title: Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration.
abstract: BACKGROUND
  The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis.
  
  
  METHODS
  The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed.
  
  
  CONCLUSIONS
  Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.
authors.affiliation: Dipartimento di Scienze per la Salute, Cattedra di Oculistica, Università degli Studi del Molise, Campobasso, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Costagliola
authors.forename: Luca
authors.initials: L
authors.lastname: Agnifili
authors.forename: Barbara
authors.initials: B
authors.lastname: Arcidiacono
authors.forename: Sarah
authors.initials: S
authors.lastname: Duse
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fasanella
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Mastropasqua
authors.forename: Marco
authors.initials: M
authors.lastname: Verolino
authors.forename: Francesco
authors.initials: F
authors.lastname: Semeraro
mesh_terms: D060433:Administration, Ophthalmic; D006801:Humans; D013923:Thromboembolism / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014822:Vitreous Body; D057135:Wet Macular Degeneration / Q000188:drug therapy*
chemical_list: D042461:Vascular Endothelial Growth Factor A