title: Histological findings of uveal capillaries in rabbit eyes after multiple intravitreal injections of bevacizumab.
abstract: OBJECTIVE
  To evaluate the potential toxicity of multiple intravitreal injections of bevacizumab on the uveal capillaries of rabbit eyes.
  
  
  METHODS
  Nine eyes of nine rabbits that received single intravitreal injections of bevacizumab (IVB) constituted the single IVB group, while nine eyes of nine rabbits that received three injections of IVB, with an interval of 28 days between injections, constituted the repeat IVB group. Seven eyes of seven rabbits constituted the control group. The rabbits in the single and repeat IVB groups were sacrificed 7 and 28 d after the single and third IVB injection, respectively. Uveal specimens were compared between groups after immunohistochemical staining. Ultrastructural findings were evaluated by electron microscopy. Control group rabbits were sacrificed 7 d after saline injection. Clinical examination and fundus fluorescein angiography were performed at baseline, 7 d after the first injection, and after the last injection.
  
  
  RESULTS
  Differences in the CD31-positive areas of the iris, ciliary body and choroid 7 d after IVB were not statistically significant among the single IVB, repeat IVB and control groups (p = 0.0749, p = 0.7237 and p = 0.7346, respectively; analysis of variance). Endothelial cell fenestrations (ECFs) in the choriocapillaris and ciliary body observed by electron microscopy on day 7 in the single and repeat IVB groups were decreased by 50% (p < 0.0001) and 33% (p < 0.0001), respectively, in both IVB groups compared with those in the control group. However, ECFs observed on day 28 in both groups were comparable to those observed in the control group.
  
  
  CONCLUSIONS
  Single IVB and repeated IVB did not have any effect on normal vessel endothelium density as per immunohistochemical findings. Ultrastructural findings revealed that IVB transiently decreased the ECFs in the choriocapillaris and ciliary body.
authors: Department of Ophthalmology and Visual Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. sugimoto@hiroshima-u.ac.jp
authors: Yosuke
authors: Y
authors: Sugimoto
authors: Hideki
authors: H
authors: Mochizuki
authors: Hidetaka
authors: H
authors: Miyagi
authors: Seiichi
authors: S
authors: Kawamata
authors: Yoshiaki
authors: Y
authors: Kiuchi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D002196:Capillaries / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D058449:Intravitreal Injections; D008854:Microscopy, Electron; D011817:Rabbits; D014602:Uvea / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab