The Effect of the Oral PKC ß Inhibitor, Ruboxistaurin, on the Progression of Diabetic Macular Edema

Abstract

Purpose:: Previously, we demonstrated that oral administration of ruboxistaurin (RBX) reduced sustained moderate visual loss (SMVL; ≥ 15 letter loss on the ETDRS scale sustained for the last 6 mo. of study participation) in patients with moderately severe to very severe nonproliferative diabetic retinopathy (NPDR) and also reduced the progression of diabetic macular edema (DME) to within 100 µm of the center of the macula in patients with clinically significant macular edema (CSME) at baseline. We present further analyses on the effect of RBX on the progression of DME as quantified with the modified ETDRS DME severity scale.

Methods:: The PKC-DRS2 was a multi-center, parallel, placebo (PBO)-controlled, double-masked, randomized phase 3 trial. Patients received either RBX 32 mg/day (N=345) or PBO (N=340) orally and were followed for 36 months. Eligible patients had type 1 or 2 diabetes, moderately severe to very severe NPDR, no previous panretinal photocoagulation (PC), and best-corrected visual acuity score (VA) of ≥45 letters (~20/125 Snellen).

Results:: Analysis of DME severity using the modified ETDRS scale demonstrated that increased DME severity was associated with lower mean VA. There was more frequent improvement and less frequent worsening in DME severity from baseline to endpoint in eyes of RBX-treated patients compared to eyes of PBO-treated patients (Wilcoxon-Mann-Whitney p=0.028), especially in eyes with CSME at baseline. In eyes treated with focal PC during the study, RBX administration reduced SMVL compared to PBO treatment (RBX 6.0% vs. PBO 11.5%; Chi square p=0.032).

Conclusions:: RBX resulted in more frequent improvement in DME severity and less frequent DME worsening in patients with moderately severe to very severe NPDR. This effect on DME may be at least partially responsible for its beneficial effect on vision loss.

Keywords: diabetic retinopathy • macula/fovea • edema