Geographic Atrophy (GA)
The macula is a small central section of the retina. It is responsible for providing the sharp vision that you need for reading, recognizing faces and driving.1 Globally, age-related macular degeneration (AMD) is a leading cause of sight loss.2 The projected number of people with AMD in 2020 is 196 million, increasing to 288 million in 2040.3
AMD can either be “dry age-related macular degeneration” or “wet age-related macular degeneration.” In the late stage of dry AMD (also called geographic atrophy [GA]), there is a gradual, patchy breakdown in the light-sensitive cells of the macula, as well as of the supporting cells beneath the macula. In the other form of advanced AMD, “wet” AMD (also called exudative or neovascular AMD), abnormal new blood vessels grow beneath the retina. These new blood vessels may leak fluid.1
Geographic atrophy (GA) is a chronic, irreversible progressive condition that can cause permanent blind spots and/or blindness, and it affects more than 5 million people globally.1,4 While approximately 20% of all patients with GA have visual acuity of 20/200 (or worse), more than half of all patients with GA experience substantial decreases in everyday visual function,4,5 which may significantly affect their quality of life. As GA progresses, it can destroy the central fovea, which is the part of the macula responsible for fine vision making it particularly hard to see in low-light conditions, to recognize faces, and to read.6,7
Common Questions about Geographic Atrophy
What is Age-Related Macular Degeneration (AMD)?
Globally, AMD is a leading cause of severe vision loss in people over the age of 50.2 It is characterized by a progressive degeneration of the central retina associated with central vision loss.1
What is Geographic Atrophy? (GA)
Geographic atrophy is the “dry” form of the late stage of age-related macular degeneration (AMD).10 (You may also hear people refer to this condition as dry macular degeneration.) As the “dry” form of AMD progresses, cells in the light-sensitive portion of the macula, as well as the cells in the supporting structures (the retinal pigment epithelium and the choriocapillaris), start to die.10 This damage starts as small spots that grow into larger patches. As the light-sensitive cells in the macula die off, the person starts to lose vision in that eye. At first, the person may notice problems with reading or night vision.9 Eventually, the person will develop large, permanent blind spots (scotomata) in the center of the visual field. When the central fovea of the macula is involved, the person loses the ability to have sharp vision, such as that needed for reading and for recognizing faces.9
It’s important to note that while GA is commonly associated with people with visual acuity (VA) of 20/200 (or worse) caused by advanced AMD, more than half of all people who develop GA may experience substantial impairment of everyday visual function, which may significantly affect their quality of life.5,11
What is the Average Age of Patients Diagnosed with GA?
The early signs of AMD (drusen and pigmentary changes) are common in individuals over age 65 and precede the late stage forms.10
What are the causes of GA?
While the mechanisms that cause GA are not fully understood, the cause of GA is thought to be multifactorial, with numerous environmental and genetic risk factors. The dysregulation of the complement cascade, an important part of the body’s immune system, may play a pivotal role.9
Is GA a Hereditary Condition?
GA is not a hereditary disease. Nevertheless, some genes do increase the risk that a person’s AMD will progress to GA.12
How is GA Diagnosed?
GA can be distinguished from other forms of dry AMD by ophthalmic exam and color fundus photography.10
Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) allow for noninvasive and rapid quantitative morphological assessment of GA in the clinical setting.10
How is GA currently treated?
In the EU, there is no approved treatment to prevent the onset and progression of GA. Several therapeutics are in various stages of clinical development.
What is the Complement System?
The complement system is an integral part of our immune defense system. In healthy people, complement orchestrates the destruction and clearance of pathogens or of the body’s own cells that need to be removed. It also has proinflammatory capabilities.8
Complement activation is regulated to avoid its overactivation and to protect the body against inappropriate immune attack. When regulation is compromised, hyperactivation of the complement cascade can lead to inflammation and inappropriate cell destruction.8
Three pathways converge with the cleavage of complement factor C3, which induces inflammation and labels cells for phagocytosis (destruction by special white blood cells). The complement cascade continues with the cleavage of complement factor C5, which triggers cell death via phagocytosis, inflammation, and ultimately activation of the membrane attack complex (MAC) which causes damage and cell death.8
References
- Age-Related Macular Degeneration (AMD). National Eye Institute Web site. 2021; Last accessed June 22, 2021.
- GBD 2019 Blindness and Vision Impairment Collaborators. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health. 2021;9(2):144-160.
- Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):106-116.
- Sunness JS, Rubin GS, Applegate CA, et al. Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity. Ophthalmology. 1997;104(10):1677-1691.
- Chakravarthy U, Bailey CC, Johnston RL, et al. Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration. Ophthalmology. 2018;125(6):842-849.
- Wang P, Cottrell GW. Central and peripheral vision for scene recognition: A neurocomputational modeling exploration. J Vis. 2017;17(4):9.
- Kolb H. Simple anatomy of the retina. Webvision Web site. 2018; Last accessed July 30, 2018.
- Murphy K, Weaver C. Innate immunity: the first lines of defense. In: Janeway’s Immunobiology. 9th ed. London, UK: Garland Science; 2016.
- Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, et al. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina. 2017;37(5):819-835.
- Vaz F, Picoto M. Geographic atrophy. AMD Book Web site. Last accessed May 7, 2018.
- Hazel CA, Petre KL, Armstrong RA, et al. Visual function and subjective quality of life compared in subjects with acquired macular disease. Invest Ophthalmol Vis Sci. 2000;41(6):1309-1315.
- Wang W, Gawlik K, Lopez J, et al. Genetic and environmental factors strongly influence risk, severity and progression of age-related macular degeneration. Signal Transduct Target Ther. 2016;1:16016.