Multifaceted behavioral interventions to improve topical glaucoma therapy adherence in adults.

Rationale: Glaucoma is a leading cause of vision loss and blindness, characterized by optic nerve damage and commonly by increased intraocular pressure (IOP). Topical medical therapy is the most common first-line treatment option, yet adherence to these medications is notably low. Improving medication adherence is critical for managing glaucoma effectively.

Objectives: To assess the impact of two or more behavioral interventions (i.e. multifaceted interventions) on topical glaucoma therapy adherence in people utilizing IOP-lowering therapy for at least three months for treating ocular hypertension or glaucoma.

Search methods: We searched four electronic databases (CENTRAL, MEDLINE, Embase, LILACS), two clinical trial registries, and checked references. The latest search date was 31 May 2024.

Eligibility criteria: We included randomized controlled trials (RCTs) evaluating multifaceted behavioral interventions (≥ 3 months) for topical glaucoma therapy adherence compared with standard care in adults with glaucoma or ocular hypertension.

Outcomes: Outcomes were change in adherence to topical IOP-lowering medications, change in IOP, optical coherence tomography (OCT) stability, visual field (VF) stability, proportion of participants with disease stability, change in quality of life scores, and adverse events. The time point for these measurements was three months or longer follow-up. We extracted any information related to equity and social determinants of health, and their potential influence on the administration of or outcomes from the interventions.

Risk of bias: We assessed the risk of bias for all outcomes reported in the summary of findings tables using the Cochrane risk of bias 2 (RoB 2) tool, except for outcomes where no data were available.

Synthesis methods: Where possible, we synthesized results for outcomes using random-effects meta-analysis of risk ratios (RRs) for dichotomous outcomes, and mean difference (MD) or standardized mean difference (SMD) for continuous outcomes. Where meta-analysis was not possible due to the available data, we synthesized the results qualitatively following Cochrane-recommended approaches; including summarizing effect estimates and vote counting, accompanied by forest plots to show estimates without meta-analyses and harvest plots. We used the GRADE approach to assess the certainty of the evidence for prespecified outcomes.

Included studies: We included 17 RCTs that enrolled 4536 participants, ranging from 64 to 1800 per study. The mean age of participants ranged from 42 to 76 years. Studies were conducted across North America, Europe, and Asia, with most in the USA (47%). Among 12 studies reporting race and ethnicity, most participants were White (62%), followed by Black (26%), Asian (7%), Hispanic (1%), and others (3%). Follow-up periods ranged from 3 to 24 months. All but one study received financial support from multiple sources. We assessed the risk of bias in 25 outcome measures across 17 studies. We judged one study to be at low risk of bias for both adherence to topical IOP-lowering medications and IOP measures. Four studies reported both outcomes and overall were judged to have some bias concerns, and we judged three studies to have some bias concerns for only adherence. Two studies reported both outcomes with high risk of bias, and another study had a high overall risk of bias for adherence and some concerns for IOP. The remaining nine studies reported adherence only, and we judged these as having some concerns (three studies) or high risk (six studies) of overall bias.

Synthesis of results: In general, evidence on the effect of multifaceted interventions in improving glaucoma-related outcomes was inconsistent. We conducted an overall meta-analysis of adherent participants that included all comparisons and related subgroups, suggesting any multifaceted intervention may increase the proportion of adherent participants over any control, but the evidence is very uncertain (RR 1.18, 95% confidence interval (CI) 1.01 to 1.38; 8 studies, 2184 participants; I² = 71%; very low-certainty evidence). Another overall meta-analysis across two comparisons and three subgroups found multifaceted interventions may have little to no improvement on adherence measured by final mean (SMD 0.03, 95% CI -0.19 to 0.09; 4 studies, 758 participants). Qualitatively, vote-counting of estimates showed 14/17 (82%) estimates in favor of multifaceted interventions for improving adherence. Overall, the certainty of the evidence for difference in adherence was 'very low.' We classified included studies into three comparisons: 1. three or more components, composed of education plus two or more (five studies); 2. two components, including education plus one component with or without standard care (11 studies); and 3. two components, including devices plus other with or without standard care (one study). The comparators were standard care or other interventions. Vote-counting for difference in adherence for comparisons 1, 2, and 3 found 5/6 (83%), 8/10 (80%), and 1/1 (100%) estimates favored intervention, respectively. Certainty of the evidence regarding differences in adherence for Comparisons 1, 2, and 3 were 'very low', 'low', and 'low' respectively, primarily due to risk of bias, imprecision, and inconsistency. We had limited and mixed evidence for IOP and VF due to variabilities in outcome measurements across studies and insufficient data. Multifaceted interventions may not result in any IOP or VF improvements. No included studies reported the other prespecified outcome measures. Only five included studies reported whether social determinants of health had any associations with adherence to topical glaucoma medications. The social determinants addressed were race, education level of the participants, marital status, employment status, income level, age, number of chronic diseases, and level of health literacy. Evidence for the influence of these characteristics on intervention effectiveness was mixed.

Authors' conclusions: Based on very low- and low-certainty evidence identified in this review, it is unclear if multifaceted behavioral interventions have a beneficial effect on patient adherence to topical IOP-lowering medications and IOP in people with ocular hypertension or glaucoma. In most cases, we were unable to conduct meta-analysis due to the diversity of interventions, varying outcome definitions, and inconsistent reporting across studies. Future research would benefit from the adoption of standardized measurements and reporting methods for adherence to medication and clinical outcomes on disease stability, while taking social determinants into account.

Funding: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health.

Registration: Protocol available via doi.org/10.1002/14651858.CD015788.