Association of Central serous chorioretinopathy with type of personality, anxiety and depression

Abstract

Purpose:

Central serous chorioretinopathy (CSCR) a relatively common cause of visual impairment, which is characterized by subretinal fluid accumulation in the macula and is more common in middle-aged males. Various risk factors have been reported in literature, among which substantial role of psychological factors is cited. Our aim was to look for the prevalence and association of the psychiatric factors in CSCR patients and to compare them with other non-chorioretinal ocular pathologies.

Methods:

A cross-sectional correlational study was undertaken involving 91 CSCR patients, along with 91 patients with other non-chorioretinal diseases. Their risk factors, clinical history, ocular examination, and psychiatric assessments were done using standardized tools, and the groups were compared in terms of scoring of Framingham Type A scale (FTAS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HDRS).

Results:

CSCR patients had a male:female ratio of 8:1. Chronic, bilateral, and recurrent diseases were found in 15%, 20%, and 23% cases, respectively. Anxiety disorder had a prevalence of 40%, followed by major depression with a prevalence of 24%, and these were significantly higher than non-chorioretinal disease patients (odds ratios 14.18 and 5.30, respectively). Also, these psychiatric disorders were significantly associated with an overall lower visual acuity and greater central macular thickness due to subretinal fluid accumulation.

Conclusion:

Psychiatric comorbidities like Type A personality trait and depression and anxiety disorders were significantly more prevalent in CSCR patients, compared to non-chorioretinal pathologies. Focus on psychological health would certainly benefit these patients in terms of better management of not only CSCR, but their psychiatric morbidity as well.

Central serous chorioretinopathy (CSCR) is an idiopathic localized serous detachment of the sensory retina at the macula related to leakage at the level of retinal pigment epithelium (RPE) due to hyperpermeability of the choriocapillaris, through one or more sites as suggested by Hussain and Gass,[1] and it is the fourth most common nonsurgical retinopathy.[2] First reported in literature by Von Graefe and later popularized as CSCR by Duke Elder,[3] CSCR typically occurs unilaterally, in the young or middle-aged (35–55 years), with a male preponderance (male:female ratio 3:1–10:1); females with CSCR tend to be older. No obvious racial association has been found.[4] Bennett (1955) reported on a series of patients with central serous retinopathy that the majority had a “tense obsessional or inadequate personality” or experienced “worry or over- work.” He predicted a great influence of psychological factors and stated, “a great awakening of interest in the effects of stress on the organism acting through the nervous and endocrine systems.”[5] Systemic associations include endogenous hypercortisolism (Cushing syndrome), systemic hypertension, obstructive sleep apnea (OSA), use of psychopharmacologic medications, pregnancy, Helicobacter pylori infection, and renal dialysis. Use of systemic corticosteroids is found to be associated with CSC, but intraocular corticosteroids do not appear to be associated.[6]

Patients generally complain of unilateral blurring of sudden onset, metamorphopsia, micropsia, occasional paracentral scotoma, and mild dyschromatopsia. Visual acuity (VA) may range from 6/9 to 6/60, however, it rarely deteriorates below 6/18. It may improve with a low-strength convex lens to correct acquired hypermetropia. When acute, there is round or oval detachment of the sensory retina at the macula involving the fovea. On chronic presentation or recurrence, one or more depigmented RPE foci pigment epithelial detachments (small PEDs) of variable sizes may be visible within the neurosensory detachment. Also, in such cases, on fundus autofluorescence imaging, small patches of RPE atrophy and hyperplasia elsewhere in the posterior pole may be seen.[7] Prolonged detachment is associated with gradual photoreceptor and RPE degeneration. When fluid tracts downward in a gravity-dependent manner, a gravitational tract is seen on fundus fluorescein angiography and fundus auto fluorescence (FAF), which may seldom progress to bullous CSR. The optic disc should be examined to exclude a congenital pit. It spontaneously resolves within 3–6 months, with return to near-normal vision in about 80%. Recurrence is seen in up to 50%. Some patients (about 15%) follow a chronic course lasting more than 12 months.[8] Optical coherence tomography (OCT) shows an optically empty neurosensory elevation with or without one or more smaller RPE detachments. The punctate white reflector dots seen in the shaggy photoreceptor layer of retina are macrophages with fluorophores from phagocytized outer segments. Enhanced depth imaging OCT (EDI-OCT) shows thickening of the choroid.[9] Fundus fluorescein angiography shows an early hyperfluorescent spot, which gradually enlarges to an “ink blot” or sometimes a vertical column known as a “smokestack.” The dye will then gradually diffuse throughout the detached area. If there is an underlying PED, the dye will “pool” in that area. Multiple focal leaks or diffuse areas of leakage are evident in chronic or recurrent disease.[10] In indocyanine green angiography (ICGA), the early phase may show dilated or compromised choroidal vessels at the posterior pole and in the mid-stage, there are areas of hyperfluorescence due to choroidal hyperpermeability.[11] Chronic CSCR is often difficult to interpret, especially with areas of leakage on fluorescein angiography (FA). However, ICGA shows choroidal leakage and the presence of dilated choroidal vessels.[12]

Mere observation is sufficient in many cases. Treatment modalities, if any, can be associated with RPE tear formation, which can also occur spontaneously. Oral spironolactone (40 mg twice daily) results in faster resorption of subretinal fluid than no treatment in acute CSR. Corticosteroids should be discontinued if possible, particularly in chronic, recurrent, or severe cases. Subthreshold (micropulse) diode laser to RPE site of leakage has shown encouraging results with less retinal damage than conventional photocoagulation. Reduced dose photodynamic therapy (PDT) at 30%–50% of the dose used for choroidal neovascularization (CNV) with 50% light intensity typically yields good results in severe chronic cases, with a lower incidence of significant choroidal ischemia.[13] Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents may be tried with PDT. Some acute cases may benefit from agents like aspirin, beta-blockers, mifepristone, and eplerenone.[14]

The importance of mental health in overall well-being cannot be overemphasized. Globally, it is one of the major factors contributing to disability and is gradually progressing to be the number 1 cause of disability-adjusted life years (DALY). With regard to CSCR, Yannuzi (1986) reported personality traits (Type A) to be associated in the former's causation.[15] Since then, various other psychological factors have been implicated in the pathogenesis of CSCR – personality disorders, anxiety, stress, obsessive–compulsive disorders, and addiction (particularly smoking), to name a few. The association is two way; psychological factors play a role in both causality as well as consequence of the disease. Not only that, it has been reported to modulate the course and prognosis of CSCR as well.[16] Stress and psychiatric disorders contribute to the pathophysiology by many factors: they increase the cardiovascular risks, trigger epigenetic modifications, cause abnormality of the hypothalamic–pituitary–adrenal (HPA) axis, derange metabolic and immune profile, and alter homoeostasis.[17] Apart from these, use of psychotropic medications has been implicated as a risk factor for CSCR.[18] Also, erectile dysfunction (ED) and OSA have been strongly correlated with CSCR, and these diseases fall partly under psychiatric domain.[6]

Psychosomatic interrelationships with ophthalmology have been cited since the 1930s, and today, it is more crucial than ever.[19] CSCR is one of the ophthalmic diseases having a strong psychological etiology, and its management also involves treatment of stress and anxiety, and psychological well-being.[20] Despite that, studies on the psychiatric aspects of CSCR have been relatively scarce, particularly from our part of the globe, even though there is evidence of different outcomes of mental illnesses between the developed and developing nations.[21]

Hence, we undertook this study to look for prevalence and the association between CSCR and its psychiatric correlates, namely, Type A personality trait, depressive disorders, and anxiety disorders, in our population and also to compare the findings with other nonretinal ocular diseases.

Methods

This 24-month comparative cross-sectional study was undertaken at a tertiary care government hospital from July 2019 to June 2021 after obtaining permission from the institutional ethics committee. Purposive sampling was done; every adult patient coming to the ophthalmology out-patient department (OPD) of our institute on every three prespecified weekdays (Monday, Wednesday, and Friday), who was subsequently diagnosed with CSCR was included in our study.

Upon presenting to our OPD, these patients went through standard protocols of clinical history, physical examinations, and investigations. Particularly, they were tested for VA, contrast sensitivity, anterior segment examination with slit-lamp biomicroscope, posterior segment evaluation with 90 D biomicroscope, followed by 3 D OCT with macular scan, and digital fluorescein angiography (DFA). They were treated as per the existing protocol.

These patients, were then informed about our study in detail, and if they agreed to take part, valid consent was taken from them. The selection criterion was the presence of CSCR, and there were no exclusion criteria per se. Their demographic profile, relevant history (recurrent disease, chronic CSCR, bilateral involvement, family history, coronary artery disease (CAD), hypertension, smoking, use of steroids, history of psychiatric illness and/or medications, OSA, etc.), and ocular examination findings (VA in log of minimum angle of resolution [LogMAR], central macular thickness from OCT, etc.) were recorded in a semi-structured proforma. The total number of CSCR patients was 91.

A comparison group was chosen from the patients coming to our OPD, which constituted patients having nonretinal ocular pathology (refractive errors, corneal diseases, cataracts, etc.). Valid consent was obtained from them after explaining about the study. The comparison group was age and gender matched to the cases. Both groups had 91 patients each.

Then, both these groups were referred to the department of psychiatry for further evaluation after blinding (the psychiatrist did not know which patient belonged to which group). In the psychiatry department, they were first evaluated clinically (history and mental status examination) for any existing psychopathology. After that, all the subjects were scored on performance of rating scales.

The Framingham Type A scale (FTAS) is a well-established tool for determining Type A personality; it was derived from the landmark Framingham Heart Study. In this 10-item instrument, five questions are answered in a 4-point Likert scale fashion and the other half has a Yes/No type of answer. Various studies have reported various norms for the cut-off scores, which were further subject of criticality. Also, the normative values for our population were not available. As a result, we have used a simpler, less-controversial method similar to that of Yannuzzi. The first five item's responses were scored 0, 0.33, 0.67, and 1 as per the norm – higher scores correspond toward Type A personality trait and vice versa. The last five questions were scored 0 “No” and 1 for “Yes | responses, with a score of 1 pointing toward Type A trait. The cumulative scores were compared between both the groups, thus eliminating the need for a cut-off score.[22]

All the patients from both groups were evaluated for depression and anxiety symptoms. Both Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HDRS or HAM-D), which were given by Max Hamilton, are widely used tools. HAM-A is a 14-item and HDRS is a 17-item clinician-rated scale for assessing the severity of symptoms of anxiety and depression, respectively, with items being scored in a Likert-scale fashion; the total scores correspond to the level of severity of symptoms. A HAM-A score of <17 indicates mild severity, 18–24 indicates mild to moderate severity, 25–30 denotes moderate to severe, and >30 denotes very severe anxiety. Similarly, for HDRS, a score of 0–7 is normal, 8–13 indicates mild severity, 14–18 indicates moderate severity, 18–22 indicates severe, and 23 and above denotes very severe depression.[23] Clinical presence of major depression and anxiety disorders was also noted and treatment was provided.

The patients were referred back to their original department for management after providing psychological treatment and follow-up advice in relevant cases.

For maintaining uniformity (as dimness of vision was variable), all the questions in the rating scales (even the self-rated ones) were asked by the researcher, and responses were noted. The collected data from all of the participants were compiled and analyzed by appropriate statistical measure using Statistical Package for the Social Sciences (SPSS)-23.

Results

The mean age of CSCR patients was 38.54 ± 6.49 years and for the comparison group was 38.79 ± 7.78 years, with a range of 28–55 years for both. The two groups had 81 male and 10 female patients (as age and gender were matched). Table 1 shows the characteristics of the patients, whereas Table 2 shows characteristics of the comparison group.

Table 1.

Characteristics of the patients

CSCR patients (case group: n=91)
Age (in years)	38.54±6.49 (range: 28–55)
Characteristics	Number	Frequency
Gender
Male	81	89.0%
Female	10	11.0%
Religion
Hindu	46	50.5%
Muslim	39	42.9%
Christian	4	4.4%
Sikh	2	2.2%
Residence
Urban	44	48.4%
Rural	47	51.6%
Associated history
Family history of CSCR	3	3.3%
Coronary artery disease	21	23.1%
Hypertension	28	30.8%
Diabetes	30	33.0%
Smoking	45	49.5%
Alcohol use	25	27.5%
History of steroid use	18	19.8%
History of psychotropic medications	15	16.5%
Use of PDE-5 inhibitors	4	4.4%
Type of CSCR
Acute	77	84.6%
Chronic	14	15.4%
Bilateral	18	19.8%
Recurrent	21	23.1%
Comorbidities (diagnosed during evaluation)
Anxiety disorder	36	39.6%
Major depression	22	24.2%
Associated history
Coronary artery disease	27	29.7%
Hypertension	29	31.9%
Diabetes	35	38.5%
Smoking	29	31.9%
Alcohol use	20	22.0%
History of steroid use	25	27.5%
History of psychotropic medications	17	18.7%

CSCR=central serous chorioretinopathy, PDE-5=Phosphodiesterase type 5

Table 2.

Characteristics of the comparison group

Comparison group: non-chorioretinal ocular conditions (n=91)
Age (in years)	38.79±7.78 (range: 28–55)
Characteristics	Number	Frequency
Gender
Male	81	89.0%
Female	10	11.0%
Comorbidities (diagnosed during evaluation)
Anxiety disorder	10	11.0%
Major depression	2	2.2%
Nature of disease
Refractive error	41	45.1%
Corneal diseases	5	5.5%
Cataract	14	15.4%
Trauma	6	6.6%
Infections	11	12.1%
Glaucoma	14	15.4%
Associated history
Coronary artery disease	11	12.1%
Hypertension	14	15.4%
Diabetes	22	24.2%
Smoking	18	19.8%
Alcohol use	20	22.0%
History of steroid use	4	4.4%
History of psychotropic medications	8	8.8%

Table 3 shows the comparison between the CSCR and the non-chorioretinal diseases groups as per the mean scores of the patients obtained by psychometric tools using unpaired t-test.

Table 3.

Comparison between CSCR and non-chorioretinal diseases groups (n=91 for both the groups)

Scales	Scores (Mean±SD)		Statistic (t)	Significance (P)
	CSCR	Non-chorioretinal diseases
FTAS	5.25±1.06	4.73±1.42	2.783	0.006*
HAM-A	20.96±9.88	11.02±6.34	8.077	0.000*
HDRS	9.36±6.34	6.37±4.75	3.600	0.000*

*P-value significant at 0.05 level. CSCR=central serous chorioretinopathy, FTAS=Framingham Type A scale, HAM-A=Hamilton Anxiety Rating Scale, HDRS=Hamilton Depression Rating Scale, SD=standard deviation

Table 4 shows the results of Pearson correlation between different ocular parameters and rating scales among the CSCR patients; statistically significant results are marked with asterisks.

Table 4.

Correlation among scores in different scales among patients of the CSCR group (n=91)

Scales	Correlation	CMTa	VAb
FTAS	Pearson correlation	0.213*	0.211*
	Sig. (2-tailed)	0.043	0.044
HAM-A	Pearson correlation	0.263*	0.283**
	Sig. (2-tailed)	0.012	0.007
HDRS	Pearson correlation	0.297**	0.310**
	Sig. (2-tailed)	0.004	0.003

^aCMT measured in μm. ^bVA assessed with Snellen’s chart was converted to LogMAR. *Correlation is significant at the 0.05 level (2-tailed). **Correlation is significant at the 0.01 level (2-tailed). CMT=central macular thickness, CSCR=central serous chorioretinopathy, FTAS=Framingham Type A scale, HAM-A=Hamilton Anxiety Rating Scale, HDRS=Hamilton Depression Rating Scale, LogMAR=log of minimum angle of resolution, VA=visual acuity

The presence or absence of major depression and anxiety disorder in both the groups was compared using the Fisher exact test, and odds ratios (ORs) were also calculated. This is shown in Table 5.

Table 5.

Association with comorbidities (Fisher exact test and odds ratio)

CSCR versus non-chorioretinal diseases
	CSCR	Non-chorioretinal diseases	Z-statistic	Fisher exact test probability (P)	Odds ratio
Major depression			3.510	0.000*	14.18
Present	22	2
Absent	69	89
Anxiety disorder			4.192	0.000*	5.30
Present	36	10
Absent	55	81

*P-value significant at 0.05 level. CSCR=central serous chorioretinopathy

Table 6 shows the list of previous studies and their findings related to this topic.

Table 6.

Findings of similar previous studies

Researcher and year	Main findings
Yannuzzi (1986)[15]	Type-A personality trait associated with CSCR
Gelber et al. (1987)[24]	Vision loss in CSCR preceded by stressful psychological event
Spaide et al. (1996)[25]	Higher male:female ratio, greater age of CSCR patients, bilateral involvement in older patients
Conrad et al. (2000, 2007, 2014)[26,27,28]	Stress is an important contributing factor in CSCR
Fok et al. (2011)[16]	Patients with a history of psychiatric illness (adjustment disorder and depression) were associated with an increased risk of CSC recurrence
Bazzazi et al. (2015)[20]	Anxiety scores higher in CSCR patients, but do not vary with sex or recurrence
Daruich (2015)[6]	Mineralocorticoid receptor overactivation could link CSCR with psychological stress and other factors
Mansour et al. (2017)[29]	CSCR associated with Type A personality type
Chatziralli et al. (2017)[30]	CSCR associated with stressful personality
Kim et al. (2018)[31]	Association of CSCR with psychosocial factors was dependent on the phase and subtype of CSCR. Psychosocial factors were associated with active phase, and severity of depression was correlated with the size of the choroidal pathology in acute active CSCR
Tan et al. (2020)[32]	Retinal abnormalities seen in depression and other psychiatric disorders
Dudani et al. (2021)[33]	CSCR associated with depression, anxiety, and stressed personality
Gundlach et al. (2021)[34]	PTSD and anxiety associated with CSCR

