Age-related macular degeneration: a review of experimental treatments

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the USA. Laser photocoagulation of choroidal neovascular membranes (CNVMs) in exudative AMD is currently the only well-studied and widely accepted treatment modality. It is beneficial for only a small minority of patients who show well-demarcated "classic" CNVMs, and it destroys normal retinal tissue, creates a scotoma, and is associated with an unacceptably high CNVM persistence and recurrence rate. Consequently, investigators have attempted to develop new modalities for treatment of CNVMs. These treatment modalities can be grouped into four major categories: photodynamic therapy; pharmacologic inhibition of CNVM formation with antiangiogenic agents; surgical intervention, including excision of subfoveal CNVMs; and radiation therapy. All of these experimental treatment modalities are directed toward destroyiing CNVMs, the end result of the exudative process, and all have limitations. The ideal treatment of the future must be based on the pathogenesis of the disease at a stage well before CNVMs develop. Investigations in nonexudative AMD are currently focusing on several major areas. Epidemiologic factors, such as genetics, sunlight, and nutrition, are being evaluated in several large studies, including the Age-Related Eye Disease Study, with the possibility of ultimately limiting the risk of AMD through behavior modification. Laser treatment of drusen is being evaluated as a means of limiting the risk of CNVM formation, although mixed results have been reported in the small number of studies to date. Choroidal perfusion abnormalities have been described in AMD, and some investigators postulate that altering blood flow may limit the risk of CNVM formation. No perfusion-treatment trials have been completed to date.