The efficacy and safety of intravitreal ranibizumab in diabetic macular oedema (DMO) has been evaluated in two parallel, methodologically identical, phase III, studies (RISE and RIDE).

The studies involved adults with vision loss from DMO (best-corrected visual acuity [BCVA], 20/40 to 20/320 Snellen equivalent) and central subfield thickness ≥ 275 microm on time-domain optical coherence tomography (OCT). They were randomised to receive monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol–specified criteria. The main outcome measure was the proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months.

The following findings were reported:

• In RISE, 377 patients were randomised (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥ 15 letters vs. 44.8% of 0.3mg (adjusted difference vs. sham 24.3%; p<0.0001); and 39.2% of 0.5mg ranibizumab patients (20.9%; p<0.001).

• In RIDE, 382 patients were randomised (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). More ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients vs. 33.6% of 0.3mg patients (p <0.0001; adjusted difference, 20.8%) and 45.7% of 0.5mg ranibizumab patients (adjusted difference, 33.3%, p <0.0001).

• Improvements in macular oedema 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 to 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, non-fatal MIs, and non-fatal 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.

The researchers conclude that the RISE and RIDE studies demonstrate that “ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular oedema in patients with DMO, with low rates of ocular and non-ocular harm, and, importantly, provides the longest term controlled evidence to date.