Compliance in glaucoma management: Challenges decoded - A review

24 h IOP curve

Because IOP changes during the 24-h period, single-day IOP assessments during office hours can only give limited information on treatment effectiveness. A diurnal tension curve, which includes numerous IOP readings at different periods throughout office hours, is the most popular approach for measuring glaucoma patients’ IOP. Mansouri et al. proposed that night-time measurements in the habitual posture are critical for IOP profile accuracy because they more closely correlate with an individual’s circadian cycle and natural body placement. This intervention demonstrates the influence of glaucoma medication adherence by outlining an IOP profile over a 24-h period, and it may be employed when inpatient and outpatient IOP values differ significantly. By exposing a typical fluctuation of IOP over the circadian cycle, this method may also help better understand the true IOP-lowering effect of treatment, improving adherence and treatment outcomes as well as opening up the possibility of individualised disease management.^[36]

Questionnaires

By asking patients if they know why they are taking their medicine, whether they have encountered any adverse effects from their eye drops, or what their motivations are for taking the prescription, questionnaires are a powerful tool that can reveal poor adherence to glaucoma treatments.^[11] In an article based on a patient interview, Lacey et al. sought to discover the motivating elements for using glaucoma medication. The interview covered topics including therapy, memory and habit of using the eye drops, problems taking the medicine, reasons for using the eye drops, and suggestions from the patients for improving future adherence. The authors observed adherence hurdles that were directly related to participant experiences, such as a lack of patient teaching and a desire for better education delivery that focused on drop application techniques and the negative effects of ineffective adherence. To increase their confidence in adherence, patients also suggested getting regular feedback regarding drop effectiveness. The adherence questions also showed that many patients had issues with drop application techniques, forgetting drops, or practical challenges like going without treatment for brief periods when their medication ran out, finding a convenient spot to apply the drops during the day, or not having enough time to administer them while at work.^[26]

With longer GAPS between visits, this strategy is more prone to mistakes. Results are susceptible to patient distortion, which frequently results in an overestimation of patient adherence.^[11] Several studies compared the reliability of self-reported measurements in glaucoma patients to more reliable ones, including electronic monitoring devices or pharmacy records, and found that they tended to overvalue the dosages given and the timing (adherence to glaucoma medication).^[35] Sayner et al., therefore, pushed the notion that ophthalmologists may need to take a cautious and comforting approach when speaking with patients to uncover difficulties with delivering drops on time, making them feel comfortable and subsequently aiding in the detection of poor adherence.^[11,35]

Rate of refilling prescriptions

In a medical system that employs electronic medical records and a closed pharmacy system, the rate of prescription refills, as an indirect technique of evaluating adherence, is an accurate measure of adherence as long as the refills are measured from time to time. Pharmacy records can give the doctor unbiased data on prescription refill rates, which can be used to determine how well a patient is following their glaucoma treatment plan. In addition, the patient’s replies to direct inquiries or questionnaires can be used to corroborate the records.^[11]However, just because a prescription is filled at the pharmacy does not ensure the patient will use the drug. To measure adherence in a cohort of glaucoma patients, researchers from the GAPS examined extensive pharmacy databases. The study brought to light various drawbacks of utilising pharmacy information to assess medication adherence for glaucoma. First, research demonstrated that patients may have wrongly assumed the second prescription should have replaced the first or that a refill of the first medication was delayed because the patient had a significant supply of it. In addition, it will be assumed that patients who obtain samples have low adherence. The lack of the samples provided by the ophthalmologist in the claims data suggests that it is impossible to quantify them and to identify the patients who could have side effects or other adherence challenges while taking the sample medicine.^[37]

Electronic medication monitoring

Electronic monitoring using a Medication Event Monitoring System, which can record and stamp the time of opening bottles and administering drops, is the most precise indirect means of identifying how patients utilise glaucoma medication.^[11] According to Kass et al., who conducted their study, patients who were interviewed reported a compliance rate of 90%, doctors predicted a compliance rate of 79% and electronic eye drop monitoring revealed a compliance rate of 75%.^[38]

It is common practice in other medical specialties to compile drug consumption data automatically (dosing history). It offers a complete description of medication adherence and makes it obvious when to initiate, execute, and stop taking a drug.

