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

Leon von der Emde; Merten Mallwitz; Marc Vaisband; Jan Hasenauer; Marlene Saßmannshausen; Jan Henrik Terheyden; H. Agostini; L. Altay; R. Atia; F. Bandello; P. G. Basile; J. Batuca; C. Behning; M. Belmouhand; M. Berger; A. Binns; C. J. F. Boon; M. Böttger; C. Bouchet; J. E. Brazier; T. Butt; C. Carapezzi; J. Carlton; A. Carneiro; A. Charil; R. Coimbra; M. Cozzi; D. P. Crabb; J. Cunha-Vaz; C. Dahlke; L. de Sisternes; H. Dunbar; R. P. Finger; E. Fletcher; H. Floyd; C. Francisco; M. Gutfleisch; S. Hinz; R. Hogg; F. G. Holz; C. B. Hoyng; A. Kilani; J. Krätzschmar; L. Kühlewein; M. Larsen; S. Leal; Y. T. E. Lechanteur; U. F. O. Luhmann; A. Lüning; I. Marques; C. Martinho; G. Montesano; Z. Mulyukov; M. Paques; B. Parodi; M. Parravano; S. Penas; T. Peters; T. Peto; M. Pfau; S. Poor; S. Priglinger; D. Rowen; G. S. Rubin; J. Sahel; C. Sánchez; O. Sander; M. Saßmannshausen; M. Schmid; S. Schmitz-Valckenberg; J. Siedlecki; R. Silva; A. Skelly; E. Souied; G. Staurenghi; L. Stöhr; D. J. Taylor; J. H. Terheyden; S. Thiele; A. Tufail; M. Varano; L. Vieweg; L. Wintergerst; A. Wolf; N. Zakaria; Kenneth R. Sloan; Steffen Schmitz-Valckenberg; Robert P. Finger; Frank G. Holz; Thomas Ach

doi:https://doi.org/10.1038/s41598-023-43417-y

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

Leon von der Emde, Merten Mallwitz, Marc Vaisband, Jan Hasenauer, Marlene Saßmannshausen, Jan Henrik Terheyden, H. Agostini, L. Altay, R. Atia, F. Bandello, P. G. Basile, J. Batuca, C. Behning, M. Belmouhand, M. Berger, A. Binns, C. J. F. Boon, M. Böttger, C. Bouchet, J. E. BrazierT. Butt, C. Carapezzi, J. Carlton, A. Carneiro, A. Charil, R. Coimbra, M. Cozzi, D. P. Crabb, J. Cunha-Vaz, C. Dahlke, L. de Sisternes, H. Dunbar, R. P. Finger, E. Fletcher, H. Floyd, C. Francisco, M. Gutfleisch, S. Hinz, R. Hogg, F. G. Holz, C. B. Hoyng, A. Kilani, J. Krätzschmar, L. Kühlewein, M. Larsen, S. Leal, Y. T. E. Lechanteur, U. F. O. Luhmann, A. Lüning, I. Marques, C. Martinho, G. Montesano, Z. Mulyukov, M. Paques, B. Parodi, M. Parravano, S. Penas, T. Peters, T. Peto, M. Pfau, S. Poor, S. Priglinger, D. Rowen, G. S. Rubin, J. Sahel, C. Sánchez, O. Sander, M. Saßmannshausen, M. Schmid, S. Schmitz-Valckenberg, J. Siedlecki, R. Silva, A. Skelly, E. Souied, G. Staurenghi, L. Stöhr, D. J. Taylor, J. H. Terheyden, S. Thiele, A. Tufail, M. Varano, L. Vieweg, L. Wintergerst, A. Wolf, N. Zakaria, Kenneth R. Sloan, Steffen Schmitz-Valckenberg, Robert P. Finger, Frank G. Holz, Thomas Ach

Ophthalmology (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	17417
Journal	Scientific reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-43417-y
Publication status	Published - 1 Dec 2023

