Blood-Based Cell-Free DNA in Ophthalmic Oncology

Cell-free DNA (cfDNA) has emerged as a useful liquid biopsy biomarker with many translational applications in oncology. Here, we review the uses of blood-based cfDNA in ophthalmic oncology, with a focus on uveal melanoma, retinoblastoma, conjunctival tumors, choroidal metastases, indeterminate choroidal lesions, and ocular histiocytosis.

A systematic literature search in MEDLINE, PubMed, Web of Science, and Scopus from October 2017 to June 2025 was performed. Data extraction included tumor diagnosis, number of patients in the cohort, characteristics of the blood-based cfDNA assay employed (including technology used for mutation identification), number and types of genes analyzed, performance metrics for the assay, and any clinical impact.

The use of blood-based cfDNA in the field of ophthalmic oncology has been studied to varying degrees. Perhaps its most well-researched area is uveal melanoma, in which applications for both primary and metastatic uveal melanoma continue to be evaluated. Its use in retinoblastoma has been investigated by a small number of groups. There is minimal but intriguing work on the use of blood-based cfDNA in for conjunctival tumors, choroidal metastases, tumors of indeterminate origin, and ocular histiocytosis.

cfDNA science bridges the gap between basic research and clinical care. Within the field of ophthalmic oncology, cfDNA may be useful as a diagnostic/prognostic tool, for surveillance of metastatic or minimally residual disease, to identify driver mutations for treatment selection, as a biomarker of treatment response, for screening for recurrent or new cancer, and to detect new molecule clones.