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Keeping an eye on geographic atrophy

Optometry Times JournalJune digital edition 2023
Volume 15
Issue 06

How to diagnose and monitor progression.

Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), is a progressive eye disease characterized by sharp, demarcated, growing atrophic lesions in the retina.1 With disease progression, irreversible vision loss may occur, which is associated with increased difficulty performing daily tasks, reading, driving, and recognizing faces.1-5 As a result, GA can lead to loss of independence and reduced quality of life.2-5 Therefore, careful diagnosis and monitoring of GA is essential to better understand disease progression and the impact of the disease on patients.

Diagnosing GA: An open dialogue with patients

The clinical hallmark of AMD is drusen—deposits of cellular debris, lipids, lipoproteins, and amyloid—accumulating between the retinal pigment epithelium (RPE) and Bruch’s membrane.6-8 In early AMD, numerous small drusen (< 63 μm in diameter) are observed. Intermediate AMD is characterized by medium drusen (63-124 μm in diameter), at least 1 large drusen (≥125 μm in diameter), and RPE pigment abnormalities.1,6 Advanced AMD can present as wet AMD, which is characterized by choroidal neovascularization (CNV); GA (atrophy of the RPE, choriocapillaris, and photoreceptors); or both.6,9 Although wet AMD has several anti-VEGF treatments that are FDA approved, GA has limited treatment options, with only 1 recently receiving FDA approval and another currently under review by the FDA.10-12 In addition, there are no established guidelines for diagnosing GA and monitoring disease progression.

AMD is not a 1-size-fits-all retinal disease process, and progression rates vary greatly among patients.13-15 For example, on clinical examination, approximately two-thirds of individuals with GA have nonfoveal lesions, and the progression rates of GA range from 0.53 to 2.6 mm2/year, further highlighting individual variability.1,16-20 Patients with GA may present to the clinic with blurry vision, visual distortions/hallucinations, or the inability to see certain parts of an image.5,21 Therefore, during clinical examination, it is important to identify not only whether the patient has GA but also how far along they are in disease progression.22

(Figure 1A-B)

(Figure 1A-B)

Diagnosis of GA can be made via ophthalmoscopy, by which the presence of drusen, abnormal retinal pigmentation, and atrophic lesions on the retina can be detected, even if the patient presents with good visual acuity.23 Further multimodal imaging techniques can help confirm and determine the degree of atrophy and corresponding disease progression.23 Nascent GA, or incomplete RPE and outer retinal atrophy (iRORA), can be observed on optical coherence tomography (OCT). Because early detection is key to preventing GA progression, it is important to detect markers that may be associated with subclinical GA. OCT can be used to visualize hyper-reflective columns and the evolution of soft to calcified drusen and other notable atrophic lesions. If complete RPE and outer retinal atrophy (cRORA) has occurred, which can be observed by OCT,24 fundus autofluorescence (FAF) may be considered as another imaging modality to measure the size and shape of the GA lesion and determine the location.24

(Figure 1C-E)

(Figure 1C-E)

I begin discussing GA as advancing dry macular degeneration when I see iRORA on OCT (Figure 1A-B). At that time, the patient’s vision is often unaffected, but preparing the patient for the future while keeping a hopeful attitude is important. When cRORA occurs, I begin referring to it as GA to the patient (Figure 1C-E). At that time, the FAF is often abnormal; therefore I begin to educate the patient on the size, shape, and location of their GA. Although the OCT gives more details to the practitioner, the FAF is more easily understood by patients.

Once the diagnosis of GA has been made, patients are typically monitored every 6 months, or more frequently if faster progression has been observed or risk factors for progression are present. Regular visits provide the opportunity for the eye care professional and the patient to understand how fast the disease is progressing and to discuss the short- and long-term prognoses. Empowering patients with education about GA allows for shared decision-making on the best course of action for their needs. In addition, the eye care professional and the patients can discuss novel treatments for GA and the importance of early intervention with low vision rehabilitation instead of waiting for severe vision loss to occur.

Monitoring GA progression

As noted earlier, GA progression is variable, and several studies have demonstrated risk factors associated with increased progression rates. Some of these include bilateral GA, multiple lesions, larger lesion sizes, past history of smoking, diet, age, specific gene alterations, and nonfoveal lesions.1,19,20,23 As the disease progresses, eyes with central foveal impairment tend to have severe visual impairment, and GA lesion enlargement is accompanied by a consistent decline in visual function.1,17,25 In a retrospective cohort study (N = 1901) of a multicenter electronic medical record database, in eyes with bilateral GA, mean visual acuity in the worse-seeing eye decreased over 2 years and continued to decline over 60 months, with a 10.9-letter loss. Over this same time frame, the better-seeing eye exhibited a steeper trajectory of visual acuity loss, with a 22.6-letter loss at month 60.26 This makes it clear how important it is to continue to follow up with patients and monitor disease progression.

(Figure 2)

(Figure 2)

To visualize the retina and monitor the growth of atrophic lesions after confirmatory diagnosis of GA, multiple imaging modalities may be needed.1,27 FAF is commonly used to help localize areas of atrophy and discriminate lesion boundaries.9 Hypoautofluorescence resulting from loss of RPE cells plus lipofuscin denote areas of atrophy (Figure 2). In addition, FAF is an especially useful tool for patient education to show changes in GA size and progression of the disease over time. Many clinics also use OCT, which allows for cross-sectional and en face images and for 3D quantitative atrophy assessment of specific retinal layers.6,24 From the patient perspective, OCT is comfortable; from the eye care perspective, it is easy to acquire images.28

While monitoring patients with GA, eye care professionals must look out for the development of CNV, which is a key characteristic of wet AMD. Wet AMD often presents on OCT with subretinal, intraretinal, or sub-RPE fluid,29 and an eye whose fellow eye has GA and/or CNV has been shown to have a significant risk of developing CNV.30 Continued monitoring of GA and CNV, although previously considered distinct entities, with imaging modalities will allow for prompt management of wet AMD with approved anti-VEGF treatments. Early diagnosis and treatment of wet AMD is key, as studies have demonstrated that baseline visual acuity at the time of treatment initiation is one of the strongest predictors of long-term preserved visual acuity.31-33 Results from a real-world retrospective study demonstrated that patients with 20/40 visual acuity at baseline maintained their visual acuity for 2 years after treatment administration.33

GA is insidious, and changes in several measures of visual functioning may be more evident before the decline of visual acuity is observed. Visual functioning can be assessed by tests such as low luminance visual acuity, contrast sensitivity, microperimetry, multifocal electroretinography, reading speed, and Amsler grid.22,34 Although the Amsler grid can be used at home by the patient, it is not sensitive enough to detect small changes over time.22,35

(Figure 3)

(Figure 3)

Patients with GA have a fear of worsening vision,4 and as a result of visual impairment, they may be less engaged or feel they are a burden to family and friends.5,36 Therefore, it is important to discuss with patients their options, which include referral to a low vision specialist early in their disease progression, prior to severe vision loss occurring, and referral to retina specialists for novel treatments in GA.


As eye care professionals, we understand the importance of early and careful diagnosis, as well as continued monitoring of our patients with GA. The American Optometric Association has provided a comprehensive adult eye and vision examination algorithm (Figure 3). Indeed, it is helpful for our patients with GA; however, specific guidelines for diagnosing, managing, and monitoring patients are needed to ensure timely treatment to minimize vision impairment. Knowing when to refer patients to low vision specialists for rehabilitation or to retina specialists for treatment with newly approved agents is of vital importance. Educating patients on GA disease progression and their options is key to ensuring optimal care is provided to them.

Medical writing support was provided by IMPRINT Science, New York, NY, USA, and was funded by IVERIC bio, An Astellas Company.
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11. Ford J. FDA approves Syfovre as first treatment for geographic atrophy. Retinal Physician. February 20, 2023. Accessed March 3, 2023. https://www.retinalphysician.com/issues/2023/january-february-2023/fda-approves-syfovre-as-first-treatment-for-geogra
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15. Sardell RJ, Persad PJ, Pan SS, et al. Progression rate from intermediate to advanced age-related macular degeneration is correlated with the number of risk alleles at the CFH locus. Invest Ophthalmol Vis Sci. 2016;57(14):6107-6115. doi:10.1167/iovs.16-19519
16. Keenan TD, Agrón E, Domalpally A, et al. Progression of geographic atrophy in age-related macular degeneration: AREDS2 report number 16. Ophthalmology. 2018;125(12):1913-1928. doi:10.1016/j.ophtha.2018.05.028
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18. Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127(9):1168-1174. doi:10.1001/archophthalmol.2009.198
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21. Taylor DJ, Smith ND, Binns AM, Crabb DP. The effect of non-neovascular age-related macular degeneration on face recognition performance. Graefes Arch Clin Exp Ophthalmol. 2018;256(4):815-821. doi:10.1007/s00417-017-3879-3
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25. Heier JS, Pieramici D, Chakravarthy U, et al. Visual function decline resulting from geographic atrophy: results from the Chroma and Spectri phase 3 trials. Ophthalmol Retina. 2020;4(7):673-688. doi:10.1016/j.oret.2020.01.019
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29. Kaiser PK, Jaffe GJ, Holz FG, et al. Considerations on the management of macular neovascularization in patients with geographic atrophy enrolled in clinical trials. Retina Today. March 2022 Supplement. Accessed March 9, 2022. https://retinatoday.com/articles/2022-mar-supplement2/considerations-on-the-management-of-macular-neovascularization-in-patients-with-geographic-atrophy-enrolled-in-clinical-trials.
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