Center of Macula (COM) Involvement by Diabetic Macular Edema (DME): Time-Dependence of Vision Loss and Implications for the FOCAL Study of Ruboxistaurin (RBX) in Patients with Mild DME
Abstract Number: 1008-P
Authors: JANET B. MCGILL, LLOYD P. AIELLO, NAZILA SHAHRI, JOHN V. FORRESTER, MATTHEW D. DAVIS, RONALD P. DANIS, RONALD KLEIN, HENRIK LUND-ANDERSEN, MATTHEW J. SHEETZ, PKC-DRS2, PKC-DMES, AND FOCAL STUDY GROUPS
Institutions: St. Louis, MO, Boston, MA, San Diego, CA, Foresterhill, Aberdeen, United Kingdom, Madison, WI, Glostrup, Denmark, Indianapolis, IN, Multiple
Results: The FOCAL study is a phase 3, randomized, double-masked, placebo (PBO)-controlled 3-year study of the effect of 32 mg/d of RBX on duration of COM involvement in patients with DME >500 microns from the COM at baseline. Data from prior phase 3 trials of RBX were used to validate the primary endpoint of duration of COM involvement. Studies PKC-DRS, PKC-DRS2, FOCAL, and PKC-DMES enrolled patients with non-proliferative diabetic retinopathy (NPDR) and various levels of DME severity ranging from none to center-involved. We analyzed the effect of duration of COM involvement on visual acuity (VA) using study eyes from the PKC-DRS2 trial. We then assessed the effect of RBX treatment on the endpoint of duration of COM involvement on all study eyes from these trials that matched FOCAL study entry criteria as well as on all eyes from the PKC-DMES trial. Duration of COM involvement appeared to be closely linked to VA decline with a duration of about 18 months being necessary for a substantial (>10 letter) mean loss. Analysis of FOCAL-eligible eyes from 32 mg/d RBX- or PBO-treated patients in studies PKC-DRS, PKC-DMES, and PKC-DRS2 showed that the mean duration of COM involvement was reduced by ∼50% in the RBX eyes (from ∼2 months to ∼1 month, p=0.064, n=146 RBX and n=174 PBO). In addition, there was a RBX dose-related decrease in the mean duration of COM involvement of approximately the same magnitude in the FOCAL-like PKC-DMES study (p=0.021). In conclusion, duration of COM involvement by DME appears to be a clinically relevant predictor of VA loss. RBX treatment appears to reduce duration of COM involvement in eyes with mild DME. Further confirmation of the relationship between duration of COM involvement and VA decline and the effects of RBX on these parameters will be obtained from the current FOCAL trial which has 360 PBO and RBX-treated (32 mg/d) patients per arm. The last patient visit will occur in 2010.