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

## TL;DR

A large study identifies inner retinal thickness as a reliable biomarker for assessing severity and guiding clinical trials in traumatic optic neuropathy.

## Contribution

GCC thickness is shown to strongly correlate with retinal ganglion cell and axon density, offering a novel biomarker for TON.

## Key findings

- GCC thickness correlated strongly with retinal ganglion cell somata (R² = 0.87) and axon density (R² = 0.89).
- Using GCC thickness as a biomarker could increase clinical trial statistical power by up to 4.5-fold.

## Abstract

Traumatic 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.

We 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.

The 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.

This 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.

Chinese Clinical Trial Registry (ChiCTR-OOC-17013437).

National 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).

This large prospective observational study of traumatic optic neuropathy identifies inner retinal thickness as a key biomarker for disease severity assessment and clinical trials design.