A randomised controlled trial (RCT) of alternative treatments to Inhibit VEGF in patients with Age-related choroidal Neovascularisation (IVAN)

Wet or neovascular macular degeneration is a condition which causes severe sight loss in older people. Neovascularisation arises in the choroid and breaches the normal anatomical barriers of Bruch's membrane and the retinal pigment epithelium. The complex of new vessels and accompanying inflammatory and glial cells is known as choroidal neovascularisation (CNV). Until recently, available treatments only limited the rate of sight loss with most patients becoming moderately or severely visually impaired in the affected eye despite optimal management. However, very recently a new treatment with a drug known as Lucentis® (Ranibizumab) was found to prevent sight loss in the affected eye in over 90% of recipients when given as intravitreal injections for periods of up to two years. Lucentis® is expensive (approximately £750 per injection) and CNV is common (about 25,000 people with incident CNV per annum in the UK). There is little evidence on which to base criteria for stopping treatment and thus considerable uncertainty about treatment costs. VEGF inhibitors are potent drugs and a recent press release from the manufacturer suggests that Lucentis® (0.5mg) may increase the risk of stroke 4-fold compared to the lower dose (0.3mg) raising concerns about its systemic safety. Another drug, called Avastin® (Bevacizumab) which is licensed for colorectal cancer therapy is similar to Lucentis® in its properties. This drug has also been used to treat neovascular AMD patients and appears to confer similar benefits but the data come from multiple small uncontrolled studies. Avastin® is extremely cheap as the dose for ocular injection is small. Although the large number of small uncontrolled studies and an internet survey which compiled information on several thousand treated patients, have not reported any serious adverse effects, there has been no systematic or robust collection of data on the systemic safety of Avastin®. The present study is therefore a proposal to undertake a prospective randomised controlled clinical trial which will (a) compare the clinical efficacy of the two drugs; (b) compare a reduced treatment regimen versus two years of continuous treatment; (c) describe the cost effectiveness of different drugs and treatment regimens; (d) describe both eye-related and systemic side effects with different drugs and treatment regimens.