Experts Define Nonadherence, Nonpersistence to Anti-VEGF Therapy for nAMD


A panel of retinal experts developed definitions for and classified the reasons behind patient nonadherence and nonpersistence.


Mali Okada, MMed

A new literature review established definitions for nonadherence and nonpersistence to anti-vascular endothelia growth factor (anti-VEGF) therapies in patients with neovascular age-related macular degeneration (nAMD).

Poor adherence has proven to be a barrier to the optimization of care for patients with wet AMD, and the challenges of the COVID-19 pandemic have particularly exacerbated these barriers.

“Previous discussions in ophthalmology have largely focused on how this behavior is associated with outcomes in glaucoma therapy,” the investigators wrote. “The concept of what constitutes adherence and persistence in nAMD, however, has not been clearly established.”

Led by Mali Okada, MMEd, Royal Victorian Eye and Ear Hospital, Australia, a team coordinated a systematic review that utilized a subcommittee panel of retinal experts, who were tasked with developing a set of definitions and classifications for validation.

As such, these definitions were restricted only to the wet AMD population.

Members of the Vision Academy, an international collaboration of >80 experts, provided external endorsement of these definitions.

Consensus was achieved through the Delphi method, which utilizes circulating questionnaires and individual scoring representing level of agreement with proposed definitions.

“If respondents disagreed, they were required to provide anonymized feedback on reasons for disagreement and suggested changes to the proposed definition,” the authors explained. 

A mean score of 7.5, the predetermined cutoff, was considered a consensus on a definition. A 50% or more positive response from the Vision Academy group constituted an external validation of the panel-determined definitions.

Defining Nonadherence and Nonpersistence

Nonadherence was thus defined as “missing ≥2 treatment or monitoring visits scheduled as advised by the treating physician over 12 months.” Since nonadherence is calculated within 12-month intervals, clinicians are able to measure changes in adherence patterns for each year.

However, a 2-week visit delay was allowed — afterwards, the clinician may indicate the appointment as missed by the patient.

Furthermore, a patient would be considered fully adherent if they attend every scheduled clinic visit and undergo every treatment or monitoring procedure over the 12-month interval.

Adherence, a much more realistic reality, was defined as missing ≤1 treatment or monitoring visit within the year.

Nonpersistence was defined as “nonattendance of any treatment or monitoring visit within the last 6 months.” According to the panel, a minimum of 6 months since the first injection was considered a reasonable period to assess persistence—especially since some treat-and-extend regimens allow for an extension up to 4 month, and no patients would have a year-long interval between visits or injections.

In their assessment of nonadherence and nonpersistence, the panel accounted for planned discontinuation—due to lack of treatment response or disease activity—and transfer of nAMD-related care to another physician.

They also proposed classifications for factors influencing nonadherence and nonpersistence, with patient associated, condition associated, therapy associated, health system and health care team associated, and social/economic as main categories. Each classification had subcategories to account for nuances.

“Understanding the prevalence and reasons behind nonadherence and nonpersistence is important, in that they remain significant barriers to optimizing outcomes for patients with nAMD,” the authors wrote.

“The validated definitions and classification system proposed […] provide an opportunity to raise awareness among health care professionals and patients. It also sets out a uniform language for use in future research for easier comparison.”

The study, “Defining Nonadherence and Nonpersistence to Anti–Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration,” was published online in JAMA Ophthalmology

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