title: Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection.
abstract: OBJECTIVE
  To measure intraocular cytokine levels in patients with exudative age-related macular degeneration and analyze changes in the cytokine profile 2 days after intravitreal bevacizumab injection.
  
  
  METHODS
  This prospective case-control study enrolled 37 patients (37 eyes) with age-related macular degeneration including polypoidal choroidal vasculopathy. Twenty-eight age-matched patients (28 eyes) who underwent cataract surgery were used as controls. Undiluted aqueous humor samples were collected after intravitreal bevacizumab injection. Two days after intravitreal bevacizumab injection, cataract surgery was performed and undiluted aqueous humor samples were collected at the beginning of surgery (10 eyes). Twenty-three cytokines were measured using flow cytometry. P values were corrected in multiple comparisons using the conservative Bonferroni-Holm method. The level of significance was set at 0.0022 (0.05/23).
  
  
  RESULTS
  At baseline, aqueous humor levels of vascular endothelial growth factor, angiogenin, interferon gamma-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1β, monokine induced by interferon γ (Mig), and monocyte chemotactic protein (MCP)-1 were significantly higher in the age-related macular degeneration group than in the control group (P < 0.0022). The result of exploratory multivariate analysis showed that elevated angiogenin level was an important factor that discriminates the two groups (P = 0.0004). Two days after intravitreal bevacizumab injection, vascular endothelial growth factor levels tended to be reduced (P = 0.049), whereas interleukin (IL)-6 and IL-8 levels increased significantly (P < 0.0022).
  
  
  CONCLUSIONS
  Vascular endothelial growth factor and also angiogenin, IP-10, MCP-1, MIP-1β, and Mig may be related to the pathogenesis of age-related macular degeneration. Intravitreal bevacizumab injection increases inflammatory cytokine levels, suggesting the induction of an inflammatory process.
authors.affiliation: *Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan; and †Department of Ophthalmology, National Defense Medical College, Saitama, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Agawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Ma
authors.initials: M
authors.lastname: Juan
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Umazume
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D054407:Chemokine CCL4 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C046366:angiogenin; D012259:Ribonuclease, Pancreatic