Carolyn Majcher, OD, FAAO, FORS
Julie Rodman, OD, MSc, FAAO
Editorially independent supported by:
Geographic atrophy (GA), a late form of age-related macular degeneration (AMD), is strongly linked to a dysregulated complement system that creates chronic inflammation which damages host tissue.1,2 Although GA is irreversible, two treatments that work differently to regulate the complement system and thereby slow progression were approved in 2023. In this new era of available therapeutic options, three related factors are magnifying the role of the comprehensive eye care provider in early identification of GA, educating patients about their disease and treatment options, and promptly referring for treatment:
No two patients are exactly alike, and not all cases of AMD progress at the same rate. However, patient characteristics (advancing age,3 any smoking history,4 family history of GA,5 and/or GA in the fellow eye6) and certain AMD disease features indicate a higher risk of developing GA, and, thus, a need for closer monitoring, including initiation of multimodal imaging where appropriate.
Disease Characteristics Associated with a Higher Risk of GA Development7
*Presence of these two features is diagnostic of intermediate AMD.
Large soft drusen on color fundus photography and OCT.
Pigmentary abnormalities on color fundus photography and hyperreflective foci on OCT.
GA is defined as atrophy of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris, meaning the disease impacts the structure of the retina—and those changes may or may not correlate with functional changes as measured by visual acuity. Thus, OCT imaging is used clinically to detect biomarkers for GA development. That is to say: identification of any of the following signs is an indication that the AMD is on the threshold of converting to GA; and, therefore, these imaging findings may be useful for finding patients before irreversible, sight-threatening damage has occurred.
1. Subretinal drusenoid deposits
Extracellular deposits located in the subretinal space.
2. Large soft drusen collapse
Occurs when drusen expand in volume and cause the RPE layer to disintegrate.
3. Loss of the ellipsoid zone
A sign of photoreceptor degeneration and atrophy.
4. Sinking of the INL & OPL
This is sometimes called a "gull-wing" configuration.
5. Hyporeflective wedges
6. Hyperreflective foci
Well-demarcated, round or dot-like lesions; the number and volume of hyperreflective foci are associated with an increased risk of atrophy.
6. Hyperreflective foci
Well-demarcated, round or dot-like lesions; the number and volume of hyperreflective foci are associated with an increased risk of atrophy.
When it comes to making a diagnosis, color fundus photography (CFP) defines GA lesions as sharply demarcated areas of hypopigmentation,7 but they may be more readily visible as areas of hypofluorescence on FAF8 or as areas of hyperreflectivity on near-infrared reflectance (NIR) imaging.9
Click/tap the images or buttons below to see the differences between CFP, FAF, and NIR imaging in three patients.
Patient A
Patient B
Patient C
A diagnosis of GA is most often confirmed on OCT, identified as increased signal transmission (ie, choroidal hypertransmission) in the areas of pathology, which indicates loss of the RPE and/or the photoreceptor layer with subsidence of the INL and OPL.10 As seen in the image gallery of representative cases below, image findings are often subtle.
Nonfoveal, multifocal lesions
Nonfoveal, multifocal lesions (note the subsidence of the INL/OPL in the areas of pathology)
Foveal, unifocal GA
Nonfoveal, unifocal GA
Despite a pervasive notion that GA is a slow progressing disease, foveal encroachment occurs in an average of 2.5 years from the time of onset.8 The resulting effect on vision can be profound, with some studies suggesting that patients can lose up to 2 lines of vision within 2 years or lose the ability to drive within 1.6 years.11 Studies also suggest that patients with visual impairment due to AMD are at higher risk for depression, anxiety, social isolation, and other detriments to mental health.12,13
Because vision loss secondary to GA has the potential to impact patients' daily functioning, affecting their ability to drive, read, recognize faces, and more generally, to enjoy life,8,14 it is important to recognize GA early, perhaps even before symptoms are evident, and refer promptly. Fortunately, research has identified certain disease features and patient characteristics indicating a higher risk of progression.
Characteristics associated with HIgher Risk of Rapid GA Progression:
GA lesion presentation is highly individualized and will vary from patient to patient, and even from eye to eye. Progression analysis, based on serial imaging over time, may be most helpful in identifying growing lesions. The sample case below shows rapid expansion of GA in just 3 years.
Click/swipe through the images below to see how different imaging modalities show the rapid expansion of GA.
(Shown on different imaging modalities)
Color fundus photography
OCT b-scan
NIR imaging
En face OCT
As demonstrated in this case, visual acuity change often does not correlate with progression of GA, and so waiting for advanced disease or central involvement may be too late to help patients preserve their ocular health. Instead, FAF imaging is helpful for identifying patients at risk for progression, particularly in assessing fluorescence at the junctional zone, or the area between normal and abnormal retina.
The image slider below shows CFP and FAF images of the same eye in two different patients. In the FAF images, note the dark areas of hypofluorescence indicating disruption/loss of the RPE and/or photoreceptors. The bright areas of hyperfluorescence indicate areas of impending RPE damage, or areas where GA may expand.
Click and drag the arrows below to see how FAF imaging can help identify areas of hypofluorescence not as easily seen on CFP.
A more nuanced appreciation of GA progression, advanced imaging technologies to detect tissue loss before patients report symptoms, and multiple treatments that can preserve viable retinal tissue for longer have converged to transform the approach to managing GA. Yet, there is a crucial window of opportunity for taking action. Currently available treatments aim to slow progression, but cannot stop or reverse it, so management requires a proactive mindset:
Earlier initiation of therapy provides the greatest treatment opportunity, helping to preserve viable retina and potentially save associated visual function.
As an increasing number of patients are treated with complement inhibitors in real-world settings, more will be learned about patient selection, expected outcomes, and how best to apply therapy. The newness of treatment also means that practice patterns are still being figured out, with specialists largely making a decision to offer treatment on a case-by-case basis. That means the comprehensive eye care provider, in addition to being an educational resource for patients, may also need to be an advocate, helping to guide the patient on his or her journey.
Taken together, the evidence points to the need to closely monitor patients with a diagnosis of intermediate AMD so that early warning signs are recognized when treatment is most likely to have a benefit.
