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Copyright © 2017 Jeffrey J. Tan et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Intravitreal bevacizumab (Avastin) use in preterm infants with retinopathy of prematurity is associated with severe neurological disabilities, suggesting vascular leakage. We examined the hypothesis that intermittent hypoxia (IH) potentiates intravitreal Avastin leakage. Neonatal rats at birth were exposed to IH from birth (P0)–P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg) was injected intravitreally into the left eye. Animals were placed in room air (RA) until P23 or P45 for recovery (IHR). Hyperoxia-exposed and RA littermates served as oxygen controls, and equivalent volume saline served as the placebo controls. At P23 and P45 ocular angiogenesis, retinal pathology and ocular and systemic biomarkers of angiogenesis were examined. Retinal flatmounts showed poor peripheral vascularization in Avastin-treated and fellow eyes at P23, with numerous punctate hemorrhages and dilated, tortuous vessels with anastomoses at P45 in the rats exposed to IH. These adverse effects were associated with robust increases in systemic VEGF and in both treated and untreated fellow eyes. Histological analysis showed severe damage in the inner plexiform and inner nuclear layers. Exposure of IH/IHR-induced injured retinal microvasculature to anti-VEGF substances can result in vascular leakage and adverse effects in the developing neonate.

Details

Title
Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy
Author
Tan, Jeffrey J 1 ; Cai, Charles L 2 ; Shrier, Eric M 1 ; McNally, Lois 1 ; Lazzaro, Douglas R 1 ; Aranda, Jacob V 3 ; Beharry, Kay D 3   VIAFID ORCID Logo 

 Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; State University of New York Eye Institute, New York, NY, USA 
 Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA 
 Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; State University of New York Eye Institute, New York, NY, USA; Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA 
Editor
Thomas Bertelmann
Publication year
2017
Publication date
2017
Publisher
John Wiley & Sons, Inc.
ISSN
2090004X
e-ISSN
20900058
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2407638137
Copyright
Copyright © 2017 Jeffrey J. Tan et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.