title: Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy.
abstract: OBJECTIVE
  To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes.
  
  
  METHODS
  Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial.
  
  
  METHODS
  Six hundred eighty-five patients randomized at 70 clinical sites.
  
  
  METHODS
  Ophthalmologic examination was performed at screening and at each 3-month visit. Retinopathy status was assessed every 6 months with Early Treatment Diabetic Retinopathy Study (ETDRS) standard 7-field 30 degrees color stereoscopic fundus photography. Levels of diabetic retinopathy and diabetic macular edema were determined by 2 independent graders masked to site and treatment assignment, with additional independent adjudication as required. Eligible patients had a best-corrected visual acuity (VA) score of > or =45 letters, retinopathy level > or = 47A and < or = 53E, and no prior panretinal photocoagulation in at least one eye.
  
  
  METHODS
  Effect of oral ruboxistaurin (32 mg/day) on reduction of sustained moderate visual loss (> or =15-letter decrease in ETDRS VA score maintained > or = 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy.
  
  
  RESULTS
  Sustained moderate visual loss occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin-treated patients after 12 months. Baseline-to-end point visual improvement of > or =15 letters was more frequent (4.9% vs. 2.4%) and > or =15-letter worsening was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to placebo (P = 0.005). When clinically significant macular edema was >100 microm from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 microm (68% vs. 50%, P = 0.003). Initial laser treatment for macular edema was 26% less frequent in eyes of ruboxistaurin-treated patients (P = 0.008).
  
  
  CONCLUSIONS
  Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with nonproliferative retinopathy.
authors.affiliation: Beetham Eye Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA. LPAiello@Joslin.Harvard.edu
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Davis
authors.forename: Aniz
authors.initials: A
authors.lastname: Girach
authors.forename: Keri A
authors.initials: KA
authors.lastname: Kles
authors.forename: Roy C
authors.initials: RC
authors.lastname: Milton
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sheetz
authors.forename: Louis
authors.initials: L
authors.lastname: Vignati
authors.forename: Xin Eric
authors.initials: XE
authors.lastname: Zhi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008269:Macular Edema / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008301:Maleimides / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta; D014786:Vision Disorders / Q000517:prevention & control; D014792:Visual Acuity / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta