title: Formation of immune complexes and thrombotic microangiopathy after intravitreal injection of bevacizumab in the primate eye.
abstract: BACKGROUND
  In this study, the effect of intravitreal injection of bevacizumab on choroidal blood vessels was examined in primate eyes.
  
  
  METHODS
  Four Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were enucleated on days 1, 4, 7 and 14. For each animal, one eye was embedded in paraffin whereas the other eye was embedded for electron microscopy. Seven untreated or PBS (phosphate buffered saline)-injected monkeys were used as controls.
  
  
  RESULTS
  Thrombotic microangiopathy was found in the choriocapillaris and choroidal vessels of all eight injected eyes. Acute microangiopathy was characterized ultrastructurally as swelling of the endothelium, loss of fenestrations and complete collapse of the capillaries, and was commonly observed in bevacizumab-treated eyes. Quantitative analysis showed reduction of the lumina of the choriocapillaris in the eyes of three of the monkeys. Bevacizumab was frequently localized inside the blood vessels, often filling the entire breadth of the vessels, and formed clusters with blood cells. Death of photoreceptors occurred in two monkeys.
  
  
  CONCLUSIONS
  This study indicate that intravitreal injection of bevacizumab in monkeys induces activation of platelets, degranulation of thrombocytes and neutrophils, formation of immune complexes, thrombotic microangiopathy and alteration of the blood flow in choroidal vessels.
authors.affiliation: Section of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Schleichstrasse 12/1, 72076 Tuebingen, Germany. Ulrich.Schraermeyer@med.uni-tuebingen.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Julien
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D001792:Blood Platelets / Q000502:physiology; D002196:Capillaries; D015550:Cell Degranulation; D002829:Choroid / Q000098:blood supply* / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D007105:Immune Complex Diseases / Q000139:chemically induced* / Q000473:pathology; D058449:Intravitreal Injections; D008252:Macaca fascicularis; D008856:Microscopy, Fluorescence; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D015539:Platelet Activation / Q000187:drug effects; D057049:Thrombotic Microangiopathies / Q000139:chemically induced* / Q000473:pathology; 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