Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with persistent/recurrent macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study)

Eye (Lond). 2012 Sep;26(9):1181-7. doi: 10.1038/eye.2012.174. Epub 2012 Aug 10.


Purpose: To determine the efficacy of intravitreal ranibizumab 2.0 mg in patients with recalcitrant neovascular age-related macular degeneration (AMD).

Methods: This single-masked, randomized, prospective, pilot study enrolled patients with subfoveal neovascular AMD. All study eyes had persistent subretinal (SRF) or intraretinal fluid (IRF) on spectral-domain optical coherence tomography (SD-OCT) <30 days following at least 6 monthly intravitreal injections of ranibizumab or bevacizumab. Patients were randomized 2 : 1 to receive either ranibizumab 2.0 or 0.5 mg. Following three-loading treatments 4-weeks apart, both groups were treated using a 'treat and extend' regimen guided by eye-tracked SD-OCT through month 12. The primary end point was the mean change in best-corrected visual acuity (BCVA) at month 6.

Results: Nine eyes of 9 patients (mean age ± SD, 82.0 ± 5.8 years) were enrolled. Seven eyes received ranibizumab 2.0 mg and two eyes received 0.5 mg. Owing to the small number of patients enrolled, no statistical comparison could be made between the two dosages. At month 6, the mean improvement in BCVA was +6.1 ± 3.7 (W=0, P<0.001) ETDRS letters and +2.0 ETDRS letters in the 2.0 and 0.5 mg groups, respectively. In the 2.0 mg group, there was a statistically significant decline in central foveal thickness, SRF and maximum pigment epithelial detachment height at 6 months compared with baseline. No adverse events were reported in either group.

Conclusion: Ranibizumab 2.0 mg has the potential to maintain or improve BCVA in some patients with persistent or recurrent SRF or IRF secondary to neovascular AMD despite prior monthly intravitreal anti-vascular endothelial growth factor therapy with the standard dose.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Female
  • Humans
  • Intravitreal Injections
  • Male
  • Pilot Projects
  • Prospective Studies
  • Ranibizumab
  • Single-Blind Method
  • Subretinal Fluid / metabolism*
  • 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 / metabolism


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