A new era in the treatment of age-related macular degeneration: from Factor X to antiangiogenesis

Abstract

Age-related macular degeneration has become the most common cause of visual loss leading to legal blindness in the industrialised world. This progressive disorder of the posterior pole of the eye involves the retinal pigment epithelium, its basal membrane (Bruch's membrane), as well as the choriocapillaris and retina. Multiple factors are thought to be involved, including oxidative damage, retinal pigment epithelium cell lysosomal dysfunction, immunological responses to extracellular matrix proteins and an imbalance between pro- and antiangiogenic cytokines. While little therapeutic options are available for the atrophic form of the disease, several treatment modalities have been developed for the exudative form of age-related macular degeneration. The first therapeutic interventions consisted in laser photocoagulation of choroidal neovascular membranes in the 1970s. In the late 1990s, photodynamic therapy with the photosensitiser verteporfin was the first step towards a more specific therapy, allowing treatment of subfoveal choroidal neovascular membranes without causing retinal damage. However, visual acuity tended to slowly deteriorate despite therapy in most patients. With the new antiangiogenic drugs available today and more in the pipeline to come, the probability to maintain or gain visual acuity has dramatically increased. This review gives an overview of the recent therapeutic advances in age-related macular degeneration with emphasis on antiangiogenic drugs, and will discuss available and future therapeutic concepts.

Keywords::

• age-related macular degeneration
• anecortave acetate
• antiproliferation
• bevacizumab
• choroidal neovascularisation
• integrins
• pegaptanib
• photodynamic therapy
• ranibizumab
• RTK inhibitors
• small interfering RNA
• squalamine lactate
• triamcinolone acetonide
• vascular endothelial growth factor
• VEGF-Trap