Compliance of Glaucoma Patients to Ocular Hypotensive Medications Among the Saudi Population

Introduction

Glaucoma is a common eye disease that may lead to irreversible blindness if left undiagnosed and untreated. ¹ Glaucoma has been classified into: primary and secondary open-angle or angle-closure glaucoma according to cause and angle status. Secondary forms of glaucoma are usually developed as a consequence of various ocular or systemic diseases. The frequency of patients presenting with glaucoma is relatively high among the Saudi population. ² Anti-glaucoma medications are considered as the first line of management among glaucoma patients including those who require surgical interventions. ³ Adherence to life-time therapies is essential to prevent progression of glaucoma and minimize its invasive effects on vision. ⁴ In contrast, nonadherence to anti-glaucoma therapy is one of the leading causes of blindness in glaucoma patients.^5–7

In this study, we looked at the pattern of compliance to treatment among glaucoma patients presenting to King Abdulaziz University Hospital (KAUH), Riyadh, Saudi Arabia, the associated factors, and the potential barriers to compliance to glaucoma medications. Such factors can be categorized into a number of domains including patient-related factors, provider-related factors, in addition to environment and culture-related factors. ⁸ The literature is vast in describing patient attitudes to glaucoma treatment where several studies report an average estimate of nonadherence to anti-glaucoma therapy as 40%.^9–11 Meanwhile, there is increasing evidence that poor adherence to anti-glaucoma therapy results in an increased risk for visual impairment and blindness.^12–14 Nevertheless, adherence to glaucoma treatment is quite variable across different communities and tricky to detect and/or to evaluate. ¹⁵ It is therefore hard to attribute poor control of intraocular pressure (IOP) either to the lack of therapeutic effect or patients' incompliance to treatment.

In this study, we aimed to assess the potential risk factors for poor compliance and to detect the causes of noncompliance to chronic glaucoma treatment.

Methods

This study adopts a cross-sectional study design, in which, the target sample size was 100 glaucoma patients recruited among the reviewers one of the specialized outpatient glaucoma clinics in KAUH, Riyadh. Ethical approval was obtained from the Institutional Research and Ethics Board at College of Medicine, King Saud University where the study adhered to the tenets of the Declaration of Helsinki for research involving humans. Patients were recruited using a block cluster sampling of the first 5 patients presenting to the one of the morning glaucoma clinics. Patients were asked whether they would participate in a research that would benefit glaucoma patients in Saudi Arabia. Inclusion criteria included having no mental or physical conditions that would disable the recruited subject of participating in the study.

Upon approval to participate, patients were asked to give a written formal consent after a brief explanation on the topic and the different questionnaire domains. In case of refusal, the next patient was targeted to replace the refusing patient. An ophthalmology resident (co-investigator) was asked to interview the recruited patient after being clinically assessed by the principal investigator (E.A.O.). The interview questionnaire consisted of 4 major sections designed to assess the following: demographic characteristics, type and pattern of utilization of the prescribed treatment, patient's attitude and practice towards treatment, and indicators on compliance. Meanwhile, clinical glaucoma indices of such patient (as assessed in the last visit) were retrieved from the medical record and linked to the gathered information via the questionnaire in a specific data base. Noncompliant patient to glaucoma treatment modality was defined as: “a patient who is not exactly following the treatment regimen as prescribed by the treating physician.” ¹⁶ This was quantitatively tackled within our questionnaire as follows: 2 questions were contextualized as a domain to indicate compliance. Inability to use the prescribed medication exactly as prescribed and/or missing at least 2 eye drops per week was termed as noncompliance. Answering either one or both questions positively would indicate whether or not a patient is compliant.

Data were collected and stored in a spreadsheet using Microsoft Excel 2010^® software. Data management and coding were both done in Excel. Data were analyzed using SPSS^® version 20.0 (IBM, Inc., Chicago, IL).

Descriptive analysis was done, where categorical variables were presented as frequencies and percentages and continuous variables as mean and standard deviation (±SD). Inferential analysis was done where chi-squared test was used to detect the association between compliance and different characteristics (Fisher Exact test whenever indicated). Mann–Whitney U test was used to investigate any significant difference per compliance in terms of continuous variables. Cronbach's alpha was used to investigate internal consistency between compliance domain questions. Confidence interval level was set to 95% where a corresponding P-value threshold was identified as 0.05. Accordingly, P-values <0.05 were interpreted as denoting statistical significance.

Results

The recruited sample comprised of 105 subjects, where 93 (88.6%) glaucoma patients with complete compliance data were finally included in the analysis. Patients were in the mean (±SD) age of 58.7 (±16.0) years, median (62), and range [14–85], where the number of males, 51 (54.8%) has slightly exceeded that of the females, 42 (45.2%). Among those 93 patients, 61 (65.6%) were bilateral and 32 (34.4%) were unilateral. The majority of patients were Saudis 89 (95.7%) residing in Riyadh 81 (87.1%). Investigations for clinical indices showed that chronic angle closure glaucoma was the most common diagnosis (42; 45.2%) followed by primary open angle glaucoma; 27 (29%). Most of the patients had undergone previous surgical interventions; 69 (74.2%) involving trabeculectomy; 26 (28%), peripheral iridotomy (20; 21.5%); deep sclerectomy; 3 (3.2%), multiple; 4 (4.3%) and combined glaucoma surgeries; 3 (3.2%). Meanwhile, a considerable number of patients, 70 (75.3%), were found to be on (nonglaucomatous) systemic medications. Demographic and clinical indices at recruitment are demonstrated in Table 1.

Assessment of glaucoma specific indices at recruitment showed that our sample more or less represents typical chronic glaucoma patients with an average (±SD) IOP of 17.2 (±6.1) on a mean number of medication of 1.8 (±0.8) and with relatively severe mean cup to disc ratio (CDR) of 0.7 (±0.2). Details of glaucoma indices at recruitment are presented in Table 2.

Self-reported indicators of drug administration revealed that 86 (92.5%) of the patients started their treatment course immediately after diagnosis. The average number of eye drops utilized was 1.7 (±0.8), where only 15 (16.1%) of the respondents were able to recognize the drug names. The majority of patients were using the eye drops by themselves; 77 (82.6%), while other 22 (23.7%) needed help in the application of eye drops who were commonly assessed by a family member; 18 (81.8%). Meanwhile, 23 (24.7%) of the reporters mentioned that they usually face difficulty in applying their eye drops for several reasons while, 26 (28%) reported that they suffer some side effects from eye drops utilization, the most common of which was burning (10; 10.8%).

The average duration of reviewing the hospital was 6.5 (±3.8) months, where 43 (46.2%) of the respondents knew that glaucoma is a chronic disease, and 27 (29%) believe that it can be cured, while 41 (44.1%) are aware of glaucoma compilations despite the fact that 87 (93.5%) of them reported that the ophthalmologist provided them with detailed explanation and gave them enough time for questions. Additionally, a relatively high number of patients were satisfied with their treatment; 86 (92.5), where around one-third of them (31; 33%) was getting such treatment for free through the insurance coverage system. Patients' affirmative responses to awareness, practices, difficulties, and satisfaction regarding prescribed glaucoma eye drops are displayed in Table 3.

Overall, noncompliance was detected in 18 (19.4%) of the recruited patients. Cronbach's alpha test showed that there is an acceptable level of agreement within the compliance domain questions (0.64). Testing for factors associated with noncompliance to glaucoma treatment; there was a trend showing that older patients, male patients, those at presentation, with higher CDR, and self administering patients were more likely to be noncompliant to glaucoma treatment, however, none of these factors have reached the statistical significance level. Patients with other systematic medications and those not getting their medications through insurance were also more likely to be noncompliant. Interestingly, there existed a statistically significant difference (P = 0.005) between patients under lifelong medications and the ones who are not under lifelong medications, where those with temporary medications were more likely to be noncompliant; 15 (83.3%) (Table 4).

Discussion

Compliance of patients to anti-glaucoma medications is known to be affected by environmental, regional, and provider factors. ⁸ Conventional treatment of glaucoma usually begins with the use of a topical β-blocker or a topical prostaglandin analog. Second-line drugs of choice may include α-agonists and topical carbonic anhydrase inhibitors. Parasympathomimetic agents, most commonly pilocarpine, are considered as third-line treatment options. Systemic carbonic anhydrase inhibitors are also used in case of an acute rise of IOP. ¹⁷

Several studies have shown an average estimate of nonadherence to glaucoma medications of around 40%.^9–11 In our study, the percent of noncompliance is estimated at 19.4%, which is relatively lower than what have been reported. This can be explained by the periodically repeated glaucoma awareness programs in our institute. This explanation may be supported by the self reported patient satisfaction, which is around 92.5%.

