A strong association between poor patient health literacy and non-adherence has been previously demonstrated (i.e., missed appointments, missed eye drops, less refills over a 6 month period;
p < 0.001) [
37,
38]. Thus researchers have conducted studies to not only establish areas where practical patient education can improve adherence, such as eye drop instillation, but also to explore broader reasons why patients are non-adherent, such as health beliefs. Gupta and colleagues’ proof of concept study on patient eye drop instillation technique found that only 6 out of 70 patients (8.57%) had correct eye drop instillation technique (i.e., one drop into the conjunctival sac without bottle tip contact) [
39]. These results indicate that even patients who “take” their ocular hypotensives may not achieve full therapeutic effect because of incorrect instillation technique [
39]. Kang and colleagues wanted to assess the relationship between health literacy and successful glaucoma drop administration with veterans receiving care at a Veterans Affair Eye Clinic with the diagnosis of open-angle glaucoma who self-endorsed poor drop adherence [
40]. Participants underwent a health literacy evaluation using the Rapid Estimate of Adult Literacy in Medicine (REALM) as well as a qualitative assessment of eye drop administration technique using three different criteria: (1) the drop was instilled in the eye, (2) only one drop was dispensed, and (3) the bottle was not potentially contaminated [
40]. A proportion of 78% of the participants read at a high school level (HSL) or higher and 22% read at less than HSL [
40]. A greater proportion of participants who read at HSL or higher successfully instilled the drop in the eye compared with those reading at less than HSL (90.6% versus 75.0%;
p = 0.02) [
40]. Criterion 2 and 3, only one drop dispensed and no contamination, were found to not be associated with health literacy level [
40]. The researchers believe poor health literacy may be associated with decreased successful eye drop instillation in patients with glaucoma and propose screening for and considering health literacy in developing interventions to improve glaucoma self-management [
40].
A study by Newman-Casey and colleagues, examined the patient perspective on why patients with glaucoma lose vision. A total of 56 patients with glaucoma, 25 with good vision and 31 with poor vision, were interviewed in 9 focus groups and asked about barriers to glaucoma management [
30]. A common theme that both patients with good and poor vision agreed upon is that due to glaucoma “being asymptomatic,” it is easy to “not prioritize [glaucoma];” however, many patients believed that adhering to medication gave them a sense of “control” over glaucoma and vision loss [
30]. The most common barrier to controlling glaucoma that participants identified was the physician–patient relationship, meaning specifically how much time the patient perceived the physician spent with them, elicited their concerns, and actively listened [
30]. The second most common barrier was knowledge about glaucoma, with the authors stating this barrier is complex and difficult to assess credibility as some participants preferred to learn about glaucoma through their physician while others preferred to learn through multiple sources (i.e., newspaper, magazine) [
30]. The third most commonly cited barrier was having an unsupportive spouse or family to remind the patient to take their drops, as glaucoma is invisible to others as well [
30].
Friedman and colleagues contended that adherence to treatment depends on the patients’ beliefs about the disease and the benefits of treatment [
29]. This study sought to examine how adherence, based on administrative claims data, is impacted by a patient’s health-related beliefs and experience with ophthalmologists [
29]. Adherence was measured with the medication possession ratio (MPR): the ratio of days of supply medication dispensed divided by the days between pharmacy fulfillments, with higher MPR indicating higher adherence [
29]. Eight variables were associated with a lower MPR (lower adherence): doctor-dependent learning about glaucoma, not believing that vision loss is a risk of non-adherence, medication cost, adherence difficulty while traveling, not experiencing adverse effects such as stinging and burning, being non-white, receiving medication samples, and not receiving a phone call visit reminder [
29]. Patients were classified as doctor-dependent learners if all of their knowledge about glaucoma came from their doctor [
29]. If a patient gained most of their knowledge from a doctor they were classified as a collaborative learner. Conversely, independent learners were patients who learned little to nothing from their doctor [
29].
The authors found that doctor-dependent learners had poorer adherence than the collaborative and independent learners (
p < 0.05) [
29]. Additionally, patients who reported receiving phone call visit reminders (with or without postcard reminders) had better adherence to drops than those who received only postcards, received no reminder, or could not recall [
29]. Overwhelmingly, 86% (258/300) of interviewed patients did believe that not taking their medications would result in vision loss [
29]. On the other hand, the 14% (42/300) of patients who did not believe the sentiment above reported receiving less information, fewer answers to questions, and no demonstration on proper use of eye drops [
29]. This culminated in lower MPR (i.e., lower adherence) and the belief that glaucoma would not result in complete vision loss, optic nerve damage, or increased IOP [
29]. Interestingly, and perhaps counterintuitively, patients who reported stinging and burning had a higher MPR, potentially because these sensations indicated some medication effect [
29]. The GAPS data suggest that a doctor-dependent learning style is associated with less concern about the future effects of glaucoma and the risks of not taking medication [
29]. Friedman and colleagues recommend that physicians implement an ask-tell-ask dialog communication strategy detailed below [
29]. The thought behind employing this communication strategy is not only to improve education for doctor dependent learners, but it may help physicians overcome some of the health belief-related barriers to adherence aforementioned [
29]. All in all, the GAPS study found reasons for non-adherence are multifactorial, including being a doctor-dependent learner, being non-white, and not having a telephone appointment reminder system at their doctor’s office [
29]. Technology advances in physician–patient communication could be similarly employed in the future including automated reminder text messages and emails. Those patients with the poorest understanding of the consequences of non-adherence had physicians who had not taught them basic information about glaucoma such as how to instill eye drops [
29]. Efforts for glaucoma physicians to improve communication and education for their patients would likely have an important impact on improving medication non-adherence. Leveraging ancillary staff such as medical assistants and nurses for basic education, as well as the possibility of group classes, can be further explored as educational avenues.
