June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Correlation of Intraocular Cytokine Expression with Quantitative Ultra-widefield Fluorescein Angiographic Features in the IMAGINE Retinal Vein Occlusion Study
Author Affiliations & Notes
  • Alison Martin
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Joseph Roy Abraham
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Charles Clifton Wykoff
    Retina Consultants of Texas, Houston, Texas, United States
  • Leina Lunasco
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Sruthi Arepalli
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Sunil K. Srivastava
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Christopher J. Mugnaini
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Ming Hu
    Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
  • Jamie Reese
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • David M Brown
    Retina Consultants of Texas, Houston, Texas, United States
  • Justis P Ehlers
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Alison Martin, None; Joseph Abraham, None; Charles Wykoff, Adverum (F), Alimera Sciences (C), Allegro (C), Allergan (F), Allergan (C), Alynylam (C), Apellis (F), Apellis (C), Bayer (C), Clearside (F), Clearside (C), D.O.R.C (C), EyePoint (F), EyePoint (C), Genentech/Roch (F), Genentech/Roche (C), Kodiak (C), Neurotech (F), Notal Vision (C), Novartis (F), Opthea (F), Regeneron (F), Regenxbio (F), Samsung (F), Santen (F); Leina Lunasco, None; Sruthi Arepalli, None; Sunil K. Srivastava, Abbvie (C), Allergan (F), Allergan (C), EyePoint (F), EyePoint (C), Eyevensys (F), Eyevensys (C), Gilead (C), Leica (P), Novartis (C), Regeneron (F), Regeneron (C), Santen (F), Zeiss (C); Christopher Mugnaini, None; Ming Hu, None; Jamie Reese, None; David Brown, Adverum (F), Allergan (F), Allergan (C), Apellis (F), Apellis (C), Bayer (C), Biotime (C), Clearside (F), Gemini (C), Genentech/Roche (F), Genentech/Roche (C), Heidelberg (C), Novartis (F), Novartis (C), OHR (C), Opthea (F), Optos (C), Regeneron (F), Regeneron (C), Regenxbio (F), Regenxbio (C), Samsung (F), Santen (F), Senju (C), Zeiss (C); Justis Ehlers, Adverum (C), Aerpio (F), Aerpio (C), Alcon (F), Alcon (C), Allegro (C), Allergan (F), Allergan (C), Boehringer-Ingelheim (F), Genentech (F), Genentech/Roche (C), Leica (C), Leica (P), Novartis (F), Novartis (C), Regeneron (F), Regeneron (C), Santen (C), Stealth (C), Thrombogenics/Oxurion (F), Thrombogenics/Oxurion (C), Zeiss (C)
  • Footnotes
    Support  RPB Cole Eye Institutional Grant, NIH/NEI K23-EY022947, Regeneron REGE1901
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2169. doi:
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      Alison Martin, Joseph Roy Abraham, Charles Clifton Wykoff, Leina Lunasco, Sruthi Arepalli, Sunil K. Srivastava, Christopher J. Mugnaini, Ming Hu, Jamie Reese, David M Brown, Justis P Ehlers; Correlation of Intraocular Cytokine Expression with Quantitative Ultra-widefield Fluorescein Angiographic Features in the IMAGINE Retinal Vein Occlusion Study. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2169.

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

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Abstract

Purpose : Retinal vein occlusions (RVO) result in the overexpression of a variety of intraocular cytokines that contribute to sequelae, such as macular edema. The ability to link imaging biomarkers with specific underlying pathways could enhance therapeutic decision-making. This study correlated cytokine expression with ultra-widefield fluorescein angiography (UWFA) quantitative imaging biomarkers in RVO.

Methods : The IMAGINE RVO study is a post-hoc assessment of the WAVE clinical trial to determine associations between cytokine expression and quantitative imaging features. The WAVE study was a randomized clinical trial that evaluated the impact of targeted retinal photocoagulation (TRP) on treatment requirement with intravitreal ranibizumab in 30 eyes with RVO. Eyes had aqueous humor samples collected and UWFA performed at baseline. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated using multiplex arrays. Quantitative assessments of ischemia and leakage on UWFA were determined using an automated feature analysis platform with manual validation. Associations between cytokines and quantitative UWFA features were assessed using Spearman’s correlation coefficients.

Results : Twenty-seven of the 30 eyes in the WAVE study had sufficient samples for analysis. Increased macular ischemia was associated with ANGPTL4 (r=0.66, p=0.0002), VEGF (r=0.52, p=0.007), and MCP-1 (r=0.40, p=0.04). Increased peripheral ischemia was associated with ANGPTL4 (r=0.52, p=0.007) and VEGF (r=0.60, p=0.002), while decreased peripheral ischemia was associated with IL-12p70 (r=-0.45, p=0.02) and MCP4 (r=-0.44, p=0.02). Increased macular leakage was associated with ANGPTL4 (r=0.42, p=0.03) and VEGF (r=0.63, p=0.0008). Increased peripheral leakage was associated with ANGPTL4 (r=0.57, p=0.002), VEGF (r=0.61, p=0.001), and LIF (r=0.42, p=0.03), while decreased peripheral leakage was associated with FGF-4 (r=-0.47, p=0.02).

Conclusions : Multiple quantitative UWFA features were associated with intraocular cytokines in eyes with RVO. VEGF and ANGPTL4 correlated with both increased ischemia and increased leakage on UWFA. Further research is needed to evaluate the possibility of using these imaging biomarkers as surrogates for cytokine expression and correlating these features with treatment response.

This is a 2021 ARVO Annual Meeting abstract.

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