Adherence and Persistence: The Challenges for Glaucoma Medical Therapy.

PERSPECTIVE

Adherence and Persistence: The Challenges for Glaucoma Medical Therapy Simon E. Skalicky, MBBS, MMed (Ophthal Sci), MPhil*Þ and Ivan Goldberg, AM, MBBS, FRANZCO, FRACS*þ Abstract: Suboptimal adherence and persistence to therapy are major challenges for patients treated with ocular hypotensive medications. The problem affects 5% to 80% of glaucoma patients from all nations, ethnicities, socioeconomic backgrounds, and education levels. Although health care providers are generally poor at detecting suboptimal or poor adherence in the clinical setting, several strategies to systematically assess adherence and persistence rates are available. One strategy involves electronic monitoring of patient dosing, which provides useful insights into specific patterns of adherence behavior among glaucoma patients. Adherence behavior is complex with multiple interrelated determinants; these can be broadly grouped into provider factors, environmental factors, medication factors, and patient factors. Targeted patient education strategies, counseling, electronic monitors, alarms, and reminders have all been used in efforts to improve adherence. These interventions probably work best in combination. Identifying tangible barriers to adherence and simple strategies to overcome these through an open, discursive relationship between clinician and patient is key to optimizing adherence. Key Words: adherence, persistence, glaucoma, topical ocular hypotensive medications (Asia-Pac J Ophthalmol 2013;2: 356Y361)

with self-administration for some individuals. These can dampen a patient’s enthusiasm for using eye drops regularly. Critically, the success of these medications in preventing glaucomatous visual loss depends on patient adherence to and persistence with fixed treatment regimens.16 Sustained and consistent patient adherence to treatment regimens with ocular hypotensive agents would significantly delay glaucomatous disease progression for most patients.17 Yet, as diagnostic techniques continue to improve,18,19 poor adherence and persistence remain significant barriers to effective treatment.20,21 Poor adherence also impairs effective treatment for chronic diseases such as diabetes, asthma, and hypertension.22,23 For these conditions, a direct association exists between poor patient adherence and negative clinical outcomes.22,23 Similarly, for glaucoma, poor adherence is associated with severity of glaucomatous visual loss.24,25 Like many chronic systemic conditions, glaucoma is initially asymptomatic or provokes only vague symptoms and progresses slowly, while treatment can be uncomfortable, cumbersome, intrusive to patients’ lifestyle, and costly. All of these factors can contribute to poor patient motivation for regular adherence to treatment regimens.26

TERMINOLOGY

T

he global disease burden due to glaucoma is large and will continue to rise.1 In 2010, 60.5 million people worldwide had glaucoma; by 2020, this will reach 79.6 million.2 In the United States, glaucoma is the leading cause of preventable, irreversible vision loss and will affect 3 million people by 2020.2,3 India in 2010 had 8.2 million people with open-angle glaucoma and 3.7 million with angle-closure glaucoma.2,4 In China today, 0.7% of the adult population has primary openangle glaucoma; 1.2% have angle-closure glaucoma.5 Elevated intraocular pressure is the major risk factor for glaucomatous progression; multiple clinical trials have demonstrated that lowering intraocular pressure reduces glaucomatous visual loss in patients with ocular hypertension or glaucoma.6Y8 Despite advances in laser and surgical therapies,9Y13 topical hypotensive medications are the mainstay of treatment for most forms of glaucoma today and will continue to be in the foreseeable future.14,15 Most patients and clinicians prefer topical agents as first-line treatment as they are effective, generally safe, widely available, and relatively simple to administer. However, they have their limitations, including ocular and systemic adverse effects, preservative-related drop toxicity, and difficulty From the *Addenbrooke’s Hospital, Cambridge, United Kingdom; †Faculty of Medicine, University of Sydney, Sydney New South Wales, Australia; and ‡Discipline of Ophthalmology, University of Sydney, Sydney, New South Wales, Australia. Received for publication August 27, 2013; accepted October 21, 2013. The authors have no funding or conflicts of interest to declare. Reprints: Simon E. Skalicky, MBBS, MMed(Ophthal Sci), MPhil, Addenbrooke’s Hospital, Hills Rd, Cambridge, UK CB2 0QQ. E-mail: [email protected]. Copyright * 2013 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0000000000000023

