Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression

Abstract

Background: To characterise early stages of geographic atrophy (GA) development in age-related macular degeneration (AMD) and to determine the prognostic value of structural precursor lesions in eyes with intermediate (i) AMD on the subsequent GA progression.

Methods: Structural precursor lesions for atrophic areas (lesion size at least 0.5 mm² in fundus autofluorescence images) were retrospectively identified based on multimodal imaging and evaluated for association with the subsequent GA enlargement rates (square-root transformed, sqrt). A linear mixed-effects model was used to account for the hierarchical nature of the data with a Tukey post hoc test to assess the impact of the local precursor on the subsequent GA progression rate.

Results: A total of 39 eyes with GA of 34 patients with a mean age of 74.4±6.7 (±SD) years were included in this study. Five precursor lesions (phenotypes 1-5) preceding GA development were identified: large, sub-retinal pigment epithelial drusen (n=19), reticular pseudodrusen (RPD, n=10), refractile deposits (n=4), pigment epithelial detachment (n=4) and vitelliform lesions (n=2). Precursor lesions exhibited a significant association with the subsequent (sqrt) GA progression rates (p=0.0018) with RPD (phenotype 2) being associated with the fastest GA enlargement (2.29±0.52 (±SE) mm/year.

Conclusions: The results indicate the prognostic relevance of iAMD phenotyping for subsequent GA progression highlighting the role of structural AMD features across different AMD stages.

Keywords: degeneration; imaging; macula; retina.

Figure 1

Typical example for the confluent drusen-associated structural precursor lesion (phenotype 1) with annual follow-up visits (A–G) as shown by multimodal imaging (for each row from left to right: colour fundus photography, fundus autofluorescence as well as near-infrared reflectance and spectral-domain optical coherence tomography (SD-OCT). Note the precursor’s extrafoveal localisation. The position of the SD-OCT line scan in the en face images is represented as a green line.

Figure 2

Precursor phenotype 2 is represented in a typical example with follow-up visits over 4 years as shown by multimodal imaging (first picture in first and fourth row: colour fundus photography and in second and third row: near-infrared image; all rows: second and third picture: fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT)). Note the absence of confluent drusen in area of following atrophy development. The position of the SD-OCT line scan in the en face images is represented as a green line.

Figure 3

Exemplary case of local precursor phenotype 3 in multimodal imaging (same arrangement of images as in figure 1). Annual follow-up visits (rows A–D) show refractile deposits preceding the development of geographic atrophy. Spectral-domain optical coherence tomography (SD-OCT) imaging (column 4, each row) demonstrates pyramidal structures (‘ghost drusen’) at the level of the retinal pigment epithelium with progressive disruption of the outer retinal bands over time as well as fading of the laminar intense hyperreflectivity associated with the occurrence of traces of choroidal hypertransmission. The position of the SD-OCT line scan in the en face images is represented as a green line.

Figure 4

A follow-up period of 5 years with annual follow-up visits (A–F) highlights precursor phenotype 4 of a central pigment-epithelial detachment (PED) with fulminant collapse. Same arrangement of images as in figure 1. Central hyperpigmentary clumping is seen in colour fundus photography on top of the PED, while fundus autofluorescence shows a corresponding cartwheel-like configuration of increased and decreased signal intensities. Spectral-domain optical coherence tomography (SD-OCT) clearly demonstrates the dome-shaped elevation of the retinal pigment epithelium with hyperreflective foci in inner and outer retinal layers on top of the PED. The position of the SD-OCT line scan in the en face images is represented as a green line. Please note, figure modified to a previous work.

Figure 5

Typical example of local precursor phenotype 5 over an observational period of 3.5 years showing yellow-shiny vitelliform material in colour fundus photography imaging which topographically corresponds to hyperreflectivity in fundus autofluorescence and near-infrared imaging. Same arrangement of images as in figure 1, except for the third picture in first row: fluorescein angiography (FAG). SD-OCT demonstrates hyperreflective material in the subretinal space. Cuticular drusen are well distinguishable in FAG due to their ‘stars-in-the-sky’ appearance. The position of the SD-OCT line scan in the en face images is represented as a green line.