TY - JOUR
T1 - A single intravitreal injection of ranibizumab provides no neuroprotection in a nonhuman primate model of moderate-to-severe nonarteritic anterior ischemic optic neuropathy
AU - Miller, Neil R.
AU - Johnson, Mary A.
AU - Nolan, Theresa
AU - Guo, Yan
AU - Bernstein, Steven L.
N1 - Funding Information:
Supported by National Eye Institute Grant R01 EY019529 (Bethesda, MD, USA). Disclosure: N.R. Miller, None; M.A. Johnson, None; T. Nolan, None; Y. Guo, None; S.L. Bernstein, None
Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015/12
Y1 - 2015/12
N2 - PURPOSE. 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 laseractivated 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.
AB - PURPOSE. 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 laseractivated 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.
KW - Anterior ischemic optic neuropathy
KW - Intravitreal injection
KW - Neuroprotection
KW - Ranibizumab
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U2 - 10.1167/iovs.15-18015
DO - 10.1167/iovs.15-18015
M3 - Article
C2 - 26624498
AN - SCOPUS:84982719835
SN - 0146-0404
VL - 56
SP - 7676
EP - 7685
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 13
ER -