Depression and Severity of Glaucoma Among Older Adults in Urban and Suburban Areas

Précis: Depression increases with severity of visual field defect in older adults with primary open-angle glaucoma (POAG). Purpose: This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults. Materials and Methods: Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is ≥8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors. Results: Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity. Conclusion: Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma.

G laucoma is a chronic disease characterized by progressive damage to the optic nerve, gradual visual field constriction, and ultimately, blindness. 1 Visual field defects initially involve the peripheral field but eventually affect the central vision. 2 Ageing is the major risk factor for glaucoma. [3][4][5] Patients with glaucoma require lifelong treatment and carry a risk of serious visual impairment. Patients with glaucoma are reported to often suffer from poor quality of life and psychosocial impairment. [6][7][8] It is reported that a third of individuals with visual impairment display clinically significant depressive symptoms. 9 The prevalence of depression among patients with glaucoma ranges between 9% and 30%. [10][11][12][13] In patients with glaucoma, the natural course of the disease, fear of future loss of vision and potential side effects of treatment, contribute to depression. 14,15 According to the study conducted by Skalicky and Goldberg, 16 the prevalence of depression increases with the severity of glaucoma among the older adults.
Depression significantly reduces adherence to treatment. [17][18][19] Adherence will be further affected by cognitive impairment in older adults, development of side effects of treatment and lack of initiative to make the effort to adhere to treatment. 17,20,21 Therefore, early identification of depression among patients with glaucoma is important in preventing the progression of the disease and eventual blindness.
There are several available depression scales such as the Zung Rating Scale, Hamilton depression scale, and Becks Depression Inventory. [22][23][24] However, these questionnaires have not been validated as suitable for the older adult population. 22,23,25 The Geriatric Depression Scale (GDS) was developed specifically to discriminate depressive symptoms from among the general characteristics of the older adult population. It focuses on the psychosocial aspects of depression. 26 Furthermore, the GDS has a sensitivity of 92% and a specificity of 89%. 27 The prevalence of depression differs according to population and is closely related to socioculture and beliefs. 28,29 There has been no study reporting depression among Malaysian patients with primary open-angle glaucoma (POAG). This study aimed to determine the prevalence of depression among older adult Malaysian patients with POAG as well as the relationship between depression and the severity of POAG.

