Geographic atrophy

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Geographic atrophy (GA), also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina (photoreceptors, retinal pigment epithelium, choriocappillaris) which can lead to a loss of visual function over time.[1][2][3][4] It is estimated that GA affects >5 million people worldwide and approximately 1 million patients in the US,[5][6] which is similar to the prevalence of neovascular (wet) AMD, the other advanced form of the disease.

The incidence of advanced AMD, both geographic atrophy and neovascular AMD, increases exponentially with age and while there are therapies for wet AMD, GA currently has no approved treatment options. The aim of most current clinical trials is to reduce the progression of GA lesion enlargement.[7]


Geographic atrophy is a chronic disease, which leads to visual function loss. This often results in difficulties performing daily tasks such as reading, recognizing faces, and driving, and ultimately has severe consequences on independence.[8][9][10]

Initially, patients often have good visual acuity if the GA lesions are not involved in the central macular, or foveal, region of the retina.[7][11] As such, a standard vision test may underrepresent the visual deficit experienced by patients who report challenges reading, driving or seeing in low light conditions.[12] While fundus autofluorescene imaging and spectral domain optical coherence tomography are today well established for diagnosing and tracking progression in geographic atrophy more complex diagnostic assessments may be required in the context of clinical trials.[13]


The pathogenesis of GA is multifactorial and is generally thought to be triggered by intrinsic and extrinsic stressors of the poorly regenerative retinal pigment epithelium (RPE), particularly oxidative stress caused by the high metabolic demand of photoreceptors, photo-oxidation, and environmental stressors such as cigarette smoke. Variations in several genes, particularly in the complement system, increase the risk of developing GA. This is an active area of research but the current hypothesis is that with aging, damage caused by these stressors accumulates, which coupled with a genetic predisposition, results in the appearance of drusen and lipofuscin deposits (early and intermediate AMD). These and other products of oxidative stress can trigger inflammation via multiple pathways, particularly the complement cascade, ultimately leading to loss of photoreceptors, RPE, and choriocapillaris, culminating in atrophic lesions that grow over time.[14][15][full citation needed]




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