Electronic monitoring does have certain technological drawbacks, though, and patients’ knowledge that they are being watched may cause them to act differently than they would if they were just being observed: this is known as ‘the Hawthorne effect.’ On the one hand, this suggests that monitoring eye drop consumption is more challenging than measuring pill usage, and on the other hand, changing the eye drop container is expensive and challenging to do.^[39] They are also impracticable for monitoring adherence in clinical settings due to their high cost, which is a significant downside. These gadgets also fail to record whether the patient dispensed the drop into the conjunctival sac. Because of this, patients may open the bottle but not apply the drop properly or may squander numerous drops at once.^[11]

According to reports based on pharmacy data, prostaglandins have better rates of adherence and persistence (the length of time spent continuing therapy with the first prescribed prescription) than other medications. The development of a way to assess adherence by electronic monitoring between once-daily hypotensive treatments and other glaucoma medications that require more frequent dosing would be of considerable interest because there has not been a direct comparison utilising electronic monitoring.^[5] The Hawthorne effect, which occurs when patients are aware they are being monitored and modify their conduct as a result of being seen, is another drawback of electronic glaucoma medication monitoring.^[40] Electronic monitoring has the drawback that it can only be used with particular prescriptions. For instance, the Travatan Dosing Aid (DA; Alcon, Fort Worth, TX) can only provide data on the usage of travoprost because no other glaucoma medication bottle fits inside of it. To release the drug, a handle on the device must be fully depressed after inserting a bottle of travoprost. The event’s date and time are recorded on a built-in memory chip, and the data are later transferred to a computer.^[41]

In 196 patients over a period of 3 months, the Travatan Dosing Aid Study evaluated patients’ adherence and patterns of use of topical once-daily treatment with travoprost (for glaucoma). The study found that 45% of patients did not use their drops at least 75% of the time, indicating low compliance even though they were aware that they were being watched and receiving free medication. In addition, patients overestimated their medicine use compared to what they took, and those who took <50% of the recommended dosages exhibited far higher dose intake shortly following the office visit and right before the follow-up appointment at 3 months.

It was determined that either improved communication skills, better technological monitoring, or both were required to identify the patients who were less adherent.^[5] When Robin et al. used electronic monitoring to assess patient adherence to once-daily prostaglandin analogues as the sole form of ocular hypotensive therapy, they also compared the prostaglandin analogues to adjunctive medications. They concluded that more complex dosing regimens lead to poorer adherence, while once-daily medications in complex dosing regimens were found to have good adherence.^[33]

The research we uncovered; however, supported the notion that electronic monitoring of glaucoma therapy offers the most precise information on medication adherence and an extremely thorough understanding of patterns of medication-taking behaviour.

Patient Education

Patient education is the first step in increasing medication adherence (glaucoma drugs are only effective if patients utilise them).^[42] Education should include both verbal and written instructions, as well as colour-coded medication regimens, illustrations, and modified material for persons with impaired vision or literacy. The ophthalmologist must ensure that the patient understands the treatment regimen, and didactic lectures on appropriate drop application are necessary for this reason. These presentations should be repeated on a regular basis to ensure that the patient continues to employ the proper method. Patients should be informed on proper dose schedules, waste minimisation, and a clear explanation about how non-adherence to prescribed medicines can cause irreversible eyesight loss. Furthermore, reviewing medicine administration at each appointment helps maintain adherence by giving the physician information about the patient’s awareness of his treatment schedule. Patients should also be encouraged to engage in their treatment by maintaining a daily record of drug dose. With the availability of cell phones and internet communication, there are several potential avenues worth exploring to improve compliance using continuous reminder systems, such as those available on the phone (alarms, applications, text messages, and phone calls) or e-mails, to reduce forgetfulness.^[5,11]

Adherence of glaucoma patients is affected by situational and environmental variables since there are individual particular everyday events that make it difficult for individuals to remain compliant.^[43] It is critical to include a regimen that is simple to apply and easy to integrate into patients’ everyday lives. Despite having greater access to technological devices, treatment adherence has been proven to be poorer in younger age groups, frequently due to a busy lifestyle and employment responsibilities. Involving patients might thus take the form of urging them to incorporate their therapy into their regular activities. They can, for example, bring a bottle of drops to work or keep the drops near their bed, desk, or toothbrush. Furthermore, physicians may recommend enlisting the assistance of a helpful family member to aid with administering drops or reminding the patient to take drops.^[11] Even though young patients can manage internet information without the assistance of a physician, it does not appear to increase their adherence. There is evidence that adherence to glaucoma therapy is poorer in the 1^st year of diagnosis, and enhanced illness information may help patients stick with their medication.^[44]

Carpenter et al. investigated whether patient–physician communication promotes glaucoma patients’ medication self-efficacy and concluded that it can improve treatment adherence. As a result, doctors should take a patient-centred approach, taking the time to educate patients about their chronic condition and analyse their perspectives on treatment. According to the study, patients who ask more medication-related inquiries may have less confidence in their ability to stick to their glaucoma regimen and should be given extra help to overcome adherence difficulties.^[45] A study of 279 glaucoma patients who were video-recorded during their visit found that while educating patients about their condition occurred during approximately two-thirds of the visits, it was not significantly associated with whether patients took their doses on time after the visit. Instead, the only provider communication component that was substantially linked with adherence was instruction about eye drop administration. As a result, health providers must devote more effort to educating people about glaucoma.^[16] Observational research assessed an intervention programme that included teaching and a reminder system. In individuals whose baseline drop-taking rate was <75%, adherence to glaucoma treatment rose from 54% to 73%. The improvement was rapid and lasted for 3 months. The study found that utilising a diverse strategy increased the likelihood that the treatments would influence medication usage. The study was unable to establish which components of the intervention were most useful or which techniques could be adopted in clinical practice. Furthermore, the researchers discovered that there was a larger improvement in adherence among white patients and those with the lowest baseline adherence. Furthermore, the increase in adherence did not correspond with the amount of IOP evaluated in the clinic. To that aim, the study’s findings revealed that many non-adherent patients had good IOP during routine visits, so IOP measurement was deemed insufficient for evaluating adherence. Finally, it was stated that more study is needed to differentiate poor adherence in patients to minimise overmedication and to discover which parts of the adherence programme were most beneficial.^[5]

Optimise treatment

Simpler drug regimens should be considered in interventions aimed at increasing patients’ medication-related self-efficacy. Many studies have emphasised the need for simplifying patients’ medication regimens, which reveals that patients on more complex regimens were less likely to take their doses on time and were less likely to take the right number of recommended doses each day.^[14,16] Furthermore, individuals using once-daily medications on a complicated dose schedule were shown to have high adherence.^[14] It has been demonstrated that 3 and 4 times-a-day dosing, as well as inappropriate dosage spacing, increase non-compliance versus twice-a-day dosing; hence, the fewest number of drugs, infused with the least frequency, improve patient satisfaction and dosing convenience.^[46]

Shirai et al. compared the adherence of Japanese patients to fixed and unfixed combination eye drops and discovered that patients on fixed combination treatment had stronger adherence to their regimens. The key explanation might be that patients prefer a fixed mix. One drop of an ophthalmic solution is easier and faster to apply than two drops from separate bottles of medicine, with no waiting period between the two types of drops, and with equivalent or potentially greater efficacies in daily practice compared to unfixed-combination therapy. Furthermore, it is more favourable due to lower preservative exposure and hence a lower chance of developing ocular surface illnesses.^[47]

When patients require several drugs and dosages, possible options include synchronising administration with daily activities such as meals or cleaning teeth, as well as employing a medication schedule.^[42] Furthermore, when patients are informed of the potential side effects of a medicine, their compliance improves, and patient education should include a discussion of treatment options. According to research, patients taking preservative-free medicine have reduced rates of non-adherence (12.5%), and moving to preservative-free therapy may be especially beneficial for adherence with self-administered treatments.^[48]

Medication costs

Several studies have found that most glaucoma clinic visits do not include a discussion of prescription costs. Providers frequently do not inquire about their patients’ glaucoma drug costs, and as a result, patients who are experiencing financial difficulties with their treatment regimen seldom discuss it with their doctors. As a result, ophthalmologists may consider discussing drug costs during office visits to enhance adherence from the start of glaucoma therapy.^[49] A viable approach to alleviating the financial and physical hardship of medicine acquisition would be to supply free eye drops to patients, either by handing out free samples on occasion or by making the medication reimbursable.

Finally, on a 60-year time horizon, a cost-utility analysis assessed the societal costs of optimal versus poor adherence to glaucoma medications among people over 40 years of age with newly diagnosed glaucoma and demonstrated that adherence to glaucoma medications resulted in improved quality of life for a relatively low increase in lifetime healthcare costs.^[50]

Drug instillation aids

The proper instillation of eye drops is one part of adherence; yet, it is well known that many patients struggle with this chore. Inadequate targeting can lead to undertreatment and disease progression. On the contrary, repeated attempts might result in over-medication and over-treatment, resulting in greater drug expenditures and an increased risk of adverse effects.^[51] Contact of the eye drop container tip with the eye or skin causes a variety of outcomes ranging from contamination to injuries.^[52-55] Difficulties may include putting their drops inside their eyes, extending their neck, limiting excessive drop leakage, avoiding contamination of the bottle tip, and producing sufficient power to release a drop from the bottle. Instillation aids are devices designed to help overcome one or more of these obstacles. Instillation aids may be especially beneficial to elderly people and those with musculoskeletal problems.^[39]

Self-measurement of IOP

One of the most significant diagnostic procedures for determining the success of glaucoma treatment is the IOP assessment. A single measurement of IOP during office visits, on the other hand, does not disclose the full amount of intraocular hypertension or the daily changes in IOP. Astakhov et al. evaluated the convenience of patients self-monitoring their IOP at home using Icare^® HOME tonometers and found an increase in treatment adherence. The study found that autonomous patient engagement in the diagnostic process increases illness knowledge and understanding, as well as the necessity of following the doctor’s advice.^[56]

Chen et al. compared the reliability of readings taken by patients utilising iCare tonometers to Goldmann applanation tonometry measurements. The study found that patients preferred the approach of self-measuring their IOP at home since it saves time for both the patients and the glaucoma care professionals. Patients responded favourably to the iCare One self-tonometer since they could view the data promptly. Furthermore, patients expressed a desire for this strategy to be used in future glaucoma monitoring. As a result, home IOP monitoring offers essential information for glaucoma therapy and may enhance treatment adherence.^[57]