Longitudinal Quantitative Analysis of Ultra-Widefield Fluorescein Angiography Leakage Metrics: Analysis of the KINGFISHER Clinical Trial
9 affiliations
- 1Doheny Eye Institute, Pasadena, California.
- 2Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California.
- 3Ophthalmology Department, Tanta University, Tanta, Egypt.
- 4Department of Neurosciences, Imaging and Clinical Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
- 5Department of Ophthalmology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
- 6Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical, Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
- 7Department of Artificial Intelligence, Tamkang University, New Taipei City, Taiwan.
- 8Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan.
- 9Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.
Abstract
Purpose: To longitudinally quantify changes in retinal vascular leakage in diabetic macular edema (DME) using ultra-widefield fluorescein angiography (UWF-FA) in patients receiving brolucizumab versus aflibercept.
Design: Retrospective post hoc analysis of the phase 3, randomized, masked KINGFISHER clinical trial.
Subjects: Eyes with center-involved DME enrolled in KINGFISHER with gradable late-phase UWF-FA images at baseline and follow-up (week 24 and/or week 52).
Methods: Two independent masked graders manually assessed late-phase UWF-FA images at baseline, week 24, and week 52 using OptosAdvance software. The leakage area, defined as regions of increased fluorescence relative to background, was manually segmented and quantified in 3 regions: the posterior pole zone (defined as the central 15-mm ring), the peripheral zone (all analyzable areas outside the posterior pole), and the total retina. The leakage index (LI) was then calculated as the ratio of the total leakage area to the total area of the corresponding region and expressed as a percentage.
Main Outcome Measures: Change in LI from baseline to week 24 and week 52 in the posterior pole, peripheral zone, and total analyzable retina, and between-treatment differences in LI change.
Results: A total of 106 cases were included (69 in the brolucizumab arm and 37 in the aflibercept arm). Both treatments significantly reduced LI from baseline to week 24 and from baseline to week 52 (P < 0.001). By week 24, the brolucizumab group demonstrated a statistically significantly greater reduction in the posterior pole LI compared to the aflibercept group (mean change, –24.7 ± 21.3 vs. –16.8 ± 12.4; P = 0.037). However, by week 52, there were no statistically significant differences between the 2 arms in any retinal region (P > 0.2).
Conclusions: Both brolucizumab and aflibercept substantially reduced UWF-FA leakage in DME over 52 weeks. Brolucizumab achieved a more pronounced early reduction in leakage within the posterior pole, although the final residual leakage at week 52 was comparable between the 2 agents.
Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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BibTeX
@article{abbasgholizadeh2026longitudinal,
title = {{Longitudinal Quantitative Analysis of Ultra-Widefield Fluorescein Angiography Leakage Metrics: Analysis of the KINGFISHER Clinical Trial}},
author = {Rouzbeh Abbasgholizadeh and Mai Alhelaly and Abbas Habibi and Ceren Soylu and Alberto Quarta and Yu-Chien Chung and Ye He and Yen-Chun Huang and Magdy Moussa and Mohamed El-Bradey and Mamdouh Kabil and Shinichiro Chujo and Jianfeng Huang and Muneeswar G Nittala and Srinivas R Sadda and Michael S Ip},
journal = {Ophthalmology Science},
year = {2026},
month = aug,
doi = {10.1016/j.xops.2026.101376},
url = {https://doi.org/10.1016/j.xops.2026.101376},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Longitudinal Quantitative Analysis of Ultra-Widefield Fluorescein Angiography Leakage Metrics: Analysis of the KINGFISHER Clinical Trial
AU - Rouzbeh Abbasgholizadeh
AU - Mai Alhelaly
AU - Abbas Habibi
AU - Ceren Soylu
AU - Alberto Quarta
AU - Yu-Chien Chung
AU - Ye He
AU - Yen-Chun Huang
AU - Magdy Moussa
AU - Mohamed El-Bradey
AU - Mamdouh Kabil
AU - Shinichiro Chujo
AU - Jianfeng Huang
AU - Muneeswar G Nittala
AU - Srinivas R Sadda
AU - Michael S Ip
PY - 2026
DA - 2026/08/19
JO - Ophthalmology Science
DO - 10.1016/j.xops.2026.101376
UR - https://doi.org/10.1016/j.xops.2026.101376
AB - Purpose: To longitudinally quantify changes in retinal vascular leakage in diabetic macular edema (DME) using ultra-widefield fluorescein angiography (UWF-FA) in patients receiving brolucizumab versus aflibercept. Design: Retrospective post hoc analysis of the phase 3, randomized, masked KINGFISHER clinical trial. Subjects: Eyes with center-involved DME enrolled in KINGFISHER with gradable late-phase UWF-FA images at baseline and follow-up (week 24 and/or week 52). Methods: Two independent masked graders manually assessed late-phase UWF-FA images at baseline, week 24, and week 52 using OptosAdvance software. The leakage area, defined as regions of increased fluorescence relative to background, was manually segmented and quantified in 3 regions: the posterior pole zone (defined as the central 15-mm ring), the peripheral zone (all analyzable areas outside the posterior pole), and the total retina. The leakage index (LI) was then calculated as the ratio of the total leakage area to the total area of the corresponding region and expressed as a percentage. Main Outcome Measures: Change in LI from baseline to week 24 and week 52 in the posterior pole, peripheral zone, and total analyzable retina, and between-treatment differences in LI change. Results: A total of 106 cases were included (69 in the brolucizumab arm and 37 in the aflibercept arm). Both treatments significantly reduced LI from baseline to week 24 and from baseline to week 52 (P < 0.001). By week 24, the brolucizumab group demonstrated a statistically significantly greater reduction in the posterior pole LI compared to the aflibercept group (mean change, –24.7 ± 21.3 vs. –16.8 ± 12.4; P = 0.037). However, by week 52, there were no statistically significant differences between the 2 arms in any retinal region (P > 0.2). Conclusions: Both brolucizumab and aflibercept substantially reduced UWF-FA leakage in DME over 52 weeks. Brolucizumab achieved a more pronounced early reduction in leakage within the posterior pole, although the final residual leakage at week 52 was comparable between the 2 agents. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
SN - 2666-9145
ER -