The reactivation time in the treatment of AMD: a forgotten key parameter?

  • J. P. Real
  • J. D Luna
  • S. D. Palma
Retinal Disorders



Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB).


Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method).


Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ).


There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.


Time-to-treatment Ranibizumab Macular degeneration Angiogenesis inhibitors/therapeutic use 


Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

For this type of study, formal consent is not required

Supplementary material

417_2018_3974_MOESM1_ESM.docx (54 kb)
ESM 1 (DOCX 54 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • J. P. Real
    • 1
  • J. D Luna
    • 2
  • S. D. Palma
    • 1
  1. 1.Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina
  2. 2.Vitreo-Retinal DepartmentCentro Privado de Ojos Romagosa SA - Fundación VERCórdobaArgentina

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