Aqueous humor cytokine levels in retinal vein occlusion patients with suboptimal response to anti-VEGF therapy and the correlation with OCT imaging biomarkers - Research article

Q: How were responders categorized in the study?

Patients were grouped into super responders, slow responders, and non-responders based on macular edema resolution using OCT-based response categories.

Q: Which cytokines were elevated in retinal vein occlusion patients at baseline?

RVO patients showed higher VEGF, PIGF, Ang-2, IL-6, IL-8, ICAM-1, and MCP-1 compared with controls.

Q: What OCT biomarkers were linked to cytokine levels?

SRF was associated with higher baseline Ang-2, while a higher number of HRF was associated with higher baseline IL-6; severe edema and high HRF also corresponded to higher IL-6.

Sep 29, 2026

Upload by Indoniesian Boy

Purpose: assess baseline and longitudinal cytokine differences among super, slow, and non-responders in retinal vein occlusion with macular edema (RVO–ME) and evaluate associations between cytokines and OCT biomarkers. Methods: 44 RVO–ME and 37 cataract controls; aqueous samples collected before first and second anti-VEGF injections and analyzed by multiplex immunoassay; OCT response categories and measures (CRT, SRF, HRF, DRIL, DROL) were used. Results: elevated VEGF, PIGF, Ang-2, IL-6, IL-8, ICAM-1, MCP-1 in RVO; lower Ang-2/IL-6 in super-responders; IL-6 higher with severe edema/high HRF; Ang-2 with SRF; multivariate regression linked SRF to Ang-2 and HRF to IL-6; non-responders remained higher after initial injection.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Purpose

Methods

Results

Conclusion

Translational relevance

Introduction

Gong et al. European Journal European Journal of Medical Research (2026) 31:12 [https://doi.org/10.1186/s40001-025-03596-y](https://doi.org/10.1186/s40001-025-03596-y of Medical Research)[ of Medical Research](https://doi.org/10.1186/s40001-025-03596-y of Medical Research) RESEARCH Open Access Aqueous humor cytokine levels in retinal vein occlusion patients with suboptimal response to anti-VEGF therapy and the correlation with OCT imaging biomarkers Yi Gong1†, Fuhua Yang1†, Xiaoying Pan1,2†, Jinzhi Zhao1, Rongguo Yu1, Xiaomin Zhang1, Yan Shao1* and Xiaorong Li 1* Abstract Purpose To assess the differences in baseline and longitudinal cytokine profiles among super responders, slow responders, and non-responders in patients with retinal vein occlusion–macular edema (RVO–ME) and evaluate the association of cytokines with biomarkers identified on optical coherence tomography (OCT) . Methods Forty-four patients with RVO–ME and 37 patients with cataract were enrolled. Aqueous humor samples were collected before the first and second anti-vascular endothelial growth factor (VEGF) injections. The aqueous samples were analyzed for cytokine levels using multiplex immunoassay. OCT-based response categories were defined as super responders, slow responders, and non-responders according to ME resolution. Central retinal thickness (CRT), subretinal fluid (SRF), hyperreflective foci (HRF), disorganization of retinal inner layers (DRIL), and disorganization of retinal outer layers (DROL) were obtained for analysis. Results At baseline, RVO patients exhibited elevated VEGF, placental growth factor (PIGF), angiopoietin-2 (Ang-2), interleukin-6 (IL-6), IL-8, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP- 1) compared with controls (p < 0. 01) . Super responders showed significantly lower baseline Ang-2 and IL-6 (p = 0.027 and 0. 034, respectively) than slow and non-responders. Patients with severe edema and high HRF were likely to have higher levels of IL-6 (p < 0. 05) . Patients who presented with SRF or DROL at baseline showed higher levels of IL-6 and Ang-2 (p < 0. 05) . Multivariate linear regression revealed that the presence of SRF was associated with higher baseline Ang-2 (p = 0 . 029), and high HRF number was associated with higher baseline IL-6 (p = 0 . 048) . After initial injection, non-responders still retained higher Ang-2 and IL-6 concentrations (p = 0.012 and p = 0 . 040, respectively) than super responders. †Yi Gong, Fuhua Yang and Xiaoying Pan contributed equally to this work and shared first authorship. *Correspondence: Yan Shao [sytmueh@163.com](sytmueh@163.com)[ ](sytmueh@163.com)Xiaorong Li [xiaorli@163.com](xiaorli@163.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Gong et al. European Journal of M

FAQs

How were responders categorized in the study?

Patients were grouped into super responders, slow responders, and non-responders based on macular edema resolution using OCT-based response categories.

Which cytokines were elevated in retinal vein occlusion patients at baseline?

RVO patients showed higher VEGF, PIGF, Ang-2, IL-6, IL-8, ICAM-1, and MCP-1 compared with controls.

What OCT biomarkers were linked to cytokine levels?

SRF was associated with higher baseline Ang-2, while a higher number of HRF was associated with higher baseline IL-6; severe edema and high HRF also corresponded to higher IL-6.

Sep 29, 2026

Upload by Indoniesian Boy