Geographic atrophy

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 fluorescein angiography and 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 not fully understood yet. It is likely multifactorial and 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]

Recent studies indicate that geographic atrophy may be due to deficiencies in blood flow within the choriocapillaris.[16][17] These studies used swept source optical coherence tomography angiography to examine the choriocapillaris. Using imaging algorithms, they then determined which regions of the choriocapillaris had deficient blood flow, thus creating a "heat-map" of the blood supply to the retinal pigment epithelium. They went on to use fundus autoflorescence to image the retinal pigment epithelium over the course of a year, this allowed them to map out the direction and magnitude with the geographic atrophy spread. They then found that regions of the choricapillaris which had less blood flow were more likely to degenerate and become geographic atrophy. Since the choriocapillaris is the main blood supply of the retinal pigment epithelium, it is leading some to believe that geographic atrophy is primarily an ischemic disease (disease due to decreased blood flow).

Diagnosis of geographic atrophy is made by an ophthalmologist in clinic. Fundus autofluorescence and optical coherence tomography angiography are imaging modalities that can be used in the diagnosis. While fundus autoflorescene is the standard modality for viewing geographic atrophy, optical coherence tomography can offer unique benefits. Optical coherence tomography angiography can help the physician see if there is any subretinal fluid in the eye.[18] This is useful because it could indicate that the patient may be developing wet AMD. Since patients with geographic atrophy are at higher risk for developing advanced wet AMD (neovascular AMD), this could be especially useful in the monitoring of patients with geography atrophy. If signs of neovascular AMD found, the physician can initiate treatment of wet age related macular degeneration.[19]

There are currently no approved treatments to reverse or halt the progression of geographic atrophy.

There are multiple types of advanced AMD: 1) neovascular AMD and 2) geographic atrophy. Although there are treatments for neovascular AMD, there are none for geographic atrophy. While there are no approved treatments for geographic atrophy, it is important they are still regularly followed by an ophthalmologist so that if patients develop neovascular AMD, they can be treated.[20]