Abstract
Purpose: :
Patients with advanced nonproliferative diabetic retinopathy (NPDR) are at increased risk of vision loss. The PKC–DRS2 study demonstrated that 32 mg/day ruboxistaurin (RBX) mesylate, an orally administered protein kinase C ß inhibitor, reduced the occurrence of sustained moderate visual loss (≥15–letter loss on the ETDRS scale sustained over the last 6 months of study participation) by 40% compared to placebo (from 9.1% to 5.5% of patients, p=0.034). We provide additional data on the effect of RBX on mean and categorical measures of visual acuity (VA) change.
Methods: :
The PKC–DRS2 study was a 36–month, randomized, double–masked, placebo–controlled, parallel, 70–center study in 685 patients (placebo, n=340; RBX, n=345), evaluating the effect of 32 mg/day RBX (po, qd) in patients with moderately severe to very severe NPDR (ETDRS retinopathy level ≥47A and ≤53E), a best–corrected ETDRS VA score of ≥45 letters (∼20/125 Snellen), and no prior panretinal photocoagulation in a study eye.
Results: :
RBX was associated with a better mean VA after ∼12 months of therapy, as compared to placebo. Mean baseline–to–endpoint change in VA (LOCF) was –0.8 vs. –2.6 letters in the RBX and placebo groups, respectively (p=0.012). From baseline to endpoint, a ≥15–letter gain in VA occurred in 4.9% vs. 2.4% of RBX and placebo study eyes, respectively (p=0.027), while a ≥15–letter loss of VA occurred in 6.7% vs. 9.9% of RBX and placebo study eyes, respectively (p=0.044). In addition to its positive effect on a sustained VA loss of ≥15–letters, RBX also reduced a sustained ≥10–letter loss (30% reduction, p=0.043) and a sustained ≥5–letter loss (23% reduction, p=0.033) when compared to placebo. There was a positive effect of RBX on VA loss both in eyes receiving and not receiving focal photocoagulation during the study.
Conclusions: :
Compared to placebo, RBX–treated patients experienced less VA loss, and had more frequent improvement and less frequent worsening of VA over the course of this 36–month study.
Keywords: diabetic retinopathy • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • visual acuity