A biofidelic Goat Model of Traumatic Optic Neuropathy with Optic Canal Fracture via Transnasal Endoscopy

Traumatic optic neuropathy (TON) is a major cause of irreversible vision loss following blunt cranial trauma. However, translational research has been significantly impeded by the lack of clinically relevant large-animal models that faithfully recapitulate the human condition. Current rodent models fail to reproduce optic canal fractures, which represent a key injury mechanism in many patients with TON. Here, we combined high-fidelity finite element analysis (FEA) with iterative engineering to establish a reproducible goat model of TON. We first developed a high-resolution finite element model of the human head to characterize force transmission to the optic nerve. During simulated clinically relevant periorbital impacts, stress preferentially concentrated in the intracanalicular segment, reaching a peak force density of approximately 500 N/m² at 50.6 ms—a magnitude approximately fivefold higher than that observed in the intraorbital segment. Further simulations demonstrated that direct impact to the optic canal reproduced comparable intracanalicular stress using a markedly lower input force (195 N) compared with periorbital impact (3 900 N). Guided by these insights, we developed transnasal endoscopic impact systems capable of inducing optic canal fractures in goats. The induction of TON was confirmed within 24 h by the presence of a characteristic relative afferent pupillary defect (RAPD). At 1 month post-injury, the goats (n=14) exhibited a 10%–20% reduction in ganglion cell complex (GCC) thickness and 40%–65% reductions in flash visual evoked potential (FVEP) and pattern electroretinogram (PERG) amplitude ratios (all P≤0.001), while the structural and functional integrity of the fellow eye was preserved. This study presents a robust, standardized, and clinically relevant large-animal platform for investigating TON pathophysiology.