Effect of Ruboxistaurin on Visual Loss in Patients With Diabetic Retinopathy

Publication Type
Journal Article
Year of Publication
PKC-DRS Group; Aiello, L; Davis, M; Girach, A; Kles, K; Milton, R; Sheetz, M; Vignati, L; Zhi, X
Start Page
Date Published
Administration- Oral; Adult; Aged; Diabetic Retinopathy; Disease Progression; Double-Blind Method; Enzyme Inhibitors; Female; Indoles; macular edema; Male; Maleimides; Middle Aged; Protein Kinase C; Vision Disorders; visual acuity
{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