title: Ocular Hypertension Following Intravitreal Antivascular Endothelial Growth Factor Therapy: Review of the Literature and Possible Role of Nitric Oxide.
abstract: OBJECTIVE
  To review the literature regarding ocular hypertension following intravitreal antivascular endothelial growth factor therapy, and to propose a novel mechanism for the development of ocular hypertension as a result of such therapy.
  
  
  METHODS
  The PubMed database was used to identify publications by using combinations of the search terms, "glaucoma," "ocular hypertension," "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-vascular endothelial growth factor," intraocular pressure," and "intravitreal." The reference lists of these publications were also reviewed for relevant articles.
  
  
  RESULTS
  Numerous articles have been published describing ocular hypertension, either immediate-term/short-term or delayed/sustained, following intravitreal antivascular endothelial growth factor therapy. Ocular hypertension has been reported following intravitreal pegaptanib, bevacizumab, and ranibizumab, and aflibercept. On the basis of the fact that vascular endothelial growth factor, normally present as a vascular modulating and reparative growth factor, is known to upregulate endothelial nitric oxide (NO) synthase, and that NO has been shown to decrease intraocular pressure in both normal and glaucomatous human and animal eyes, we propose a novel mechanism for sustained ocular hypertension following intravitreal antivascular endothelial growth factor therapy. We propose that such intravitreal therapy may lead to decreased NO in the anterior segment, which then leads to trabecular meshwork constriction, decreased outflow facility, and increased intraocular pressure.
  
  
  CONCLUSIONS
  Sustained ocular hypertension following the intravitreal administration of antivascular endothelial growth factor agents is a potentially serious side effect that has not been adequately explained. Further investigation is necessary to determine the role of NO in the mediation of this adverse effect.
authors.affiliation: *Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR †John A. Moran Eye Center, University of Utah, Salt Lake City, UT.
authors.forename: R Grant
authors.initials: RG
authors.lastname: Morshedi
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Ricca
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Wirostko
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000009:adverse effects; D000068258:Bevacizumab / Q000009:adverse effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D058449:Intravitreal Injections; D009569:Nitric Oxide / Q000502:physiology*; D009798:Ocular Hypertension / Q000139:chemically induced* / Q000378:metabolism; D000069579:Ranibizumab / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D014065:Tonometry, Ocular; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; C495058:pegaptanib; D000068258:Bevacizumab; D009569:Nitric Oxide; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab