A.J. Lotery

The last twelve months have seen major developments in the treatment of neovascular age-related macular degeneration (AMD). In 2005 we were able to offer our patients photodynamic therapy (PDT) with verteporfin. Although results from the PDT trials showed significant benefits in patients with predominantly classic and 100% classic choroidal neovascularization (CNV); patients with minimally classic CNV were not eligible for therapy and the benefit for occult lesions was marginal.^1,2 Disappointingly, improvement in vision with PDT was found to be only 6% at one year.¹ In our department specifically, patients with predominantly classic CNV had an average loss of vision of around 1.5 lines.³

Why did we choose an off-label agent?

In mid-2005, Dr Rosenfeld from the Bascom Palmer Eye Institute of the University of Miami School of Medicine in the US, began to describe his experience with bevacizumab (off-label Avastin). His group had begun to use this drug because ranibizumab (Lucentis) was still not available to non-trial patients. They demonstrated visual improvement in patients with neovascular AMD following systemic administration of the agent.⁴ Angiographic evidence of vascular closure was also noted. Following this revelation, US physicians began to use the drug intravitreally to reduce the incidence of systemic side effects.⁵ As the drug had not gone through the usual drug development pathway, an online adverse event reporting system was launched.⁶

Presentations at the 2006 Association for Research in Vision and Ophthalmology (ARVO) conference began to demonstrate favourable outcomes in a variety of other retinal diseases where there was over-expression of vascular endothelial growth factor (VEGF). These included diabetic maculopathy, proliferative diabetic retinopathy and retinal vein occlusions.⁷ In general, results supported bevacizumab as a safe and effective treatment for retinal vascular conditions and for neovascular AMD. Since then many reports on the efficacy and safety of intravitreal bevacizumab for the treatment of neovascular AMD have been published.^8-13

The introduction of anti-VEGF treatment has revolutionized our management of neovascular AMD, in that many previously untreated CNV lesion types, including minimally classic, occult lesions, retinal pigment epithelial detachment, retinal angiomatous proliferation, can now be considered for treatment.

Our treatment regimen

The Southampton Eye Unit is one of the first UK centres to use intravitreal bevacizumab for neovascular AMD; we have used this therapy now for almost two years. Initially we chose patients who were not eligible for PDT but, as our experience developed with the drug, we found that all lesion types responded well to bevacizumab.

Informed consent is obtained from all patients and the off-label status of treatment is discussed as well as the pros and cons of alternative laser and anti-VEGF treatments. It should be noted, however, that prior to definitive guidance from the UK government, these patients either had to self-pay for the treatment or were approved treatment as a compassionate use by their local health authority. All of our patients receive 1.25 mg of intravitreal bevacizumab injected through the pars plana under sterile conditions.

In terms of our therapeutic regimen, we prescribe topical antibiotics one day before treatment and postoperatively for five days. Patients are initially followed up at six weeks and then retreated if there is still active leakage or at increasing intervals if there is closure of the CNV membrane. At each visit, best corrected Snellen visual acuity is recorded and the macula reassessed clinically. Typically patients have a fundus fluorescein angiogram (FFA) and an Optical Coherence Tomogram (OCT) at their first visit. FFA and OCT are then repeated as deemed necessary by the clinician. Repeat injections are offered in the event of persistent CNV activity as shown by the presence of macular oedema, sub-retinal fluid or persistent pigment epithelial detachment (PED). All patients are also monitored for any systemic and ocular adverse events.