Associations of tear mediators with ocular surface symptoms, signs, and corneal nerve morphology in dry eye disease: a cross-sectional study

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Purpose To investigate associations between tear mediators and ocular symptoms, signs, and corneal nerve parameters in patients with dry eye disease (DED). Methods This cross-sectional study included 101 DED patients. Six tear mediators (IL-6, NGF, SP, CGRP, MMP-9, β-endorphin) were measured by Luminex. Symptoms (10-item questionnaire and OSDI), signs (TMH, TBUT, CFS), and corneal subbasal nerve parameters were assessed. Spearman's correlation was used. For eye-specific parameters, values from both eyes were averaged to obtain patient-level measurements. Results β-Endorphin showed a strong negative correlation with ocular pain ( r = −0.813, p < 0.001) and a positive correlation with corneal nerve fiber length ( r = 0.722, p = 0.030). Microneuroma count correlated positively with IL-6 ( r = 0.285), SP ( r = 0.294), and MMP-9 ( r = 0.376), and negatively with β-endorphin ( r = −0.212, all p < 0.05). MMP-9, NGF, and SP strongly correlated with OSDI ( r = 0.907, 0.901, 0.894, respectively, all p < 0.001). All tear mediators except β-endorphin correlated with CFS, but none correlated with TMH or TBUT. Conclusion Tear β-endorphin is uniquely associated with less pain and better corneal nerve preservation. Microneuromas link to pro-inflammatory mediators. Tear mediators reflect ocular surface damage (CFS) but not tear quantity and stability, suggesting that tear mediators profiling may reflect inflammatory and neuropathic mechanisms in DED, warranting further validation in controlled studies.