title: Association of Circulating Markers With Outcome Parameters in the Bevacizumab and Ranibizumab in Diabetic Macular Edema Trial.
abstract: The purpose of this study was to evaluate selected candidate biomarkers as potential markers for patients with diabetic macular edema (DME) who receive antivascular endothelial growth factor (VEGF) therapy.
  
  
  
  Selected biomarkers included blood levels of messenger RNA (mRNA) of retinoschisin, RPE65, rhodopsin, and endothelial progenitor cell markers CD34 and CD133. Blood samples were obtained from 89 patients with DME according to the study protocol of the Bevacizumab and Ranibizumab in Diabetic Macular Edema (BRDME) study. During each monthly visit, patients underwent optical coherence tomography scanning and visual acuity was measured. Anti-VEGF injections were administered at fixed monthly intervals over 6 months. Analyses of covariance using simplified and linear mixed models were used to examine the correlations between candidate markers and changes in visual acuity and central subfield thickness.
  
  
  
  Plasma mRNA levels of retinoschisin were negatively associated with visual acuity, and plasma mRNA levels of rhodopsin were positively associated with visual acuity in patients with DME (P < 0.01 and P < 0.05, respectively). In addition, changes in central subfield thickness between baseline and months 1, 2, and 3 during anti-VEGF treatment were associated with mRNA levels of retinoschisin, rhodopsin, and the ratio of retinoschisin-to-rhodopsin (P < 0.01, all).
  
  
  
  This prospective, multicenter study found that circulating mRNA levels of retinoschisin and rhodopsin are associated with visual acuity and changes in central subfield thickness during anti-VEGF therapy in patients with DME. (ClinicalTrials.gov number: NCT01635790.).
authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 2Research Institute GUIDE, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Ward
authors.initials: W
authors.lastname: Fickweiler
authors.affiliation: Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klaassen
authors.affiliation: Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ilse M C
authors.initials: IM
authors.lastname: Vogels
authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: Hooymans
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 5W.J. Kolff Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Leonoor I
authors.initials: LI
authors.lastname: Los
authors.affiliation: Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 6Department of Ophthalmology, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000097:blood* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D000069579:Ranibizumab / Q000008:administration & dosage*; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D005136:Eye Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab