title: Retinal toxicity of intravitreal trastuzumab in a rabbit model: preliminary results of an experimental study.
abstract: OBJECTIVE
  To evaluate the retinal toxicity of intravitreal trastuzumab in a rabbit model.
  
  
  METHODS
  Fourteen New Zealand albino rabbits, weighing between 2.5 and 3 kg were used for this study. In the first group (n=6), 0.1 mL trastuzumab 10 mg/mL was injected into the vitreous. In the second group (n=6), the same volume of sterile balanced saline solution was injected intravitreally (sham injection). Additionally, 0.1 mL of 2 other concentrations of trastuzumab (7.5 and 5 mg/mL, respectively), was injected into the vitreous of 2 rabbits. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of inflammation, infection, and toxicity. An electroretinogram (ERG) was performed at baseline and 14 days after the injection. The animals were killed on day 14 and a histological examination was performed in the enucleated eyes.
  
  
  RESULTS
  The clinical examination was unremarkable on either sham or intravitreal injection of trastuzumab. Conversely, the ERG was greatly affected and in 2 cases extinguished 14 days after trastuzumab injection. Consistent with electrophysiological abnormalities of the retina, signs of retinal edema in experimented eyes, suggesting morphologic retinal damage, were observed. In contrast, in the sham injected eyes, the ERG was normal without histopathologic retinal changes.
  
  
  CONCLUSIONS
  Intravitreal trastuzumab seems to be toxic to the retina in albino rabbits even at a concentration of 5 mg/mL. Further studies are needed to evaluate the safety of intravitreal trastuzumab in models of choroidal neovascularization, as well as to obtain experience concerning the intravitreal toxicity of trastuzumab in primates too and not only in rabbits.
authors.affiliation: 1 Laboratory of Electrophysiology, 1st Department of Ophthalmology, University of Athens , Athens, Greece .
authors.forename: Marilita M
authors.initials: MM
authors.lastname: Moschos
authors.forename: Irini P
authors.initials: IP
authors.lastname: Chatziralli
authors.forename: Christos
authors.initials: C
authors.lastname: Kalogeropoulos
authors.forename: Vasilios
authors.initials: V
authors.lastname: Georgountzos
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Agapitos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D058449:Intravitreal Injections; D010211:Papilledema / Q000139:chemically induced / Q000473:pathology; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D000068878:Trastuzumab
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab