title: Evaluation of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy.
abstract: OBJECTIVE
  To evaluate the effects of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy (SEM).
  
  
  METHODS
  Twenty-eight female rabbits were randomly divided into four equal groups. Rabbits in groups 1 and 2 underwent intracameral injection of 1 mg/0.1 mL and 0.5 mg/0.05 mL ranibizumab, respectively; group 3 was injected with 1.25 mg/0.05 mL bevacizumab. All three groups were injected with a balanced salt solution (BSS) into the anterior chamber of the left (fellow) eye. None of the rabbits in group 4 underwent an injection. Corneal thickness and intraocular pressure were measured before the injections, on the first day, and in the first month after injection. The rabbits were sacrificed and corneal tissues were excised in the first month after injection. Specular microscopy was used for the corneal endothelial cell count. Endothelial cell density was assessed and comparisons drawn between the groups and the control. Micrographs were recorded for SEM examination. The structure of the corneal endothelial cells, the junctional area of the cell membrane, the distribution of microvillus, and the cell morphology of the eyes that underwent intracameral injection of vascular endothelial growth factor (VEGF), BSS, and the control group were compared.
  
  
  RESULTS
  Corneal thickness and intraocular pressure were not significantly different between the groups that underwent anti-VEGF or BSS injection and the control group on the first day and in the first month of injection. The corneal endothelial cell count was significantly diminished in all three groups; predominantly in group 1 and 2 (P<0.05). The SEM examination revealed normal corneal endothelial histology in group 3 and the control group. Eyes in group 1 exhibited indistinctness of corneal endothelial cell borders, microvillus loss in the luminal surface, excessive blebbing, and disintegration of intercellular junctions. In group 2, the cell structure of the corneal endothelium and intercellular junctions were normal. However, a relative reduction was observed in the microvillus density of endothelial cells. Although eyes in group 3 were morphologically similar to fellow eyes and the control group, disarrangement in endothelial cell borders was evident.
  
  
  CONCLUSIONS
  The SEM examination pointed out deterioration in endothelial cell morphology after intracameral injection of 1 and 0.5 mg ranizumab. However, the effects of intracameral bevacizumab injection on corneal endothelial cells were similar to those found in fellow eyes and the control group. Further large-scale studies that examine the cellular changes by transmission electron microscopy are required to support the results of the present study that evaluates the structural changes in endothelial cells by SEM.
authors.affiliation: 1 Department of Ophthalmology, Dicle University Medical School , Diyarbakir, Turkey .
authors.forename: Seyhmus
authors.initials: S
authors.lastname: Ari
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Nergiz
authors.forename: Ihsan
authors.initials: I
authors.lastname: Aksit
authors.forename: Alparslan
authors.initials: A
authors.lastname: Sahin
authors.forename: Kursat
authors.initials: K
authors.lastname: Cingu
authors.forename: Ihsan
authors.initials: I
authors.lastname: Caca
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D003315:Cornea / Q000187:drug effects / Q000648:ultrastructure; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D056965:Injections, Intraocular; D007429:Intraocular Pressure / Q000187:drug effects; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011817:Rabbits; D011897:Random Allocation; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab