Two parallel, methodologically identical, phase III, multicenter, double-masked,
sham injection-controlled, randomized studies.
PARTICIPANTS: Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT).
INTERVENTION: Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months.
RESULTS: In RISE (NCT00473330), 377 patients were randomized (127 to
sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of
sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs
sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg
ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to
sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more
ranibizumab-treated patients gained ≥15 letters: 12.3% of
sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg
ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in
macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in
ranibizumab-treated patients.
Ranibizumab-treated patients underwent significantly fewer macular
laser procedures (mean of 1.8 and 1.6
laser procedures over 24 months in the
sham groups vs 0.3-0.8 in
ranibizumab groups). Ocular safety was consistent with prior
ranibizumab studies;
endophthalmitis occurred in 4
ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal
myocardial infarctions, and nonfatal
cerebrovascular accidents, which are possible effects from systemic
vascular endothelial growth factor inhibition, was 4.9% to 5.5% of
sham patients and 2.4% to 8.8% of
ranibizumab patients.
CONCLUSIONS: