title: Effects of subconjunctival tocilizumab versus bevacizumab in treatment of corneal neovascularization in rabbits.
abstract: OBJECTIVE
  The aim of this study was to compare the antiangiogenic effects of subconjunctival application of bevacizumab and tocilizumab on the regression of corneal neovascularization (NV) in rabbits.
  
  
  METHODS
  Corneal neovascularization was induced in 48 eyes of 24 rabbits. Seven days after suture placement, the rabbits were divided into 4 groups of 6 rabbits each and treated subconjunctivally with 0.1 mL balanced salt solution (group 1), 0.1 mL tocilizumab (0.25 mg per 0.1 mL and 2.5 mg per 0.1 mL, groups 2 and 3), or 0.1 mL bevacizumab (2.5 mg per 0.1 mL) (group 4). Digital photographs of the eyes were obtained and the surface areas of corneal neovascularization were measured on days 7 and 14 after subconjunctival injections. On days 7 and 14, 3 rabbits were randomly chosen and the eyes were extracted. Half of the corneal specimens were analyzed histopathologically, and the other half were used to measure the concentrations of vascular endothelial growth factor (VEGF) and IL-6 using a multiplex bead assay, and the levels were compared with those of the controls.
  
  
  RESULTS
  The surface areas of induced corneal neovascularization were significantly smaller in groups 3 and 4 (2.5 mg of tocilizumab and 2.5 mg of bevacizumab) compared with the control group on days 7 and 14 (P < 0.05). Group 2 did not show significant difference from the control group on days 7 and 14. There were no differences observed in the reduced neovascularization areas in groups 3 and 4 on days 7 and 14. The concentrations of VEGF in groups 3 and 4 were significantly lower than in the control group, and IL-6 mRNA levels were significantly lower in group 3 than in the other groups (P < 0.001) on days 7 and 14. Immunohistochemical analysis confirmed the reduced expression of VEGF in all 3 experimental groups compared with the control group.
  
  
  CONCLUSIONS
  An antiangiogenic effect was observed after subconjunctival injection of 2.5 mg tocilizumab to an extent similar to that seen with 2.5 mg bevacizumab, which indicates that subconjunctival application of tocilizumab is effective for the inhibition of corneal neovascularization.
authors.affiliation: *Department of Ophthalmology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea; and †Department of Ophthalmology and Visual Science, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, Republic of Korea.
authors.forename: Ae Ri
authors.initials: AR
authors.lastname: Yoo
authors.forename: Sung Kun
authors.initials: SK
authors.lastname: Chung
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D003228:Conjunctiva; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab