The Evolving Landscape of Geographic Atrophy Management

See related multimedia content on Eyetube

Check it Out

Although it is difficult to get exact statistics on the prevalence of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), we know from studies that the disease burden is significant and that it is expected to increase as the population ages (see GA By the Numbers). The best data we have suggest that the prevalence of GA is probably higher in European populations compared to African and Asian populations. However, in all the countries, under-diagnosis of the disease is obvious. In short, the numbers are already overwhelming, but we might even have higher numbers due to under-diagnosis.

One of the contributing factors to under-diagnosis is that many cases of GA are not recognized until they become visually symptomatic. This is not entirely unsurprising, given that until recently, the pathophysiology of this disease was not well characterized. However, a wealth of recent research has helped to identify warning signs of progression toward GA and progression of GA. This new information comes at a fortuitous time for patients, as for the first time in history, treatment options are emerging. Complement inhibitors, which have been demonstrated to slow the progression of GA over time, are approved in the United States and Australia, and are the subject of clinical trials around the world. Indeed, patients in many parts of the world where complement inhibitors are not yet approved may be able to access these therapeutic options through clinical trials and compassionate use protocols.

Above and beyond the potential for offering treatment, though, there is urgent need to recognize the conversion of intermediate AMD to GA at the earliest possible timepoint and to have these patients referred to retina specialists for monitoring. Some of the lessons we have learned regarding GA are that lesions are heterogenous, progression is highly individualized, and that an individual’s prior rate of progression is prognostic of future progression rates. Therefore, it is important for us to follow these patients longitudinally so that in the future we can offer the personalized care they will need.

The evolving landscape of GA does not necessarily require a whole new way of approaching patient care. Rather, the expected rise in GA prevalence, coupled with the potential future availability of viable treatment options, suggest a greater need for awareness about GA, how to diagnose it, and when to refer patients on to specialists. In the interest of helping our colleagues better understand some of the nuances of managing GA—now and in the future—I recently sat down for a wide-ranging discussion with my colleagues Patricio G. Schlottmann, MD; Paulo-Eduardo Stanga, MD; and Daniel Ting, MD, PhD. A summary of our conversation follows.

— Anat Loewenstein, MD, MHA

Setting the Stage

Anat Loewenstein, MD, MHA: How are eye care providers thinking about age-related macular degeneration (AMD) in general, and geographic atrophy (GA) in particular, when looking at the forecasted increases in prevalence of these diseases? Are we worried about the burden on our clinics?

Patricio G. Schlottmann, MD: The reported prevalence of AMD and GA is already high and expected to increase, but I suspect that both conditions are underdiagnosed—especially GA. Unfortunately, a lot of patients with GA do not get diagnosed until it starts to affect visual acuity, which is typically late in the disease process. It is likely that a lot of patients with nonsubfoveal lesions go undetected. Eye care providers in my part of the world are overwhelmed with managing wet AMD because there are treatments available, and they are not prepared yet for what is coming when treatments for GA become available in the clinic.

Paulo-Eduardo Stanga, MD: It is not surprising that the prevalence of GA may be higher in the European population. But when I see the data, I ask myself whether the statistics in less developed parts of the world are accurate, because we don’t know whether they are accurate for Europe. In less developed parts of the world where there’s lower access to early diagnosis and advanced imaging technology, the situation may be different. Regardless, GA certainly is a significant burden on any healthcare system, and we may not have an accurate assessment of how great that burden is. In the United Kingdom, most of these patients are managed by optometrists, and they are being told there is no treatment for their eye disease. I think that is a big mistake, because we need to educate patients so they are prepared when treatments become available.

Prof. Loewenstein: In Israel, many GA patients are being followed by general ophthalmologists that might tell them there is nothing that can be done, which was true until recently. They are not being referred to retina specialists, which is unfortunate because we are learning more about how GA affects patients’ visual function and daily living. Many of my GA patients are complaining that they don’t see well, that they cannot pour coffee into a cup, and that they cannot read comfortably because letters are missing. And many times, while this is the situation, their visual acuity is still unaffected, or at least stable.

Prof. Schlottmann: The reason for this phenomenon is that when patients are tested for visual acuity, they are evaluated in high-contrast settings, whereas low-contrast vision, which is what we use for activities of daily life, is more likely to be compromised in early GA. This is important to recognize, as a change in contrast sensitivity may be the first sign of the disease. Ideally, we are catching patients early in the disease progression so we can offer treatments that slow the rate of progression and thus preserve viable retina for visual tasks. This is especially important given data from studies showing that visual compromises in the late stages of the disease can lead to social limitations, isolation, depression, and an overall decrease in quality of life.^1,2

Prof. Loewenstein: There are data that suggest about 40% to 60% of GA patients lose the ability to drive within 2 years of being diagnosed.³ As well, studies show that patients with advanced AMD are more prone to falls and injuries.⁴

Daniel Ting, MD, PhD: GA lesions tend to start in regions outside the fovea and grow toward the periphery faster than they do toward the fovea.⁵ And so, in the patient with a parafoveal lesion, parts of the visual field may be compromised even if the visual acuity is stable. These compromises make performing activities of daily living more difficult, which is often what patients and their families start to recognize early in the disease continuum.

Making the Diagnosis

Prof. Loewenstein: What are the most important imaging modalities for establishing a diagnosis of GA?

Dr. Ting: Before we discuss imaging, I will say that a thorough clinical examination is very important. As for imaging methods, because it correlates well with ophthalmoscopy, color fundus photography (CFP) is useful for identifying GA; in my clinic, I like to capture CFP at baseline and again at follow-up visits to track lesion progression over time. The other two imaging modalities we use regularly for diagnosing and following GA are OCT and fundus autofluorescence (FAF).

Prof. Loewenstein: Are you using artificial intelligence (AI) in any capacity with imaging?

Dr. Ting: AI holds tremendous promise to detect lesion areas that may not be immediately visible to the human eye; however, it is more useful as a research tool at the current time than as a clinical adjunct. The reason for that is AI algorithms have not been integrated into the imaging devices clinicians use on a regular basis. And because of that, there is a need for a lot of manual processing, which is inefficient in a busy clinic setting. I am hopeful that AI algorithms get integrated into the imaging devices we use to diagnose and track GA, and hopefully that will come soon.

Prof. Loewenstein: What should clinicians look for on the various imaging modalities to make a diagnosis of GA?

Prof. Stanga: GA is visible on CFP as sharply demarcated areas of hypopigmentation, and often, choroidal vessels are evident due to the absence of overlying retinal pigment epithelium (RPE) (Figure 1). However, CFP is not very useful for quantifying lesion size.^6,7 For that, we turn to FAF, which shows GA lesions as areas of hypofluorescence, or darker regions contrasting with the lighter background (Figure 2). On FAF, we are also looking at the lesion margins to detect any hyperfluorescence—light areas—which indicate potential areas of lesion expansion.⁶

On OCT, GA presents as loss or attenuation of retinal layers, which correspond with loss of the RPE and photoreceptors. Another hallmark finding is hypertransmission, or an increase in choroidal reflectivity (Figure 3).⁶ We also use OCT to classify the atrophy according to the definitions set forth by the Classification of Atrophy Meeting (CAM) group.⁸ Specifically, we are seeing if the lesion fits the criteria for complete RPE and outer retinal atrophy (cRORA), and if not, whether it is classified as incomplete RPE and outer retinal atrophy (iRORA), as iRORA has been confirmed as an evident risk factor for cRORA development (see Guidelines for Categorizing Atrophy on OCT).⁹ In our clinic, we also look at the ellipsoid zone (EZ) for any signs of attenuation; for that, we do cross-sectional, high-resolution OCT, and we also use AI, because we want to detect any change there as soon as it is evident.

Prof. Loewenstein: As we are discussing making a diagnosis, it is important to mention that there is a lack of correlation between GA and visual function. Therefore, it is often difficult to assess visual impairment in patients with GA. There is a lot of ongoing research into the clinical utility of various functional tests; in particular, microperimetry has garnered a lot of attention for this purpose. The various tests that can be performed using microperimetry may be able to tell us a lot about not only the patient’s current visual functional ability, but also about the risk of progression. For example, there are data showing a correlation between the number of scotomatous points and growth of GA lesions.¹⁰ Other research is looking at microperimetry in the perilesional area to determine if deficits might predict areas of future lesion growth.¹¹

Prof. Stanga: Another test available on microperimetry is the preferential fixation locus, which indicates where the patient is fixating to use functional parts of the retina for visual tasks. I am very interested in the research looking at how the preferential fixation locus changes as the lesion progresses or changes.

Prof. Schlottmann: Microperimetry is a complicated test for patients to complete, particularly elderly individuals. Very few patients can complete the study, but when it’s properly done, it gives us a lot of information. It will be particularly interesting as patients are followed longitudinally with microperimetry to see if there are any correlations on the various testing modalities and changes in the GA lesion.

Another test we can perform in the clinic, which is much simpler, is low luminance visual acuity. In this test, we are looking at the difference in how the patient performs on a standard reading chart compared to their performance on the same chart with a low luminance filter placed in front of the eye to stimulate low lighting conditions. The higher the delta, the more affected the contrast sensitivity is.

Prof. Loewenstein: For the sake of discussion, let’s say that GA is detected early. When do you think is the best time to refer that patient to your clinic? Is it when it shows signs of progression? Is it upon diagnosis? Is it only after the disease is fairly developed?

Prof. Schlottmann: The earlier the better, because we know that what looks like an innocent drusen today may be something more complicated in the future. The earlier we have the patient within our control, the sooner we can develop an idea of how rapidly the lesion is progressing, which in turn will inform our treatment approach once we have complement inhibitors or other modalities available to us.

Prof. Loewenstein: So you want every intermediate AMD patient to be referred to you?

Prof. Schlottmann: Ideally, yes. Many of them will just be imaged and returned to the referral source with instructions to capture imaging every 6 months—and if anything changes, to return to our clinic. But we want to have at least a quick conversation with every single patient. As well, studies have identified a number of imaging biomarkers in eyes with intermediate AMD that predict a higher risk of progression to GA (see AMD Characteristics Associated With a Higher Risk of GA Development).

Prof. Loewenstein: I follow many intermediate AMD patients, and I have been surprised how fast some of them progress, especially the severe ones.

Prof. Stanga: I also prefer to see the patient when they are diagnosed with intermediate AMD. Unfortunately, we do not usually get to see the patients at that stage, as they are typically being followed in the community. But that is really why GA is under-diagnosed. It is very easy for us to perform high-resolution OCT to detect the earliest signs of GA so we can start treatment before the patient develops loss of vision.

Dr. Ting: I agree that intermediate AMD patients should be referred, especially because some of the treatment modalities in the pipeline are targeting high-risk intermediate AMD to prevent the progression to GA. It is therefore advantageous for us to see patients at this earlier stage in case we might be able to get them enrolled in a clinical trial.

Discussing Treatment and Management Strategies

Prof. Loewenstein: Let us assume a patient has been referred to you and a diagnosis of GA has been confirmed. What treatment options do you discuss with that patient? Are AREDS vitamins still part of the conversation?

Prof. Stanga: I am in the unique position of working at a clinical trial center, so I have the opportunity to offer my patients the choice of receiving treatment. For clinicians in settings that do not have access to therapy, recommending AREDS vitamins is a reasonable starting point, especially in light of recent data suggesting that the AREDS supplements can decrease progression of GA by 50% at 3 years.¹²

Prof. Schlottmann: The recent data you mentioned may change how AREDS supplements are used. They have always been recommended for patients with intermediate AMD, but we may have stopped them once the patient progressed to advanced AMD. Now, with data suggesting that AREDS supplements slow the progression of GA toward the central macula, it makes sense to start them as soon as the patient develops intermediate AMD, and to keep them on the formulation even when they progress to GA as we wait for treatments to become available.

Prof. Loewenstein: What is the role of recommending lifestyle modifications in any patient with AMD, and GA in particular?

Dr. Ting: I recommend that patients stop smoking regardless of the stage of AMD, and I also ask about secondhand smoke exposure, because I think that is a risk factor for progression. AREDS vitamins are a regular part of my conversation with AMD patients, and I also suggest eating more fish, fruits, and vegetables—whether or not it is good for the eye, that is beneficial for the patient.

Prof. Loewenstein: I tell my patients that anything that is good for the heart is probably good for macular degeneration, meaning a healthy diet with a lot of fish and vegetables and regular exercise. For patients with GA, if they are eligible, we offer the choice of starting complement inhibition therapy. In Israel, we can use drugs that are not registered yet if they are approved in the United States. We have to go through some paperwork, but we feel an obligation to at least let patients know about this option.

Dr. Ting: Complement inhibitors are not yet approved in Singapore. As we are discussing management strategies, I feel it is important to add that we can and should refer these patients to low vision specialists if they are available. Helping patients learn to manage life with a paracentral or peripheral scotoma can be very beneficial.

Prof. Stanga: There are not approved therapies in the United Kingdom, or Europe for that matter. We do discuss clinical trials so patients can decide if that may be right for their situation.

Prof. Loewenstein: How do conversations around GA differ from conversations around neovascular AMD, retinal vein occlusion, and diabetic macular edema? Do you think that there is something special in the conversation with GA specifically?

Prof. Stanga: The main difference is that with the neovascular conditions, we are trying to restore vision, whereas with the current therapy options for GA, we are attempting to preserve vision. It’s an important distinction, because when we administer an anti-VEGF injection, the patient often has an improvement in vision that incentivizes them to be compliant with the injection protocol. With complement inhibitors for GA, we have to educate that their vision will not improve, and if we preserve vision, then we are successful.

Prof. Loewenstein: When I am recommending complement inhibitors to patients with GA, I tell them up front that their vision will not improve. That the deterioration will not stop, but it will be slower. Patients need to be aware of this so they can make the choice that is best for them.

Prof. Schlottmann: The conversation with GA patients is longer and more involved compared to AMD, retinal vein occlusion, and diabetic macular edema. It takes more time to educate about the disease state, and then when we get to treatment, we need to have a careful discussion about expectations for outcomes so they can make an informed decision about what is the best option for their particular situation.

