title: Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.
abstract: OBJECTIVE
  To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial.
  
  
  METHODS
  Discussion of treatment protocol for DME.
  
  
  METHODS
  Subjects with vision loss resulting from DME involving the center of the macula.
  
  
  METHODS
  The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale.
  
  
  METHODS
  Clinical guidelines based on a DRCR.net protocol.
  
  
  RESULTS
  The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed.
  
  
  CONCLUSIONS
  Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.forename: David J
authors.initials: DJ
authors.lastname: Browning
authors.forename: K V
authors.initials: KV
authors.lastname: Chalam
authors.forename: Matthew
authors.initials: M
authors.lastname: Davis
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Adam R
authors.initials: AR
authors.lastname: Glassman
authors.forename: Raj K
authors.initials: RK
authors.lastname: Maturi
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Stockdale
authors.forename: Trexler M
authors.initials: TM
authors.lastname: Topping
mesh_terms: D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D035843:Biomedical Research / Q000458:organization & administration / Q000592:standards*; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D000069579:Ranibizumab; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab