Ranibizumab and retinal vein occlusion. Too many outstanding questions.

A loss of visual acuity due to macular oedema is a complication of retinal vein occlusion. Vision improves spontaneously within 3 to 6 months in about 50% of cases. There are no drugs with proven benefits in this setting. In addition to its indications in the treatment of age-related macular degeneration (AMD) and diabetic macular oedema, ranibizumab, an anti-VEGF antibody, has now been approved in the European Union for the treatment of visual impairment associated with macular oedema due to retinal vein occlusion. In this setting, clinical evaluation of ranibizumab (Lucentis, Novartis) is based on two double-blind randomised trials comparing ranibizumab (0.3 mg or 0.5 mg) versus placebo in a total of 795 patients. Compared with placebo, about 30% more patients receiving ranibizumab (0.3 mg or 0.5 mg) experienced a tangible improvement in their visual acuity (gain of at least 15 letters on the ETDRS scale) after 6 months of treatment. Efficacy was similar in patients with central retinal vein occlusion and those with occlusion of a peripheral branch. All patients received ranibizumab after the initial 6-month period; the lack of a placebo group means that the long-term effects of ranibizumab cannot be distinguished from spontaneous improvement. There were too few cases of ischaemic occlusion to assess the efficacy of ranibizumab in this subgroup of patients, who are most in need of treatment. The adverse effects of ranibizumab were the same as those observed in other clinical situations. They mainly consisted of ocular adverse reactions, such as haemorrhage, pain, and elevated intraocular pressure. Uncertainties persist as to the long-term risk of recurrent occlusion or progression to retinal ischaemia. The frequency of systemic adverse events was similar in the ranibizumab and placebo groups. The incidence of heart failure and transient ischaemic attacks was higher during the second year of ranibizumab therapy than during the first year of treatment. The packaging (bottles) available in early 2012 creates a risk of handling errors, and improvements are needed to prevent these errors. Monthly ranibizumab administration is expensive. In practice, the decision to grant marketing authorisation for ranibizumab in macular oedema due to retinal vein occlusion was premature. Ranibizumab is one option that should be assessed in clinical trials. Patients should be informed of the potential adverse effects and uncertainties and be reminded that this condition improves spontaneously in about 50% of cases.

RCT Entities:   Population Interventions Outcomes