title: Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection.
abstract: OBJECTIVE
  To examine the histopathologic effect of a single intravitreal injection of bevacizumab on newly formed vessels in eyes with proliferative diabetic retinopathy (PDR).
  
  
  METHODS
  Interventional case series and laboratory investigation.
  
  
  METHODS
  Two days after intravitreal injection of bevacizumab (1.25 mg/eye), pars plana vitrectomy or trabeculectomy was performed for the treatment of PDR or neovascular glaucoma (NVG) associated with PDR. Ten surgically removed preretinal proliferative tissues and 6 deep scleral flaps containing trabecular meshwork were fixed in 2% glutaraldehyde or 4% paraformaldehyde and were subjected to transmission electron microscopic analysis, immunohistochemical analysis, and terminal deoxyuridiine triphosphate (dUTP) nick-end labeling staining. Two surgically removed preretinal proliferative tissues and 2 deep scleral flaps from patients with PDR and NVG, but without preoperative intravitreal injection of bevacizumab (IVB), served as controls.
  
  
  RESULTS
  In control tissues, vascular endothelial cells possessed many fenestrations and were accompanied by pericytes. Apoptotic vascular endothelial cells frequently were observed in tissue after intravitreal injection of bevacizumab, whereas they were not observed in control tissues. Additionally, no apparent fenestration was observed in newly formed vessels from either proliferative tissue or trabecular meshwork after intravitreal injection of bevacizumab. In both PDR and NVG tissues after intravitreal injection of bevacizumab, overexpression of smooth muscle actin was observed in newly formed vessels, suggesting that the treatment may have increased pericytes on the vasculature as compared with control tissue.
  
  
  CONCLUSIONS
  Intravitreal injection of bevacizumab may induce changes in immature, newly formed vessels of PDR or NVG tissue, leading to endothelial apoptosis with vascular regression, while inducing normalization of premature vessels by increasing pericyte coverage and reducing vessel fenestration.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ri-ichiro
authors.initials: R
authors.lastname: Kohno
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hata
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Arita
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kawahara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kita
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Hisatomi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D015355:Glaucoma, Neovascular / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D006442:Glycated Hemoglobin; D006801:Humans; D020287:In Situ Nick-End Labeling; D007267:Injections; D008875:Middle Aged; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D014129:Trabecular Meshwork / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D014130:Trabeculectomy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014821:Vitrectomy; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D006442:Glycated Hemoglobin; D042461:Vascular Endothelial Growth Factor A