Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy

Ophthalmology. 2006 Dec;113(12):2221-30. doi: 10.1016/j.ophtha.2006.07.032. Epub 2006 Sep 20.


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.

Design: Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial.

Participants: 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.

Main outcome measure: 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).

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetic Retinopathy / drug therapy*
  • Disease Progression
  • Double-Blind Method
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Macular Edema / drug therapy
  • Macular Edema / physiopathology
  • Male
  • Maleimides / adverse effects
  • Maleimides / therapeutic use*
  • Middle Aged
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C beta
  • Vision Disorders / prevention & control
  • Visual Acuity / drug effects*


  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • ruboxistaurin
  • Protein Kinase C
  • Protein Kinase C beta