title: The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema.
abstract: OBJECTIVE
  To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).
  
  
  METHODS
  A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.
  
  
  METHODS
  We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.
  
  
  METHODS
  Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).
  
  
  METHODS
  Mean average change in BCVA from baseline to month 1 through 12 and safety.
  
  
  RESULTS
  Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.
  
  
  CONCLUSIONS
  Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.
authors: Centre for Vision Research (Westmead Millennium Institute), University of Sydney, Sydney, Australia. paul.mitchell@sydney.edu.au
authors: Paul
authors: P
authors: Mitchell
authors: Francesco
authors: F
authors: Bandello
authors: Ursula
authors: U
authors: Schmidt-Erfurth
authors: Gabriele E
authors: GE
authors: Lang
authors: Pascale
authors: P
authors: Massin
authors: Reinier O
authors: RO
authors: Schlingemann
authors: Florian
authors: F
authors: Sutter
authors: Christian
authors: C
authors: Simader
authors: Gabriela
authors: G
authors: Burian
authors: Ortrud
authors: O
authors: Gerstner
authors: Andreas
authors: A
authors: Weichselberger
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000069579:Ranibizumab; D012160:Retina / Q000473:pathology; D019233:Retreatment; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab