Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study

Ophthalmology. 2011 Apr;118(4):663-71. doi: 10.1016/j.ophtha.2010.12.019.


Objective: To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration.

Design: Twelve-month, phase III, multicenter, open-label, single-arm study.

Participants: A total of 513 ranibizumab-naïve SUSTAIN patients.

Intervention: Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe.

Main outcome measures: Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed.

Results: A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity [VA], vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 μm from baseline to month 3 and -91.5 μm from baseline to month 12.

Conclusions: The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies; individualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with individualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Female
  • Fluorescein Angiography
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Ranibizumab
  • Retina / pathology
  • Retreatment
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / physiopathology


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