Interventions and Potential Solutions for Patient Education
Several studies have focused on implementing interventions or multiple simultaneous interventions targeting patient education and measuring their effects on adherence.
Kosoko and colleagues evaluated patients from an urban area and found that after giving written instructions, the ability to accurately answer questions about glaucoma and eye drop management improved both in patients who did and did not graduate high school (23.36 ± 30.8% to 88% and 8.46 ± 21.7% to 96% for participants who did and did not graduate high school, respectively) [
41].
One randomized controlled study with a patient population of veterans assessed the number of days without medicine (DWM) after intervention with a glaucoma education video geared toward a patient’s literacy level (i.e., adequate, marginal, or inadequate) [
42]. Overall, they found the number of DWM was similar for the intervention and control groups over 6 months (63 ± 198 versus 60 ± 198;
p = 0.708) [
42]. While a glaucoma education video alone may not be an effective intervention to improve adherence, the authors suggested that those with lower health literacy may most benefit from educational efforts in the future because this group reported lower self-reported satisfaction with care compared with patients with higher health literacy levels (
p = 0.002) [
42].
Miller and colleagues investigated the effect of their new program—Support, Educate, Empower (SEE)—on medication adherence rates [
43]. The SEE program is a personalized coaching intervention that uses customized medication reminders, education, and motivational interviewing [
43]. Participants were included if they had an electronically measured adherence < 80% [
43]. The intervention occurred over 7 months [
43]. Medication adherence was monitored electronically as the percentage of doses taken correctly [
43]. There were 39 participants, 56% of which were male, 44% were white, and 49% were Black [
43]. Overall, medication adherence improved from a baseline of 59.9% [standard deviation (SD) 18.5%] to 83.6% (SD 17.5%) [
43]. Participants with lower income (< $25,000 and $25,000–$50,000 versus > $50,000) had lower baseline adherence (48.4% and 64.1% versus 70.4%) but had greater increases in adherence during the first month of medication reminders (19.6% and 21.6% versus 10.2%;
p = 0.05 and
p = 0.007, respectively) [
43]. Participants taking fewer glaucoma medications also had significantly greater increases in adherence with medication reminders (
p < 0.001) [
43]. All together, the SEE program did improve adherence, especially in lower income groups.
The literature that focuses on improving glaucoma topical medication adherence typically targets interventions at the patient level through education, demonstrating, and understanding the “why;” however, one randomized controlled trial by Cate and colleagues sought to do the same through a Behavior Change Counseling (BCC) intervention and found that their program did not improve adherence nor was it cost effective [
44]. BCC is a modified version of Motivational Interviewing that is less time intensive and allows for the exchange of information in addition to asking open ended questions [
44]. Improvement in glaucoma adherence was measured using an electronic adherence monitoring device that is able to record the time, date, and number of drops of medication released from the bottle [the Travatan Dosing Aid (TDA)] over an 8-month follow-up period with Travoprost [
44]. The TDA data was also used to categorize participants based on baseline adherence behaviors: discontinuation of dosing after a short time interval, adherence > 97%, adherence 80–97%, frequent drug holidays, and variable with frequent missed doses [
44]. Patients who received BCC did not have different adherence compared to those who did not receive BCC (77.2% versus 74.8%;
p = 0.471) [
45]. There also was no statistically significant difference in proportion obtaining > 80% adherence between the intervention and control group (66.7% versus 62.5%;
p = 0.685) [
45]. Similarly, there was no significant difference in IOP reduction (27.6% versus 25.3%;
p = 0.45) between the intervention and control group [
45]. Although the intervention group was more satisfied with information about glaucoma medication due to BCC, the outcomes between groups did not differ and BCC was found to not be cost effective [
45].
