Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey

Arch Ophthalmol. 2005 Apr;123(4):509-16. doi: 10.1001/archopht.123.4.509.


Objective: To study the safety and efficacy of intravitreal injections of anti-vascular endothelial growth factor antibody fragment (ranibizumab [formerly known as rhuFabV2], Lucentis; Genentech, South San Francisco, Calif) in combination with intravenous verteporfin (Visudyne; Novartis, East Hanover, NJ) photodynamic therapy (PDT) on experimental choroidal neovascularization in the monkey eye.

Methods: Choroidal neovascularization was induced by laser injury in both eyes of cynomolgus monkeys and followed with weekly fundus photography and fluorescein angiography. Two weeks after induction, weekly treatments were initiated. These treatments included using either an intravitreal injection of ranibizumab (previously known as rhuFabV2) in combination with verteporfin PDT or a ranibizumab vehicle (placebo) in combination with verteporfin PDT (PDT only). Six animals (group 1) initially received intravitreal injections followed 1 week later by PDT. Four animals (group 2) initially received PDT followed 1 week later by intravitreal injection. Two animals (group 3) received injections and PDT on the same day at 2-week intervals. Photodynamic therapy was applied in all 3 groups every 2 weeks for 3 treatments with follow-up through 2 weeks after the last PDT treatment. Fluorescein angiograms were graded using a masked standardized protocol. The data were analyzed using the McNemar chi(2) test for matched pairs.

Results: No choroidal neovascularization leakage was observed in the eyes of animals treated with ranibizumab and PDT at day 21 or 42 after the start of the first treatment. Leakage persisted in eyes treated with PDT alone at 21 days (3 of 12 eyes) and 42 days (2 of 12 eyes). At all time points studied, the ranibizumab and PDT-treated eyes experienced better angiographic outcomes than the eyes receiving PDT alone.

Conclusion: These preliminary data indicate that an intravitreal ranibizumab injection in combination with verteporfin PDT (ranibizumab and PDT) causes a greater reduction in angiographic leakage than PDT and intravitreal vehicle injection (PDT only) in experimental choroidal neovascularization.

Clinical relevance: This combination therapy can potentially offer a new treatment modality for choroidal neovascularization in patients with macular degeneration and other diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Capillary Permeability
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / pathology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Fluorescein Angiography
  • Injections
  • Macaca fascicularis
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / therapeutic use*
  • Ranibizumab
  • Safety
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / immunology
  • Verteporfin
  • Vitreous Body


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Photosensitizing Agents
  • Porphyrins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Verteporfin
  • Ranibizumab