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Radiomics-based assessment of ultra-widefield leakage patterns and vessel network architecture in the PERMEATE study: insights into treatment durability
  1. Prateek Prasanna1,2,
  2. Vishal Bobba1,
  3. Natalia Figueiredo3,
  4. Duriye Damla Sevgi3,
  5. Cheng Lu1,
  6. Nathaniel Braman1,
  7. Mehdi Alilou1,
  8. Sumit Sharma3,
  9. Sunil K Srivastava3,
  10. Anant Madabhushi1,4,
  11. Justis P Ehlers3
  1. 1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
  2. 2Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA
  3. 3The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  4. 4Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA
  1. Correspondence to Justis P Ehlers, The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Ave/i32, Cleveland, OH 44195, USA; ehlersj1{at} and Prateek Prasanna, Department of Biomedical Engineering, Case Western Reserve University, 2071 MLK Drive, Cleveland, OH 44106, USA; prateek{at}


Aim To evaluate the potential of radiomics-based ultra-widefield fluorescein angiography (UWFA)-derived imaging biomarkers in retinal vascular disease for predicting therapeutic durability of intravitreal aflibercept injection (IAI).

Methods The Peripheral and Macular Retinal Vascular Perfusion and Leakage Dynamics in Diabetic Macular Edema and Retinal Venous Occlusions During Intravitreal Aflibercept Injection (IAI) Treatment for Retinal Edema (PERMEATE) study prospectively evaluated quantitative UWFA dynamics in diabetic macular oedema or macular oedema secondary to retinal vascular occlusion. 27 treatment-naïve eyes were treated with 2 mg IAI q4 weeks for the first 6 months, and then administered q8 weeks. Morphological and graph-based attributes were used to model the spatial distribution of leakage areas, while tortuosity measures were used to model the vessel network disorder. Eyes were grouped based on functional tolerance of the first 8-week treatment interval challenge. ‘Non-rebounders’ (N=15) maintained/improved best-corrected visual acuity (BCVA) following the 8-week challenge. ‘Rebounders’ (N=12) exhibited worsened BVCA. The image biomarkers were used with a machine learning classifier to preliminarily evaluate their ability to predict BCVA stability.

Results Two new UWFA image-derived biomarkers were identified and extracted. The cross-validated area under the receiver operating characteristic curve (AUC) was 0.77±0.14 using baseline leakage distribution features and 0.73±0.10 for the UWFA baseline tortuosity measures. Additionally, the change in vascular tortuosity between month 4 and baseline yielded an AUC of 0.73±0.08. Three baseline clinical features of letter score, macular volume and central subfield thickness yielded a corresponding AUC of 0.42±0.09.

Conclusions Two computer-extracted UWFA radiomics-based descriptors were identified as potential biomarkers for predicting treatment durability and tolerance of longer treatment intervals. Conventional treatment parameters were not significantly different between these same groups.

  • Retina
  • Imaging
  • Diagnostic tests/Investigation

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  • Acknowledgements Research was supported in part by Regeneron (VGFTe-DME-1431, K23-EY022947-01A1, 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1 and 1U01 CA239055-01), National Center for Research Resources under award number 1 C06 RR12463-01 VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), and the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, the Department of Defense or the United States Government.

  • Contributors PP, VB, AM, JPE; study concepts/study design or data acquisition or data analysis/interpretation, manuscript drafting or manuscript revision for important intellectual content; approval of the final version of submitted manuscript, agrees to ensure any questions related to the work are appropriately resolved: all authors; literature research: PP, VB, NF, JPE; clinical studies: NF, SS, SKS, JPE; experimental studies: PP, VB; statistical analysis: PP, VB; and manuscript editing: PP, VB, NF, DDS, CL, NB, MA, SS, SKS, AM, JPE.

  • Funding PP, VB, NF, CL, DDS, NB, MA, AM: none. SS: consultant: Eyepoint; research funding: Roche. SKS: consultant: Bausch + Lomb, Novartis, Carl Zeiss Meditec; research funding: Allergan and Bausch + Lomb; AM: research funding: Astrazeneca, Bristol Myers-Squibb, Philips. Equity: Inspirata, Elucid Bioimaging, consultant: Aiforia. JPE: consultant: Alcon, Allergan, Leica, Santen, Thrombogenics, Genentech, Novartis, Aerpio, Allegro, Regeneron, Roche and Zeiss; has intellectual property licensed to Leica; research funding: Alcon, Genentech, Regeneron, Boehringer-Ingelheim, Novartis, Aerpio and Thrombogenics.

  • Competing interests None declared.

  • Ethics approval The PERMEATE study is a Cleveland Clinic IRB-approved study (15-442) that involved human subjects. All participant provided written informed consent to participate.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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