Intersession Repeatability of Structural Biomarkers in Early and Intermediate Age-Related Macular Degeneration: A MACUSTAR Study Report

Abstract

Purpose To analyze the intersession repeatability of structural biomarkers in eyes with early and intermediate age-related macular degeneration (iAMD) within the cross-sectional part of the observational multicenter MACUSTAR study. Methods Certified site personnel obtained multimodal imaging data at two visits (38 ± 20 [mean ± standard deviation] days apart), including spectral-domain optical coherence tomography (SD-OCT). One junior reader performed systematic and blinded grading at the central reading center, followed by senior reader review. Structural biomarkers included maximum drusen size classification (>63 to ≤125 µm vs. >125 µm), presence of large pigment epithelium detachments (PEDs), reticular pseudodrusen (RPD), vitelliform lesions, and refractile deposits. Intrasession variability was assessed using Cohen's κ statistics. Results At the first visit, 202 study eyes of 202 participants were graded as manifesting with either early ( n = 34) or intermediate ( n = 168) AMD. Grading of imaging data between visits revealed perfect agreement for the maximum drusen size classification (κ = 0.817; 95% confidence interval, 0.70–0.94). In iAMD eyes, perfect to substantial agreement was determined for the presence of large PEDs (0.87; 0.69–1.00) and RPD (0.752; 0.63–0.87), while intersession agreement was lower for the presence of vitelliform lesions (0.649; 0.39–0.65) and refractile deposits (0.342; −0.029–0.713), respectively. Conclusions Multimodal retinal imaging analysis between sessions showed a higher repeatability for structural biomarkers with predefined cutoff values than purely qualitative defined parameters. Translational Relevance A high repeatability of retinal imaging biomarkers will be important to implement automatic grading approaches and to establish robust and meaningful structural clinical endpoints for future interventional clinical trials in patients with iAMD.

Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration

“…Images were graded by a junior reader followed by a senior reader and reviewed according to a standardized predefined grading protocol. 26 Inclusion and exclusion criteria have been previously published. 8,14 Briefly, in addition to satisfying disease classification criteria, participants were required to be aged between 55 and 85 years and able to provide informed consent and comply with study visits.…”

“…Disease classifications were based on the Beckman classification system determined by a central reading center on the basis of multimodal imaging including color fundus photography, confocal infrared photography, fundus autofluorescence, and spectral-domain optical coherence tomography images obtained during a dedicated screening visit. Images were graded by a junior reader followed by a senior reader and reviewed according to a standardized predefined grading protocol . Inclusion and exclusion criteria have been previously published .…”

Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report

“…In the prospective European MACUSTAR study, participants with iAMD and neighboring disease stages (early AMD, late AMD) as well as healthy controls were clinically evaluated with multimodal imaging and functional testing for a study period of 3 years 8 , 36 . For the current analysis, images from the cross-sectional arm of the MACUSTAR clinical study with available QAF images (6 study sites, 120 participants) were included.…”

“…Inclusion and exclusion criteria of the MACUSTAR study have been reported elsewhere 7 . Briefly, subjects aged 55–85 at baseline, AMD (with the largest cohort being iAMD) or healthy eyes and the absence of other eye disorders were included 36 . iAMD was defined as bilateral large drusen and/or pigment abnormalities or extrafoveal geographic atrophy in the partner eye (for a full list of AMD disease stage criteria see Table 1 in Terheyden et al 36 ).…”

Relative ellipsoid zone reflectivity and its association with disease severity in age-related macular degeneration: a MACUSTAR study report

“…The dense SD-OCT raster scan was primarily assessed for the determination of structural iAMD image features as follows, while other modalities provided complementary and confirmatory information 31 . Reticular pseudodrusen (RPD) were defined as hyperreflective irregularities and elevations above the RPE/Bruch's membrane band in SD-OCT imaging, presenting with medium-reflective mounds or cones at the level of the EZ or between the EZ and the RPE surface.…”