What is Geographic Atrophy?
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of vision. Geographic atrophy appears as sharply demarcated atrophic lesions of the outer retina from the loss of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. The macula is the center part of the retina and the area responsible for central vision.
In geographic atrophy, the lesions appear first around the macula, but over time often expand and coalesce to include the central area of vision, called the fovea. Visual acuity does not correspond directly to GA lesion size as the fovea (central vision) may often be spared. It is estimated that geographic atrophy affects approximately 5 million individuals globally.
- Geographic atrophy is an advanced stage of dry AMD which results in irreversible vision loss.
- The condition appears as demarcated lesions around and into the fovea.
- There is currently no approved treatment for geographic atrophy
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What Happens During Geographic Atrophy
It is thought that oxidative damage could trigger chronic inflammation in Bruch’s membrane-retinal pigment epithelium-choriocapillaris complex, due to overactivation of the complement pathway. Some individuals with mutations in the complement system and other factors have less ability to modulate inflammation. The inflammation results in cell damage and waste accumulation. This accumulation of intracellular and extracellular waste products causes drusen and pigmentary changes prior to the death of photoreceptors, retinal pigment epithelium, and choriocapillaris.
How Common is Geographic Atrophy?
Geographic atrophy is estimated to affect 1 million people in the United States. Geographic atrophy is the advanced form of dry AMD. The prevalence of geographic atrophy increases with age and it is slightly less common than neovascular (wet) AMD. In the United States, researchers estimate that the prevalence of geographic atrophy is approximately 0.81% in all adults, but increases to 3.5% in patients older than 75.
Risk Factors for Geographic Atrophy
AMD risk involves many factors, but genetics is a contributor. It is estimated that genetic factors can account for between 55% and 57% of the total variability in disease risk. Other risk factors include cigarette smoking, poor nutrition and cardiovascular diseases. Environmental and demographic factors can also have an impact.
Geographic Atrophy Symptoms
- Central vision loss
- Black spot in central vision
- Difficulty with reading
- Increased glare
- Reduced night vision and dark adaptation
Diagnosing Geographic Atrophy
The diagnosis is made by ocular examination and can be confirmed using advanced imaging techniques including retinal photography, angiography, and optical coherence tomography.
Sharply demarcated atrophic lesions can be seen during a dilated eye exam and documented using retinal photography. On fluorescein angiogram, areas of geographic atrophy appear hyperfluorescent with good visibility of the choroidal vessels. An optic coherence tomography (OCT) of the macula can identify geographic atrophy. Early studies indicate that OCT angiography may be useful in predicting GA growth over time.
It is reported that geographic atrophy progression ranges from 0.53 to 2.6 mm2/year (median, ∼1.78 mm2/year). Progression is assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging.
Geographic Atrophy Treatment
There is currently no approved treatment; however, Pegcetacoplan by Apellis Pharmaceuticals is expected to be approved by the end of 2022. This drug has demonstrated promising results.
Pegcetacoplan is a complement system inhibitor that has previously been used to treat paroxysmal nocturnal hemoglobinuria, which is a rare autoimmune disorder linked to the complement cascade. Patients who received the drug monthly showed a 17% reduction in geographic atrophy lesions after 12 months, compared to those who received sham injections. Patients with extrafoveal lesions had a 26% reduction in lesions with monthly injections and 23% reduction with every-other-month injections when compared to the sham group.