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von der Emde, L., Mallwitz, M., Vaisband, M., Hasenauer, J., Saßmannshausen, M., Terheyden, J. H., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Batuca, J., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J. F., Böttger, M., Bouchet, C., ... Ach, T. (2023). Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report. Scientific reports, 13(1), Article 17417. https://doi.org/10.1038/s41598-023-43417-y

@article{95938c80de2c41df9c1ec55035827599,

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

abstract = "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.",

author = "{von der Emde}, Leon and Merten Mallwitz and Marc Vaisband and Jan Hasenauer and Marlene Sa{\ss}mannshausen and Terheyden, {Jan Henrik} and H. Agostini and L. Altay and R. Atia and F. Bandello and Basile, {P. G.} and J. Batuca and C. Behning and M. Belmouhand and M. Berger and A. Binns and Boon, {C. J. F.} and M. B{\"o}ttger and C. Bouchet and Brazier, {J. E.} and T. Butt and C. Carapezzi and J. Carlton and A. Carneiro and A. Charil and R. Coimbra and M. Cozzi and Crabb, {D. P.} and J. Cunha-Vaz and C. Dahlke and {de Sisternes}, L. and H. Dunbar and Finger, {R. P.} and E. Fletcher and H. Floyd and C. Francisco and M. Gutfleisch and S. Hinz and R. Hogg and Holz, {F. G.} and Hoyng, {C. B.} and A. Kilani and J. Kr{\"a}tzschmar and L. K{\"u}hlewein and M. Larsen and S. Leal and Lechanteur, {Y. T. E.} and Luhmann, {U. F. O.} and A. L{\"u}ning and I. Marques and C. Martinho and G. Montesano and Z. Mulyukov and M. Paques and B. Parodi and M. Parravano and S. Penas and T. Peters and T. Peto and M. Pfau and S. Poor and S. Priglinger and D. Rowen and Rubin, {G. S.} and J. Sahel and C. S{\'a}nchez and O. Sander and M. Sa{\ss}mannshausen and M. Schmid and S. Schmitz-Valckenberg and J. Siedlecki and R. Silva and A. Skelly and E. Souied and G. Staurenghi and L. St{\"o}hr and Taylor, {D. J.} and Terheyden, {J. H.} and S. Thiele and A. Tufail and M. Varano and L. Vieweg and L. Wintergerst and A. Wolf and N. Zakaria and Sloan, {Kenneth R.} and Steffen Schmitz-Valckenberg and Finger, {Robert P.} and Holz, {Frank G.} and Thomas Ach",

note = "Funding Information: Open Access funding enabled and organized by Projekt DEAL. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 116076. This Joint Undertaking receives support from the European Union{\textquoteright}s Horizon 2020 research and innovation programme and EFPIA NIH/NEI R01EY027948 (TA). Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

year = "2023",

month = dec,

day = "1",

doi = "https://doi.org/10.1038/s41598-023-43417-y",

language = "English",

volume = "13",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Springer Nature",

number = "1",

}

von der Emde, L, Mallwitz, M, Vaisband, M, Hasenauer, J, Saßmannshausen, M, Terheyden, JH, Agostini, H, Altay, L, Atia, R, Bandello, F, Basile, PG, Batuca, J, Behning, C, Belmouhand, M, Berger, M, Binns, A, Boon, CJF, Böttger, M, Bouchet, C, Brazier, JE, Butt, T, Carapezzi, C, Carlton, J, Carneiro, A, Charil, A, Coimbra, R, Cozzi, M, Crabb, DP, Cunha-Vaz, J, Dahlke, C, de Sisternes, L, Dunbar, H, Finger, RP, Fletcher, E, Floyd, H, Francisco, C, Gutfleisch, M, Hinz, S, Hogg, R, Holz, FG, Hoyng, CB, Kilani, A, Krätzschmar, J, Kühlewein, L, Larsen, M, Leal, S, Lechanteur, YTE, Luhmann, UFO, Lüning, A, Marques, I, Martinho, C, Montesano, G, Mulyukov, Z, Paques, M, Parodi, B, Parravano, M, Penas, S, Peters, T, Peto, T, Pfau, M, Poor, S, Priglinger, S, Rowen, D, Rubin, GS, Sahel, J, Sánchez, C, Sander, O, Saßmannshausen, M, Schmid, M, Schmitz-Valckenberg, S, Siedlecki, J, Silva, R, Skelly, A, Souied, E, Staurenghi, G, Stöhr, L, Taylor, DJ, Terheyden, JH, Thiele, S, Tufail, A, Varano, M, Vieweg, L, Wintergerst, L, Wolf, A, Zakaria, N, Sloan, KR, Schmitz-Valckenberg, S, Finger, RP, Holz, FG & Ach, T 2023, 'Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report', Scientific reports, vol. 13, no. 1, 17417. https://doi.org/10.1038/s41598-023-43417-y

