title: A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy.
abstract: OBJECTIVE
  Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION).
  
  
  METHODS
  We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes.
  
  
  RESULTS
  A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes.
  
  
  CONCLUSIONS
  A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION.
authors.affiliation: The Wilmer Eye Institute the Johns Hopkins Medical Institutions, Baltimore, Maryland, United States 2Department of Ophthalmology and Visual Sciences, the University of Maryland School of Medicine, Baltimore, Maryland, United States.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Miller
authors.affiliation: Department of Ophthalmology and Visual Sciences, the University of Maryland School of Medicine, Baltimore, Maryland, United States.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Resources, the University of Maryland School of Medicine, Baltimore, Maryland, United States.
authors.forename: Theresa
authors.initials: T
authors.lastname: Nolan
authors.affiliation: Department of Ophthalmology and Visual Sciences, the University of Maryland School of Medicine, Baltimore, Maryland, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Ophthalmology and Visual Sciences, the University of Maryland School of Medicine, Baltimore, Maryland, United States.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Bernstein
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005451:Fluorescein Angiography; D058449:Intravitreal Injections; D008253:Macaca mulatta; D008297:Male; D009389:Neovascularization, Pathologic; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology*; D018917:Optic Neuropathy, Ischemic / Q000473:pathology*; D000069579:Ranibizumab / Q000008:administration & dosage / Q000494:pharmacology*; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D012395:Rose Bengal / Q000494:pharmacology; D041623:Tomography, Optical Coherence
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D012395:Rose Bengal; D000069579:Ranibizumab