Changing therapeutic paradigms for exudative age-related macular degeneration: antiangiogenic agents and photodynamic...

Age related macular degeneration (AMD) is the leading cause of irreversible visual loss in the United States. Overall, approximately 10 - 20% of patients with AMD exhibit the exudative form, which is responsible for most of the estimated 1.2 m cases of severe visual loss from AMD. Visual loss develops in the exudative form of AMD due to abnormal choroidal neovascular membranes (CNVM) that develop under the retina, leak serous fluid and blood, and ultimately cause a blinding disciform scar in, and under, the retina. Currently, the only well-studied and widely accepted method of treatment is laser photocoagulation of the CNVM. However, only a minority of patients with exudative AMD show well-demarcated 'classic' CNVM amenable to laser treatment, and at least half of these patients suffer persistent or recurrent CNVM formation within two years. In addition, since the treatment itself causes a blinding central scotoma when the CNVM is located subfoveally, many clinicians do not treat subfoveal CNVM. With these treatment limitations, there has been a great deal of interest in alternative therapies for AMD, including anti-angiogenic agents and photodynamic therapy. Angiogenesis involves a complex interplay of cellular events involving a cascade of factors that are both inhibitory and stimulatory. Soluble growth factors have been the best-known cell modulating agents in ophthalmology, but there are a multitude of potential sites for inhibition of angiogenesis by pharmacological agents. With regard to photodynamic therapy, a photosensitising dye is injected intravascularly and low power laser light is used to activate the dye within the CNVM to cause vascular occlusion by a photochemical reaction. Closure of the CNVM is achieved without severe collateral damage to the non-vascular tissues as occurs with laser photocoagulation.