Project Summary Uveal melanoma (UM) is a prevalent intraocular cancer, with approximately 3,000 new cases annually and an estimated total of 60,000-70,000 affected individuals in the US. This malignancy poses a distressing reality as around 50% of patients develop metastatic diseases within 5 years, leading to devastating consequences for patients and healthcare providers. Current methods for predicting metastasis risk rely on invasive needle biopsies based on gene expression profiles (GEP), which are performed once and can cause discomfort and complications. The urgent need to address this challenge calls for the development of an effective and least invasive prognostic tool that can accurately predict metastatic risk, enhance safety, and guide treatment decisions worldwide, thereby offering better surveillance for patients with reduced costs and alleviating their concerns. To tackle this challenge, we've established a novel approach for predicting metastasis risk using proteomic analysis of aqueous humor (AH), the clear fluid of the front chamber from eyes. AH paracentesis, a safe procedure routinely performed in ophthalmology practice for decades, enabled the identification of differentially expressed proteins in AH samples. With this STTR Phase 1 application, we aim to develop a fit-for-purpose test based on our innovation, aiming to provide an easy-to-use pre-clinical test that utilizes safely accessible AH-based protein biomarkers, ultimately improving prediction accuracy and informing patient care.