June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Computational Imaging Biomarker Correlation with Intraocular Cytokine Expression in Diabetic Macular Edema: Findings from the IMAGINE DME Study
Author Affiliations & Notes
  • Sudeshna Sil Kar
    Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
  • Joseph Roy Abraham
    Cleveland Clinic, Cleveland, Ohio, United States
  • Charles Clifton Wykoff
    Retina Consultants of Houston, Texas, United States
  • Duriye Damla Sevgi
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Leina Lunasco
    Cleveland Clinic, Cleveland, Ohio, United States
  • David M Brown
    Retina Consultants of Houston, Texas, United States
  • Sunil K. Srivastava
    Cleveland Clinic, Cleveland, Ohio, United States
  • Anant Madabhushi
    Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
  • Justis P Ehlers
    Cleveland Clinic, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Sudeshna Sil Kar, None; Joseph Abraham, None; Charles Wykoff, Adverum (F), Alimera Sciences (C), Allegro (C), Allergan (C), Allergan (F), Alynylam (C), Apellis (C), Apellis (F), Bayer (C), Clearside (C), Clearside (F), D.O.R.C. (C), EyePoint (C), Genentech/Roch (F), Kodiak (C), Neurotech (F), Notal Vision (C), Novartis (F), ONL Therapeutics (C), Opthea (F), PolyPhotonix (C), RecensMedical (C), Regeneron (C), Regenxbio (F), Santen (F); Duriye Damla Sevgi, None; Leina Lunasco, None; David Brown, Adverum (F), Allergan (C), Allergan (F), Apellis (C), Apellis (F), Bayer (C), Biotime (C), Clearside (F), Gemini (C), Genentech/Roche (C), Genentech/Roche (F), Heidelberg (C), Novartis (C), Novartis (F), OHR (C), Opthea (F), Optos (C), Regeneron (C), Regeneron (F), Regenxbio (C), Regenxbio (F), Samsung (F), Santen (F), Senju (C), Zeiss (C); Sunil K. Srivastava, Abbvie (C), Allergan (C), Allergan (F), Eyepoint (C), Eyepoint (F), Eyevensys (C), Eyevensys (F), Gilead (C), Leica (P), Novartis (C), Regeneron (C), Regeneron (F), Santen (F), Zeiss (C); Anant Madabhushi, Aiforia Inc (C), AstraZeneca (F), Boehringer-Ingelheim (F), Bristol Meyers-Squibb (F), Elucid Bioimaging (P), Elucid Bioimaging (I), Inspirata Inc (F), Inspirata Inc (I), PathCore Inc (F), Philips (F); Justis Ehlers, Adverum (C), Aerpio (C), Aerpio (F), Alcon (C), Alcon (F), Allegro (C), Allergan (C), Allergan (F), Boehringer-Ingelheim (F), Genentech (F), Genentech/Roche (C), Leica (C), Leica (P), Novartis (C), Novartis (F), Regeneron (C), Regeneron (F), Santen (C), Stealth (C), Thrombogenics/Oxurion (C), Thrombogenics/Oxurion (F), Zeiss (C)
  • Footnotes
    Support  Regeneron [REGE1901], RPB Unrestricted Grant to the Cole Eye Institute [RPB1508DM], the National Institutes of Health [K23 -EY022947]
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2513. doi:
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      Sudeshna Sil Kar, Joseph Roy Abraham, Charles Clifton Wykoff, Duriye Damla Sevgi, Leina Lunasco, David M Brown, Sunil K. Srivastava, Anant Madabhushi, Justis P Ehlers; Computational Imaging Biomarker Correlation with Intraocular Cytokine Expression in Diabetic Macular Edema: Findings from the IMAGINE DME Study. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2513.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Various pathways and cytokines are implicated in pathogenesis of diabetic macular edema (DME). Recent work from our group has identified computational imaging biomarkers (CIBs) of vessel tortuosity from quantitative ultra-widefield angiography (UWFA) and texture patterns from optical coherence tomography (OCT) that are associated with response to anti-VEGF therapy in DME. The goal of this study was to establish the underlying molecular basis of the radiomic features. Hence, we sought to evaluate the association between underlying expression of specific cytokines and CIBs from UWFA and OCT scans.

Methods : The IMAGINE study is post-hoc assessment of aqueous cytokine expression and in-depth assessment of the imaging studies obtained throughout the DAVE DME study. The study included 24 eyes from 20 patients. The concentrations of cytokines including VEGF, ANG2, MCP-1, IL-6, and IL-8 were measured. 598 texture-based radiomic features were extracted from the baseline OCT images for heterogeneity assessment and 156 morphological and vessel tortuosity features were extracted from the baseline UWFA scans. Biclustering allows simultaneous clustering of rows (patients) and columns (features) of a data matrix and was employed on UWFA and OCT features to identify eyes with similar morphological phenotypes. Pearson correlation coefficients (R) assessed the correlation between the OCT and UWFA features that were identified by the most consistent BCs and the cytokines.

Results : Strong correlations were identified between VEGF and 7 morphology-based FA features (R=0.44-0.51, p<0.05), 1 tortuosity based FA feature (R=0.45, p=0.004) and 2 OCT-derived intraretinal fluid (IRF) Laws texture features (R=0.48-0.49; p=0.01). Strong correlation between IRF Laws texture feature and ANGPTL4 (R=0.52, p=0.008) were identified. Additionally, IRF Laws feature and u-PAR (R=0.41, p=0.04), HGF (R=0.47, p=0.01) and TIMP-1 (R=0.40, p=0.004) were also observed.

Conclusions : This study demonstrates a link between multiple radiomics-based CIBs and pathway-associated cytokine expression in eyes with DME, including a strong link between VEGF levels with retinal leakage morphology and vessel tortuosity.

This is a 2021 ARVO Annual Meeting abstract.

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