Diabetic macular oedema (DME) responds to ranibizumab (Lucentis, Genentech), according to the results of a phase II trial: 12-month analysis of ranibizumab in DME on behalf of the RESOLVE study group, said Dr Pascale Massin, PhD.

The patient responses to the drug in the changes in the visual acuity (VA) and central macular thickness were significantly better in the groups treated with two concentrations of ranibizumab compared with the sham-treated group, said Dr Massin, university professor at the Department of Ophthalmology, Hôpital Lariboisière, Paris, and principal investigator in the RESOLVE and RESTORE studies.

The RESOLVE study was a multicentre, randomized, double-masked, phase II trial designed to evaluate the safety and efficacy of ranibizumab in 151 patients with DME that affects the centre of the macula. The study included 42 patients (group A) who had been included in the pilot study and were analysed at 6 months; the other 109 patients (group B) had been included in the confirmatory study and were analysed at 12 months. The safety and efficacy of the drug were evaluated in the entire cohort (group C) of patients.

All patients had had either type 1 or type 2 diabetes and 12% Hb1c; the DME involved the centre of the macula in at least one eye. Two concentrations of ranibizumab, 0.3 mg and 0.5 mg were evaluated; patients not randomly assigned to receive one of those doses received sham treatment. All patients had a central macular thickness of 300 °m or more and received three monthly injections, then were retreated as needed from month 3 to month 12.

If the DME did not resolve, the dose of the drug could be doubled at month 2 to a maximum concentration of 0.6 or 1 mg, she said. The treatment could be discontinued if no improvement after three injections was found, if a decrease in retinal thickness of at least 20% occurred, or an increase in the VA of at least five letters was seen.

Study results

"Seventy percent of the patients were treated with a double dose of ranibizumab, and the mean number of injections was 10 in the treatment groups," she said. "In group B, the mean average change in the VA from baseline and from 1 to 12 months was 7.6 letters for both the high and the low concentrations of ranibizumab compared with 1.2 in the sham-treated (p = 0.0002).Interestingly, the group that received the low concentration did better than the other groups."

In the treated patients in groups A and B, the VA improvement started early after the first injection and was continuous throughout the study, with an average 10.3-letter increase in vision compared with –1.4 letters in the sham-treated group. Central retinal thickness decreased from baseline to month 12 a mean of –200 °m in the groups treated with ranibizumab compared with –50 °m in the sham-treated group.

Serious complications associated with ranibizumab were one case each of vitreous hemorrhage, transient retinal arterial occlusion, and severe peripheral retinal ischemia; one case of retinal detachment occurred in the sham-treated group, Dr. Massin said. Nonocular serious adverse events were balanced between treatment groups, including hypertension and arterial thromboembolic events.

"These results provide a sound basis for continuing the evaluation of ranibizumab in a phase III trial," Dr. Massin said.