DESIGN: Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of
ranibizumab for the treatment of DME.
PARTICIPANTS: Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment.
METHODS: Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point).
RESULTS: At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with
ranibizumab 0.3 mg,
ranibizumab 0.5 mg, and
sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal
photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all
ranibizumab vs.
sham comparisons, P < 0.05). In patients with baseline DR levels 47/53,
ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with
sham treatment (12.4% and 11.9% vs. 35.2% for
ranibizumab 0.3 mg,
ranibizumab 0.5 mg, and
sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P > 0.4).
CONCLUSIONS:
Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53).
Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36.