title: Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit.
abstract: OBJECTIVE
  To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira) in the rabbit eye.
  
  
  METHODS
  Twelve New Zealand albino rabbits received unilateral intravitreous injections of 0.1 ml of adalimumab 0.25 mg (three eyes), 0.50 mg (three eyes), 1.0 mg (three eyes) or 0.1 ml balanced salt solution (BSS, three eyes). Slit-lamp biomicroscopy and fundoscopy were carried out at baseline, day 1, 7 and 14 following intravitreous injection, while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed.
  
  
  RESULTS
  Slit-lamp biomicroscopy and fundoscopy were normal in eyes having received BSS, 0.25 mg or 0.50 mg adalimumab; however, inflammation was present in two of three eyes having received 1.0 mg adalimumab. Similarly, comparison of scotopic and photopic ERG light at baseline and day 14 demonstrated no changes in eyes receiving BSS, 0.25 mg or 0.50 mg adalimumab, but two of three eyes having received 1.0 mg adalimumab showed a greater than 30% reduction in a and b wave. Finally, histopathology demonstrated no differences between eyes receiving BSS, 0.25 mg or 0.50 mg of adalimumab, but two of three eyes injected with 1.0 mg demonstrated inflammatory cell infiltration of the vitreous and anterior chamber, with one of these eyes demonstrating retinal necrosis.
  
  
  CONCLUSIONS
  Escalating doses of intravitreous adalimumab in rabbit eyes caused no detectable functional or structural ocular toxicity up to a dose of 0.50 mg. Administration of 1.0 mg in 0.1 ml was associated with an inflammatory reaction and retinal necrosis.
authors.affiliation: Department of Ophthalmology, University of São Paulo, Aramanaí St. 307, Alto de Pinheiros, 05450-030 São Paulo, SP, Brazil. roberta.manzano@gmail.com
authors.forename: Roberta P A
authors.initials: RP
authors.lastname: Manzano
authors.forename: Gholam A
authors.initials: GA
authors.lastname: Peyman
authors.forename: Petros E
authors.initials: PE
authors.lastname: Carvounis
authors.forename: Muhamet
authors.initials: M
authors.lastname: Kivilcim
authors.forename: Palwasha
authors.initials: P
authors.lastname: Khan
authors.forename: Patricia
authors.initials: P
authors.lastname: Chevez-Barrios
authors.forename: Walter
authors.initials: W
authors.lastname: Takahashi
mesh_terms: D000085:Acetates / Q000008:administration & dosage; D000068879:Adalimumab; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D004596:Electroretinography / Q000187:drug effects*; D007267:Injections; D008269:Macular Edema / Q000188:drug therapy; D008903:Minerals / Q000008:administration & dosage; D009887:Ophthalmoscopy; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012965:Sodium Chloride / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy; D014822:Vitreous Body
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C030660:BSS solution; D004338:Drug Combinations; D008903:Minerals; D014409:Tumor Necrosis Factor-alpha; D012965:Sodium Chloride; D000068879:Adalimumab