The Ocular Signature of TBI: A Narrative Review of Structural Changes and Potential Candidate Biomarkers.

BACKGROUND: Traumatic brain injury (TBI) damages brain tissues and affects the ocular system. Ocular manifestations such as orbital fractures, ocular surface disease, photosensitivity, impaired pupillary response, and retinal damage often co-occur with TBI. Despite established diagnostic criteria, a gap remains, particularly in detection, monitoring, and recovery prediction. Since ocular manifestations co-occur with TBI, they may offer non-invasive means to address this gap. Accordingly, this review evaluates whether TBI-associated ocular manifestations can serve as biomarkers for TBI detection, monitoring, and recovery. METHODS: A literature search was conducted across three databases for studies that address ocular manifestations of TBI listed above. RESULTS: Orbital fractures occur in 69%, matching TBI severity. Occult fractures may indicate unseen mild TBI on advanced neuroimaging. Dry eye disease prevalence is inconsistent (15 and 37%). Tear film proteomics show altered inflammatory and repair proteins, though this area remains understudied. Vitreous total tau and neurofilament light chain correlate with brain levels in chronic traumatic encephalopathy. Photosensitivity affects approximately 50% of acute TBI and declines to 14% after three months. NPi-200 pupillometer shows high specificity in triaging acute injury but with low sensitivity. PLR-3000 pupillometer and smartphone applications require further validation. Retinal imaging shows biphasic thickening then progressive thinning, modulated by sex, severity and duration. CONCLUSIONS: No single ocular biomarker fulfills all roles. Instead, different markers map into distinct stages of the clinical course. Future research should prioritize molecular markers in the tear film, combined with changes in corneal nerves across different TBI severities.