Large-scale survey, animal models, and computational modeling identify histological neurodegenerative biomarkers for traumatic optic neuropathy

BACKGROUNDTraumatic optic neuropathy (TON) is a leading cause of blindness following closed traumatic brain injury, with no effective treatments available. Previous interventional clinical trials were complicated by its low prevalence, variability in neurodegenerative severity, and unavailability of reliable biomarkers.METHODSWe analyzed data from 1,226 patients enrolled in the prospective National Multi-Center Collaborative Clinical Research Program of China (2017-2024) to establish a clinical profile and identify noninvasive biomarkers for neurodegenerative severity. Subgroup analysis of patients with monocular TON revealed potential biomarkers, including visual functional parameters, inner retinal thickness, and time postinjury.RESULTSThe ganglion cell complex (GCC) thickness showed a strong correlation with retinal ganglion cell somata (R² = 0.87, P < 0.0001) and axon density (R² = 0.89, P < 0.0001) in a clinically relevant large animal model. Computational analysis demonstrated that using GCC thickness as a biomarker could substantially enhance the statistical power of clinical trials (by up to 4.5-fold), as verified by real-world data.CONCLUSIONThis study presents the largest epidemiological analysis of TON to date and establishes GCC thickness as a crucial biomarker for stratifying disease severity and improving the efficiency of clinical trials.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR-OOC-17013437).FUNDINGNational Key R&D Program of China (Grant No. 2022YFA1105500), Key Science and Technology Program of Wenzhou (Grant No. ZY2022021), National Natural Science Foundation of China (Grant No. 82471080).

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Publication Details

Journal
JCI Insight
Published
2025-06-17
DOI
https://doi.org/10.1172/jci.insight.190682
Primary Topic
Traumatic Brain Injury and Neurovascular Disturbances
Type
article
Field-Weighted Citation Impact
0.00

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article

Large-scale survey, animal models, and computational modeling identify histological neurodegenerative biomarkers for traumatic optic neuropathy

Wentao Yan, Shiwei Huang, Jun Kang, Zhigang Ge et al.
JCI Insight
Traumatic Brain Injury and Neurovascular Disturbances
article

Large-scale survey, animal models, and computational modeling identify histological neurodegenerative biomarkers for traumatic optic neuropathy

Wentao Yan, Shiwei Huang, Jun Kang, Zhigang Ge, Yunhai Tu, G. Liu, Ningyu An, Defu Chen, Wei Xiong, Boyue Xu, Yuehua Zhang, Yukun Luo, Zhonghao Yu, Xiaohua Deng, Shuxian Huang, Linlin Chen, Hao Chen, Gen Li, Yongjie Zhang, Kang Zhang, Ruijun Wang, Mingyue Liu, Chunxia Wang, Hailong Shi, Wencan Wu, Ende Wu, Zhihong Shi, Jingwei Zheng, Shenghai Huang, Shihui Wei, Z. Wang, Bingjing Jia
article en

Abstract

BACKGROUNDTraumatic optic neuropathy (TON) is a leading cause of blindness following closed traumatic brain injury, with no effective treatments available. Previous interventional clinical trials were complicated by its low prevalence, variability in neurodegenerative severity, and unavailability of reliable biomarkers.METHODSWe analyzed data from 1,226 patients enrolled in the prospective National Multi-Center Collaborative Clinical Research Program of China (2017-2024) to establish a clinical profile and identify noninvasive biomarkers for neurodegenerative severity. Subgroup analysis of patients with monocular TON revealed potential biomarkers, including visual functional parameters, inner retinal thickness, and time postinjury.RESULTSThe ganglion cell complex (GCC) thickness showed a strong correlation with retinal ganglion cell somata (R² = 0.87, P < 0.0001) and axon density (R² = 0.89, P < 0.0001) in a clinically relevant large animal model. Computational analysis demonstrated that using GCC thickness as a biomarker could substantially enhance the statistical power of clinical trials (by up to 4.5-fold), as verified by real-world data.CONCLUSIONThis study presents the largest epidemiological analysis of TON to date and establishes GCC thickness as a crucial biomarker for stratifying disease severity and improving the efficiency of clinical trials.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR-OOC-17013437).FUNDINGNational Key R&D Program of China (Grant No. 2022YFA1105500), Key Science and Technology Program of Wenzhou (Grant No. ZY2022021), National Natural Science Foundation of China (Grant No. 82471080).

JCI InsightVol. 10(14)
Beijing Tongren Hospital (CN), Central South University (CN), Sun Yat-sen University (CN), Jinan University (CN), Xuzhou Medical College (CN), Nantong University (CN), Wenzhou Medical University (CN), Chinese PLA General Hospital (CN), Affiliated Hospital of Nantong University (CN), Affiliated Eye Hospital of Wenzhou Medical College (CN), The Fourth People's Hospital (CN), Fourth Affiliated Hospital of China Medical University (CN), Ningxia Hui Autonomous Region Peoples Hospital (CN), Suzhou Vocational Institute of Industrial Technology (CN), Tongren University (CN), First Hospital of Jiaxing (CN), Second Affiliated Hospital of Jilin University (CN), Xuzhou No.1 People's Hospital (CN), Third Affiliated Hospital of Sun Yat-sen University (CN), Ningbo University Affiliated Hospital (CN), He Eye Hospital (CN), Third Xiangya Hospital (CN), Shenyang The Fourth Hospital of People (CN), Xiangya Hospital Central South University (CN), Dali University (CN), China Medical University (CN)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 78%
Traumatic Brain Injury and Neurovascular Disturbances
DOIOpen Access PDFOpenAlex
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