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The Effect of Ruboxistaurin on Visual Loss in Patients With Moderately Severe to Very Severe Nonproliferative Diabetic Retinopathy

Initial Results of the Protein Kinase C ß Inhibitor Diabetic Retinopathy Study (PKC-DRS) Multicenter Randomized Clinical Trial

The purpose of this study was to evaluate the Safety and efficacy of the orally administered protein kinase C (PKC) ß isoform-selective inhibitor ruboxistaurin (RBX) in subjects with moderately severe to very severe nonproliferative diabetic retinopathy (NPDR). In this multicenter, double-masked, randomized, placebo-controlled study, 252 subjects received placebo or RBX (8, 16, or 32 mg/day) for 36–46 months. Patients had an Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy severity level between 47B and 53E inclusive, an ETDRS visual acuity of 20/125 or better, and no history of scatter (panretinal) photocoagulation. Efficacy measures included progression of DR, moderate visual loss (MVL) (doubling of the visual angle), and sustained MVL (SMVL). RBX was well tolerated without significant adverse effects but had no significant effect on the progression of DR. Compared with placebo, 32 mg/day RBX was associated with a delayed occurrence of MVL (log rank, P = 0.038) and of SMVL (P = 0.226). RBX reduction of SMVL was evident only in eyes with definite diabetic macular edema at baseline (10% 32 mg/day RBX vs. 25% placebo, P = 0.017). In multivariable Cox proportional hazard analysis, 32 mg/day RBX significantly reduced the risk of MVL compared with placebo (hazard ratio 0.37 [95% CI 0.17–0.80], P = 0.012). In this clinical trial, RBX was well tolerated and reduced the risk of visual loss but did not prevent DR progression.

Abbreviations: ACEI, ACE inhibitor; ARB, angiotensin receptor blocker; AREDS, Age-Related Eye Disease Study; DME, diabetic macular edema; DR, diabetic retinopathy; ECG, electrocardiogram; ETDRS, Early Treatment Diabetic Retinopathy Study; MVL, moderate visual loss; NPDR, nonproliferative DR; PRP, panretinal photocoagulation; PDR, proliferative DR; PKC, protein kinase C; PKC-DRS, Protein Kinase C ß Inhibitor Diabetic Retinopathy Study; PKC-DMES, Protein Kinase C ß Inhibitor Diabetic Macular Edema Study; RBX, ruboxistaurin; SMVL, sustained MLV; VEGF, vascular endothelial growth factor; VFQ, Visual Function Questionnaire

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