Consideration of patient phenotypes in geographic atrophy due to age-related macular degeneration

Abstract

Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding the risk of progression to GA and factors contributing to GA growth may aid in patient selection and guide patient-level management and treatment.

Keywords: Geographic Atrophy; Imaging; Macular Degeneration.

Figure 1. Progression to subfoveal geographic atrophy (GA) with good visual acuity. (A) At presentation in 2017, fundus autofluorescence (FAF) of the left eye shows early small multifocal non-subfoveal GA lesions. Reticular pseudodrusen are present. Vision measures 20/30. (B) 3 years later in 2020, FAF shows enlargement and increased number of hypoautofluorescent GA lesions, vision remains 20/30. (C) 6 years later in 2023, FAF shows progression of GA to involve the fovea. Vision continues to measure 20/30. (D) Near-infrared reflectance and (E) optical coherence tomography (OCT) simultaneous with FAF (C) in 2023 demonstrates hypertransmission of OCT signal reflectivity in the choroid from loss of retinal pigment epithelium (RPE). Incomplete RPE and outer retinal atrophy are present with disruption of the external limiting membrane.

Figure 2. Subfoveal geographic atrophy (GA) progression in the left eye and retinal pigment epithelium (RPE) tear from neovascular age-related macular degeneration (nAMD) in the fellow right eye. (A) Fundus autofluorescence (FAF) of the right eye shows hypoautofluorescence corresponding to subretinal fibrosis from nAMD and RPE tear. (B) Optical coherence tomography (OCT) of the right eye demonstrates elevated fibrotic RPE. The right eye is maintained on intermittent antivascular endothelial growth factor injections. (C) FAF in 2021 in the left eye demonstrates GA and reticular pseudodrusen. (D) FAF in 2023 in the left eye shows GA progression in size. (E) OCT in 2023 demonstrates complete RPE and outer retinal atrophy with subfoveal GA.

Figure 3. Non-subfoveal geographic atrophy (GA) and large coalescing multifocal GA lesions. (A) Fundus autofluorescence of the right eye demonstrating multifocal GA coalescing in the perifoveal region. (B) Optical coherence tomography (OCT) B-scan confirms the central fovea is not involved by GA (consistent with non-subfoveal GA). There is complete retinal pigment epithelium (RPE) and outer retinal atrophy with complete loss of the photoreceptor, RPE and outer retina anatomy with hypertransmission of OCT signal into the choroid. Visual acuity measures 20/20.