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Focus On Improving Care | May 2015

Adherence and Persistence

Tips for improving patients' role in their own care.

The word adherence characterizes the doctor-patient relationship as a partnership. Unlike the traditional, more paternalistic and absolute term compliance, adherence implies that patients are actively involved in their own care. Adherence can be quantified by the extent to which a patient follows an agreed-upon recommendation without a lapse in treatment. This differs from persistence, which measures the time that a medication is used continuously.

The breadth of poor adherence and persistence is expansive. At best, patients’ medical adherence is estimated to be 75%,1 with approximately 9% of all prescriptions never being filled2 and even more remaining unclaimed.3 Furthermore, adherence and persistence become worse with time.4,5 Among glaucoma patients, persistence rates are low, ranging from 20%6 to 64%,7 with reports finding that, of patients who filled at least one prescription, almost one-half discontinued treatment within 6 months.8


In general, physicians are poor detectors of patients’ adherence to and persistence with treatment.9 Doctors typically do not ask the right questions, and patients usually overestimate their medication use. For instance, 97% of glaucoma patients reported that they never missed an eye drop despite evidence of significantly lower rates with electronic monitoring.10 This discrepancy is likely secondary to not wanting to be perceived as “bad” patients.11 Furthermore, physicians may be misled by the cyclical use of medications in which adherence improves acutely just prior to an appointment, subsequently declines, and may restart again.12 This behavior may lead to a false conclusion of an adequate response to a medication.

Being unable to effectively discern patients’ adherence to a medical regimen affects how physicians care for patients. In a common scenario, a disease state progresses, and the extent of nonadherence is undetermined. The physician does not know if progression is secondary to an inconsistent use of medication or if an escalation in treatment is mandated.


As expected, adherence rates are typically higher among patients with acute conditions.4 It seems that, when patients experience a debilitating change in vision accompanied with pain, such as with a corneal ulcer, they are motivated to adhere to a treatment plan in hopes of a rapid resolution. In contrast, because chronic conditions are often asymptomatic, the benefits of taking medications may not be immediately realized.

Much of what is known about adherence and persistence comes from research on chronic systemic diseases and open-angle glaucoma. To a certain extent, these findings can be extrapolated to other chronic diseases such as dry eye syndrome and blepharitis, which require sustained and often multimodal therapies. To be effective care providers, physicians must be proactive in determining adherence and persistence, identifying barriers, and tailoring interventions that motivate patients.


Clues to nonadherent behavior and poor persistence can be subtle, but an awareness of common barriers may heighten physicians’ index of suspicion. What follows is a review of the prevalent issues that patients face and how to address them.


The American Glaucoma Society identified forgetfulness as the leading barrier to adherence.13 Weekends, vacations, and major life events require special attention, as these times are often when routines are discarded. Suggestions for tackling forgetfulness include associating administration of eye drops with daily activities such as brushing teeth, keeping an extra bottle at work for midday dosing, setting an alarm, and using color-coded schedule sheets. Practitioners can encourage patients to have a spare bottle in case of an unforeseen delay in obtaining a refill. Prescribing a longer-lasting supply has also been shown to increase adherence.14

It is not surprising that not returning for follow-up visits is strongly associated with the poor use of eye drops.12,15 Adherence to appointments can be improved with the use of mail or telephone reminders.16 It is imperative to track patients who fail to follow up.

Complex Medical Regimens

Many patients have multiple comorbidities, and their medical regimen is complicated. Adherence to prescribed drug therapy has been shown to decrease as more doses and/or medications are added.4,17 If a patient’s condition is not responding to treatment, poor adherence should always be considered before treatment is intensified.

When appropriate, combination eye drops may help to limit the complexity of medical regimens. In postsurgical patients, to enhance adherence and thus reduce the risk of postoperative complications, consider prescribing nonsteroidal anti-inflammatory drugs that are dosed once daily such as 0.07% bromfenac or 0.3% nepafenac versus four doses per day of a generic drug.

Education Level

The lack of a high school-level education may affect a patient’s comprehension of eye drop use.18 Understanding and adherence improve with the use of written instructions, picture charts, educational videos, and Internet resources.15 Demonstrating how to correctly administer eye drops should also be covered periodically.

Lack of Interest

Notably, patients who rely solely on the information provided by their doctor demonstrated poorer adherence and persistence than those who sought information from other sources such as printed material and the Internet.16 Identifying patients who do not demonstrate interest in their own health or seek additional information can help target adherence reinforcement efforts.

Furthermore, patients who do not demonstrate concern about vision loss are significantly less adherent to prescribed therapy and follow-up appointments.16 Physicians should make an extra effort to educate patients who exhibit ambivalence by emphasizing the consequences of the disease.

Financial Issues

Financial concerns are often assumed to be a barrier to adherence, but studies of glaucoma patients have not shown a consistent relationship. Of note, however, patients who underuse their medications because of cost often do not inform their physician of financial hardship.19 Physicians should take care to directly address cost issues with patients to identify poor adherence and offer alternatives such as generics.20

Specific Patient Populations

Glaucoma studies have demonstrated that nonwhites, primarily African Americans, are less adherent to prescribed medical therapy than whites.21-24 The significance of this finding may be compounded by the greater prevalence of the disease and its severity in this population. Taking extra care to identify barriers among nonwhites may improve adherence and outcomes.

