The prevalence of neovascular age-related macular degeneration (wet AMD) is predicted to rise to more than 300,000 patients in the UK alone by the year 2025. The personal and economic costs are considerable. It leads to worsening of vision-related function and overall wellbeing, with one third developing clinical depression. The majority of patients progress to legal blindness in the affected eye within two years of diagnosis, and healthcare utilisation costs are seven times higher in affected patients compared to age-matched controls. Thus, the development of new treatments for wet AMD, and of access to such treatments, is clearly important.
Vascular endothelial growth factor (VEGF) plays a critical role in stimulating abnormal neovascularisation, inflammation and vascular permeability, all factors involved in the pathogenesis of wet AMD. Inhibition of VEGF with intravitreal ranibizumab, pegaptanib and (off-licence) bevacizumab is currently first-line therapy for this condition.
However, VEGF plays a pivotal role in maintaining vascular integrity, particularly under conditions of ischaemia and hypoxia. This is particularly significant since most (but not all) studies have suggested that patients with wet AMD have a higher incidence of coronary heart disease and stroke, and because treatment with VEGF inhibitors may be required for some years in an elderly cohort of patients.
This supplement provides clinicians with detailed information about some of the current issues in this field. It discusses the determination of cardiovascular risk related to current treatment of wet AMD; the properties and functions of the VEGF system, including its complex roles in neuroprotection and inflammation; the effects of VEGF and anti-VEGF treatments on the vasculature, indicating that VEGF inhibition could have unwanted effects such as prothrombotic and vasoconstrictive effects; and, finally, findings on efficacy and safety of intravitreal pegaptanib in the treatment of wet AMD. This agent binds with high specificity to isoform 165 of VEGF, the isoform preferentially involved in choroidal neovascularisation.
