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

Author

Garzone, Davide, Terheyden, Jan Henrik, Morelle, Olivier, Wintergerst, Maximilian W.M., Saßmannshausen, Marlene, Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Thiele, Sarah, Poor, Stephen, Leal, Sergio, Holz, Frank G., Finger, Robert P., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., Schmid, M., Ophthalmology, Amsterdam Neuroscience - Complex Trait Genetics, Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J. F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T. E., Luhmann, U. F. O., Lüning, A., Marques, I., Martinho, C., Montesano, G., Mulyukov, Z., Paques, M., Parodi, B., Parravano, M., Penas, S., Peters, T., Peto, T., Priglinger, S., Rowen, D., Rubin, G. S., Sahel, J., Sánchez, C., Sander, O., Schmid, M., Schrinner-Fenske, H., Siedlecki, J., Silva, R., Skelly, A., Souied, E., Staurenghi, G., Stöhr, L., Taylor, D. J., Tufail, A., Varano, M., Vieweg, L., Wintergerst, L., Wolf, A., and Zakaria, N.

Subjects
diagnosis [Macular Degeneration], methods [Tomography, Optical Coherence], Fovea Centralis, Multidisciplinary, Humans, ddc:600, Retina, Software
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.

Published
2022

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

Author

Saßmannshausen, Marlene, Behning, Charlotte, Isselmann, Ben, Schmid, Matthias, Finger, Robert P., Holz, F. G., Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Finger, R. P., Fletcher, E., Floyd, H., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Leal, S., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., Marques, I., Saßmannshausen, Marlene, Behning, Charlotte, Isselmann, Ben, Schmid, Matthias, Finger, Robert P., Holz, F. G., Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Finger, R. P., Fletcher, E., Floyd, H., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Leal, S., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., and Marques, I.

Abstract

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.

Published
2022

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

Author

Garzone, Davide, Terheyden, Jan Henrik, Morelle, Olivier, Wintergerst, Maximilian W.M., Saßmannshausen, Marlene, Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Thiele, Sarah, Poor, Stephen, Leal, Sergio, Holz, Frank G., Finger, Robert P., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., Schmid, M., Garzone, Davide, Terheyden, Jan Henrik, Morelle, Olivier, Wintergerst, Maximilian W.M., Saßmannshausen, Marlene, Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Thiele, Sarah, Poor, Stephen, Leal, Sergio, Holz, Frank G., Finger, Robert P., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., and Schmid, M.

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.

Published
2022

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