Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab.
OBJECTIVE
To examine the ultrastructural effect of intravitreal bevacizumab on primate eyes with particular focus set on the choriocapillaris and to examine the influence of vascular endothelial growth factor (VEGF) inhibition on endothelial cell fenestration.


METHODS
Animal study.


METHODS
Four Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were enucleated and prepared for light and electron microscopy on days one, four, seven, and 14. Control eyes remained untreated. Choriocapillaris endothelial cell fenestrations were quantified.


RESULTS
Choriocapillaris endothelial cell fenestrations were significantly reduced after intravitreal injection of bevacizumab. Fenestration was lowest on day four (15.9 +/- 6.7 per 25 microm) and increased again from days seven to 14, but was still significantly lower than in the control (66.2 +/- 9.5 per 25 microm). Densely packed thrombocytes and leukocytes regionally occluded the choriocapillaris lumen of treated eyes. On day one an increased number of leukocytes filled in the choriocapillaris lumen. Photoreceptors were damaged in two of 40 light microscopic sections. On days one to seven, choroidal melanocytes contained giant melanosomes. None of these described features was found in controls.


CONCLUSIONS
Intravitreal bevacizumab causes ultrastructural changes in the choriocapillaris of primate eyes. A significant reduction of choriocapillaris endothelial cell fenestrations is seen as early as 24 hours after injection and their number increases again after two weeks. These findings may play a role in the early clinical effect of intravitreal bevacizumab for macular edema. Because an increased risk of circulation disturbances in the choriocapillaris cannot be excluded, patients should be carefully monitored.
Peters
Swaantje
S
University Eye Hospital Tübingen, Tübingen, Germany. Swaantje.Peters@googlemail.com
Heiduschka
Peter
P
Julien
Sylvie
S
Ziemssen
Focke
F
Fietz
Heike
H
Bartz-Schmidt
Karl Ulrich
KU
Schraermeyer
Ulrich
U
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D002196:Capillaries / Q000648:ultrastructure*; D002452:Cell Count; D002829:Choroid / Q000098:blood supply* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure*; D007267:Injections; D007962:Leukocytes / Q000187:drug effects / Q000648:ultrastructure; D008252:Macaca fascicularis; D008544:Melanocytes / Q000187:drug effects / Q000648:ultrastructure; D020460:Melanosomes / Q000187:drug effects / Q000648:ultrastructure; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab