Abstract
Objectives
To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients.
Methods
An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed.
Results
The automatic MPCLEIA system was able to provide results in 45 min with only 20 μL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤−25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category.
Conclusions
Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.
Funding source: Shaanxi Province Key Research and Development Project
Award Identifier / Grant number: 2021sf-162
Funding source: CAMS Innovation Fund for Medical Sciences
Award Identifier / Grant number: 2022-I2M-C&T-B-026
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 82271112
Funding source: Beijing Natural Science Foundation Beijing-Tianjin-Hebei Basic Research Foundation
Award Identifier / Grant number: J200007
Funding source: Beijing Municipal Science & Technology Commission Capital Health Development Scientific Research Project
Award Identifier / Grant number: Z191100007719002
Funding source: National High Level Hospital Clinical Research Funding
Award Identifier / Grant number: 2022-PUMCH-B-101
Funding source: Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences
Award Identifier / Grant number: 2022-JKCS-23
Acknowledgments
The authors would like to express gratitude to all those who participated in assisting with information gathering and collecting water samples, including members of the ophthalmology team at Peking Union Medical College Hospital and members of the ophthalmology team at Xi’an People’s Hospital.
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Research ethics: This study adhered to the tenets of the Declaration of Helsinki, and was approved by the ethics committee of the Peking Union Medical College Hospital (No. ZS-1366) and Xi’an People’s Hospital (No. 20220062).
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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Author contributions: Yuelin Wang and Siqi Zhang involved in the acquisition of data and the drafting of the manuscript. Weixing Zhong was in charge of data measurement and technical guidance. Huan Chen and Hang Song contributed to manuscript revision. Yiming Zhao involved in data analysis. Tien Yin Wong contributed to the design of the work and revised the manuscript critically for important intellectual content. Chan Zhao, Yanchun Zhang and Youxin Chen have substantial contributions to conception of the work, and manuscript revision. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Weixing Zhong is employee of Sightnovo Medical Technology Co., Ltd. Yiming Zhao and Chan Zhao are consultants of Signtnovo Medical Technology Co., Ltd.
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Research funding: This work was supported by (1) CAMS Innovation Fund for Medical Sciences: 2022-I2M-C&T-B-026. (2) Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences: 2022-JKCS-23. (3) National Natural Science Foundation of China: 82271112; (4) Beijing Natural Science Foundation Beijing-Tianjin-Hebei Basic Research Foundation: J200007; (5) Beijing Municipal Science & Technology Commission Capital Health Development Scientific Research Project: Z191100007719002; (6) National High Level Hospital Clinical Research Funding: 2022-PUMCH-B-101; (7) Shaanxi Province Key Research and Development Project: 2021sf-162.
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Data availability: The raw data can be obtained on request from the corresponding author.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0749).
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