title: Early and Long-Term Responses to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I Data.
abstract: OBJECTIVE
  To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome.
  
  
  METHODS
  Post hoc analysis of randomized controlled trial data.
  
  
  METHODS
  Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52-156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [<5, 5-9, or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] in BCVA).
  
  
  RESULTS
  In the analysis population (340 eyes), <5-, 5- to 9-, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2%, and 37.1% of eyes, respectively, at 12 weeks, and 34.2%, 16.5%, and 49.3% of eyes at 156 weeks. Within each early BCVA response category (<5, 5-9, and ≥10 letters of improvement at 12 weeks), mean CFB BCVA at 52-156 weeks varied by <5 letters from that at 12 weeks. CFB BCVA and <5-letter improvement at 12 weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156 weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders.
  
  
  CONCLUSIONS
  Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks).
authors.affiliation: Valley Retina Institute, McAllen, Texas. Electronic address: maculadoc@aol.com.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Gonzalez
authors.affiliation: Allergan plc, Irvine, California.
authors.forename: Joanna
authors.initials: J
authors.lastname: Campbell
authors.affiliation: Pepose Vision Institute and Washington University School of Medicine, St Louis, Missouri.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Holekamp
authors.affiliation: Weill Cornell Medical College, New York, New York.
authors.forename: Szilárd
authors.initials: S
authors.lastname: Kiss
authors.affiliation: Department of Ophthalmology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Loewenstein
authors.affiliation: Department of Ophthalmology, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Augustin
authors.affiliation: Allergan plc, Irvine, California.
authors.forename: Julia
authors.initials: J
authors.lastname: Ma
authors.affiliation: Wills Eye Hospital, Philadelphia, Pennsylvania.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Ho
authors.affiliation: Allergan plc, Irvine, California.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Patel
authors.affiliation: Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Whitcup
authors.affiliation: Retinal Consultants of Arizona, Phoenix, Arizona; Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Pravin U
authors.initials: PU
authors.lastname: Dugel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D003930:Diabetic Retinopathy / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000008:administration & dosage*; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab