title: Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.
abstract: OBJECTIVE
  Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration.
  
  
  OBJECTIVE
  To examine patterns of visual and anatomical response to ranibizumab treatment.
  
  
  METHODS
  This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015.
  
  
  METHODS
  Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12).
  
  
  METHODS
  Changes from baseline in BCVA and central foveal thickness (CFT).
  
  
  RESULTS
  In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month 12, early vs delayed responders in the PRN treatment groups received 7.5 vs 7.4 ranibizumab injections, respectively (P = .84). More than 80% of early responders receiving PRN treatment maintained 15-letter or greater gains at month 24. At baseline, early vs delayed responders had worse BCVA (49.8 vs 55.4 letters; P < .001) and greater CFT (374.9 vs 339.0 µm; P = .02), although anatomical results were comparable by month 3 (CFT, 187.7 vs 188.9 µm).
  
  
  CONCLUSIONS
  Improvement of 15 letters or more from baseline occurred in 266 (25.2%) of 1057 patients within 3 months of beginning ranibizumab treatment, whereas an additional 135 (13.7%) of 988 patients achieved this gain by 12 months. The 2 cohorts had similar anatomical temporal response patterns. PRN treatment with monthly monitoring was effective in maintaining early vision gains and allowing delayed vision gains. These results suggest that vision improvement can continue in some patients after macular edema resolves and CFT decreases stabilize.
authors.affiliation: Ophthalmic Consultants of Long Island, Lynbrook, New York.
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Stoller
authors.affiliation: The Retina Center at Pali Momi, Aiea, Hawaii3Retina Consultants of Hawaii, University of Hawaii School of Medicine, Honolulu.
authors.forename: Gregg T
authors.initials: GT
authors.lastname: Kokame
authors.affiliation: Retina Northwest, Portland, Oregon.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Dreyer
authors.affiliation: Genentech Inc, South San Francisco, California.
authors.forename: Howard
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: Genentech Inc, South San Francisco, California.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Tuomi
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D000069579:Ranibizumab / Q000627:therapeutic use*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology*; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab