The reactivation time in the treatment of AMD: a forgotten key parameter?
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.
KeywordsTime-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.
For this type of study, formal consent is not required
- 3.Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I (2008) The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 115(1):116–126CrossRefPubMedGoogle Scholar
- 5.ANCHOR Study Group; Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Lanchulev T (2006) Ranibizumab versus Verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 116(1):57–65Google Scholar
- 7.Real JP, Tártara I, Allemandi D, Granero G, Palma SD (2011) Tratamiento de la degeneración macular asociada a la edad (DMAE). Atención Farmacéutica. (European Journal of Clinical Pharmacy) Barcelona: rasgo editorial. 13(3):160–171Google Scholar
- 13.Moraleda A, Villalba CM (2013) Modelado y Simulación de Eventos Discretos (ebook), 1ra edicion edn. Uned. Universidad Nacional de Educacion a Distancia, EspañaGoogle Scholar
- 16.Arroyo I, Bravo LC, Llinas H, Munoz FL (2014) Distribuciones Poisson y Gamma: Una Discreta y Continua Relación. Prospect. [online], 12(1):99–107. http://www.scielo.org.co/pdf/prosp/v12n1/v12n1a12.pdf
- 17.Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration; http://handbook-5-1.cochrane.org. Accessed 6 Jul 2015
- 18.Berg K, Hadzalic E, Gjertsen I, Forsaa V, Berger LH, Kinge B, Henschien H, Fossen K, Markovic S, Pedersen TR, Sandvik L, Bragadóttir R (2015) Ranibizumab or Bevacizumab for neovascular age-related macular degeneration according to the Lucentis compared to Avastin study treat-and-extend protocol: two-year results. Ophthalmology 123(1):51–59CrossRefPubMedGoogle Scholar
- 19.IVAN study investigators [IVAN], Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, Reeves BC (2013) Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet 382(9900):1258–1267CrossRefGoogle Scholar