Brief Summary: Geographic Atrophy
Symptoms: Early GA; blind spots, reduced contrast sensitivity, delayed dark adaptation. Late GA; distorted vision, marked reduction in contrast sensitivity
Diagnosis: Retinal Imaging, functional tests, Patient-reported outcome (PRO)
Treatments: No currently approved treatments.

What is GA?

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 choriocapillaries.1,2 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 is a leading cause of visual impairment in the elderly, affecting more than 5 million people worldwide.3 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 age.4

Several studies have also estimated the incidence of GA (new cases of GA diagnosed in a population over a specified time period). One of these studies evaluating the incidence of AMD in the US white population reported annual GA incidence rates of 1.9 per 1000 aged ≥50 years; rates increased significantly with age, rising from 0.3 per 1000 in individuals aged 60-64 years, to 3.0 per 1000 in those aged 75–79, to 22.0 per 1000 in those aged >90 years.5

As a result of population growth and aging, the number of people affected by AMD and GA are expected to increase considerably over the next few decades.3,6

GA is responsible is for approximately 20% of all cases of legal blindness in the United States1 and 26% of cases in the United Kingdom. With no approved treatments to prevent or slow its progression and the number of people affected expected to increase, GA represents a significant unmet medical need.


Many studies have been conducted reporting prevalence and/or incidence data for late AMD (GA and neovascular AMD) in different countries and regions around the world. As the numbers of those impacted by AMD and GA are forecast to increase in the decades ahead, in line with population growth and ageing, it is increasingly important to gather data on a national and regional basis to inform healthcare policy into the future.

Prevalence Data – Late AMDIncidence Data – Late AMD

This video has been provided by Roche.
© 2017 F. Hoffmann-La Roche Ltd. All rights reserved.

Symptoms of 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.7 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.7,8

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 coloured.9

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, 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.

Marked reduction in contrast sensitivity

This is where there is difficulty discerning between simil

Symptoms of Geographic Atrophy vary between individuals, depending upon how each eye is affected and how progressed the disease is.

Symptoms of Geographic Atrophy

GA diagnosis

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
  • 25-item (question) instrument that measures the influence of visual dysfunction on functional aspects (e.g. reading the newspaper).
  • Questionnaire has not been widely used in the GA patient population.

Diagnosis and management of GA is currently typically achieved through a combination of retinal imaging techniques. Functional tests and PRO measures are not widely used in clinical practice, although the latter may be included in clinical trials of new drugs in development.

Retinal Imaging Techniques
Functional Tests For GA
VFQ-25 – Self Administered
VFQ-25 – Interviewer Administered
NEI VFQ-25 Scoring Algorithm

Causes & progression

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.

Depiction of the progression from an intact retina through development of drusen (early/intermediate AMD) to GA & nvAMD.


The pathophysiological mechanisms leading to the development of AMD and subsequent progression to late-AMD are not fully understood. Likewise factors affecting the rate of GA progression are not fully understood.

Risk Factors for Geographic AtrophyProgression to Late-AMD (GA & Neovascular AMD)Factors Affecting Geographic Atrophy Progression Rate

Coping with a diagnosis


There are currently no approved treatments to prevent, slow or reverse the progression of GA. (Progress into understanding the pathogenesis of GA has led to the clinical development of potential new therapies, which are under investigation.)

Rehabilitation Services & Supports

In the early stages of vision loss many patients with GA can manage very adequately with visual tasks. However, as sight worsens some adaptation will be required. Common sense and imagination will help maintain independence (e.g. Illumination – spotlight work areas, use brighter globes; Contrast – use coloured coasters or backgrounds; Size – use larger and bolder text; and Tactile – use nail polish or hard setting putty to mark dials and devices). As sight worsens assistive devices may be necessary. For an assistive device to be successful 3 important steps need to be followed: accurate assessment, good choice of device and training in use of the device.


It is important that rehabilitation services are identified and accessed as early as possible, before significant deterioration in sight is experienced. While some service providers offer a total and comprehensive service in other cases more than one provider will be needed. Services may be made available via hospitals, universities, charitable organisations (NGO’s) and state or commercial specialist service providers. Sources of information on local services include healthcare providers, NGOs (including blind organisations and Retina International), internet.


VIAOPTA is a recently developed suite of mobile applications that have been developed to assist visually impaired people with their daily lives. These apps allow individuals to maintain their independence by assisting with daily activities, navigating your local region and recognising people and places using image analysis technology.

Where are we with GA?

Over the last decades much research has been undertaken on AMD, and in particular late-AMD, giving rise to a breakthrough therapy (anti-VEGF) for the treatment of neovascular AMD in the mid-2000s. This has had a profound impact on the lives of affected individuals. Research across all areas of GA (incidence & prevalence, natural history, diagnosis, treatment) is however required if similar progress is to be made for patients with GA.

Incidence and prevalence

Several population-based cohort studies have provided prevalence and incidence estimates of AMD and GA rates in the older population. In the future, it will be important to have country-specific incidence estimates relating to the number of patients affected by GA so that health care provision can be planned accordingly. This will be particularly important with the emergence of potential new therapies for the treatment of GA.

