WAMD: from pathophysiology to therapeutic treatments

Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss [1]. Aging of the eye is accompanied by the buildup of uncleared cellular debris that originates from the retinal pigment epithelium (RPE) and accumulates where the RPE interfaces with Bruch’s membrane and the neurosensory retina. These deposits, known as drusen, are typically the first ophthalmoscopic sign of AMD, appearing before visual function is appreciably affected. Drusen are composite structures, primarily consisting of lipids as well as proteins and carbohydrates that can be visualized as small white or yellowish deposits on the macula [2]. Drusen deposition in Bruch’s membrane concomitant with other structural and biochemical changes associated with AMD pathogenesis (including persistent activation of the complement cascade and inflammation) lead to thickening and decreased permeability of the membrane [3]. This obstructs both nutrient transport to the retina and waste exchange to the choroid and is accompanied by the thinning of the choroidal vasculature. These steps, combined with neurodegenerative changes within the photoreceptor–RPE complex, result in pigmentary abnormalities of the RPE, including hypo- or hyperpigmentation, in early or intermediate stages of disease [4