Differential Diagnosis and Diagnostic Criteria
Diseases that Resemble Geographic Atrophy
To make an accurate diagnosis and initiate the correct treatment, geographic atrophy (GA) must be differentiated from similar diseases. The presence of well-defined lesions is the most distinct characteristic of GA. However, none of the lesions are GA-specific. Diseases such as neovascular age-related macular degeneration (nAMD), myopic maculopathy and different types of retinal dystrophies can all resemble GA.
As discussed in Introduction and Overview, nAMD is the exudative form of late AMD, also called “wet AMD”. It is caused by the formation of new blood vessels in the choriocapillaris that grow into the subretinal and/or sub-retinal pigment epithelium (RPE) space. The immature, newly formed vessels leak blood and other fluids into the macula, causing serious and/or hemorrhagic detachment of the RPE or neurosensory retina. The main distinction between nAMD and GA is that there is no neovascularization and no leakage with GA. These…
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Diseases that Resemble Geographic Atrophy
To make an accurate diagnosis and initiate the correct treatment, geographic atrophy (GA) must be differentiated from similar diseases. The presence of well-defined lesions is the most distinct characteristic of GA. However, none of the lesions are GA-specific. Diseases such as neovascular age-related macular degeneration (nAMD), myopic maculopathy and different types of retinal dystrophies can all resemble GA.
As discussed in Introduction and Overview, nAMD is the exudative form of late AMD, also called “wet AMD”. It is caused by the formation of new blood vessels in the choriocapillaris that grow into the subretinal and/or sub-retinal pigment epithelium (RPE) space. The immature, newly formed vessels leak blood and other fluids into the macula, causing serious and/or hemorrhagic detachment of the RPE or neurosensory retina. The main distinction between nAMD and GA is that there is no neovascularization and no leakage with GA. These differences can be visualized via optical coherence tomography (OCT) and fundus autofluorescence (FAF), making proper imaging assessment the essential step in differential diagnosis. Neovascular AMD and GA can also coexist in the same eye.
Myopic maculopathy is a disease that can lead to chorioretinal and macular atrophy. Unlike GA, it affects people of any age and in some cases, the progression rate can even slow down or stop in adult years. The main characteristic distinguishing myopic maculopathy from GA is the presence of lacquer cracks, yellow lines forming in a branching pattern that represent a rupture in the RPE, Bruch’s membrane and choriocapillaris. Patients with myopic maculopathy will also often have oblique insertion of their optic nerves and posterior staphylomas.
Stargardt disease is a common form of inherited macular dystrophy, caused by mutations in the ABCA4 gene. Compared to GA, which most often develops in patients older than 65 years, Stargardt disease typically starts in childhood or adolescence. The two diseases can be distinguished by FAF imaging, where Stargardt disease shows hyper-autofluorescent flecks at early stages and hypo-autofluorescence as the disease progresses and RPE cells undergo atrophy, while GA exhibits progressively expanding hypo-autofluorescent lesions.
Classification Systems
In addition to the differential diagnosis where the focus is on ruling out other diseases, standardizing GA diagnosis by utilizing well-defined classification systems ensures consistency in assessment and improves clinical decision-making. The Beckman Initiative for Macular Research Classification defined early AMD as medium drusen (between 63 μm and 125 μm) and no associated pigmentary abnormalities, intermediate AMD as large drusen (>125 μm) and/or any pigmentary abnormalities and late AMD as lesions associated with nAMD or GA (Table 2-1).
The American Academy of Ophthalmology uses an AMD classification system developed for the Age-Related Eye Disease Study (AREDS) trials (see Introduction and Overview and Treatment Options and Therapies). This system is presented in Table 2-2.
The International Age-Related Maculopathy Epidemiological Study Group defined GA as well-demarcated, round or oval region of hypopigmentation or depigmentation characterized by increased visibility of the underlying choroidal vessels, with a minimum diameter of 175 μm on color fundus photographic images. Furthermore, in 2018, the Classification of Atrophy Meeting (CAM) group developed consensus terminology and criteria for defining atrophy based on OCT findings in the setting of AMD. They proposed the terms incomplete RPE and outer retinal atrophy (iRORA), complete RPE and outer retinal atrophy (cRORA), complete outer retinal atrophy and incomplete outer retinal atrophy. To meet the iRORA criteria, there had to be evident thinning or disruption of the RPE, photoreceptor degradation and increased signal transmission into the choroid on OCT. Patients who present with iRORA have a higher risk of developing cRORA. The CAM group established four specific OCT criteria for diagnosing cRORA:
- a region of hypertransmission of at least 250 μm in diameter;
- a zone of attenuation or disruption of the RPE of at least 250 μm in diameter;
- evidence of overlying photoreceptor degeneration; and
- absence of scrolled RPE or other signs of an RPE tear.
References
- Alibhai AY, Mehta N, Hickson-Curran S, et al. Test-retest variability of microperimetry in geographic atrophy. Int J Retina Vitreous. 2020;6:16.
- Anderson WJ, Akduman L. Management of Myopic Maculopathy: A Review. Turk J Ophthalmol. 2023;53(5):307-312.
