Background: Corneal chemical burns are a common form of ocular injury that can result in severe visual impairment and complications. In recent years, studies have shown that unilateral ocular diseases can induce changes in the contralateral eye; however, the impact of unilateral chemical injury on the contralateral eye remains unclear. This study aims to evaluate the contralateral ocular surface alterations in patients and experimental mice model with unilateral chemical injury.

Methods: 29 patients with single-eye chemical injuries and 28 normal volunteers as controls were included. Contralateral unaffected eyes were studied in the chemical injury group, while we picked one eye at random in the control group. All subjects completed the ocular surface disease index (OSDI) questionnaire and underwent a routine ophthalmic examination, including tear film break-up time (BUT), Schirmer I test (SIT), fluorescein staining and corneal sensitivity. Tear film height and bulbar redness were assessed using the Oculus Keratograph® (Wetzlar, Germany). In vivo confocal microscopy (IVCM) was employed to evaluate corneal nerve characteristics, Langerhans cell (LC) density, and their correlation with post-injury time. Additionally, an alkali ocular burn model was established in Bagg Albino Laboratory-bred strain (BALB/c) mice to observe corneal fluorescein staining, β-tubulin immunohistochemistry of the corneal nerve, and hematoxylin and eosin (H&E) staining. Furthermore, tear fluid from mice was collected for cytokine liquid chip analysis to assess the ocular surface inflammatory status.

Results: Compared to controls, the contralateral unaffected eyes of patients with unilateral chemical injury showed significantly higher OSDI scores and bulbar redness scores, along with significantly lower SIT and tear film height values (p < 0.05). In the chemical injury group, corneal nerves exhibited increased branching, severe tortuosity, along with higher sensitivity. Post-injury time was inversely correlated with corneal nerve branch density (p = 0.02) and nerve tortuosity (p = 0.038). The clinically unaffected eyes exhibited significantly higher LC density (p < 0.0001) in center cornea compared to the control group. In the experimental mouse model, the contralateral eye exhibited epithelial damage, characterized by increased fluorescein staining, corneal nerves tortuosity, and altered nerve direction. H&E staining revealed stromal thinning and widened interstitial spaces between collagen fibers. Additionally, tear fluid analysis of uninjured eyes indicated altered expression of fifteen inflammatory factors, with sustained upregulation of monocyte chemoattractant protein (MCP-1) after chemical injury.

Conclusion: In both clinical and animal experiments, we observed that unilateral ocular chemical injury can induce functional alterations in the contralateral ocular surface. The inflammatory response triggered by chemical injury is not confined to the injured eye. It is necessary for a comprehensive evaluation of the contralateral eye in clinical practice.