Evaluation of antiglaucoma drug treatment awareness and patient-reported medication adherence: Determinants of glaucoma managementRK Tripathi1, A Shah1, SV Jalgaonkar1, S Kerkar2
1 Department of Pharmacology and Therapeutics, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Ophthalmology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_905_22
Source of Support: None, Conflict of Interest: None
Keywords: Antiglaucoma drugs, eye drop, POAG, prescription variability, questionnaire, timolol
Primary open angle glaucoma (POAG) is a common, chronic ophthalmologic degenerative disorder in adults. According to the World Health Organization (WHO), POAG is the second leading cause of avoidable permanent blindness in the world. India also emerges as the second-largest country, with a prevalence of glaucoma being reported as 11.9 million, which varies region-wise, with rates ranging from 2.3 to 4.7% and contributing to 0.6 million disability-adjusted life years.
Patients with glaucoma most often require lifelong medical treatment and follow-up care to preserve vision. A plethora of antiglaucoma drugs such as prostaglandin analogues, beta-blockers, carbonic anhydrase inhibitors, α-2 adrenergic agonists, and cholinergic drugs are available and are used in varying combinations depending on the patient's symptoms and treatment response, thus leading to differences in the prescribing practices.
When drug treatments are prescribed for a prolonged duration, it is important for the patient to be aware of the need for this treatment, the exact way to take the drugs, and their possible adverse effects. Adequate knowledge about medication has been recognized as one of the determinants of treatment compliance. Low awareness about the disease and its treatment is coupled with decreased drug adherence and is a probable factor contributing to a poor disease outcome. There are questionnaire-based studies to study awareness about glaucoma. A study conducted by Krishnaiah et al. in South India revealed that only 18/7775 (0.33%) were healthy individuals, while another study conducted by Prabhu et al., stated that only 4.8% of patients were aware about glaucoma., Another study conducted by Tenkir et al. in Ethiopia revealed that only 8/340 (2.3%) patients were aware about glaucoma. Thus, it is evident that the disease awareness is poor.
Several studies have been conducted to analyze prescription patterns, treatment adherence, and disease awareness, but none have been conducted to assess the patient's awareness about pharmacological treatment. Hence, the present study was planned to evaluate drug treatment awareness, patient-perceived drug adherence, and prescription patterns in POAG patients.
This was a cross-sectional, single-center, questionnaire-based study conducted in the ophthalmology OPD of a tertiary care hospital from April 2020 to November 2021. The study was initiated after obtaining permission from the Institutional Ethics Committee (EC/44/2019) and registration with the Clinical Trials Registry of India at www.ctri.nic.in (CTRI/2020/03/024217). This study was conducted in compliance with the National Ethical Guidelines for Biomedical and Health Research Involving Human Patients and the ICH E6 Good Clinical Practice guidelines.
Patients of either gender aged 40–70 years with a confirmed diagnosis of POAG, having records of POAG medications for >3 months, and providing written informed consent were included in the study. Patients admitted to the emergency department, critically ill patients, those having visual acuity ≤3/60 and patients suffering from neurodegenerative/mental illness were excluded. It was a universal sampling technique, hence all patients satisfying the selection criteria in the given time period were included.
The following demographic and disease details were noted: age, gender, education, and socio-economic status according to the modified Kuppuswamy scale, POAG disease/treatment duration, and presence of comorbid conditions. Prescription details such as drug generic/brand name, class of antiglaucoma drug, dosage form, dose, frequency, and duration of therapy from the current and immediate previous (within the last 3 months) prescription (if it differed from the current prescription) were also recorded. Prescriptions were evaluated for completeness and were further assessed for deficiency in terms of dose, dosage form, frequency, and duration.
The patients were subsequently administered a pre-validated (10 expert Content Validity Index i.e. CVI = 0.82) drug treatment awareness (14 items) questionnaire. The responses were recorded as 'Yes' (scored as 1) or 'No' (scored as 0), accounting for a total score of 14. The items were grouped under 3 domains viz Domain I: awareness about drug regimen (4 items, total score 4), Domain II: awareness about eye drop usage (6 items, total score 6), [Table 1], and Domain III: awareness about adverse drug reactions (ADR) (4 items, total score 4) [Table 2].
The patients were then administered a pre-validated (10 experts, CVI = 0.78) self-reported medication adherence 9-item questionnaire, which had dichotomous responses as 'Yes' (scored as 1) or 'No' (scored as 0), accounting for a total score of 9 [Table 3]. All the patients were then further requested to perform eye drop instillations, exactly in the same way as they performed this instillation at their home, using the dummy eye drop bottle containing water in a simulated setting. This eye drop instillation was performed on patients in a separate room with restricted access in the OPD. The steps of eye drop instillation were ticked off by the study coordinator using a 9-step pre-validated (10 experts CVI = 0.86, standardized in 6 patients) checklist., Each step performed by the patient, if correct, was scored as 1; if incorrect, it was scored as 0, thus the total score was 9 [Table 4].
The data was entered into Microsoft Excel, and patient demographic characteristics, POAG disease/treatment duration, and presence of co-morbidities were analyzed using descriptive statistics. The response toward each item in the drug treatment awareness questionnaire/medication adherence questionnaire was analyzed as a percentage of patients who responded Yes or No/item. Total and domain-wise treatment awareness scores, perceived adherence scores, eye drop instillation performance scores were calculated. A correlation analysis was done between the participant's demographic characteristics (i.e., age, socioeconomic status, and education status), duration of treatment, and their drug treatment awareness/adherence scores. The correlation coefficient was calculated using Spearman's correlation test, and a P value <0.05 was considered statistically significant.
Prescription pattern data were analyzed according to WHO drug utilization indicators: prescribed daily dose/defined daily dose (PDD/DDD) ratio, average number of drugs/class prescribed per encounter, and average number of eye drops of each drug class. In addition, % of prescriptions with individual/fixed dose combinations (FDCs), % of drugs prescribed by generic/brand name, % of complete/incomplete prescriptions, % of drugs from the WHO essential drugs list (2019), and National List of Essential Medicine (NLEM), India (2015) were also calculated.
A total of 180 glaucoma patients receiving treatment were enrolled in the study. The mean age of patients was 57.58 ± 7.93 years, and there were 107/180 (59%) males and 73/180 (41%) female patients. The majority of the patients belonged to the upper lower class (66/180, 36.66%), followed by the lower middle class (54/180, 30%), the lower class (45/180, 25%), and the least from the upper middle class (15/180, 8.4%). Regarding the literacy level, most of the patients were having high school education (83/180, 46.2%), followed by intermediate education (44/180, 24.4%), and graduates were 26/180 (14.4%), while illiterate patients were 27/180, 15%). The majority of POAG patients were taking antiglaucoma treatment for >4–6 years (68/180, 37.77%). Comorbid conditions were encountered in 147/180 (82%) patients, with hypertension being the most common comorbidity recorded (62/180, 34.4%), followed by diabetes mellitus (44/180, 24.44%).
Drug treatment awareness and perceived adherence scores
The mean drug treatment awareness score was 8.18 ± 3.30 (correct response scored as 1 for each item, total correct responses given by the patient adding up as the total score for each patient), and 135 (75%) patients scored more than 50%, that is, ≥7 out of 14. The mean Domain I, Domain II, and Domain III scores were 2.05 ± 0.91, 4.4 ± 1.37, and 1.72 ± 0.94, respectively. All patients could enumerate the number of drugs prescribed, dosage form, frequency, and duration of each medicine accurately, but only 3 (1.66%) patients said they were aware of the names of the medicines written in their prescriptions, and 135/180 (75%) patients had awareness regarding adverse effects, but hardly anyone could state the preventive measures. The domain-wise responses for the drug treatment awareness questionnaire are depicted in [Table 1] and [Table 2]. There was no statistical correlation between the drug treatment awareness score with patient's age (r = -0.15 P = 0.33), socio-economic status (r = 0.005 P = 0.42), education status (r = 0.06 P = 0.37), and duration of POAG medications (r = 0.045 P = 0.27).
Total 159/180 (83.33%) patients scored >50% (i.e., >5 out of 9) with a mean score of 6.30 ± 1.70 (correct response scored as 1 for each item, total correct responses given by the patient adding up as the total score for each patient) in the medication treatment adherence questionnaire. Item-wise responses of the patient-self-reported medication adherence questionnaire are mentioned in [Table 3]. There was no statistical correlation between the patient-perceived adherence score with patient's age (r = 0.1 P = 0.22), socio-economic status (r = 0.005 P = 0.94), education status (r = 0.017 P = 0.81), and duration of POAG medications (r = 0.1 P = 0.14). A statistically significant correlation (r = 0.66 P = 0.0001) between drug treatment adherence score and drug treatment awareness score was detected [refer [Figure 1]].
Eye drop instillation patient performance in a simulated setting
The mean eye drop instillation performance score was 7.18 ± 1.20 (correct step on checklist scored as 1 and total score 9). Patients demonstrated most of the steps accurately, but only 13/180 (7.22%) patients demonstrated the step of applying pressure over the inner corner of the eyes next to his/her nose after instillation of eye drops. The result of the eye drop instillation performance in a simulated setting has been summarized in [Table 4].
POAG prescriptions (n = 200) were collected from 180 patients. The majority of the patients received the same prescription that was prescribed in the last 3 months, except for 20 patients who received a changed prescription (wherein data from both old and new prescriptions were captured). Thus, 200 prescriptions containing 306 drugs were analyzed. Beta blockers 184/200 (92%) was the highest prescribed class followed by carbonic anhydrous inhibitors 75/200 (37.5%); alpha-2 adrenergic blockers 34/200 (17%), prostaglandin analogs 11/200 (5.5%), cholinergic agonist 1/200 (0.5%), and Rho kinase inhibitor 1/200 (0.5%). Timolol (168/200, 84%) was the most commonly prescribed antiglaucoma drug followed by acetazolamide (51/200, 25.5%) and brimonidine (34/200, 17%). 100 (50%) prescriptions were prescribed as monotherapy with timolol 79/200 (39.5%) being the most frequently prescribed drug, followed by brimonidine 10/200 (5%), betaxolol 10/200 (5%), and latanoprost 1/200 (0.5%). Combination therapy was prescribed in 100 prescriptions either as FDC alone (33/200), 2 concurrent drugs (39/200), or FDC with an additional antiglaucoma drug (28/200). FDC were prescribed in 33/200 (16.5%) prescriptions, among which timolol + dorzolamide 21/200 (10.5%) was the most common FDC prescribed followed by timolol + bimatoprost 7/200 (3.5%) and timolol + brimonidine 5/200 (2.5%). Among the dual concurrent drug therapy, timolol + acetazolamide 33/200 (16.5%), followed by betaxolol + acetazolamide 6/200 (3%) was the most frequent prescribed combination. The most common triple drug combination was timolol + brimonidine (FDC) + acetazolamide 21/200 (10.5%), followed by timolol + brimonidine (FDC) + dorzolamide 7 (3.5%). There were 98/200 (49%) prescriptions with additional drugs, and the most common drug was potassium supplement 30 (15%).
The average number of drugs per encounter was 2.53 ± 0.61. Prescriptions were complete in terms of dose, dosage form, dose frequency, and prescriber designation with signature. The strength of the prescribed eye drop was not mentioned in 183/200 prescriptions. The PDD/DDD ratio of all the prescribed antiglaucoma drugs was 1, indicating there was no under or overdosing.
It was seen that the following antiglaucoma drugs – dorzolamide, brimonidine, bimatoprost, and travoprost – were not mentioned in both the WHO (2019) and NLEM (2015) lists, while pilocarpine and latanoprost were not mentioned in the NLEM list. Only timolol was freely available in the hospital pharmacy. The results of the WHO prescribing indicators have been summarized in [Table 5].
Patient awareness about his/her drug treatment, that is treatment literacy, is an important contributing factor toward treatment adherence, and subsequently, better disease control, especially for chronic non-communicable diseases. In this study, we have attempted to evaluate patient-reported treatment adherence and awareness toward drug treatment in POAG patients
In our study, 59.44% were males and 40.56% were females. A systematic review conducted by Tham et al. also revealed similar results, in which male preponderance was more as compared to females. In our study, the mean age of patients was 57.58 ± 7.93 years similar to the study conducted by Ramakrishnan R et al., in rural South India, which reported mean age as 53.78 ± 10.72. In the current study, hypertension (147/180) was the most common comorbidity. A meta-analysis conducted by Bae et al. revealed that individuals with hypertension have an approximately 1.2-fold higher risk of developing POAG than individuals without hypertension. Similar findings were noted in the Blue Mountains Eye Study conducted by Mitchell et al.
Among 180 patients, 75% patients scored more than 50% in the drug treatment awareness questionnaire, and the mean score was 8.18 ± 3.30, thus documenting satisfactory awareness. Patients were aware of drug dose, frequency, and duration accurately. In our study, as patients belonged to low socioeconomic status and had a low level of literacy, awareness about a proper drug regimen is commendable. This is because at all the visits, ophthalmologist counseled the patients adequately in terms of their treatment regimen and future complications of glaucoma. In addition to this, at the study site, along with ophthalmology OPD, there was special dedicated glaucoma clinic where all the glaucoma patients were evaluated by glaucoma expert and received counseling about drug therapy. So even in the scenario of heavy patient load (as the site was Govt. hospital) and treating ophthalmologists having time constraints, such dedicated reinforcement about the therapy offered by glaucoma specialists led to good treatment awareness among these patients.
A disappointing fact was that only 1.66% of patients were able to tell the correct names of their medication. This could be due to the fact that they found it difficult to recall, read, or pronounce the medication names written on the prescription. In order to avoid this, ophthalmologists must ask the patients to reiterate the medication names. It is important for the patients to know about the names of their medications to avoid dispensing errors at the level of the pharmacist, as they can themselves verify the same. Similarly, awareness regarding all the possible ADR of the drugs prescribed was poor, though patients were aware about 1 or 2 adverse effects. ADR awareness is vital, as it will help patients recognize and report ADR to treating ophthalmologist. Hence, patient awareness programs on drug treatment with a special focus on ADR detection and reporting must be developed and implemented. In our study, we found that the patient's awareness score did not correlate with factors like age, education/socioeconomic status, and disease duration. This is because all the patients were repeatedly counseled about drug treatment and the complications of developing blindness by the treating ophthalmologist and glaucoma specialist visiting the OPD.
In this study, we found that 88.33% of patients were able to score more than 50%, with a mean score of 6.30 ± 1.70 on the self-reported medication adherence questionnaire. Thus, we can see that the patient perception about adherence is quite satisfactory. A study assessing adherence to antiglaucoma medication in POAG patients (n = 181) done in Canada by Djafari et al. revealed that the adherence to anti-glaucoma medications was 88.3%. The authors stated that the follow-up in a specialized clinic may have contributed to patients being more aware of the severity of their disease, thus explaining their better adherence.
Better self-reported adherence could probably be due to the fact that POAG patients may fear becoming blind if they do not adhere to drug therapy. In addition, proper counseling by the prescribing ophthalmologist and reinforcement by a glaucoma specialist were the main reasons for the good perception about drug adherence seen in our patients. A similar finding was noted in the study conducted by Lacey et al., which stated that the fear of blindness appeared to be the universal motivation for adherence in glaucoma patients.