Screening for AMD

AMD is a painless condition and people with the early and intermediate stages of the disease do not usually experience any symptoms. It is essential that regular eye examinations are performed in order to detect the early signs of AMD and ensure patients receive appropriate treatment. LINK TO “Your Eyes – Eye Disease: AMD – The role of early diagnosis”

Diagnosis & monitoring: imaging and functional tests

A range of imaging modalities currently exist for the diagnosis and morphological quantitative assessment of GA. Colour fundus photography (CFP), spectral domain-optical computed tomography (SD-OCT) and fundus autofluorescence (FAF) are the main clinical techniques used.

Validated functional tests that truly capture the impact of the disease on the patients’ visual function and quality of life are needed. A number of assessments that can potentially reveal visual function deficits in people with GA exist, including low-luminance visual acuity (LLVA), contrast sensitivity, microperimetry and reading speed.24 These functional tests will become increasingly important for determining the value of future therapies for GA as part of a multimodal assessment of visual function. Many of them are currently undergoing evaluation and validation as endpoints in clinical studies of GA.

Patient reported outcome measures are becoming an increasingly important element of the toolkit available to clinicians and researchers when diagnosing and studying AMD and GA. These include the FRI Index and 25-item Visual Function Questionnaire (VFQ-25).


There a currently no approved treatment to prevent or impede the progression of GA. However, improved understanding of the disease pathophysiology has led to the development of potential new therapies. A large number of clinical trials of these new medicines is currently ongoing.


  1. Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M. Geographic atrophy: clinical features and potential therapeutic approaches. Ophthalmology. 2014;121(5): 1079-1091.
  2. Sunness JS. The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration. Molecular vision. 1999;5: 25.
  3. Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global health. 2014;2(2): e106-116.
  4. Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology. 2012;119(3): 571-580.
  5. Rudnicka AR, Kapetanakis VV, Jarrar Z, Wathern AK, Wormald R, Fletcher AE, et al. Incidence of Late-Stage Age-Related Macular Degeneration in American Whites: Systematic Review and Meta-analysis. American journal of ophthalmology. 2015;160(1): 85-93 e83.
  6. Colijn JM, Buitendijk GHS, Prokofyeva E, Alves D, Cachulo ML, Khawaja AP, et al. Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future. Ophthalmology. 2017.
  7. Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology. 2007;114(2): 271-277.
  8. Sunness JS, Rubin GS, Zuckerbrod A, Applegate CA. Foveal-Sparing Scotomas in Advanced Dry Age-Related Macular Degeneration. Journal of visual impairment & blindness. 2008;102(10): 600-610.
  1. Sunness JS, Rubin GS, Applegate CA, Bressler NM, Marsh MJ, Hawkins BS, Haselwood D. 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.
  2. Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, Henry EC, Brittain C. Clinical Endpoints for the Study of Geographic Atrophy Secondary to Age-Related Macular Degeneration. Retina. 2016;36(10): 1806-1822
  3. Kimel M, Leidy NK, Tschosik E, Dolan C, Souied EH, Varma R, Bressler NM. Functional Reading Independence (FRI) Index: A New Patient-Reported Outcome Measure for Patients With Geographic Atrophy. Investigative ophthalmology & visual science. 2016;57(14): 6298-6304.
  4. Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. Development of the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25)(2001). Archives of Ophthalmology. 119, 1050-1058
  5. Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, Henry EC, Brittain C. 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.
  6. Sardell RJ, Persad PJ, Pan SS, Whitehead P, Adams LD, Laux RA, et al. Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus. Investigative ophthalmology & visual science. 2016;57(14): 6107-6115.
  7. Grob S, Luo J, Hughes G, Lee C, Zhou X, Lee J, et al. Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization. Eye. 2012;26(8): 1106-1113.
  8. Kaszubski P, Ben Ami T, Saade C, Smith RT. Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review. Ophthalmic research. 2016;55(4): 185-193.
  1. Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M. Geographic atrophy: clinical features and potential therapeutic approaches. Ophthalmology. 2014;121(5): 1079-1091.
  2. Schmitz-Valckenberg S, Sahel JA, Danis R, Fleckenstein M, Jaffe GJ, Wolf S, et al. Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study). Ophthalmology. 2016;123(2): 361-368.
  3. Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology. 2007;114(2): 271-277.
  4. Joachim N, Mitchell P, Kifley A, Rochtchina E, Hong T, Wang JJ. Incidence and progression of geographic atrophy: observations from a population-based cohort. Ophthalmology. 2013;120(10): 2042-2050.
  5. Grunwald JE, Pistilli M, Ying GS, Maguire MG, Daniel E, Martin DF, Comparison of Age-related Macular Degeneration Treatments Trials Research G. Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2015;122(4): 809-816.
  6. Fleckenstein M, Schmitz-Valckenberg S, Adrion C, Visvalingam S, Gobel AP, Mossner A, et al. Progression of age-related geographic atrophy: role of the fellow eye. Investigative ophthalmology & visual science. 2011;52(9): 6552-6557.
  7. Grassmann F, Fleckenstein M, Chew EY, Strunz T, Schmitz-Valckenberg S, Gobel AP, et al. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration. PloS one. 2015;10(5): e0126636.
  8. Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, Henry EC, Brittain C. Clinical Endpoints for the Study of Geographic Atrophy Secondary to Age-Related Macular Degeneration. Retina. 2016;36(10): 1806-1822.