Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration

Graefes Arch Clin Exp Ophthalmol. 2013 Feb;251(2):453-8. doi: 10.1007/s00417-012-2038-0. Epub 2012 May 11.


Background: Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities.

Methods: Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected.

Results: After an initial increase to a value of +5.0 ± 11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of -0.66 ± 16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1 ± 191.4 μm at baseline to a value of 289.9 ± 138.6 μm after initial therapy and stabilized at a value of 322.4 ± 199.5 μm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (-2.2 ± 5.0 versus 0.4 ± 7.4 letters; p = 0.046).

Conclusions: Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Delayed Diagnosis*
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Prospective Studies
  • Ranibizumab
  • Recurrence
  • Retina / pathology
  • Retreatment
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / physiopathology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ranibizumab