title: AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.
abstract: OBJECTIVE
  To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema.
  
  
  METHODS
  A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 μm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone.
  
  
  RESULTS
  Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03).
  
  
  CONCLUSIONS
  Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.
authors.affiliation: *Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada; †Department of Ophthalmology, St Michael's Hospital, Toronto, Ontario, Canada*; ‡Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; §Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ¶The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada*; **Department of Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; ††Centre for Research on Inner City Health, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Roxane J
authors.initials: RJ
authors.lastname: Hillier
authors.forename: Elvis
authors.initials: E
authors.lastname: Ojaimi
authors.forename: David T
authors.initials: DT
authors.lastname: Wong
authors.forename: Michael Y K
authors.initials: MY
authors.lastname: Mak
authors.forename: Alan R
authors.initials: AR
authors.lastname: Berger
authors.forename: Radha P
authors.initials: RP
authors.lastname: Kohly
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kertes
authors.forename: Farzin
authors.initials: F
authors.lastname: Forooghian
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Boyd
authors.forename: Kenneth
authors.initials: K
authors.lastname: Eng
authors.forename: Filiberto
authors.initials: F
authors.lastname: Altomare
authors.forename: Louis R
authors.initials: LR
authors.lastname: Giavedoni
authors.forename: Rosane
authors.initials: R
authors.lastname: Nisenbaum
authors.forename: Rajeev H
authors.initials: RH
authors.lastname: Muni
mesh_terms: D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008266:Macula Lutea / Q000473:pathology; D008269:Macular Edema / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D014792:Visual Acuity
chemical_list: D015415:Biomarkers; D016207:Cytokines