MATERIALS AND METHODS
A cross-sectional study was conducted involving 360 patients with POAG recruited from 2 tertiary centers in Malaysia: Hospital Selayang, Selangor, and Hospital Universiti Sains Malaysia, Kelantan. This study was carried out between July 2014 and February 2016. Ethical approval was provided by the Research and Ethical Committee, School of Medical Sciences, Universiti Sains Malaysia (USM/JEPeM/ 131032). This study was conducted according to the tenets of the Declaration of Helsinki for human research. All recruited patients gave their written informed consent before their inclusion as participants in this study.
Three hundred and sixty patients with POAG were recruited from 2 ophthalmology clinics in Malaysia: 276 from Hospital Selayang, Selangor (urban) and 84 from Hospital Universiti Sains Malaysia, Kelantan (suburban). Patients with POAG were selected from glaucoma clinics during their follow-ups. POAG was diagnosed based on progressive visual field loss and optic nerve cupping, often associated with an elevated intraocular pressure with visually open anterior chamber angles by gonioscopy, without underlying secondary ocular disease. 30 Convenience sampling was adopted in this study. The sample size was calculated using Power and Sample Size Calculation (PS) software version 3.0.10 based on a study conducted by Skalicky and Goldberg 16 with a power of 0.8, and the smallest significant difference of depression according to severity was 10%.
Older adults are individuals who are above 60 years old. 31 Only patients who fit this criterion were selected to participate in this study. Those who were on medical therapy or a combination of medical and surgical therapy (cataract and/or trabeculectomy) for glaucoma were included. However, the exclusion criteria were as follows: (i) patients with a history of intraocular surgery other than cataract surgery and trabeculectomy; (ii) those who had undergone cataract surgery or trabeculectomy <3 months from the recruitment period; (iii) those experiencing media opacity such as cataract of modified Lens Opacities Classification System II (mLOCS II) of grade 1 or higher; (iv) those with coexisting retinal disease (eg, age-related macular degeneration, proliferative diabetic retinopathy, retinitis pigmentosa, retinal detachment, and pigmentary retinopathy); and (v) those with optic nerve abnormality other than glaucomatous changes (eg, optic atrophy, anterior ischemic optic neuropathy, and tilted disc). Patients with memory loss, pre-existing Alzheimer disease or psychiatric disorders such as a known depression or bipolar disorder were also excluded.
Demographic data related to age, race, sex, history of systemic disease, living arrangements and education levels were acquired from the patients and documented. A thorough ocular examination which included visual acuity, anterior segment, and posterior segment examination, gonioscopy, and intraocular pressure using Goldmann applanation tonometry (Haag-Streit International, Switzerland) was conducted. All recruited patients were subjected to visual field assessment using SITA Standard 24-2 Humphrey Visual Field Analyzer (HVF) (Carl Zeiss, USA). Only those who were able to provide 2 consecutive reliable and reproducible HVF within 6 months of the recruitment period were included. A reliable visual field was based on the following: percentage of fixation loses of <20%, false positive response of <33% and false negative response of <33%. Three hundred and seventy-two patients fulfilled the criteria but 12 patients who failed to provide reliable and reproducible visual field were excluded from the analysis. The final analysis was performed on 360 patients.
On the basis of the HVF, patients with POAG were stratified according to severity of POAG using the Modified Advanced Glaucoma Intervention Study (AGIS) scoring. 32 The score was acquired from the total deviation plot of HVF 24-2. The scoring of HVF was done by 2 investigators (Y.A. and A.T.L.-S.) who were blinded to the modified Geriatrics Depression Scale 14 (mGDS-14) questionnaire scores, and scoring was done separately. The final score was based on the average of the scoring of the 2 blinded investigators. The eye with the better AGIS score was selected for statistical analysis. Severity was divided into 4 stages: 1 to 5 for mild, 6 to 11 for moderate, 12 to 17 for severe, and 18 to 20 for end stage of glaucoma. 32 The primary investigator (S.T.) conducted one-on-one interviews using the previously translated and validated Bahasa Malaysia version of the mGDS-14 questionnaire. The primary investigator (S.T.) explained each question to the patient and only after proper understanding of the question did the patient answer, and these were then recorded. If difficulty comprehending the question arose, a relative or caregiver present helped explain the question to the patient. Only 2 patients required some explanation by their relative. The mGDS-14 questionnaire consists of 14 questions. It has a yes/no answer and is scored 1 or 0 for each question. Patients with a score of 8 and above are considered depressed.

Statistical Analysis
All relevant data such as age, race, sex, history of systemic disease, living conditions and education levels from the case record form and mGDS-14 questionnaire scores were analyzed using Statistical Package for the Social Sciences (SPSS) for Mac Version 22. All data were rechecked to avoid incorrect data entry and missing data.
Demographic data was analyzed using descriptive statistics. The Pearson χ 2 test was used to compare between the severity of POAG based on demographic details, ocular characteristics, and scores from the mGDS-14 questionnaire. One-way analysis of variance was used to compare the mean depression score of the mGDS-14 questionnaire with the different glaucoma severity scores. The mGDS-14 has a yes/no answer and is scored 1 or 0. Multifactorial analysis of variance was used to compare the mean depression score between the different severity of glaucoma scores after adjustments for systemic disease, living conditions and vision. The post hoc Bonferroni test was conducted to determine which pairing of severity of POAG displayed a significant difference. A P-value of <0.05 was considered statistically significant.

RESULTS
Three hundred and sixty patients with POAG participated in this study with a slightly higher female preponderance (54.2%) ( Table 1). Most of the participants were no longer working (88.9%) and were living with their families (68.1%). Most of them had received primary and secondary education but 30 of 360 participants (8.3%) had not receive any formal education (Table 1).
On the basis of the AGIS score of HVF of the better eye of the participants, 64 (17.8%) were classified as having mild, 93 (25.8%) moderate, 115 (31.9%) severe, and 88 (24.4%) end stage of POAG (Table 2). There was a higher number of patients with POAG with severe visual defects. Worsening severity of visual field loss was associated with poorer vision (< 6/60) and greater likelihood of living with the family (Table 2).
There was equally a significant number of patients with POAG who were depressed as the severity of POAG increased (Table 3). Patients with POAG with a more advanced visual field defect of the better eye reported being unsatisfied with life, abandoning their hobbies, not being in the best of spirits, being afraid of something bad that may happen, and fearing memory loss. Many of them also reported feeling emptiness, boredom, helplessness, hopelessness, worthlessness, and impression of inferiority (Table 3). They also felt less grateful to be alive, unhappy most of the time and experienced a lack of energy (Table 3).
Depression was diagnosed based on the scores from the mGDS-14 questionnaire. There was a significant increase of the mean scores of the mGDS-14 questionnaire according to the severity of HVF of the better eye in patients with POAG (Table 4). There was also a significant difference in the scores of the mGDS-14 questionnaire between pairing of severity of patients with POAG except between the mild and moderate, as well as the severe and end stage after adjustment for confounding factors of living conditions, visual acuity, and the presence of systemic comorbidities (Table 5).

DISCUSSION
Depression is the most common psychiatric disorder among older adults and is usually undetected. 33,34 The mGDS-14 questionnaire was used in this study to assess depression among older adult patients with POAG. This questionnaire was translated and validated from the modified Geriatric Depression Score (which originally consists of 15 questions) to suit the local older adult population as it focuses on psychosocial aspects of depression rather than somatic complaints. 26,35 During the validation process, one question was left out ("do you prefer to stay at home, rather than going out and doing new things") because of its poor discriminatory value as our local population is relatively introverted. 35 On the basis of the validation study, the mGDS-14 was able to discriminate depressive symptoms from the general characteristics of the older adults population. 35 Fifty-nine (16%) of the patients with POAG in this study were diagnosed as facing depression based on their scores. This percentage is similar to other studies of depression in older adult patients with glaucoma. 10,12,13,16 Prevalence of depression among glaucoma patients has been studied in other populations as well: 10.9% in Japan, 12.2% in the United States, 16.4% in China, 11.4% in Australia, 13.5% in Turkey, and 16.4% in China. 10,12,13,16,36,37 POAG is a progressive disease. 2 Progression is associated with slow constriction of the visual field and an inability to perform many visual related activities. These disabilities may affect the psychosocial aspect of older adults. The current study found that higher mGDS-14 scores were associated with worse visual field defects in patients with POAG. Patients with end stage POAG in our study expressed feeling of emptiness (30.7%), helplessness (28.4%), worthlessness (29.5%), and hopelessness (27.3%). A study by Skalicky and Goldberg found an increasing trend of depression with increasing age. It was more significant in patients in their 70s. 16 Patients with depressive POAG in this study were not stratified according to age, but almost half of the study population were aged 70 and above.
On the contrary, a study by Wilson et al 15 found no association between the severity of glaucoma and depression. In their study, glaucoma suspects without any visual field changes were included. This may have led to an inaccurate association between depression and visual field constriction. As this study excluded glaucoma suspects, the analysis of depression better reflects the target population, which is older adult patients with glaucoma. In our study, 30.7% of patients with end stage POAG did not feel grateful to be alive compared with 3.1% of patients with mild POAG. Those with end stage severity of POAG will have more fear of completely losing their vision, hence increasing the risk of depression and suicidal tendencies. Suicidal risk among older adults with visual impairment increased by nearly 50% (hazard ratio: 1.5; 95% confidence interval: 0.90-2.49) and indirectly through associated systemic disease by 5% (hazard ratio: 1.05; 95% confidence interval: 1.02-1.08). 38 Men with visual impairment were at a higher risk to commit suicide based on a retrospective study on postmortem suicidal reports. 39 Depression and anxiety were found in patients with progressive/near total loss of vision. 39 This was attributed to the persistence of false hopes frequently seen among patients with glaucoma with residual light perception or fluctuations in vision. 39 A similar finding was also reported in patients with progressive diabetic retinopathy. Those with progressive blindness, displayed psychiatric symptoms such as suicidal ideations. 40 This could be because patients with diabetic retinopathy with total blindness were forced to accept that their disease was irreversible. POAG also causes irreversible blindness, similar with diabetic retinopathy.
Those with progressive diabetic retinopathy usually have poorer control of their diabetes and other associated complications, which contributes to more disabilities. 41 Systemic disease is another risk factor for depression in older adults. 42 In this study, a high percentage of patients with POAG were diagnosed with systemic comorbidities especially diabetes and systemic hypertension. However, after including the presence of systemic comorbidities in the multivariate analysis, there was still a significant association between the mGDS-14 score and the severity of POAG.
Unfortunately, the specific treatment for systemic comorbidities was not included in this study. Systemic beta-blocker is one of the commonest medication prescribed to patients with systemic hypertension in Malaysia. 43 Similarly, there is potential systemic effect of topical beta-blockers used as treatment of glaucoma. 44 There is reported potential association between systemic beta-blockers and depression in older adults based on case report. 45,46 However, there was no significant association based on case control study, prospective cohort study and randomized controlled trials with larger sample size. 47,48 Because of these conflicting evidences, we believed that systemic and ophthalmic beta-blockers probably do not cause depression and that the risk of developing depression while on beta-blockers is probably no different than that with other drugs. 44,47,48 Systemic disabilities such as using a wheelchair or walking frame were also not documented in this study.
