PROJECT SUMMARY Photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) are surgical procedures used to correct refractive errors, with approximately 600,000 surgeries performed in the United States each year. A proportion (10 - 20%) of individuals develop persistent ocular pain after refractive surgery, which is a source of tremendous morbidity, limiting the ability to work, impacting mental health, and leading to suicidal ideation in severe cases. We hypothesize that proteins in the tear fluid modulate corneal nerve function, increasing the risk of and contributing to persistent pain after refractive surgery. As such, our studies will use proteomic analysis of tear fluid after surgery to identify diagnostic biomarkers for persistent ocular pain. We will also examine tear proteins prior to surgery in an effort to identify prognostic biomarkers that predict which individuals are likely to develop persistent pain after surgery. R33 Phase studies will use an alternative proteomics platform for analytical validation, and an additional new patient population for clinical validation. This knowledge can lead to better preventative and therapeutic algorithms to combat this debilitating condition and thus improve quality of life and decrease patient suffering.