Are There Different Phenotypes in Geographic Atrophy of AMD? - Pilot Study on Differentiation Using Multimodal Imaging

Abstract

Geographic atrophy (GA) in patients with age-related macular degeneration (AMD) involves a loss of photoreceptors (PR), retinal pigment epithelium (RPE) and choriocapillaris (CC). For treatment decisions, it is crucial to discern which of these layers the damage originates, subsequently spreading to the others. It has long been thought that the RPE, with its accumulation of lipofuscin, is the site of primary damage in the development of GA. However, histological studies have shown that in some patients, the PR are affected first, followed by secondary damage to the RPE and CC, and in others regression of the CC is the first manifestation. The aim of this study was to use multimodal imaging to determine the extent of the damage at the levels of the PR, RPE and CC, to characterise the individual phenotypic variations of GA and to investigate the corresponding functional impairment. Twenty eyes of 20 patients (mean age 78 years; 14 female, 6 male) with the clinical diagnosis of GA were examined by means of fundus autofluorescence (FAF) to evaluate the damage to the RPE, en face SD-OCT at the level of the PR to characterise the area of cell loss in this layer and OCT angiography (OCT-A, AngioVue, Optovue; 50 µm CC-segmentation with localization below the RPE) to assess regression of the CC. The affected area of each layer was measured. Best-corrected visual acuity (BCVA) test and fundus correlated automated 10° microperimetry (MAIA Microperimetry, CENTERVUE; 4-2 strategy, 68 stimuli) were performed in all patients. The results of these examinations were evaluated and correlated. All eyes showed a different extent of the areas of atrophy in the PR, RPE and CC. The layer with the largest area of atrophy was the RPE in 13 eyes (65%), the PR in 3 eyes (15%) and the CC in 4 eyes (20%). While the visual loss depended entirely on the presence of foveal sparing, microperimetry revealed a correlation between the extent of detectable functional deficit and the largest atrophic area. Multimodal imaging with FAF, en face OCT, OCT-A and a correlation with microperimetry enables a clinical phenotypic differentiation in GA as well as a more precise characterisation of the associated functional impairment. This confirms clinically the histologically demonstrated diversity of the damaged structure (PR, RPE or CC) in patients with GA. However, the variations identified in this pilot study must be confirmed in Reading Center-based larger cohorts. The approach described here may lead to differentiated consideration of the anatomical and functional aspects of the disease and turn out to be helpful in patient selection as well as in identifying and monitoring future therapeutic approaches.