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Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD). GA primarily affects the macular region of the retina, and is characterized by the gradual, progressive loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. The progressive loss of retinal cells is associated with a gradual and irreversible loss of central visual function, that can affect one or both eyes.
GA Symptoms/When should I see a doctor/ophthalmologist
Early GA
Early GA typically first develops in the region of the macula surrounding the fovea (the parafoveal region), sparing the fovea until late in the course of the disease.16 People with foveal-sparing disease may not have a reduction in central visual acuity but can experience other symptoms of visual decline including:
Blind spots
These impair vision such that full words or a full face do not ‘fit’ on the spared central foveal region. As a result, people may have difficulty recognizing faces or reading, which may be accompanied by a reduction in reading speed. Blind spots are also known as parafoveal scotomas.28
Reduced contrast sensitivity
This occurs when the eyes’ ability to see an image against a ‘similar’ background is reduced. Low contrast sensitivity may cause difficulties with night driving, including difficulty seeing pedestrians walking along poorly lit streets. Reduced contrast sensitivity can also increase the risk of a fall, when surfaces at different levels are similarly coloured29.
Delayed dark adaptation
This occurs when it becomes increasingly difficult for eyes to adjust when moving from bright to dim lighting (e.g. entering a dimly lit room such as a dark theatre, from bright daylight outside).
Late GA
Late GA; when atrophy affects both the extra-foveal region and the fovea, is associated with severe deterioration of visual acuity and patients experience symptoms that may include:
Distorted vision
This is where straight lines appear wavy.
Retinal Imaging
Currently GA can only be effectively diagnosed with a full dilated eye exam, involving retinal imaging techniques. The examination is typically undertaken in a specialist ophthalmology clinic. Several retinal imaging techniques are used, usually in combination, to diagnose GA and monitor GA progression.
Functional Tests
The standard ‘functional’ vision test that people are familiar with is the visual acuity test, which checks how well you see the details of a letter or symbol from a specific distance. However, GA is generally a slowly progressing disease and the early stages are typically not associated with a loss in central visual acuity. The visual acuity test is thus not adequate to detect functional deficits experienced by people with GA. Alternative assessments of visual function are needed in order to identify deterioration of visual function that occur before the loss of foveal function; several functional tests are being investigated in patients with GA.
Patient-Reported Outcome (PRO)
These measures are designed to gain the patient’s insights into the impact of a disease on different aspects of their everyday quality of life, including physical, mental, and social functioning. Two PRO instruments (questionnaires) are mainly used to collect information from patients with AMD:
Functional Reading Independence (FRI) Index11
7-item questionnaire that evaluates the effect of GA on a patient’s ability to independently perform reading activities.
FRI index score has been shown to be sensitive to GA lesion size as well as changes in GA lesion size over time.
This instrument is publicly available through Mapi Research Trust
25-item Visual Function Questionnaire (VFQ-25)12
Developed by the National Eye Institute, the 25-item (question) instrument measures the influence of visual dysfunction on functional aspects (e.g. reading the newspaper).
This questionnaire has not been widely used in the GA patient population.
GA is a leading cause of visual impairment in the elderly, affecting more than 5 million people worldwide. GA is responsible for approximately 20% of all cases of legal blindness in the United States and 26% of cases in the United Kingdom.
A study in people with European ancestry showed the prevalence of GA (% of people with GA in the population) rises sharply with age, increasing approximately 4-fold with every decade of life beyond the age of 50 years; from 0.7% in people aged 70 years, to 2.9% in people aged 80 years and 11.3% at 90 years of age15.Prevalence of GA increases significantly with age with approximately 1 in 5 persons aged 85 and above having GA in at least one eye8,15
The pathophysiological mechanisms leading to the development of AMD and subsequent progression to late-AMD are not fully understood. It is generally thought that GA is caused by a complex interaction of metabolic, genetic and environmental factors.13 Several risk factors (age, smoking, ethnicity and genetics) have been strongly associated with the development of GA, most of which are also risk factors for other forms of AMD.
Progression to late-AMD (GA & Neovascular AMD)
Progression from early- to late- AMD (GA and/or neovascular AMD) is a complex process. Some people progress quickly to late- AMD (either GA or neovascular AMD), whereas others may progress slowly over several years.14 The underlying mechanisms that cause an eye to develop GA versus neovascular AMD are not fully understood. No reliable genetic or environmental risk factors have been identified to predict whether a patient will develop one form or the other.15 Both types can occur simultaneously in the same eye, or simultaneously in different eyes; it has in fact been suggested that GA and neovascular AMD are not mutually exclusive diseases, but that they lie on the same disease continuum.16 Eyes developing both types may in fact be at a more advanced stage than either GA or neovascular AMD alone.
Factors affecting GA progression rates
Once GA has been diagnosed, the rate of progression varies between individuals. Mean growth rates of atrophic areas ranging from 1.2 to 2.8 mm2 per year have been reported.17,18 Factors associated with variations in GA growth rates include size, configuration and location of atrophic areas,19,20,21 fellow eye status,22 genetic factors,23 smoking, diet and sun exposure.
Treatment of Geographic Atrophy (GA) – Two FDA approved therapies (Pegcetacoplan and avacincaptad pegol) are available in the US with none currently available in Europe.12Both these therapies aim to slow down the progression of GA to advanced stages and hence delay sight loss. A recent study that conducted a post hoc analysis of the Age-Related Eye Disease Study (AREDS) studies showed that the AREDS supplements slow progression of disease in late GA also and may be a potential therapeutic option.13
Several other therapeutic options for GA involving gene therapy, cell therapy and microcurrent stimulation are currently in early phase clinical trials. 20–22 A significant amount of research has focused on the complement pathway as a target for therapies and the current two FDA approved therapies both target complement. However, results from other clinical trials of anti-complement therapies suggests that some patients do not respond to these therapies and that other pathways need to be targeted i.e. there maybe multiple GA subtypes23. Further research is required to enable clinicians to predict disease progression in patients and identify biomarkers to predict response to therapies.23
To read more on Research and Clinical Trials, Please CLICK HERE
GA Risk Factors and Progression
Factors affecting GA progression rates
Once GA has been diagnosed, the rate of progression varies between individuals. Mean growth rates of atrophic areas ranging from 1.2 to 2.8 mm2 per year have been reported.24,25 Factors associated with variations in GA growth rates include size, configuration and location of atrophic areas, fellow eye status, genetic factors, smoking, diet and sun exposure.10,26,27
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