2 The technology
2.1 Ranibizumab (Lucentis, Novartis) belongs to a class of drugs that block the action of vascular endothelial growth factor (VEGF)‑A. Retinal vein occlusion (RVO) is a common cause of reduced vision as a result of retinal vascular disease. Thrombosis in the retinal veins causes an increase in retinal capillary pressure, resulting in increased capillary permeability and the discharge of blood and plasma into the retina. This leads to macular oedema and varying levels of ischaemia through reduced perfusion of capillaries. These changes trigger an increase in VEGF, which increases vascular permeability and new vessel proliferation. By inhibiting the action of VEGF‑A, ranibizumab reduces oedema and limits visual loss or improves vision. Ranibizumab has a UK marketing authorisation for 'the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO)'.
2.2 The summary of product characteristics states that treatment should be given monthly and continued until maximum visual acuity is reached – that is, until visual acuity has been stable for 3 consecutive months. Thereafter, visual acuity should be monitored monthly. Treatment should be resumed if monitoring indicates a loss of visual acuity caused by macular oedema secondary to RVO, and continued until visual acuity has remained stable for 3 consecutive months. The interval between doses should not be shorter than 1 month. If there is no improvement in visual acuity over the course of the first 3 injections, continued treatment is not recommended.
2.3 Contraindications to ranibizumab include known hypersensitivity to the active substance or to any of its excipients, active or suspected ocular or periocular infections, and active severe intraocular inflammation. Adverse reactions to treatment are mostly limited to the eye. Those commonly reported in clinical trials include vitritis, vitreous detachment, retinal haemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival haemorrhage, eye irritation, sensation of a foreign body in the eye, increased production of tears, blepharitis, dry eye, ocular hyperaemia, itching of the eye and increased intraocular pressure. Nasopharyngitis, arthralgia and headaches are also commonly reported. For full details of adverse reactions and contraindications, see the summary of product characteristics.
2.4 Ranibizumab is administered as a single 0.5 mg intravitreal injection. Each vial of ranibizumab contains 2.3 mg in 0.23 ml; overfilling is considered necessary to achieve an injectable dose of 0.5 mg. The list price of ranibizumab is £742.17 per vial (excluding VAT; 'British national formulary' [BNF] edition 64). The manufacturer of ranibizumab (Novartis) has agreed a patient access scheme with the Department of Health, revised in the context of technology appraisal guidance 274, which makes ranibizumab available with a discount applied to all invoices. The level of the discount is commercial‑in‑confidence (see section 5.3). The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. The manufacturer has agreed that the patient access scheme will remain in place until any review of this technology by NICE is published.