title: Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: relationships to bevacizumab treatment.
abstract: OBJECTIVE
  To characterize the differential expression of intraocular inflammatory cytokines in eyes with branch retinal vein occlusion (BRVO) and to assess their roles as prognostic determinants of BRVO.
  
  
  METHODS
  A prospective cohort study of 38 eyes with BRVO. Aqueous humor samples were collected just before the intravitreal injection of bevacizumab and were assessed for 18 cytokines, chemokines, and growth factors. For control, aqueous humor was collected from 28 eyes before cataract surgery.
  
  
  RESULTS
  In the aqueous of eyes with BRVO, the IL-23, IL-8, IL-6, IL-15, IL-12, and IL-17 levels were significantly higher than that in control eyes. Pretreatment visual acuity was significantly correlated with the concentrations of IL-8, IL-10, IL-2, IL-1β, IL-5, IL-6, IL-23, IL-4, MCP-1, IL-1α, IL-12, IL-13, IFN-γ, and IL-15. The pretreatment nonperfused area (NPA) was significantly correlated with the concentrations of IL-8, IL-2, MCP-1, and IL-6. Logistic regression analyses revealed significant associations between the BRVO and the concentrations of IL-8, IL-23, IL-12, IL-15, IL-10, IL-1β, and IL-13. IL-8 had the highest odds ratio (OR) and was significantly associated with NPA, central retinal thickness (CRT), and visual acuity. Bevacizumab treatment significantly improved visual acuity and CRT after 1 month. Refractoriness to bevacizumab (defined as CRT recovery 1 month after treatment by <90%) was significantly associated with the IL-12 level.
  
  
  CONCLUSIONS
  Of the induced cytokines in eyes with BRVO, IL-8 was the most significantly associated with the disease parameters of BRVO. IL-12 is most likely a factor that blocks the effect of bevacizumab treatment. (www.umin.ac.jp/ctr number, UMIN000003854.).
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Kaneda
authors.forename: Dai
authors.initials: D
authors.lastname: Miyazaki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Yakura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Terasaka
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Miyake
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Taisaku
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Baba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D016207:Cytokines / Q000378:metabolism*; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D015999:Multivariate Analysis; D016017:Odds Ratio; D009887:Ophthalmoscopy; D011446:Prospective Studies; D012170:Retinal Vein Occlusion / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab