Differences in pre-surgical baseline tear proteome are associated with persistent post-refractive surgery pain.

PURPOSE: Most patients who undergo refractive surgery have excellent outcomes, but a subset experience persistent eye pain after the procedure. We hypothesized that pre-operative tear fluid proteins are distinct in patients who develop pain after surgery. METHODS: Patients undergoing refractive surgery (LASIK or PRK) provided tear fluid samples and eye pain reports (numeric rating scale (NRS) 0-10) before (baseline) and after surgery. Patients reporting no baseline pain, but pain (NRS ≥3) at 3 months (Pain group, n = 31), were compared to patients with no pain before or 3 months after surgery (No Pain group, n = 47). Baseline samples were analyzed by tandem mass tag spectrometry. Proteins demonstrating differential expression based on fold change thresholds, area under the ROC curve (AUC), or feature importance in random forest classification were identified and used to construct multi-protein models. RESULTS: Thirty-nine proteins showed differential expression between Pain and No Pain patients. Multi-protein models showed that a subset of 4 proteins classified the Pain group with an AUC of 0.87 (95 % CI, 0.79-0.96). This model contained 2 proteins that increased (PGRC1 and PFD3) and 2 proteins that decreased (IBP3 and SPB9) in Pain patients, showing bi-directional, dynamic effects. CONCLUSION: Analysis of pre-surgical tears reveals proteome differences in patients who go on to experience persistent pain 3 months after refractive surgery. Since these tear samples were taken prior to surgery, when patients were not experiencing pain, these protein patterns may inform the discovery of risk biomarkers for persistent post-refractive surgery eye pain.