title: Aqueous cytokine levels are associated with reduced macular thickness after intravitreal ranibizumab for diabetic macular edema.
abstract: OBJECTIVE
  It is controversial whether the administration of anti-vascular endothelial growth factor drugs for diabetic macular edema (DME) affects intraocular inflammatory cytokines. In this study, we measured cytokine concentration in aqueous humor before and after intravitreal injection of ranibizumab (IVR). The aim was to determine changes in cytokine concentration and their effects on DME reduction.
  
  
  METHODS
  Twelve patients (13 eyes) with DME received two IVR (0.5 mg) with a 1 month interval, and a total of 26 aqueous humor samples were obtained. Macular thickness was measured with an optical coherence tomography (OCT) using thickness-map mode with an Early Treatment Diabetic Retinopathy Study (ETDRS) 9-zone grid that was divided into two zones: a central circle with a diameter of 1 mm (zone1); and an outer circle with a diameter of 6 mm (zone2).
  
  
  RESULTS
  The concentration of eotaxin-1 in aqueous humor samples decreased significantly after IVR. Baseline cytokine concentration was associated with IVR-induced DME reduction. In zone1, higher baseline concentration of interferon-induced protein (IP)-10, and in zone 2, higher baseline concentration of granulocyte-macrophage colony-stimulating factor, IP-10, and tumor necrosis factor (TNF) α; and lower baseline concentration of eotaxin-1, interleukin (IL)-5, and IL-8 were associated with improved DME. Cytokine changes were associated with IVR-induced DME reduction. In zone1, lower concentration of IP-10 compared to baseline or higher concentration of macrophage inflammatory protein (MIP) -α, and in zone 2, lower concentration of IL-5 compared to baseline, IL-8, and IP-10 or higher concentration of eotaxin-1 and MIP-1β were associated with improved DME.
  
  
  CONCLUSIONS
  These findings suggest that ranibizumab affects the concentration of cytokines in aqueous humor. Various cytokines contribute to a decrease in retinal thickness, both in the center of the macula and in a larger area of the retina.
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoyasu
authors.identifier: http://orcid.org/0000-0001-5022-9856
authors.initials: T
authors.lastname: Shiraya
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Araki
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueta
authors.affiliation: Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tempei
authors.initials: T
authors.lastname: Miyaji
authors.affiliation: Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D001082:Aqueous Humor / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D058449:Intravitreal Injections; D008266:Macula Lutea / Q000187:drug effects* / Q000473:pathology*; D008269:Macular Edema / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069579:Ranibizumab / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D016207:Cytokines; D007155:Immunologic Factors; D000069579:Ranibizumab