Increased age is often associated with greater adherence, but all elderly patients should be evaluated for challenges such as impaired vision, hearing, or health literacy; physical or cognitive disability; lack of social support; limited financial resources; and the influence of comorbidities such as depression.15,25 As many as 17% of older individuals rely on others to administer their eye drops.26 The influence of a caregiver is variable and depends on his or her understanding of the disease, its sequelae, and the treatment protocol.27

Adherence is not always relative to disease severity. Patients diagnosed either as glaucoma suspects or with severe glaucomatous disease exhibit worse adherence to medications and follow-up appointments than those with early to moderate disease.8,21,28 Perhaps extra efforts should be made at investigating and mitigating adherence barriers in patients on either end of the spectrum of disease severity.

In reality, barriers to appropriate treatment are multifactorial and may only be identified with appropriate inquiries.


In the words of Former US Surgeon General C. Everett Koop, “Drugs don’t work in patients who don’t take them.” The physician has a duty to identify barriers and find innovative solutions. Adherence and persistence are known to diminish over time4,5 and must be addressed repeatedly. Nonetheless, as with any successful partnership, adherence relies on the collaboration of both parties. Patients and their families must take responsibility and actively participate in their care. With open communication and targeted goals, adherence and persistence can be enhanced, resulting in improved outcomes. n

1. DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42:200-209.

2. Lash S, Harding J. Abandoned prescriptions: a quantitative assessment of their cause. J Managed Care Pharm. 1995(1);193-199.

3. Kirking MH, Kirking DM. Evaluation of unclaimed prescriptions in an ambulatory care pharmacy. Hosp Pharm. 1993;28:102;190-194.

4. Osternerg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487-497.

5. Brenner JS, Glynn RJ, Mogun H, et al. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288:455-461.

6. Spooner JJ, Bullano MF, Ikeda LI, et al. Rates of discontinuation and change of glaucoma therapy in a managed care setting. Am J Manag Care. 2002;8:S262-270.

7. 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:S255-S261.

8. Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598-606.

9. Okeke Co, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan dosing aid study. Ophthalmology. 2009;116:191-199.

10. Kass MA, Meltzer DW, Gordon M, et al. Compliance with topical pilocarpine treatment. Am J Ophthalmol. 1986;101:515.

11. Hahn SR. Patient-centered communication to assess and enhance patient adherence to glaucoma medication. Ophthalmology. 2009;116:S37-S42.

12. Schwartz GF, Quigley HA. Adherence and persistence with glaucoma therapy. Surv Ophthalmol. 2008;52(suppl1):S57-S68.

13. American Glaucoma Society. Patient Care Improvement Project. Pearls to improve patient compliance. http://www.supereyecare.com/resources/GreatHelp.pdf. Accessed April 8, 2015.

14. Batal HA, Krantz MJ, Dale RA, et al. Impact of prescription size on statin adherence and cholesterol levels. BMC Health Services Research. 2007;7:175.

15. Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology. 2009;116:S30-S36.

16. Friedman DS, Hahn Sr, Gelb L, et al. Doctor-patient communication and health related beliefs: results from the Glaucoma Adherence and Persistence Study (GAPS). Ophthalmology. 2008;115:1320-1327.

17. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296-310.

18. Kharod BV, Johnson PB, Nesti HA, Rhee DJ. Effect of written instructions on accuracy of self-reporting medication regimen in glaucoma patients. J Glaucoma. 2006;15:244-247.

19. Piette JD, Heisler M, Wagner TH. Cost-related medication underuse: do patients with chronic illnesses tell their doctors? Arch Intern Med. 2004;164:1749-1755.

20. Stein JD, Shekhawat N, Talwar N, et al. Impact of the introduction of generic latanoprost on glaucoma medication adherence. Ophthalmology. 2015;122(4):738-747.

21. 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(12):2398-2402.

22. Sleath B, Ballinger R, Covert D, et al. Self-report prevalence and factors associated with nonadherence with glaucoma medications in veteran outpatients. Am J Geriatr Pharmacother. 2009;7:67-73.

23. Friedman DS, Okeke CO, Jampel HD, et al. Risk factors for poor adherence to eyedrops in electronically monitored patients with glaucoma. Ophthalmology. 2009;116:1097-1105.

24. Patel SC, Spaeth GL. Compliance in patients prescribed eye drops for glaucoma. Ophthalmic Surg. 1995;26:233–236.

25. Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology. 2009;116(11 suppl):S30-S36.

26. Tsai T, Robin Al, Smith JP III. An evaluation of how glaucoma patients use topical medications: a pilot study. Trans Am Ophthalmol Soc. 2007;105:29-35.

27. Budenz DL. A clinician’s guide to the assessment and management of nonadherence in glaucoma. Ophthalmology. 2009;116:S43-S47.

28. Ung C, Murakami Y, Zhang E. The association between compliance with recommended follow-up and glaucomatous disease severity in a county hospital population. Am J Ophthalmol. 2013;156(2):362-369.

Divya M. Varu, MD
• in private practice at Dell Laser Consultants, Austin, Texas
• serves on the AAO Cornea/External Disease Preferred Practice Pattern Panel
• Financial disclosure: None acknowledged

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