Abstract
PURPOSE: To investigate the association between ocular surface parameters and corneal higher-order aberrations (cHOAs) in dry eye disease (DED) populations. METHODS: This cross-sectional study included 164 DED patients. Patients’ signs were categorized into mild, moderate, and severe groups. All subjects underwent assessment of ocular surface parameters, including the Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS) score, and Schirmer test I (STT-I). Corneal higher-order aberrations (coma, trefoil, spherical aberration) were measured using the iTrace Visual Function Analyzer (iTrace version 6.1.0; Tracey Technologies, Houston, TX, USA). Statistical analyses included correlation analysis, restricted cubic splines (RCS), and Bayesian Kernel Machine Regression (BKMR) to evaluate relationships. In the BKMR mixture exposure–response association analysis model, the four ocular surface parameters (OSDI, TBUT, CFS, STT-I) were modeled simultaneously as a mixture to assess their joint effects on cHOAs, with TBUT and STT-I reverse-coded to ensure consistency with disease severity. RESULTS: Coma and trefoil increased with the severity of DED signs. After adjusting for age and sex, both coma and trefoil showed associations with the ocular surface parameters (OSDI, TBUT, CFS, and STT-I). Central corneal staining was more correlated with cHOAs. RCS analysis revealed nonlinear relationships, with coma showing inflection points at approximately OSDI = 40, TBUT = 5 s, and CFS = 1, while trefoil shows inflection points at approximately TBUT = 4.5 s and CFS = 2. BKMR suggested TBUT as the main factor for trefoil, with a negative correlation. Greater severity of the mixture of ocular surface parameters (≥ 70th percentile, with TBUT and STT-I reverse-coded) was significantly associated with increased trefoil levels. CONCLUSION: The association between ocular surface parameters (OSDI, TBUT, CFS, and STT-I) and cHOAs (coma, trefoil, spherical aberration) may provide preliminary insights for the clinical evaluation and management of visual quality in DED patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-026-04609-y.