PURPOSE: To investigate beta-amyloid precursor protein (beta-APP), ubiquitin, and glial fibrillary acid protein (GFAP) immunostaining as a diagnostic tool to aid in the discrimination between abusive head trauma and nonabusive head trauma in postmortem ocular histopathologic investigation. DESIGN: Retrospective cross-sectional study. METHODS: Seventy-four eyes of 37 infants were studied for hemorrhage and immunohistochemical expression of beta-APP, ubiquitin, and GFAP in the retina and optic nerve. Infants were assigned to abusive head trauma or control groups, according to published criteria. RESULTS: In the abusive head trauma group, positive beta-APP and ubiquitin immunostaining of the retina was significantly more likely to be found than in the control group, odds ratio (OR) 11.4, confidence interval (CI) 2.9-44.3; P <.001 and OR 8.8, CI 2.2-34.5; P = .002, respectively. Positive correlations were found between retinal expression of beta-APP and ubiquitin immunostaining and retinal hemorrhage. Vitreal hemorrhages, orbital fat hemorrhages, and macular folds could only be identified in abusive head trauma cases. Retinal hemorrhages were significantly more severe, occupied a larger proportion of the retina, and involved more retinal layers in abusive head trauma compared to controls (OR 2.7, CI 1.7-4.4; P <.001). CONCLUSIONS: This study shows correlations between positive retinal beta-APP and ubiquitin immunostaining as a sign of axonal injury in abusive head trauma. Axonal injury is a useful pathologic feature that can be demonstrated in postmortem ocular investigation of deceased children using immunohistochemical staining for beta-APP and ubiquitin with a high OR for abusive head trauma when compared to controls.