Ophthalmology science · 2026
Automated Quantification of Decreased Fundus Autofluorescence in Stargardt Disease Using Starguage: Validation against Manual Grading Standards.
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Ahmed Mohamed I, Yucel Hikmet, Afridi Rubbia, de Guimarães Thales A C, Sendino-Tenorio Isabel, Nguyen Nam V, Kiran Romaisa, Khan Sidrah, Khan Ufaq, Sharaf Un Nisa Syeda, Campigotto Mauro, Hariri Amir, Michaelides Michel, Scholl Hendrik P N, Mata Nathan, Nguyen Quan D, Sepah Yasir J
Аннотация
PURPOSE: To evaluate the repeatability and reproducibility of Starguage, a novel automated method, compared with manual segmentation for measuring decreased autofluorescence (DAF) and definitely decreased autofluorescence (DDAF) in fundus autofluorescence (FAF) images of patients with Stargardt disease.
DESIGN: A cross-sectional reproducibility and agreement study.
PARTICIPANTS: A total of 316 eyes from 158 genetically confirmed Stargardt patients were analyzed. For intragrader repeatability, 114 FAF images were reassessed in a masked, repeated-measures design.
METHODS: Decreased autofluorescence and DDAF lesion areas were independently quantified by five certified graders using either manual delineation with Heidelberg RegionFinder or a threshold-based automated algorithm, with automated quantification and cross-method agreement analyses restricted to a prespecified central 6-mm fovea-centered region. Agreement and repeatability were assessed using intraclass correlation coefficients (ICCs), standard error of measurement (SEM), minimal detectable change (MDC), Lin's concordance correlation coefficient (CCC), Bland-Altman plots, and Passing-Bablok regression. Both raw and square-root-transformed lesion areas were evaluated.
MAIN OUTCOME MEASURES: Repeatability (intragrader ICC, SEM, and MDC), reproducibility (intergrader ICC), and agreement (CCC and bias in regression analysis) between and within manual and automated methods.
RESULTS: The automated method achieved excellent intragrader repeatability for both DAF and DDAF (ICCs ≥0.988, SEM ≤0.71 mm2, MDC ≤1.98 mm2), with minimal operator influence. Manual measurements showed variable repeatability (DAF ICCs 0.909-0.974; DDAF ICCs as low as 0.837), with square-root transformation reducing SEM and MDC. Intergrader reproducibility was highest for automated methods (ICC = 0.988-0.992), whereas manual methods ranged from 0.764-0.939 (raw) and 0.867-0.922 (transformed). Cross-method agreement was strong (CCC = 0.91-0.96), though minor proportional and constant bias was observed in raw DAF data.
CONCLUSIONS: The automated approach provides near-perfect repeatability and high agreement with manual grading, offering a scalable, objective alternative for quantifying hypo-auto-fluorescent lesions in Stargardt disease. Manual methods are generally reliable but more variable, especially for DDAF, and benefit from square-root transformation. Findings reflect a pediatric/adolescent single-trial predominantly Asian cohort.
FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.
DESIGN: A cross-sectional reproducibility and agreement study.
PARTICIPANTS: A total of 316 eyes from 158 genetically confirmed Stargardt patients were analyzed. For intragrader repeatability, 114 FAF images were reassessed in a masked, repeated-measures design.
METHODS: Decreased autofluorescence and DDAF lesion areas were independently quantified by five certified graders using either manual delineation with Heidelberg RegionFinder or a threshold-based automated algorithm, with automated quantification and cross-method agreement analyses restricted to a prespecified central 6-mm fovea-centered region. Agreement and repeatability were assessed using intraclass correlation coefficients (ICCs), standard error of measurement (SEM), minimal detectable change (MDC), Lin's concordance correlation coefficient (CCC), Bland-Altman plots, and Passing-Bablok regression. Both raw and square-root-transformed lesion areas were evaluated.
MAIN OUTCOME MEASURES: Repeatability (intragrader ICC, SEM, and MDC), reproducibility (intergrader ICC), and agreement (CCC and bias in regression analysis) between and within manual and automated methods.
RESULTS: The automated method achieved excellent intragrader repeatability for both DAF and DDAF (ICCs ≥0.988, SEM ≤0.71 mm2, MDC ≤1.98 mm2), with minimal operator influence. Manual measurements showed variable repeatability (DAF ICCs 0.909-0.974; DDAF ICCs as low as 0.837), with square-root transformation reducing SEM and MDC. Intergrader reproducibility was highest for automated methods (ICC = 0.988-0.992), whereas manual methods ranged from 0.764-0.939 (raw) and 0.867-0.922 (transformed). Cross-method agreement was strong (CCC = 0.91-0.96), though minor proportional and constant bias was observed in raw DAF data.
CONCLUSIONS: The automated approach provides near-perfect repeatability and high agreement with manual grading, offering a scalable, objective alternative for quantifying hypo-auto-fluorescent lesions in Stargardt disease. Manual methods are generally reliable but more variable, especially for DDAF, and benefit from square-root transformation. Findings reflect a pediatric/adolescent single-trial predominantly Asian cohort.
FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.