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This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability., (© 2023. Springer Nature Limited.)

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., (© 2022. The Author(s).)

Quantification of the relative ellipsoid zone reflectivity (rEZR) might be a structural surrogate parameter for an early disease progression in the context of age-related macular degeneration (AMD). Within the European multicenter, cross-sectional MACUSTAR study, we have devised an automatic approach to determine the mean rEZR [arbitrary units, AU] at two independent visits in SD-OCT volume scans in study participants. Linear mixed-effects models were applied to analyze the association of AMD stage and AMD associated high-risk features including presence of pigmentary abnormalities, reticular pseudodrusen (RPD), volume of the retinal-pigment-epithelial-drusenoid-complex (RPEDC) with the rEZR. Intra-class correlation coefficients (ICC) were determined for rEZR reliability analysis. Within the overall study cohort (301 participants), we could observe decreased rEZR values (coefficient estimate ± standard error) of - 8.05 ± 2.44 AU (p = 0.0011) in the intermediate and of - 22.35 ± 3.28 AU (p < 0.0001) in the late AMD group. RPD presence was significantly associated with the rEZR in iAMD eyes (- 6.49 ± 3.14 AU; p = 0.0403), while there was a good ICC of 0.846 (95% confidence interval: 0.809; 0.876) in the overall study cohort. This study showed an association of rEZR with increasing disease severity and the presence of iAMD high-risk features. Further studies are necessary to evaluate the rEZR's value as a novel biomarker for AMD and disease progression., (© 2022. The Author(s).)