TY - JOUR

T1 - Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration

T2 - a MACUSTAR study report

AU - von der Emde, Leon

AU - Mallwitz, Merten

AU - Vaisband, Marc

AU - Hasenauer, Jan

AU - Saßmannshausen, Marlene

AU - Terheyden, Jan Henrik

AU - Agostini, H.

AU - Altay, L.

AU - Atia, R.

AU - Bandello, F.

AU - Basile, P. G.

AU - Batuca, J.

AU - Behning, C.

AU - Belmouhand, M.

AU - Berger, M.

AU - Binns, A.

AU - Boon, C. J. F.

AU - Böttger, M.

AU - Bouchet, C.

AU - Brazier, J. E.

AU - Butt, T.

AU - Carapezzi, C.

AU - Carlton, J.

AU - Carneiro, A.

AU - Charil, A.

AU - Coimbra, R.

AU - Cozzi, M.

AU - Crabb, D. P.

AU - Cunha-Vaz, J.

AU - Dahlke, C.

AU - de Sisternes, L.

AU - Dunbar, H.

AU - Finger, R. P.

AU - Fletcher, E.

AU - Floyd, H.

AU - Francisco, C.

AU - Gutfleisch, M.

AU - Hinz, S.

AU - Hogg, R.

AU - Holz, F. G.

AU - Hoyng, C. B.

AU - Kilani, A.

AU - Krätzschmar, J.

AU - Kühlewein, L.

AU - Larsen, M.

AU - Leal, S.

AU - Lechanteur, Y. T. E.

AU - Luhmann, U. F. O.

AU - Lüning, A.

AU - Marques, I.

AU - Martinho, C.

AU - Montesano, G.

AU - Mulyukov, Z.

AU - Paques, M.

AU - Parodi, B.

AU - Parravano, M.

AU - Penas, S.

AU - Peters, T.

AU - Peto, T.

AU - Pfau, M.

AU - Poor, S.

AU - Priglinger, S.

AU - Rowen, D.

AU - Rubin, G. S.

AU - Sahel, J.

AU - Sánchez, C.

AU - Sander, O.

AU - Saßmannshausen, M.

AU - Schmid, M.

AU - Schmitz-Valckenberg, S.

AU - Siedlecki, J.

AU - Silva, R.

AU - Skelly, A.

AU - Souied, E.

AU - Staurenghi, G.

AU - Stöhr, L.

AU - Taylor, D. J.

AU - Terheyden, J. H.

AU - Thiele, S.

AU - Tufail, A.

AU - Varano, M.

AU - Vieweg, L.

AU - Wintergerst, L.

AU - Wolf, A.

AU - Zakaria, N.

AU - Sloan, Kenneth R.

AU - Schmitz-Valckenberg, Steffen

AU - Finger, Robert P.

AU - Holz, Frank G.

AU - Ach, Thomas

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 116076. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA NIH/NEI R01EY027948 (TA). Publisher Copyright: © 2023, Springer Nature Limited.

PY - 2023/12/1

Y1 - 2023/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85174293610&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s41598-023-43417-y

DO - https://doi.org/10.1038/s41598-023-43417-y

M3 - Article

C2 - 37833348

SN - 2045-2322

VL - 13

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 17417

ER -

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

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