Effect of Ruboxistaurin on the Visual Acuity Decline Associated with Long-standing Diabetic Macular Edema

Abstract

To compare relationships between severity and duration of diabetic macular edema (DME) and visual acuity (VA) observed in the PKC-DRS2 with those from the Early Treatment Diabetic Retinopathy Study (ETDRS) and to assess the effect of the orally administered PKC beta inhibitor ruboxistaurin (RBX) on these parameters. In the PKC-DRS2, patients with moderately severe to very severe nonproliferative diabetic retinopathy (n = 685) were randomly assigned to 32 mg/d RBX or placebo and followed up for 36 months with ETDRS VA measurements and fundus photographs (FP) every 3 to 6 months. Mean VA was calculated across all FP visits for eyes in each level of the ETDRS DME severity scale at those visits. For eyes with baseline VA > or = 20/40, relationships between change in VA from baseline to last visit and duration of severe DME were analyzed with linear regression. Mean VA decreased by approximately 22 letters between the mildest and most severe levels of the DME scale in the PKC-DRS2, compared with 27 letters in the ETDRS. In the placebo group, the rate of decrease in VA over time associated with duration of severe DME was 0.67 letters per month (24 letters over 36 months, compared with 20 letters over 28-36 months in the ETDRS). This rate was 30% less in the RBX group (0.47 letter per month, P = 0.022). The VA decrease in the PKC-DRS2 associated with long-standing DME agrees well with estimates from the ETDRS. RBX appears to ameliorate this decrease, an effect that could be important clinically. (ClinicalTrials.gov number, NCT00604383.).