Adverse Effects, Adherence and Cost–Benefits in Glaucoma Treatment
Adherence is uniformly a problem in glaucoma since the disease is asymptomatic until the very late stages, and because treatment prevents further vision loss but does not result in any perceptible improvement in visual status. Thus, there is little positive feedback to encourage adherence, and issues such as adverse effects, difficulty administering eye-drop medications and cost are also limiting factors for good adherence to treatment in most countries. A poly-drug regimen can also result in diminished effectiveness through the wash-out effect, in which multiple eye drops administered without proper spacing between them can lead to wash-out of earlier medications by later medications, before optimal ocular penetration has occurred.
The association between patient satisfaction and treatment compliance, or at least intention to or persistence in taking medications, has been documented.10
Specifically, glaucoma patient
In a representative sample of patients treated with an IOP-lowering therapy, some associations were found between burning and stinging, vision-related quality of life and compliance. Patients with reported adverse events frequently missed instillation.12 The relative convenience and adverse effect profiles of therapies may be additional important factors in treatment decision making. More complex medication dosing schedules have been shown to negatively impact adherence in glaucoma patients.13–15
Quantifying non-adherence, and assessing the contribution of different factors, can be problematic using conventional study designs. The prevalence of self-reported non-adherence to glaucoma medication is high (27.3 % according to a Dutch survey),16
satisfaction with treatment has been demonstrated to be a key driver of compliance.11
Figure 1: Kaplan-Meier Plots Representing Time to Optic Nerve Head and/or Visual Field Deterioration According to Adverse Effects (Wilcoxon Test)20
1.0 0.8
0.2 0.4 0.6
0 0 400 Time (days) With side effects No side effect
Figure 2: Kaplan-Meier Plots Corresponding to Time to Optic Nerve Head and/or Visual Field Deterioration Based on Patient Dissatisfaction with Antiglaucoma Treatment (Wilcoxon Test)20
1.0 0.8
0.2 0.4 0.6
but
may actually underestimate true non-adherence over time.16,17 Randomised controlled trials can achieve strong internal validity (an unbiased estimate of difference between groups); however, their external validity (applicability to everyday clinical practice) can be limited because enrolling onto a trial may influence patient behaviour. This is particularly relevant when assessing adherence, which is likely to improve when patients know that they are under observation. Multiple obstacles to adherence have already been identified, including poor education, lack of motivation, forgetfulness, drop application and age differences. Motivation for adherence is also determined by fear of blindness and a faith in drop efficacy.18
Non-adherence
may also be attributable to poor eye-drop application technique by older patients.19
We have developed a specific methodology both to assess medical outcomes over time and to identify factors that influence these outcomes.20
0 0 400 Time (days) Dissatisfaction throughout the study follow-up (2.6 %).20 No dissatisfaction Patients with disease
progression appeared to have more changes in treatment and adverse events and they were also more likely to have complained about being unhappy with their treatment.
Role of Treatment Adverse Effects Adverse effects of topical hypotensive therapy for glaucoma, such as conjunctival hyperaemia, discomfort and itching, are a leading cause of non-adherence.21–23
Patients taking fewer doses than prescribed may be at risk of having worse outcomes than those taking a higher proportion.
An initial study recruited 127 representative patients with primary open-angle glaucoma (POAG), normal-tension glaucoma or ocular hypertension via a randomly selected list of ophthalmologists.20 Disease progression, defined as a deterioration of optic nerve head and/or visual field within 2.5 years of initial diagnosis, occurred in 12 patients (9.5 %) during a mean follow-up of 2.4 years, but was not linked to any of the main clinical characteristics except time since diagnosis. However, there were significant correlations between disease progression and adverse effects or dissatisfaction with treatment (see Figures 1 and 2).20
The study also linked treatment
An analysis of 36 randomised controlled trials that included 17,511 patients identified adverse effects as the most common cause of withdrawals: 945/2,060 (46 % of withdrawals) compared with 197/2,060 (10 % of withdrawals) for inadequate IOP control.22
800 1,200 800 1,200
About
one in 20 patients (5.4 %) withdrew overall owing to adverse effects.22 Survey results confirmed the impact of adverse effects on adherence in ‘real life’ as well as in clinical trials.12
Adverse effects of topical
glaucoma treatment correlated with vision-related quality of life, treatment satisfaction and adherence to therapy.12
Disease progression was 3.3-fold higher in patients who experienced adverse events and 2.4-fold higher in patients who were dissatisfied with treatment.20
changes to disease progression, with an 8.7-fold increase in progression after one change (22.6 %) and a 17.7-fold increase after multiple changes (46.2 %) compared with patients who stayed on the same treatment
EUROPEAN OPHTHALMIC REVIEW
Prostaglandin analogues (PGAs) are widely used and are recommended as first-line therapy by national and international guidelines such as the European Glaucoma Society and the UK’s National Institute for Health and Clinical Excellence.9,24
Studies have demonstrated that PGAs
can control IOP with acceptable tolerability: patients are more likely to experience hyperaemia but less likely to have respiratory adverse
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