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The first step in understanding the problem is to clarify the terminology. ‘‘Persistence,’’ ‘‘compliance,’’ and ‘‘adherence’’ are frequently used with various meanings.26,27 One working group defined persistence as ‘‘the act of continuing the treatment for the prescribed duration’’ or ‘‘time from initiation to discontinuation of therapy.’’27 It considered compliance and adherence to be synonyms, defined as the ‘‘extent of conformity to the recommendations about day-to-day treatment by the provider with respect to the timing, dosage, and frequency.’’27 Other authors would suggest there is an important difference between ‘‘compliance’’ and ‘‘adherence’’; the term ‘‘adherence’’ implies an open discursive therapeutic relationship between the informed patient and physician, whereas ‘‘compliance’’ suggests that the patient passively follows the doctors’ orders.28 A therapeutic alliance based on trust and open dialogue using treatment tailored to suit the individual is pivotal to optimize patient participation in treatment regimens; hence, ‘‘adherence’’ is the preferred term.

THE SIZE OF THE PROBLEM A substantial proportion of patients treated for glaucoma or ocular hypertension have poor or suboptimal adherence and/or persistence with therapy. This applies to patients from all nations, communities, socioeconomic backgrounds, and education levels.4,26,29,30 On average, patients with chronic medical conditions take 30% to 70% of prescribed medication doses, and up to half discontinue medications in the first few months of therapy.31,32 The adherence and persistence figures for glaucoma are similar, with adherence reported to range anywhere from 5% to 80%.33

MEASURING ADHERENCE Reported rates of adherence vary widely, partly because adherence is difficult to quantify. Several measurement techniques

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have been used producing varying results; each has its own advantages and limitations. These include clinical interview, selfreport surveys, pharmacy claims data analysis, electronic monitoring systems, and direct observation of drop-instillation technique.26,28,29,34Y39

Clinical Interview Discussion between the health care provider and patient regarding adherence, persistence, and practical aspects of drop administration should be encouraged. It may yield useful information regarding factors influencing administration of glaucoma medication and may reveal obstacles to effective treatment. However, health care providers in general are poor at distinguishing more adherent from less adherent patients and tend to overestimate adherence.34,40,41 It can be difficult for patients to discuss the extent of their adherence behavior as they commonly want to ‘‘please’’ their clinicians and wish to give the impression that they are looking after themselves well. However, clinicians can use clues from physical examination, including signs of droprelated effects such as lash changes from prostaglandin analogs.

Self-report Surveys Formal self-assessment questionnaires may be slightly more accurate than clinical interview.42 Sleath et al37,43 devised questionnaires to reflect eye-drop self-instillation efficacy and instillation technique; these correlate with objective markers of adherence and eye-drop technique, respectively. However, self-report surveys are subjective and influenced by personality, recall bias, mood, memory, and white-coat syndrome.44 Like clinical interview, selfreport surveys often overestimate adherence.34,41

Pharmacy Claims Data Analysis Pharmacy claims data analysis compares the number of scripts written by clinicians with bottles dispensed at pharmacies. These provide important insights into adherence rates.20,30,35,45Y47 According to a systematic literature review, patients had access to glaucoma medications for 56% (range, 37%Y92%) of days in the first year of prescription, and 31% (range, 10%Y68%) were persistent after 1 year.26 Pharmacy claims data analysis studies have demonstrated that adherence is greatest for simpler routines with daily dosing drops. In general, it is greatest for monotherapy, in particular with prostaglandin analogs.20 Pharmacy claims analysis has the advantage of evaluating real-world data retrospectively, outside clinical studies; as such, all patients are evaluated, not just those enrolled in studies and completing follow-up. Furthermore, patients are unaware they are being monitored, which otherwise could inflate adherence rates artificially. However, pharmacy claims analysis has several inherent inaccuracies in measurement. Some patients receive free drop samples or receive unnecessary script duplicates from 1 or several health care providers. Added medications can be misclassified as switched medications, and patients previously on medication can be misidentified as new to treatment.48 Furthermore, bottles

Challenges for Glaucoma Medical Therapy

dispensed are measured, not drops administered, and probably adherence and persistence are overestimated.

Electronic Monitoring Systems With proper patient training and instruction, electronic dose monitoring devices reliably and accurately record the number, time, and date of eye-drop administration.34,49,50 These involve sensors in medication bottles that are activated when the medication is administered, for example, a lever that is pushed on a dosing aid to dispense the drop, as in the Travatan Dosing Aid (Travalert; Alcon Inc, Fort Worth, Tex). Electronic monitoring directly measures the patterns of drop-administration behavior and is probably the most direct and accurate means available to evaluate adherence.40,51 Electronic monitoring additionally provides useful information on the time and date of each dose to better assess patterns of drop administration. Weaknesses include selection bias, as poorly adherent patients may drop out of the study before completion, and measurement bias, as patients are generally aware that their medication usage is being assessed, known as the Hawthorne effect.52 These can lead to overestimation of real-life adherence rates. Electronic dose monitoring provides insights into patterns of adherence behavior for a variety of chronic medical conditions, which may apply to glaucoma. In the treatment of hypertension longer-duration medication, omissions are less common than single-day omissions.53 Renal transplant patients on multiple daily dose medications showed an 86% nonadherence rate, with nighttime doses in particular being missed or taken erratically.54 Electronic monitoring studies for glaucoma have identified 4 broad types of adherence behavior: early discontinued usage, good adherence (980% of doses), poor adherence (G80%) with drug holidays, and poor adherence (G80%) with frequently missed doses.55,56 Drug holidays are defined as substantial periods of time (often 7 days) without any drop administration; frequently missed doses include shorter periods of inconsistent or erratic drop usage. A significant proportion of patients with suboptimal drop usage improve adherence after the office visit and just before the return visit.34 The proportion of patients with each type of adherence behavior was recently evaluated in 2 UK electronic monitoring studies. Cate et al57 followed up 88 of an original 98 patients with primary open-angle glaucoma over 2 months. Ajit et al56 followed up 37 of an original 53 patients with chronic open-angle or narrow angle glaucoma over 3 months. The proportion of patients with each type of adherence behavior type is outlined in Table 1.

Assessment of Drop-Instillation Technique Assessment of eye-drop-instillation technique provides useful insights into barriers against good adherence. Although self-assessment questionnaires can be useful, more fruitful analysis can be provided by objective patient demonstrations of drop-instillation technique. A recent video analysis of patients on regular topical medication has demonstrated that 62% have imperfect technique; either the drops miss the conjunctiva;

TABLE 1. Patterns of Adherence Behavior in Patients Treated With Topical Hypotensive Medications56,57 Adherence Behavior Type 1 2 3 4

Description Early discontinuation Good adherence: 980% adherence rate G80% adherence rate with frequent drug holidays G80% adherence rate with variable and frequent missed doses

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Percentage (n) of Patients Percentage (n) of Patients (Ajit et al56) (Cate et al57) 10% 56% 10% 24%

(9) (49) (9) (21)

8% 62% 11% 19%

(3) (23) (4) (7)

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the bottle touches the lashes, eye, or face; or too many drops are instilled at once.24 Similar studies have demonstrated an alarmingly high prevalence of poor drop technique.39 However, technique is probably a less important predictor of glaucomatous progression than adherence as measured by electronic monitoring.24

DETERMINANTS OF ADHERENCE Treatment adherence is a complex behavior23 that is influenced by multiple interrelated factors.58,59 Personality, beliefs, culture, motivation, age, and health literacy are all important determinants, as are drop-related blurriness, redness or stinging, and frequency or complexity of the administration regimen. Furthermore, many patients’ physical ability to self-administer drops can be limited by comorbidities that influence cognition or dexterity.4,60 Because of its chronicity, the lack of specific symptoms in early to moderate disease stages, and the lack of immediately perceived consequences if medications are not used, by its very nature glaucoma promotes nonadherence and nonperseverance. Specific determinants of a patient’s adherence and persistence to glaucoma treatment can be broadly divided into 4 categories: provider factors, environmental factors, medication factors, and patient factors.61

Provider Factors Communication and trust in the relationship between health care provider and patient influence adherence.58,59 In a study, adherence was highest among patients who felt that their clinicians had time to explain the condition and treatment and that they could ask health care providers or pharmacists questions regarding treatment.29

Environmental Factors Major life events, travel, and changes in routine (eg, moving residence) can reduce adherence.62 Some factors are simply distracting, whereas others impair a patient’s ability to administer drops on a very practical level, for example, loss of a partner who always reminded/aided the patient in drop administration, or admission to a hospital for an intercurrent illness where the drops are temporarily omitted or unavailable.

Medication Factors Adherence and persistence are influenced by drop adverse effects, local discomfort, and exacerbation of ocular surface disease,29,63 which is an important cause of morbidity in glaucoma patients.64 Adherence and persistence are substantially reduced by medication regimen complexity,29,63 in particular the number of medications, the number of doses of each medication, and differences between the eyes.30 More than 2 drop administrations per day are associated with significantly reduced glaucoma medication adherence,33,65 perhaps due to the complexity of the regime or perhaps due to exacerbation of ocular surface disease.66,67 Cost and availability of medication also influence adherence and persistence.38,58,68

Patient Factors Poor or suboptimal adherence and low persistence are common irrespective of background, ethnicity, socioeconomic status, education, and sex; these factors are not consistently predictive of adherence behavior.17,29,30,33,69 Some US studies found that nonwhite people had a higher rate of nonadherence, but these findings are limited by confounding factors.17,24,36,68Y70 Poor adherence is more common in older patients,70,71 which can be influenced by comprehension, memory,38,59,68 difficulty reading bottle labels and instructions,36,38,60 coordination, and

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dexterity.4,60,72 In addition, younger (G50 years) patients are at increased risk of poor adherence and persistence.17,30,70 Poor vision, due to reduced acuity or field loss, is associated with reduced adherence.29,38,60 This is a particular challenge for patients with advanced glaucoma. Cognitive factors are important; the most influential is forgetfulness.59 This is not limited to those with cognitive impairment; a busy schedule, low priority for health care issues, and multiple life distractors all contribute.29,38,65,68,73 Poor comprehension of the disease process and treatment, lack of perceived benefit from treatment, or satisfaction with treatment commonly contribute to poor adherence.29,59,74 Depression, which is more common in patients with increasing glaucoma severity,75 has been associated with self-report of nonadherence, as are stress and certain personality traits.58,76,77 Attitudes, beliefs, and social supports can all influence treatment adherence and persistence.29,61

INTERVENTIONS TO IMPROVE ADHERENCE AND PERSISTENCE Efforts to improve adherence and persistence rates among glaucoma patients are critically important to optimize medical treatment and prevent progressive field loss.16,24,25 Interventions that address the issues listed above are likely to improve adherence and persistence rates and should be considered and/or discussed at every clinical interview with a high priority. Several interventions have been proposed and tested; not all have been consistently successful. Education about glaucoma, counseling, electronic reminders, and medication alarm devices have been evaluated systematically.33,77 Educational interventions to improve general health literacy and knowledge about glaucoma have a small but significant impact on improving adherence.77Y80 In general, such interventions are most useful in populations with low health literacy levels and low background adherence rates. Counseling regarding drop technique, the importance of daily adherence, and strategies to overcome barriers to adherence may lead to increased adherence.79,81 Automated telephone reminders have been evaluated in the context of treatment adherence for other systemic chronic diseases, and many studies show they have a positive impact on health outcomes.82 Regular automated text messaging has been shown to improve medication adherence in asthma and may also be useful in glaucoma.83 Telephone and text reminders appear to be most beneficial if they are frequent (eg, daily) as opposed to infrequent (eg, monthly).77,79,83 One current clinical trial is evaluating the effectiveness of e-monitoring and electronic text messaging for children with asthma treated with regular aerosols. Tailored text messages are sent only when emonitoring detects a dose at risk of omission.84 Perhaps such tailored use of available social media and e-monitoring will help improve adherence rates for glaucoma patients.85 In particular, midappointment interventions can be used to prevent the rapid decline in adherence in the weeks following 1 medical appointment and preceding the next.34,40,77 New smartphone or tablet computer technology may see the introduction of applications to remind patients to use their medications; at least 1 such ‘‘app’’ has been introduced (MyEyedrops 1.9; Singapore National Eye Centre Pte Ltd; http://www.snec.com.sg). These may improve adherence rates. Lim et al77 recently evaluated the efficacy of monthly automated telephone calls and an educational intervention by the physician at month 3: these did not improve adherence rates after 5 months. A similar study by Okeke et al79 involving patients with a low background adherence rate used multiple * 2013 Asia Pacific Academy of Ophthalmology



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intervention types including watching an educational video, reviewing current barriers to adherence and possible solutions, regular telephone call reminder, and audible and visible reminders on dosing aid devices. In contrast to the study of Lim et al,77 this resulted in a significant improvement in adherence during the 3 months of intervention.79 Perhaps the most effective solution will involve multiple strategies simultaneously, as demonstrated by Okeke et al.79 Alternatively, the contradictions in the literature may reflect the complex nature of adherence behavior, which is influenced by multiple determinants. Accordingly, strategies to improve a patient’s involvement in their own care program need to be flexible, adapting to an individual’s specific requirements and expectations.