The only statistically significant risk factor associated with noncompliance in our study is attributed to whether or not the medication is a lifetime treatment. This factor is highly associated with patient's perspective to glaucoma and its medications. Masoud et al. ¹⁸ reported that lack of knowledge and misunderstanding were the main factors associated with having a noncompliance rate >57%. Similarly, a recent study by Khandekar et al. reported an even higher nonadherence rate among Oman glaucoma Arab patients (up to 75.2%) where the factors related to knowledge and awareness to glaucoma and its potential complications were the major risk factors for noncompliance. ¹⁹ Meanwhile, other previous studies have provided more insight into the factors associated with nonadherence to anti-glaucoma medications. Lacey et al. ²⁰ have reported multiple obstacles to adherence including poor education, lack of motivation, forgetfulness, difficulties in drop application, in addition to some other practical issues, along with specific individual and age differences. Additionally, Friedman et al. ²¹ have found that doctor–patient communications and health-related beliefs of patients and patient education, risk of vision loss, cost, traveling, side effects, and other socio-demographic factors would significantly affect patient adherence to anti-glaucoma treatment.

Several studies have shown that less awareness to health issues is associated with poor adherence.^22–24 Meanwhile, Gelb et al. ²⁵ demonstrated that lower adherence to medications may be associated with certain physician beliefs and behaviors. Moreover, Tsai et al. ⁴ described and categorized common obstacles to medication adherence (ie, compliance) of patients with glaucoma by using patient interviews. Tsai et al. have reported the widest range ever of barriers where they listed 71 distinct obstacles to compliance, which they further categorized into 4 major domains: situational/environmental factors (35 of 71 situations; 49%), medication regimen (23 of 71; 32%), patient factors (11 of 71; 16%), and provider factors (2 of 71; 3%).

Overall, the detected variation among different studies may suggest that adherence to glaucoma treatment is a complex behavior with multifactorial nature where internal reactions may also take place among such multiple contributing factors.

In our study, there was a trend showing that older patients, being male, lower IOP at presentation, higher CDR, and self administering patients are more likely to yield noncompliance attitude to glaucoma treatment. In consistency with our study, several studies reported higher prevalence rates of noncompliance among the elderly, mainly due to improper installation of eye drops and other age-related medical illnesses, such as dementia and arthritis. ²⁶

On the other hand, our study shows that 23 patients (24.7%) usually face difficulty in applying their eye drops for several reasons. Consistent with our results, several studies have shown that glaucoma patients frequently have difficulty with drop instillation. For example, in a study to evaluate eye drop instillation, Gupta et al. stated that “only 6 patients (8.57%) were able to correctly instill the eye drops.” ²² This remark highlights the importance of monitoring patient's utilization pattern of medication. Although patients tend to self report proper utilization, in an objective evaluation study, Stone et al. reported that under direct observation, patients who use topical ocular hypotensive agents performed relatively poorly when instilling a single eye drops into the eye. ²⁷ Therefore, good communication between physicians and patients is a major factor in increasing patients' compliance to anti-glaucoma medications. ²⁸ Despite the fact that physicians usually train their patients on how to instill their eye drops in the proper way and inform them about perfect timing between drops, they should also do a kind of follow-up reorientation on these procedures. Additionally, patients should be educated in terms of medication side effects, contamination issues, and how to overcome any undesired emerging issue.

Although we spent a considerable time in preparation, our study has some limitations in terms of data assessment. As the compliance questionnaire has been administered by our residents in the outpatient clinic, patients may have tended to self report better compliance. Furthermore, IOP was a poor surrogate for adherence because patients commonly increase their adherence in the day before visiting their eye care provider. ²⁹

In conclusion, noncompliance to anti-glaucoma medication is commonly seen in our practice. The causes of noncompliance are multifactorial and interacting. However, doctor–patient communication may be the best approach to increase such compliance.