Precision Oncology in Ocular Melanoma: Integrating Molecular and Liquid Biopsy Biomarkers

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management.