Four RCTs were included in the review (1,476 patients according to the study characteristics table, range 126 to 854 patients per trial). Total length of follow-up ranged from 12 to 24 months. Two trials had low risk of bias for all seven domains assessed. One trial had an unclear risk of bias for allocation concealment but low risk for all other domains. The other trial had low risk of bias for incomplete outcome data, selective reporting and other bias; this trial's risk of bias for all other domains was assessed as being unclear.
Ranibizumab versus non-drug controls: Compared with non-drug controls, ranibizumab groups demonstrated a significantly greater increase in best-correct visual acuity from baseline to 12 months (MD 7.50, 95% CI 3.43 to 11.58; two trials; Ι²=55%) and significantly greater reduction in central macular thickness (MD -94.42, 95% CI -174.22 to -14.62; two trials; Ι²=82%).
Two trials reported no statistically significant differences between ranibizumab and non-drug controls regarding the incidence of eye pain, hypertension and arterial thromboembolism.
Ranibizumab and focal/grid laser versus laser alone: Compared with those treated with laser alone, ranibizumab-laser combination groups demonstrated a significantly greater increase in best-correct visual acuity from baseline at 12 months (MD 5.83, 95% CI 4.07 to 7.59; two trials; Ι²=0%) and at 24 months (MD 3.95, 95% CI 1.07 to 6.84; two trials; Ι²=8%). At 12 months, significantly greater reduction in central macular thickness (MD -46.82, 95% CI -83.98 to -9.65; two trials; Ι²=69%) was observed among ranibizumab-laser combination groups versus groups that received laser alone.
Ranibizumab versus ranibizumab and focal/grid laser: None of the data from relevant trials were amenable to meta-analysis. Individual trials demonstrated no significant differences between the groups for change in best-corrected visual acuity at 12 and 24 months and reduction in central macular thickness at 12 months. The trial with the poorest quality reported that reduction in central macular thickness at 12 months was significantly greater among ranibizumab-laser combination groups compared with those that received ranibizumab alone.