CSCR=central serous chorioretinopathy, PTSD= Post-traumatic stress disorder

Discussion

Our study showed that CSCR was prevalent in the middle-aged population in their 40s, with a clear male preponderance (male:female ratio 8:1), and 60% of these patients had a white collar job, corroborating with earlier studies.[14,25] The best corrected VA (BCVA) tested at the time of presentation ranged from Snellen's 6/18 to 6/60, corresponding to LogMAR 0.48–1.00, with a mean of 0.72 ± 0.20 and a median value of 0.78, corroborating with earlier studies reporting moderate to severe visual loss in CSCR.[35] The central macular thickness (CMT) measured by OCT ranged from 325 to 556 μm, with a mean of 469.12 ± 67.21 μm.[36]

Among the CSCR patients, 3.3% had a positive family history of the same illness. CAD, hypertension, and diabetes were present in 23%, 31%, and 33% patients, respectively. Smoking habits were found in half of the CSCR patients. Various other risk factors as found in Table 1 have been reported diversely in other studies.[37,38]

We found that 85% patients had presented with acute-onset CSCR; only 15% had chronic CSCR. Also, 20% cases had bilateral presentation and 23% cases were recurrent. These frequencies were slightly lesser compared to a prevalence study done in our country, but the rates do vary from region to region.[38]

During psychiatric evaluation, 40% CSCR patients were found to be suffering from anxiety disorder and a quarter had major depression, compared to 11% and 2.2% prevalence of the same among those in the non-chorioretinal diseases group, respectively.

CSCR patients had statistically significant higher scores on tests for Type A personality as well as clinical anxiety and depression compared to patients with non-chorioretinal diseases. This association of CSCR and the said comorbidities is further confirmed by ORs shown in Table 5 – major depression has the highest OR of 14.18, followed by anxiety disorders (OR 5.30). This has been thoroughly pointed out in numerous studies across the globe.[20] Furthermore, when the scores of HDRS were correlated with those of CMT and VA, there was a strong statistical correlation (P values 0.004 and 0.003, respectively) between them. This further emphasizes the importance of depression in CSCR. The association among stress, anxiety, and depression has been amply described in literature.[17] Depression alters the normal physiology and plays an important role in the pathophysiology of CSCR via similar mechanisms implicated with anxiety states and stress (nonsuppression of the HPA axis, hypercortisolemia, corticotrophin releasing factor [CRF]-induced cytotoxicity, altered immune status, and inflammation).[39]

The scores of CMT and VA of the CSCR patients were correlated with those on FTAS and HAM-A. We found that FTAS and HAM-A scores positively correlated with CMT and VA. Psychiatric symptoms have been previously reported in studies to be associated with retinal pathologies not exclusive to CSCR.[32] Several studies have reported the associations of Type A personality and anxiety to be known risk factors for CSCR [OR 5.30 in Table 4], but this study shows that severity of anxiety further affects not only the visual loss, but also possibly the extent of subretinal fluid accumulation.[26]

In spite of our best efforts, some limitations were present in our study. The sample size was moderate, and the longitudinal course of the illness was not studied. One crucial confounder would be that the scores on psychometric tests might have been due to the presence of visual impairment which, for obvious reasons, very distressing to any individual; but this confounder is inevitable in studies where anxiety and depression are assessed face to face in patients with any disability.

Conclusion

Despite these shortcomings, our study was able to demonstrate the role of personality type, anxiety, and, particularly, depression in CSCR. Depression has already been associated with many disease entities like ischemic heart disease, diabetes, hypertension, and thyroid dysfunction, to name a few.[40] It would thus be fair to recognize its importance in CSCR also. To conclude, we would like to mention that recognition of psychiatric disorders in ophthalmology and vice versa would ultimately lead to betterment of care. Psycho-ophthalmology would certainly be hoped to flourish in the near future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.