Persistence and correct topical drug administration are the key elements for successful topical pharmacotherapy in glaucoma patients. Inability to instill the eye drops correctly often results in wastage of medication, while overmedication can lead to systemic absorption and ADR. Moreover, eye dropper contact can also lead to corneal abrasions and ulcerations. Hence, in this study, we focused not only on treatment awareness but also asked patients to perform eye drop instillation in a simulated setting. It was seen that the majority of the patients were able to correctly demonstrate all the steps of eye drop instillation except that they (93%) did not perform the step of applying pressure over the inner canthus of the eye to prevent systemic absorption of drugs. While the failure of demonstrating this step signifies the fact that patients may have less understanding of the undesirable effects of drugs and their possible prevention methods, which was evident from treatment awareness questionnaire too.
A study conducted by Tatham et al. revealed 54.1% had poor eye drop instillation technique, while 81.2% of patients could not recall ever being shown how to instill their drops. A study conducted by Gupta R et al., showed that only 6/70 POAG patients were able to correctly instill the eye drops while Rajurkar et al. stated that only 54/151 (35.76%) patients performed improper drop administration technique. Reinforcement of the correct technique should occur at future visits, with a periodic observation of the patient instilling the eye drops in presence of a healthcare professional. Further reinforcing (illustrative pictures/videos displayed in the OPD) and retraining approaches will supplement to motivate the patient to adhere to the medication regimen.
There are few studies about POAG prescription patterns in western India;,, hence, we conducted the study wherein the average number of drugs was 2.53. In a study done by Advani et al., in western India, the average number of antiglaucoma drugs per prescription was 1.36, and 54% of drugs were prescribed with their generic name. A prescription pattern study (n = 1400) conducted by Dhali et al. in western India revealed that only 34.3% prescriptions had generic names of drugs. As per the WHO's good prescribing practices, the ophthalmologists must ideally prescribe the drugs by generic name rather than the brand names.
Antiglaucoma drugs such as dorzolamide, brimonidine, bimatoprost, travoprost, pilocarpine, and latanoprost were not available on the NLEM list, as prostaglandin analogs and brimonidine are costly drugs. Alternatively, drugs with similar efficacy, for example timolol and betaxolol are mentioned in the NLEM, as any country-specific list of essential medicines will incorporate cost-effective, good-quality, accessible medicines. The majority of prescriptions were incomplete in terms of the strength of eye drops. Timolol was available in a single strength in the hospital pharmacy, hence the ophthalmologist did not mention the strength while writing prescriptions, but ideally strength/concentration of the drug prescribed topically needs to be mentioned in the prescriptions as multiple strengths of the drug are available in the market and patients may go to other pharmacies too.
The most common class of drugs prescribed was beta blockers (92%), with timolol being the most common drug prescribed. Similar findings were seen in studies done in Udaipur by Yadav et al. (n = 297), and Mahajan et al. in northern India which revealed that the most commonly prescribed drug was timolol (82.22% and 66%, respectively). A study conducted in Australia and New Zealand by Carroll et al. revealed that ophthalmologists favored beta-blockers as their first-line agent because of cost and familiarity. In the current study too, the majority of the patients belonged to the lower socioeconomic status, and timolol was the only freely available drug in the hospital pharmacy, so accounting for a higher number of prescriptions containing timolol. Though prostaglandin analogs are the first-line drug class for POAG but in our study, only 5.5% of prescriptions contained prostaglandin analogs, as they were expensive and not available in hospital pharmacy. In our study, the most common FDC prescribed was timolol and dorzolamide combination, as this combination significantly improves retinal hemodynamics in POAG. A similar finding was observed in the study conducted by Mahajan et al., in which timolol + dorzolamide (10.5%) was the most commonly prescribed FDC.
The study did have limitations as we evaluated perception about drug adherence while actual compliance of the patients was not calculated. This was a questionnaire-based study, so the possibility of recall bias cannot be denied. In addition, it was convenience-based duration-based sampling, and patients were not randomly selected.
Glaucoma patients did have adequate awareness about their drug regimen, but awareness regarding specifying names of the drugs and prevention of adverse effects was poor; hence the need for patient reinforcement education programs on these aspects is essential. Patient reported that medication adherence and performance of the eye drop instillation technique was good. The most common drug prescribed was timolol for glaucoma patients in our setting.
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Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]