Tear proteomics for the understanding of corneal biomechanical weakness in offspring of keratoconus patients

Aim: To analyze the tear proteome of offspring of keratoconus patients (O‐KC) to elucidate the molecular mechanisms involved in corneal weakening in high‐risk individuals. Methods: 80 O‐KC young participants matched with 42 control subjects without KC family history were involved in this case‐control study. Corvis® ST and Pentacam® HR were used for the biomechanical and tomographic assessment. O‐KC eyes were classified as low, moderate, and high risk of KC development (O‐KC‐LR, O‐KC‐MR, and O‐KC‐HR) based on the corneal biomechanical behavior. Tear fluid was extracted using Schirmer strips, and the proteomic profile was analyzed using micro–liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS). SWATH‐MS method was used for protein quantification. Relationship and molecular characteristics of the proteins with differential expression between groups were explored using in silico tools. SPSS was used for statistical analysis. Results: Biomechanical analysis showed that 18% of O‐KC eyes had moderate risk of KC development [O‐KC‐MR], and 11% biomechanical alterations compatible with high‐risk for ectasia development [O‐KC‐HR]. Of the total proteins quantified, 15 were dysregulated (p