There was a significant difference in all pairing of severity of POAG except for those between the mildmoderate and the severe-end stage. This is most likely because of small differences in visual field defects between the early stage (mild-moderate) and the most advanced stage (severe-end stage) using the AGIS score. 32 Depression in older adults is also affected by living conditions and socioeconomic status. 49,50 This study found that dependency was higher as the visual field defect progressed. The ratio of those staying alone and with family reversed from mild severity (2:1) to end stage (1:2) in the current study. Living alone was found to be closely linked with depression among older adults in many studies. [49][50][51][52][53][54] However, living with families also does not guarantee protection against depression. 50 Staying with second and third generation of family members may cause different psychosocial stress. 50  Socioeconomic factors also play a role, especially on the financial support and the living environment. 49 Majority of them were no longer working (88.9%). However, their retirement and/or pensioner scheme and household income were not included in this study. 55,56 Household income is important among those staying with their extended family. Financial security to a certain extend reduce the risk of depression among older adults. 55,56 Financial support is essential for treatment and transportation to hospital appointment. In addition, the financial need differs between those living in rural and urban area. 49,51 In this study, patients with POAG were recruited from 2 different states in Malaysia to represent urban and suburban areas. Hospital Selayang covers a densely populated urban area, while Hospital Universiti Sains Malaysia covers a less densely populated suburban area. 57 Although there were patients from rural areas under the follow-up of both clinics, the representation is not well-defined, and the comparison is not possible in this study. Therefore, this study may only partly reflect the true evaluation of depression among patients with POAG in the Malaysian population.
This study was a cross-sectional study. Therefore, it only provides a snapshot of the situation. Patients answered the questionnaire based on their emotion or understanding at the time the questionnaire was administered. There might have been a differing response, had a different time been chosen. For future studies, questionnaires could be administered on 2 different occasions. In addition, this study was a questionnaire-based study. Therefore, it is subject to recall bias. Patients, specifically the older adults, might not be able to remember their daily activities or feel uncomfortable answering certain questions. Consequently, they might not have divulged all the relevant information. In contrast, they might have overstated their emotions. However, it is difficult to eliminate these biases in a questionnaire-based study.
Moreover, this study focused on depression among older adults aged 60 years and above with POAG. Although this study might have been able to capture depression among older adults with POAG, it fails to determine depression among patients with POAG in general. As POAG is a disease diagnosed after the age of 40 years, future studies need to be done taking this age factor into consideration. Aging process has been implicated as the potential link between POAG and dementia. 58 While depression may co-occur with dementia. 59 Thus, it is important to assess the mental status of the recruited patients to rule out dementia in this study. The absent of any mental status assessment is the weakness of the present study. Although, patients with memory loss, preexisting Alzheimer disease and known case of psychiatric disorder were already excluded but the mild or early dementia might have been missed. In contrast, there are evidences of the sensitivity and specificity of GDS in detection of depression in older adults even with mild to moderate dementia and among those with psychiatric illness. 60,61 In addition, face-to-face interview, to a certain degree, may detect the cognitive impairment of patients with POAG.
On the basis of the finding from the present study, physicians especially, ophthalmologists, psychiatrists, and gerontologists should possess a higher index of suspicion of depression in treating older adults with POAG, especially those with systemic comorbidities. Addressing this problem may improve the quality of life of older adults and prevent unwanted sequelae, including suicide.

CONCLUSIONS
Depression among older adults is often difficult to detect in the presence of other comorbidities and physiological changes of ageing. Constricted visual field because of chronic ocular disease such as glaucoma may increase dependency and reduce quality of life, which may lead to undetected depression. Therefore, the detection of depression is important among older adults with glaucoma to improve the quality of life and adherence to treatment.