Identifying Treatment Nonadherence Factors in nAMD May Improve Outcomes

Precocious Senile Macular Degeneration In 46 Year Old Man With Choroidal Neovascularization. Photograph Of The Back Of Eye. (Photo By BSIP/UIG Via Getty Images)
An investigation uncovers the reasons behind the nearly 60% nonadherence and nonpersistence rate in patients with neovascular age-related macular degeneration after 24 months.

Patient illness, fear of intraocular injections and discomfort following intraocular injections top the list of reasons patients with neovascular age-related macular degeneration (nAMD) are either nonadherent or nonpersistant, according to a study published in Ophthalmology. 

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections require patients with nAMD to travel to an ophthalmologist for frequent and ongoing injections. Research shows that rate of reported nonadherence and nonpersistence in nAMD is up to 60% at 24 months follow-up, with the majority of cases occurring within 6 to 12 months. The objective of this study was to identify the factors affecting this lack of treatment adherence and undertreatment.

In this systematic review, researchers reviewed studies that reported various factors for nonadherence and undertreatment related to anti-VEGF injections in nAMD. The researchers also looked into studies that examined strategies to improve adherence, and those that examined general treatment barriers. The primary outcome measure was risk factors or reasons for nonadherence and undertreatment following at least one intravitreal anti-VEGF injection. Secondary outcome measures were the efficacy of strategies to improve adherence and persistence and rates of nonadherence and nonpersistence.

Nonadherence was defined as:

1. No treatment or consultation with a measure of visual acuity and OCT at least every 6 weeks.
2. Extreme violation of prescribed treatment.
3. Non-attendance of every clinic appointment.
4. Receiving less than the recommended 8 injections over 12 months.
5. Deviation from treatment recommendations with gap in treatment or consultation by more than 8 weeks.
6. Visit outside of the prescribed 28 days (± 7 days) window.

Non-persistence was defined as: 

  1. Treatment discontinuation before 12 months, study period or permanently.
  2. No treatment or visit at clinic for more than 4 months, 6 months or 12 months.
  3. No follow up by any ophthalmologist for 3 months.
  4. No follow up within a 12 months period after receiving at least 1 anti-VEGF injection.
  5. Loss of follow up of at least 24 months.

Researchers revealed that of the 1284 studies yielded from the database, 37 met inclusion criteria. Rates of nonadherence to treatment were high with variable rates between 32% and 95%. Between 3% and 30% of patients with nAMD discontinued treatment due to disease remission or treatment futility as determined by their physicians. 

Factors identified to affect nonadherence were broken into 5 categories. They included those that were condition-related (eg, worsened visual acuity), patient-related (eg, fear of injections, illness), therapy-related, health system-related (eg, inconvenient appointments, insufficient clinic capacity), and social (eg, financial burden). Factors identified to affect undertreatment were similar to those that affected treatment nonadherence. The patient-related variables were significant, with patient illness (21.0 – 42.8%) and fear of injections (n = 30, 21%) both proving to be a barrier to treatment. Health-system factors were also substantial with patients saying they forgot their appointment (15%), the appointments were too frequent or inconvenient (10%) or there was insufficient clinic capacity with no available appointments in the time frame the patient required (47%). Many also cited a social factor; a lack of caretakers to take them to appointments (25.9%).

Patients whose vision improved with treatment of > 3 lines were more likely to be adherent (19.9% vs 12.0%, P =6 0.04). 

The study researchers concluded that reasons for patient nonadherence and nonpersistence to intravitreal injections in nAMD are complex and that these terms should be standardized and better defined to identify at-risk patients and to develop meaningful interventions and favorable long-term visual outcomes.

Disclosure: This clinical trial was supported by Bayer Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures.


Okada M, Mitchell P, Finger RP, et al. Non-adherence or non-persistence to intravitreal injection therapy for neovascular age-related macular degeneration: a mixed-methods systematic reviewOphthalmol. [Published online August 5, 2020]. doi: 10.1016/j.ophtha.2020.07.060