A systematic review done by Newman-Casey and colleagues in 2014 reviewed eight studies that implemented educational interventions to improve glaucoma medication adherence [
46]. The examined studies enacted varying interventions ranging from educational videos about glaucoma treatment, nurse and ophthalmic technician-led individual educational sessions to motivational interviewing, and lectures led by ophthalmologists [
46]. Five of the educational intervention strategies produced significant improvements in glaucoma adherence and three other studies found an improvement that did not reach statistical significance [
46]. The strategies that found a statistically significant improvement were: (1) Okeke and colleagues’ study (discussed in greater detail below) that implemented glaucoma education, addressed barriers, and created a reminder system, (2) educational slideshow and pamphlet with questions answered by an ophthalmic technician, (3) visit with ophthalmologist or nurse dedicated to glaucoma education, (4) multiple motivational interviews with patients to address barriers, and (5) creation of a glaucoma club with ophthalmologists and patients who interact and learn about glaucoma [
46]. Based on these studies, Newman-Casey and colleagues created a conceptual model that included frameworks such as types of barriers to adherence that were categorized into “patient and situation factors” (i.e., lack of understanding, forgetfulness, drop administration difficulty) and “regimen factors” (i.e., cost, side effects, regimen complexity) [
46]. They asserted that patient and situation factors can be addressed and improved by educational interventions and advocated for with individually tailored educational material since most of the studies that found a statistically significant improvement used a personalized educational approach [
46]. Ultimately, Newman-Casey and colleagues demonstrated that addressing knowledge deficiencies and barriers increased medication adherence.
Waterman and colleagues conducted a systematic review of randomized (or quasi randomized, where the method of allocation is not truly random) controlled trials of interventions for improving adherence to ocular hypotensive therapy, with 16 studies (1565 participants) being included in the review [
17]. Of the 16 studies, seven implemented a patient education intervention, 8 studies compared different drug regimens, and the remaining study incorporated a reminder device [
17]. Similar to Newman-Casey, Waterman and colleagues detailed three studies that significantly increased ocular hypotensive adherence through incorporation of a complex combination of education and personalized interventions, which are discussed below.
The first study by Gray and colleagues in 2011 involved a multifocal intervention: an assessment of healthcare needs and beliefs about medicine and illness, an educational session, and an interactive training session to learn how to instill eye drops [
47]. Adherence was measured using the Reported Adherence to Medication scale, directly asking the participants how often they missed drops using an ordinal scale, and a final questionnaire at the 12-month follow-up [
47]. The researchers found that at the final questionnaire, 70% of the intervention group were classified as adherent compared with 43% in the control group [
47]. Ultimately, Gray and colleagues surmised that those who received a personally tailored education plan had a better knowledge of glaucoma treatment than those who received standard care (
p < 0.001) [
47]. The second study by Norell and colleagues implemented a 30-min education and tailoring program where participants were first taught about glaucoma treatment through a slideshow and a leaflet [
48]. Their knowledge and understanding were then reexamined by an ophthalmic assistant [
48]. The ophthalmic assistant also spoke to participants about their daily routines and gave advice on the best times to instill their eye drops [
48]. To measure adherence, a medication monitor device that replaced the eye dropper cap and was able to tell whether the bottle has been opened during the last hour [
48]. The authors found that participants in the intervention group significantly improved adherence measured by decreased number of missed doses and the proportion of time that exceeded the 8-h dose interval (
p = 0.004 and
p ~ 0, respectively) [
48]. The third study by Okeke and colleagues implemented a complex intervention that consisted of a 10-min educational video used to promote the importance of taking regular drops and a discussion with the study coordinator to develop a personalized strategy to improve adherence along with scheduled telephone call reminders that occurred on a weekly basis for 1 month and every other week for 2 months [
49]. Okeke and colleagues divided up their participants into baseline adherence rates (i.e., > 75%, 50–74%, and < 50%) and tracked adherence rates at the end of the 3-month study period, finding that all groups except the 50–74% adherence rate group (
p = 0.57) had statistically and clinically significantly improvement in adherence rates (> 75% adherence group
p < 0.0001; < 50%
p = 0.03) [
49]. In brief, the three aforementioned studies have shown that creating an interactive, personalized, and complex intervention for patients can improve adherence.
Hahn and colleagues researched whether changes in physician education could improve patient adherence. Twenty-three ophthalmologists were analyzed before and after a 3-h training course that included teachings of a four-step adherence assessment and use of structured open-ended questions (i.e., ask-tell-ask) [
50]. A statistically significant difference was found after the training in the use of open-ended questions (
p = 0.001), increased discussions of adherence (
p < 0.001), and ophthalmologists’ being able to elicit from patients that they have been non-adherent (
p = 0.03); however, although the study demonstrated improved interviewing by ophthalmologists it did not determine if there was an impact on patient adherence [
50].
Patient education and literacy are well-established factors in glaucoma treatment adherence, with most adherence interventional studies targeting patient education. Various efforts to improve adherence through patient education have demonstrated promising results. Interventions that increased adherence included: written instructions targeting glaucoma-specific health literacy, literacy level appropriate glaucoma education videos, the SEE program, and interactive and personalized educational programs. The Behavior Change Counseling (BCC) intervention did not improve adherence. Lastly, physician training on patient interactions can help physicians elicit information and address non-adherence with patients.