soraya: Data curation; Formal analysis; Investigation; Writing – original draft.

Nadia Artha Dewi: Supervision.

Lely Retno Wulandari: Supervision.

Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval: For this type of study (meta-analysis), ethical committee approval is not required.

ORCID iD: Zulvikar Syambani Ulhaq Inline graphic https://orcid.org/0000-0002-2659-1940

Supplemental material: Supplemental material for this article is available online.

Contributor Information

Zulvikar Syambani Ulhaq, Research Center for Pre-Clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong, Indonesia; Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Malang 65151, East Java, Indonesia.

Gita Vita Soraya, Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

Nadia Artha Dewi, Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

Lely Retno Wulandari, Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

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Supplemental material, sj-tif-1-oed-10.1177_25158414221090100 for The prevalence of anxiety symptoms and disorders among ophthalmic disease patients by Zulvikar Syambani Ulhaq, Gita Vita Soraya, Nadia Artha Dewi and Lely Retno Wulandari in Therapeutic Advances in Ophthalmology

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