SUMMARY Suboptimal adherence and persistence to treatment for patients with glaucoma or ocular hypertension can be difficult to detect and treat. These problems account for a large proportion of progression in known glaucoma patients from all backgrounds. Directly questioning patients regarding adherence may not be productive; however, indirect methods may be useful. For example, stating ‘‘some people may have difficulty remembering or instilling their dropsVwhat is your experience?’’ or asking ‘‘Do you have any particular challenges when instilling your drops?’’ may yield more clinically relevant information than ‘‘Do you ever forget?’’ Holistic approaches to identifying tangible barriers to adherence and simple strategies to overcome these are important. Optimizing the ocular surface, inquiring about drop-related adverse effects, simplifying the drop regimen, and discussing drop-instillation technique are some strategies that may improve adherence rates. Discussing ways of remembering drops, creating daily routines or drop diaries, or taking advantage of emerging smartphone technologies can be helpful for some patients, whereas others may benefit from a discussion involving relatives or carers as to who will be able to help or supervise drop administration. Patient education, counseling, and appropriate access to information and resources from health care providers are important. A tight network with open communication avenues between physician, practice nurse, optician, pharmacist, general practitioner, and patient results in improved drop adherence and persistence. Electronic monitoring offers useful insights into adherence and persistence rates and patterns of adherence behavior and may be used in combination with tailored digital alarm systems to optimize adherence. A broad array of strategies to improve adherence, including education, counseling, electronic monitors, and alarm devices, is probably most useful when used in combination. Above all, clinicians should strive to maintain an open, discursive relationship with the patient in a therapeutic alliance against the disease. REFERENCES 1. Cedrone C, Mancino R, Cerulli A, et al. Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects. Prog Brain Res. 2008;173:3Y14. 2. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262Y267. 3. Friedman DS, Wilson MR, Liebmann JM, et al. An evidence-based assessment of risk factors for the progression of ocular hypertension and glaucoma. Am J Ophthalmol. 2004;138:S19YS31. 4. Sleath BL, Krishnadas R, Cho M, et al. Patient-reported barriers to glaucoma medication access, use, and adherence in southern India. Indian J Ophthalmol. 2009;57:63Y68.



5. Cheng JW, Cheng SW, Ma XY, et al. The prevalence of primary glaucoma in mainland China: a systematic review and meta-analysis. J Glaucoma. 2013;22:301Y306. 6. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701Y713; discussion 829Y830. 7. Leske MC, Heijl A, Hyman L, et al. Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999;106:2144Y2153. 8. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the early manifest Glaucoma trial. Arch Ophthalmol. 2002;120:1268Y1279. 9. Khaw PT, Chiang M, Shah P, et al. Enhanced trabeculectomyVthe Moorfields safer surgery system. Dev Ophthalmol. 2012;50:1Y28. 10. Gedde SJ, Schiffman JC, Feuer WJ, et al. Tube versus Trabeculectomy Study Group. Treatment outcomes in the tube versus trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153:789Y803. 11. Dashevsky AV, Lanzl IM, Kotliar KE. Non-penetrating intracanalicular partial trabeculectomy via the ostia of Schlemm’s canal. Graefes Arch Clin Exp Ophthalmol. 2011;249:565Y573. 12. Shi JM, Jia SB. Selective laser trabeculoplasty. Int J Ophthalmol. 2012;5:742Y749. 13. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23:96Y104. 14. Chae B, Cakiner-Egilmez T, Desai M. Glaucoma medications. Insight. 2013;38:5Y9; quiz 10. 15. Lee AJ, Goldberg I. Emerging drugs for ocular hypertension. Expert Opin Emerg Drugs. 2011;16:137Y161. 16. Lee PP, Walt JW, Rosenblatt LC, et al. Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. Am J Ophthalmol. 2007;144:901Y907. 17. Dreer LE, Girkin C, Mansberger SL. Determinants of medication adherence to topical glaucoma therapy. J Glaucoma. 2012;21:234Y240. 18. McManus JR, Netland PA. Screening for glaucoma: rationale and strategies. Curr Opin Ophthalmol. 2013;24:144Y149. 19. Grewal DS, Tanna AP. Diagnosis of glaucoma and detection of glaucoma progression using spectral domain optical coherence tomography. Curr Opin Ophthalmol. 2013;24:150Y161. 20. Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598Y606. 21. Zhou Z, Althin R, Sforzolini BS, Dhawan R. Persistency and treatment failure in newly diagnosed open angle glaucoma patients in the United Kingdom. Br J Ophthalmol. 2004;88:1391Y1394. 22. Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998;36:1138Y1161. 23. DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42:200Y209. 24. Sleath B, Blalock S, Covert D, et al. The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity. Ophthalmology. 2011;118:2398Y2402. 25. Rossi GC, Pasinetti GM, Scudeller L, et al. Do adherence rates and glaucomatous visual field progression correlate? Eur J Ophthalmol. 2011;21:410Y414. 26. Reardon G, Kotak S, Schwartz GF. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular

www.apjo.org


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Skalicky and Goldberg


hypertension: a systematic review. Patient Preference Adherence. 2011;5:441Y463. 27. Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11:44Y47. 28. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487Y497. 29. Stryker JE, Beck AD, Primo SA, et al. An exploratory study of factors influencing glaucoma treatment adherence. J Glaucoma. 2010;19:66Y72. 30. Quek DT, Ong GT, Perera SA, et al. Persistence of patients receiving topical glaucoma monotherapy in an Asian population. Arch Ophthalmol. 2011;129:643Y648. 31. Haynes RB, McDonald HP, Garg AX. Helping patients follow prescribed treatment: clinical applications. JAMA. 2002;288:2880Y2883. 32. DiMatteo MR, Giordani PJ, Lepper HS, et al. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002;40:794Y811. 33. Olthoff CM, Schouten JS, van de Borne BW, et al. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005;112:953Y961. 34. Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116:191Y199. 35. Rait JL, Adena MA. Persistency rates for prostaglandin and other hypotensive eyedrops: population-based study using pharmacy claims data. Clin Experiment Ophthalmol. 2007;35:602Y611. 36. Sleath B, Ballinger R, Covert D, et al. Self-reported prevalence and factors associated with nonadherence with glaucoma medications in veteran outpatients. Am J Geriatr Pharmacother. 2009;7:67Y73.

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48. Friedman DS, Quigley HA, Gelb L, et al. Using pharmacy claims data to study adherence to glaucoma medications: methodology and findings of the Glaucoma Adherence and Persistency Study (GAPS). Invest Ophthalmol Vis Sci. 2007;48:5052Y5057. 49. Hermann MM, Bron AM, Creuzot-Garcher CP, et al. Measurement of adherence to brimonidine therapy for glaucoma using electronic monitoring. J Glaucoma. 2011;20:502Y508. 50. Friedman DS, Jampel HD, Congdon NG, et al. The Travatan Dosing Aid accurately records when drops are taken. Am J Ophthalmol. 2007;143:699Y701. 51. Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther. 1999;21:1074Y1090; discussion 3. 52. Fernald DH, Coombs L, DeAlleaume L, et al. An assessment of the Hawthorne effect in practice-based research. J Am Board Fam Med. 2012;25:83Y86. 53. Grigoryan L, Pavlik VN, Hyman DJ. Patterns of nonadherence to antihypertensive therapy in primary care. J Clin Hypertens. 2013;15:107Y111. 54. Russell CL, Cetingok M, Hamburger KQ, et al. Medication adherence in older renal transplant recipients. Clin Nurs Res. 2010;19:95Y112. 55. Hermann MM, Ustundag C, Diestelhorst M. Electronic compliance monitoring of topical treatment after ophthalmic surgery. Int Ophthalmol. 2010;30:385Y390. 56. Ajit RR, Fenerty CH, Henson DB. Patterns and rate of adherence to glaucoma therapy using an electronic dosing aid. Eye. 2010;24:1338Y1343. 57. Cate H, Bhattacharya D, Clark A, et al. Patterns of adherence behaviour for patients with glaucoma. Eye. 2013;27:545Y553. 58. Tsai JC. Medication adherence in glaucoma: approaches for optimizing patient compliance. Curr Opin Ophthalmol. 2006;17:190Y195.

37. Sleath B, Blalock SJ, Robin A, et al. Development of an instrument to measure glaucoma medication self-efficacy and outcome expectations. Eye. 2010;24:624Y631.

59. Taylor SA, Galbraith SM, Mills RP. Causes of non-compliance with drug regimens in glaucoma patients: a qualitative study. J Ocul Pharmacol Ther. 2002;18:401Y409.

38. Sleath B, Robin AL, Covert D, et al. Patient-reported behavior and problems in using glaucoma medications. Ophthalmology. 2006;113:431Y436.

60. Winfield AJ, Jessiman D, Williams A, et al. A study of the causes of non-compliance by patients prescribed eyedrops. Br J Ophthalmol. 1990;74:477Y480.

39. Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eyedrop instillation in patients with glaucoma. Arch Ophthalmol. 2009;127:732Y736.

61. Tsai JC, McClure CA, Ramos SE, et al. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393Y398.

40. Kass MA, Gordon M, Meltzer DW. Can ophthalmologists correctly identify patients defaulting from pilocarpine therapy? Am J Ophthalmol. 1986;101:524Y530. 41. Kass MA, Gordon M, Morley RE Jr, et al. Compliance with topical timolol treatment. Am J Ophthalmol. 1987;103:188Y193. 42. Konstas AG, Maskaleris G, Gratsonidis S, et al. Compliance and viewpoint of glaucoma patients in Greece. Eye. 2000;14(pt 5):752Y756. 43. Sleath B, Blalock SJ, Stone JL, et al. Validation of a short version of the glaucoma medication self-efficacy questionnaire. Br J Ophthalmol. 2012;96:258Y262. 44. Feinstein AR. On white-coat effects and the electronic monitoring of compliance. Arch Intern Med. 1990;150:1377Y1378. 45. Dasgupta S, Oates V, Bookhart BK, et al. Population-based persistency rates for topical glaucoma medications measured with pharmacy claims data. Am J Manag Care. 2002;8:S255YS261. 46. Reardon G, Schwartz GF, Mozaffari E. Patient persistency with topical ocular hypotensive therapy in a managed care population. Am J Ophthalmol. 2004;137:S3YS12. 47. Reardon G, Schwartz GF, Mozaffari E. Patient persistency with pharmacotherapy in the management of glaucoma. Eur J Ophthalmol. 2003;13(suppl 4):S44YS52.

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www.apjo.org

62. Schwartz GF. Compliance and persistency in glaucoma follow-up treatment. Curr Opin Ophthalmol. 2005;16:114Y121. 63. Shaya FT. Compliance with medicine. Ophthalmol Clin North Am. 2005;18:611Y617. 64. Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012;153:1.e2Y9.e2. 65. MacKean JM, Elkington AR. Compliance with treatment of patients with chronic open-angle glaucoma. Br J Ophthalmol. 1983;67:46Y49. 66. Baudouin C, Renard JP, Nordmann JP, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol. 2012 [Epub ahead of print]. doi: 10.5301/ejo.5000181. 67. Detry-Morel M. Side effects of glaucoma medications. Bull Soc Belge Ophtalmol. 2006;299:27Y40. 68. Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26:233Y236. 69. Racette L, Wilson MR, Zangwill LM, et al. Primary open-angle glaucoma in blacks: a review. Surv Ophthalmol. 2003;48:295Y313. 70. Friedman DS, Okeke CO, Jampel HD, et al. Risk factors for poor adherence to eyedrops in electronically monitored patients with glaucoma. Ophthalmology. 2009;116:1097Y1105.




