Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration

Mali Okada, Tien Yin Wong, Paul Mitchell, Bora Eldem, S James Talks, Tariq Aslam, Vincent Daien, Francisco J Rodriguez, Richard Gale, Jane Barratt, Robert P Finger, Anat Loewenstein

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Importance: Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context.

Objective: To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy.

Design, Setting, and Participants: Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions.

Main Outcomes and Measures: Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD.

Results: Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD.

Conclusions and Relevance: This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalJAMA Ophthalmology
Issue number7
Early online date3 Jun 2021
Publication statusPublished - 1 Jul 2021


  • Angiogenesis Inhibitors/administration & dosage
  • Consensus
  • Delphi Technique
  • Humans
  • Intravitreal Injections
  • Macular Degeneration/drug therapy
  • Medication Adherence
  • Neovascularization, Pathologic
  • Practice Patterns, Physicians'
  • Signal Transduction
  • Socioeconomic Factors
  • Terminology as Topic
  • Vascular Endothelial Growth Factor A/antagonists & inhibitors


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