Internal medicine

Enucleation

Uvea

Melanoma

Population

BAP1

Colorectal cancer

Gene

Cancer

Surgery

Oncology

Dermatology

Neuroblastoma RAS viral oncogene homolog

Chemistry

GNAQ

Malignancy

Ocular Melanoma

Mutation

KRAS

Cancer research

Biochemistry

Medicine

Environmental health

Nature Reviews Disease Primers

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments. Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. This Primer describes the clinical and biological features of primary UM, and highlights how therapies to prevent and treat the (currently) deadly metastases are urgently needed.

Uveal melanoma