Systematic review: non-adherence and non-persistence in intravitreal treatment

Graefes Arch Clin Exp Ophthalmol. 2020 Oct;258(10):2077-2090. doi: 10.1007/s00417-020-04798-2. Epub 2020 Jun 22.


Purpose: Intravitreal injection of VEGF inhibitors has become the standard of care for different macular diseases within the last years resulting in improved visual outcomes. Under real-life conditions, however, the necessity for frequent retreatments and reexaminations poses a burden for patients and treatment centers. Non-adherence and non-persistence to intravitreal treatment may lead to inferior clinical outcomes, and knowledge of contributing factors is crucial to improve adherence. This systematic review analyzes current literature for potential factors involved in non-adherence and non-persistence.

Methods: A systematic search was conducted in PubMed and Embase including three different aspects of intravitreal injection therapy: (1) diseases with intravitreal injections as treatment, (2) intravitreal injection, and (3) aspects of therapy adherence or therapy persistence. Data from identified quantitative studies were further extracted and grouped according to WHO criteria (condition, socio-economy, therapy, patient, and health system). The methodological quality of identified studies was graded. Identified qualitative studies (i.e., interviews) were descriptively analyzed and their findings narratively reported.

Results: Twenty-four publications were included. In 16 of those publications, a quantitative data analysis was conducted, analyzing factors associated with non-adherence. Worse visual acuity at baseline and unfavorable development of visual acuity, higher age, and greater distance to the treatment center were associated with non-adherence, while there was inconsistent evidence for an association of comorbidity. In qualitative studies, high follow-up/treatment burden, fear and anxiety, disappointed patient expectations, and lack of motivation to continue treatment were reported as reasons for non-persistence.

Conclusions: Knowledge of potential barriers in IVT treatment may improve adherence and potentially clinical results. Improvements can be achieved particularly in the healthcare complex (organizational improvements) and the "patient" complex by establishing realistic expectations. Recurrent education of the patient may be necessary.

Keywords: AMD; Adherence; DME; Intravitreal; Persistence; VEGF.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors* / therapeutic use
  • Humans
  • Intravitreal Injections
  • Ranibizumab*
  • Vascular Endothelial Growth Factor A
  • Visual Acuity


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Ranibizumab