Nonadherence or Nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration: A Mixed-Methods Systematic Review

Abstract

Topic: Systematic review of risk factors for nonadherence and nonpersistence to intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy for neovascular age-related macular degeneration (nAMD).

Clinical relevance: Lack of adherence (nonadherence) or undertreatment (nonpersistence) with respect to evidence from clinical trials remains a significant barrier to optimizing real-world outcomes for patients with nAMD. Contributing factors and strategies to address this are poorly understood.

Methods: Studies that reported factors for nonadherence and nonpersistence to anti-VEGF therapy as well as studies examining strategies to improve this were included. Trial eligibility and data extraction were conducted according to Cochrane review methods. Risk of bias was assessed using the Mixed Method Assessment Tool and certainty of evidence evaluated according to the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool. Data were collated descriptively.

Results: Of the 1284 abstract results screened, 124 articles were assessed in full and 37 studies met the inclusion criteria. Definitions of nonadherence and nonpersistence varied or were not reported. Nonpersistence occurred early, with up to 50% of patients stopping treatment by 24 months. High rates of nonadherence were similarly reported, occurring in 32% to 95% of patients. Certainty of this finding was downgraded to a moderate level because of the heterogeneity in definitions used across studies. Multiple factors determine nonadherence and nonpersistence, including at the condition, therapy, patient, social/economic, and health systems/healthcare team levels. Moderate quality evidence points to lower baseline vision and poorer response to treatment as condition-related variables. The effects of other factors were of lower certainty, predominantly due to small numbers and potential biases in retrospective assessment. Although many factors are not modifiable (e.g., patient comorbidity), other factors are potentially correctable (e.g., lack of transport or mismatched patient expectations). Evidence on strategies to improve adherence and persistence is limited, but where available, these have proven effective.

Conclusions: Awareness of factors related to poor patient adherence and persistence in nAMD could help identify at-risk populations and improve real-world outcomes. Further work is required to develop uniform definitions and establish high-quality evidence on interventions that can be easily implemented.

Keywords: Adherence; age-related macular degeneration; anti-VEGF; compliance; intravitreal; nonadherence; nonpersistence; persistence.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses–based flow diagram of screening process. nAMD = neovascular age-related macular degeneration.