title: Effects of intravitreal bevacizumab in repeated doses: an experimental study.
abstract: OBJECTIVE
  To evaluate the effects of repeated 1.25-mg intravitreal bevacizumab injections on cornea and uveoretinal tissues using histologic and biochemical analyses.
  
  
  METHODS
  Twenty-four New Zealand albino rabbits were used. Twelve rabbits received an injection of bevacizumab in their right eyes three times with an interval of 25 days (Group 1); their contralateral eyes served as controls (Group 2). Six rabbits had an injection of vehicle in both eyes (Group 3), with the same regimen as bevacizumab, and six rabbits' eyes were used as a sham group (Group 4). Enucleated eyes were used for histologic and biochemical analyses, which included the activities of caspase 3 and 8 enzymes, glutathione content, catalase activity, and malondialdehyde content.
  
  
  RESULTS
  No inflammation in aqueous humor and no sign of corneal or uveoretinal toxicity was found in bevacizumab-injected eyes. The difference of activity of corneal caspase 8 enzyme between Groups 1 and 2 and between Groups 1 and 4 was statistically significant (P < 0.05). In the uveoretinal tissue, in Group 1, the activities of caspase 3 and 8 enzymes were the lowest, and uveoretinal malondialdehyde content was also significantly lower than Group 4.
  
  
  CONCLUSIONS
  A repeated dose of intravitreal bevacizumab injection did not cause a toxic effect on cornea and uveoretinal tissue. Biochemically, it also did not cause any apoptosis, oxidative reaction, or lipid peroxidation. Instead, bevacizumab injection caused a considerable decrease in the apoptotic enzyme activities and lipid peroxidation in the uveoretinal tissue. Further studies are needed to be conducted for possible detrimental side effects and apoptotic and oxidative effects of repeated bevacizumab injections on both the injected and the contralateral eyes.
authors.affiliation: Department of Ophthalmology, Mersin University Faculty of Medicine, Mersin, Turkey. docayc@yahoo.com
authors.forename: Ayca
authors.initials: A
authors.lastname: Sari
authors.forename: Ufuk
authors.initials: U
authors.lastname: Adiguzel
authors.forename: Necmiye
authors.initials: N
authors.lastname: Canacankatan
authors.forename: Necat
authors.initials: N
authors.lastname: Yilmaz
authors.forename: Erdem
authors.initials: E
authors.lastname: Dinc
authors.forename: Ozay
authors.initials: O
authors.lastname: Oz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D000068258:Bevacizumab; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007267:Injections; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D008315:Malondialdehyde; D002374:Catalase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione