The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration

Abstract

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm/year (median, ∼1.78 mm/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.

Multimodal Imaging of Nonneovascular Age-Related Macular Degeneration

“…7). 36 137 In another report by Sunness et al, 138 eyes with baseline unifocal lesions progressing to multifocal, horseshoe, ring, or solid configurations had greater GA progression rates than eyes with a stable configuration. 138 Qualitative FAF patterns of the hyperautofluorescence surrounding the GA lesions have been shown to correlate with growth rates of GA. 36,137,[139][140][141] The FAF in AMD (FAM) study classified GA according to the associated or adjacent hyperautofluorescent patterns, including none, focal, banded, patchy, or diffuse, with diffuse patterns further categorized as reticular, branching, fine granular, fine granular with peripheral punctate spots, or trickling (Fig.…”

“…These results have been replicated to some extent in subsequent reports. 36,137,140,141 Additionally, the extent of hyperautofluorescence surrounding atrophic lesions, defined as the rim-area focal hyperfluorescence or the convex hull (the convex polygon outlining the hyperautofluorescent area surrounding the lesion), have been positively correlated with lesion growth rates (Fig. 7).…”

“…Recent studies have demonstrated that specific SD-OCT features, such as splitting of the RPE/ Bruch's membrane complex band may indicate a high risk for progression to GA. 35 Anatomic tracking functions are especially important and employ precise alignment of baseline and follow-up images enabling meticulous and accurate analysis of the evolution of morphologic findings. The introduction of enhanced-depth imaging (EDI) SD-OCT provides better penetration and visualization of the choroid with depth resolution, and some reports have suggested that choroidal thickness may be reduced in the late stages of AMD 36 and may be associated with certain nonexudative AMD phenotypes, including reticular pseudodrusen. 37 There are currently three types of OCT devices commercially available.…”

“…36,45,46 As melanin is autofluorescent under infrared light and typically present in functioning RPE cells, atrophic areas appear hypoautofluorescent. Like NIR imaging, NIR-AF provides the capability to identify RPE atrophy.…”

“…Drusen typically stain while atrophic areas may show early transmission hyperfluorescence or a ''window defect,'' due to atrophy of the RPE and an intact choriocapillaris. 6,36 Disadvantages of this system include the need for invasive dye injection, risk of allergic reaction to the dye, long image acquisition times, and lack of depth-resolved segmentation and lateral resolution.…”