Conclusion

Prof. Loewenstein: We have discussed a number of important points. To summarize:

• GA is very prevalent and it is more prevalent in Europe than in Asia.
• However, GA is likely underdiagnosed.
• Many patients are not referred to retina specialists in a timely manner.
• There is a lack of correlation between the severity of GA and visual acuity.
• OCT is the ideal reference modality for diagnosing and following GA, as well as for staging its severity according to criteria established by the Classification of Atrophy Meetings program.
• Diagnosing and following GA requires a multimodal imaging approach—in addition to OCT, FAF provides important information that is relevant for establishing a diagnosis and predicting future progression.

Given these facts, what advice can we give to general ophthalmologists or optometrists regarding educating patients about their options?

Dr. Ting: Primary eye care physicians can play a big role in the management of GA. First, our colleagues in general ophthalmology and optometry can learn to diagnose lesions at their earliest stage. Second, they can educate patients that GA is a significant eye disease even if it may not be symptomatic. In this respect, there are similarities to diabetic retinopathy, in which vision may not be impacted, or glaucoma that has not yet impacted the central field. Patients need to understand the importance of monitoring visits so GA can be detected at the earliest stage possible. Some practices do this with simulators that mimic what happens when you have a central scotoma, which can be very effective. And third, I would recommend to not wait until there is a decrease in vision before referring the patient to a specialist, because declines in visual acuity typically do not occur until late in the disease when the fovea becomes involved. When they are available, we want to offer treatments before that happens in the hopes of preserving vision.

Prof. Stanga: I agree that general ophthalmologists and optometrists are really pivotal in managing GA, because they are the ones most likely to encounter patients when they have the early warning signs of impending GA. Being able to recognize those signs is, of course, important, but they can also start to educate that there are treatment options for their eye disease—and follow that with the message that the goal of therapy is to preserve their vision rather than to restore it. I think that will help patients understand the role of early diagnosis. One of the challenges we face is that for years, it has been established dogma that GA secondary to AMD is a slowly progressing disease. Unfortunately, that is not entirely correct. Rather, we have learned that it may take years for the patient with intermediate AMD to develop GA, but once it is present, it progresses rapidly. The average time from diagnosis until involvement of the fovea is around 2.5 years.¹³ And we also know that patients who already have subfoveal GA can lose vision entirely by the time they get to our clinic.

Prof. Schlottmann: My advice is that one single large drusen is enough for you to refer the patient. It’s not an innocent age-related lesion. There’s a lot going on in that eye. We have to remember that many cases of GA start not affecting the central retina, and, over the course of months or years, expand to involve the fovea. That means that every patient with advanced, subfoveal GA at one point in time had a parafoveal lesion that may have been eligible for treatment. So, send the patient over.

1. Patnaik JL, Lynch AM, Pecen PE, et al. The impact of advanced age-related macular degeneration on the National Eye Institute’s Visual Function Questionnaire-25. Acta Ophthalmol. 2021;99(7):750-755.

2. Williams RA, Brody BL, Thomas RG, Kaplan RM, Brown SI. The psychosocial impact of macular degeneration. Arch Ophthalmol. 1998;116(4):514-520.

3. 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.

4. Anastasopoulos E, Yu F, Coleman AL. Age-related macular degeneration is associated with an increased risk of hip fractures in the Medicare database. Am J Ophthalmol. 006;142(6):1081-1083.

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. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390.

7. Holz FG, Sadda SR, Staurenghi G, et al; CAM group. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from Classification of Atrophy Consensus Meetings. Ophthalmology. 2017;124(4):464-478.

8. Sadda SR, Guymer R, Holz FG, et al. Consensus definition for atrophy associated with age-related macular degeneration on OCT: Classification of atrophy report 3. Ophthalmology. 2018;125(4):537-548.

9. Vallino V, Berni A, Coletto A, et al. Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD. Graefes Arch Clin Exp Ophthalmol. 2024;262(11):3421-3436.

10. Meleth AD, Mettu P, Agrón E, et al. Changes in retinal sensitivity in geographic atrophy progression as measured by microperimetry. Invest Ophthalmol Vis Sci. 2011;52(2):1119-1126.

11. Csaky KG, Patel PJ, Sepah YJ, et al. Microperimetry for geographic atrophy secondary to age-related macular degeneration. Surv Ophthalmol. 2019;64(3):353-364.

12. Keenan TDL, Agrón E, Keane PA, et al; Age-Related Eye Disease Study Research Group; Age-Related Eye Disease Study 2 Research Group. Oral antioxidant and lutein/zeaxanthin supplements slow geographic atrophy progression to the fovea in age-related macular degeneration. Ophthalmology. 2025;132(1):14-29.

13. Lindblad AS, Lloyd PC, Clemons TE, et al; Age-Related Eye Disease Study Research Group. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127(9):1168-1174.