Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report

Abstract

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991-0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757-0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD.Trial registration: ClinicalTrials.gov NCT03349801. Registered on 22 November 2017.

Figure 1

Comparison of Drusen segmentation of the same eye with iAMD, assessed with Cirrus ((A) enface projection, (C) foveolar B-scan) and Spectralis OCT ((B) enface projection, (D) foveolar B-scan), showing similar identification. (E) (Cirrus) and (F) (Spectralis) showing failure to detect (white arrows) or adequately segment (orange arrows) RPE elevations by automated segmentation algorithms in a corresponding macular B-scan.

Figure 2

Bland–Altman plot showing differences stratified per AMD stage between the two algorithms (A,B) and the two scans (C,D), respectively. A Least Absolute Shrinkage and Selection Operator (LASSO) regression line was added in (B) to highlight a linear inter-device trend at lower drusen volume measurements and flattening of the curve with increasingly broader confidence intervals at higher values, indicating lower comparability. AMD age-related macular degeneration, diff. difference.