Abstract
Background/objectives
Retinal vein occlusion (RVO) is the second most common retinal vascular disorder. Despite promising advances with anti-VEGF therapy, select patients are unresponsive to therapy. A precision medicine-based approach for therapeutic decision-making based on underlying biomarkers may facilitate treatment based on the underlying pathway. This study aims to identify the baseline and longitudinal cytokine profiles of RVO-related macular oedema and correlating these expression profiles with higher order OCT features using a novel retinal segmentation and feature extraction platform.
Subjects/methods
The IMAGINE study is a post-hoc assessment of aqueous humour cytokines with correlation to higher level analysis of imaging studies. OCT scans underwent machine learning enhanced segmentation of the internal limiting membrane (ILM), ellipsoid zone (EZ) and retinal pigment epithelium (RPE), as well as evaluating volumetric fluid metrics. Samples of aqueous humour were obtained at baseline, as well as months 4 and 9 prior to treatment. These samples were analysed for the expression of multiple cytokines. Patients were divided into Responders and Non-Responders based on OCT profiles. Additionally, patients were categorised as a Rebounder if their CST increased by 50% after initial improvement.
Results
Twenty-six eyes were included. The OCT-based response schema identified 21 Responders (81%) and 5 Non-Responders (19%). VEGF levels directly correlated with intraretinal fluid volume and angiogenin was inversely correlated with fluid indices. Multiple cytokines, including ANGPTL4, were directly correlated with ellipsoid zone disruption. The baseline VEGF levels were significantly higher in all responders compared to Non-Responders (p = 0.02). Rebounders tended to have significantly decreased levels of angiogenin and TIMP-1 (p = 0.019, p = 0.015).
Conclusions
Cytokine expression was linked to specific OCT features and treatment response in RVO. Identification of an imaging phenotype that could serve as a surrogate for underlying active disease pathways could enhance treatment decision-making and precision medicine.
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Data availability
Additional data are available upon request.
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Funding
Funding was in part provided by NIH/NEI K23-EY022947-01A1 (JPE).
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Study design: JPE, CCW; Funding: CCW, JPE; Data Acquisition: JRA, SAA, LL, HJY, CCW, JPE; Manuscript drafting: SA; Manuscript Editing/Revision: All authors; Supervision: JPE, CCW, SKS, JLR; Statistical support: MH.
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CCW has research support from the following: Adverum, Allergan, Apellis, Clearside, EyePoint, Genentech/Roch, Neurotech, Novartis, Opthea, Regeneron, Regenxbio, Samsung, Santen; is a consultant for the following: Alimera Sciences, Allegro, Allergan, Alynylam, Apellis, Bayer, Clearside, D.O.R.C., EyePoint, Genentech/Roche, Kodiak, Notal Vision, Novartis, ONL Therapeutics, PolyPhotonix, RecensMedical, Regeneron, Regenxbio, Santen; and is a speaker for Regeneron. SKS has research support from Regeneron, Allergan, and Gilead; is a consultant for Bausch and Lomb, Novartis, and Regeneron. DMB has research support from the following: Adverum, Allergan, Apellis, Clearside, Genentech/Roch, Novartis, Opthea, Regeneron, Regenxbio, Samsung, Santen; is a consultant for the following: Regeneron, Bayer, Senju, Allergan, Optos, Zeiss, Heidelberg, OHR, Biotime, Gemini, Genentech/Roche, Novartis, Apellis, Regenxbio, Chengdu Kanghong Biotechnology. JPE has research support from the following: Aerpio, Alcon, Thrombogenics/Oxurion, Regeneron, Genentech, Novartis, Allergan; is a consultant for the following: Aerpio, Alcon, Allegro, Allergan, Adverum, Genentech/Roche, Novartis, Thrombogenics/Oxurion, Leica, Zeiss, Regeneron, Stealth; and holds a patent with Leica. JRA, SA, LL, HJY, MH, JLR have no financial disclosures to report. The authors declare no competing interests.
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Arepalli, S., Wykoff, C.C., Abraham, J.R. et al. Longitudinal analysis of aqueous humour cytokine expression and OCT-based imaging biomarkers in retinal vein occlusions treated with anti-vascular endothelial growth factor therapy in the IMAGINE study. Eye 37, 1928–1935 (2023). https://doi.org/10.1038/s41433-022-02265-2
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DOI: https://doi.org/10.1038/s41433-022-02265-2
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