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71. Rossi GC, Pasinetti GM, Scudeller L, et al. Monitoring adherence rates in glaucoma patients using the Travatan Dosing Aid. A 6-month study comparing patients on Travoprost 0.004% and patients on Travoprost 0.004%/timolol 0.5% fixed combination. Expert Opin Pharmacother. 2010;11:499Y504. 72. Kahook MY. Developments in dosing aids and adherence devices for glaucoma therapy: current and future perspectives. Expert Rev Med Devices. 2007;4:261Y266. 73. Kosoko O, Quigley HA, Vitale S, et al. Risk factors for noncompliance with glaucoma follow-up visits in a residents’ eye clinic. Ophthalmology. 1998;105:2105Y2111. 74. Day DG, Sharpe ED, Atkinson MJ, et al. The clinical validity of the treatment satisfaction survey for intraocular pressure in ocular hypertensive and glaucoma patients. Eye. 2006;20:583Y590. 75. Skalicky S, Goldberg I. Depression and quality of life in patients with glaucoma: a cross-sectional analysis using the Geriatric Depression Scale-15, assessment of function related to vision, and the Glaucoma Quality of Life-15. J Glaucoma. 2008;17:546Y551. 76. Pappa C, Hyphantis T, Pappa S, et al. Psychiatric manifestations and personality traits associated with compliance with glaucoma treatment. J Psychosom Res. 2006;61:609Y617. 77. Lim MC, Watnik MR, Imson KR, et al. Adherence to glaucoma medication: the effect of interventions and association with personality type. J Glaucoma. 2013;22:439Y446. 78. Norell SE. Improving medication compliance: a randomised clinical trial. Br Med J. 1979;2:1031Y1033.


79. Okeke CO, Quigley HA, Jampel HD, et al. Interventions improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009;116:2286Y2293. 80. Muir KW, Ventura A, Stinnett SS, et al. The influence of health literacy level on an educational intervention to improve glaucoma medication adherence. Patient Educ Couns. 2012;87:160Y164. 81. Sclar DA, Skaer TL, Chin A, et al. Effectiveness of the C Cap in promoting prescription refill compliance among patients with glaucoma. Clin Ther. 1991;13:396Y400. 82. Friedman RH, Kazis LE, Jette A, et al. A telecommunications system for monitoring and counseling patients with hyper-tension. Impact on medication adherence and blood pressure control. Am J Hypertens. 1996;4(pt 1):285Y292. 83. Strandbygaard U, Thomsen SF, Backer V. A daily SMS reminder increases adherence to asthma treatment: a three- month follow-up study. Respir Med. 2009;104:166Y171. 84. Vasbinder EC, Janssens HM, Rutten-van Molken MP, et al. e-Monitoring of asthma therapy to improve compliance in children using a real-time medication monitoring system (RTMM): the e-MATIC study protocol. BMC Med Inform Decis Mak. 2013;13:38. 85. Chen ZW, Fang LZ, Chen LY, et al. Comparison of an SMS text messaging and phone reminder to improve attendance at a health promotion center: a randomized controlled trial. J Zhejiang Univ Sci B. 2008;9:34Y38.

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Pediatric glaucoma medical therapy: who more accurately reports medication adherence, the caregiver or the child?

Persistence with topical glaucoma therapy among newly diagnosed Japanese patients.

Understanding patient management: the need for medication adherence and persistence.

[Complexities of Medical Glaucoma Therapy--the Elderly Patient in Focus].

Electronic medical record and glaucoma medications: connecting the medication reconciliation with adherence.

Drug persistence and adherence in the treatment of overactive bladder.

Medical adherence to acne therapy: a systematic review.

Common Molecular Challenges in Glaucoma.

Management of exfoliative glaucoma: challenges and solutions.

Re: Adherence to NICE guidelines for new glaucoma referrals.

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study).

Improving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery.

Medical therapy for glaucoma: what to add after a prostaglandin analogs?

Targeting Schlemm's Canal in the Medical Therapy of Glaucoma: Current and Future Considerations.

Systematic review of migraine prophylaxis adherence and persistence.

Retention in care and medication adherence: current challenges to antiretroviral therapy success.

Medication adherence in the management of nocturia: challenges and solutions.

Study on Incentives for Glaucoma Medication Adherence (SIGMA): study protocol for a randomized controlled trial to increase glaucoma medication adherence using value pricing.

New challenges for the graduate medical educator: implementing the milestones.

Patient race, reported problems in using glaucoma medications, and adherence.

Medical Marijuana-Opportunities and Challenges.

Using fluorouracil in surgical therapy for glaucoma.

Medical management of exfoliative glaucoma.

A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy.