Optical coherence tomography retinal biomarkers for traumatic brain injuries: a systematic review and meta-analysis

Traumatic brain injury (TBI) is associated with impaired cognitive, psychological, and neurological functions. As an embryological extension of the central nervous system, the retina allows non-invasive assessment of cerebral pathology via optical coherence tomography (OCT). This systematic review and meta-analysis evaluated whether consistent OCT-derived retinal changes occur in TBI and their potential as biomarkers. A systematic search of five electronic databases identified studies comparing OCT parameters between individuals with TBI and controls. Retinal biomarkers included optic nerve, macular, and choroidal thickness metric. A random-effects meta-analysis was conducted, and study quality assessments were performed. Seven studies involving Olympic boxers, collision-sport athletes, rugby players, veterans, and the general population with mild-to-moderate TBI were included. Across studies, peripapillary retinal nerve fibre layer (RNFL) findings were heterogeneous, ranging from minor thickening (+1.7 µm) to pronounced thinning (-14 µm) relative to controls. RNFL thickness was significantly reduced in collision-sport athletes, especially boxers, and in veterans. Longitudinally, veterans showed faster RNFL loss (-1.47 ± 0.24 µm/year vs - 0.31 ± 0.32 µm/year; <i>p</i> = 0.004). The meta-analysis demonstrated a small, non-significant global effect (Hedges' g = -0.21; 95% CI -2.51 to 0.33; <i>p</i> = 0.84), corresponding to an estimated peripapillary RNFL thinning of approximately 1-1.5 µm in TBI cases compared with controls. Macular thickness was decreased in boxers compared to controls (<i>p</i> < 0.05). The ganglion cell complex was thinner in boxers (76.7 ± 2.1 µm vs 81.6 ± 0.5 µm; <i>p</i> = 0.02) but unchanged longitudinally. The ganglion cell layer showed localised thinning (<i>p</i> < 0.05) without global change. The sub-foveal choroidal thickness was reduced in patients with TBI (211 µm vs 369.5 µm; <i>p</i> = 0.05), while the Henle fibre layer was thicker (8.4 ± 0.9 vs 7.7 ± 1.1 pixels; <i>p</i> = 0.02). RNFL thinning was the most frequently examined OCT-based retinal biomarker, with variable findings across other retinal parameters. The meta-analysis revealed a non-significant effect, highlighting the need for further longitudinal research.