Large-scale survey, animal models, and computational modeling identify histological neurodegenerative biomarkers for traumatic optic neuropathy
Year: 2025
Type: article
Study design: Observational Study
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).
Source: JCI Insight
Authors: YiKui Zhang, BoYue Xu, ShiWei Huang, ZhaoHui Shi, Wei Xiong, Ruijun Wang, GuiQin Liu, Linlin Chen, ZhenHua Ge, YongJie Zhang, HongLei Liu, BaoYun Jia, ChunXia Wang, HaiHong Shi, Jun Kang, NingYu An, ShuRui Huang, DeFu Chen, ShengHai Huang, YuTing Luo, MingYue Liu, ZhuoWei Wang, ZhongHao Yu, Jingwei Zheng, Wentao Yan, Gen Li, Hao Chen, XingGuang Deng, ShiHui Wei, YunHai Tu, EnDe Wu, Kang Zhang, WenCan Wu
Institutions: Wenzhou Medical University, Affiliated Eye Hospital of Wenzhou Medical College, Jilin University, Second Affiliated Hospital of Jilin University, Third Affiliated Hospital of Sun Yat-sen University, Third Xiangya Hospital, Ningbo University, Jinan University, Shenyang The Fourth Hospital of People, China Medical University, Xuzhou No.1 People's Hospital, Northwest University, Dali University, Fourth Affiliated Hospital of China Medical University, Affiliated Hospital of Nantong University, Beijing Tongren Hospital, Capital Medical University, Ningxia Hui Autonomous Region Peoples Hospital, Jiangsu Industry Technology Research Institute, Chinese PLA General Hospital, Chinese People's Liberation Army
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: G2523662861, G8604112561
OpenAlex ID: W4411363367