Uveal Melanoma: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Uveal melanoma is the most common primary intraocular malignancy in adults, arising from melanocytes in the choroid (85%), ciliary body (10%), or iris (5%). Approximately 2,500 new cases occur per year in the US. It is biologically distinct from cutaneous melanoma with a different mutational landscape and treatment approach.

Fair complexion, blue or grey eyes, oculodermal melanocytosis (nevus of Ota), dysplastic nevus syndrome, and BAP1 tumor predisposition syndrome are established risk factors. UV radiation is not directly causative unlike cutaneous melanoma. Key oncogenic mutations: GNAQ or GNA11 in approximately 90% of uveal melanomas; SF3B1 mutation (better prognosis) and BAP1 loss or monosomy 3 (high metastatic risk).

Visual disturbances (blurring, photopsia, visual field defect), floaters, and visual acuity decline. Choroidal melanomas are often asymptomatic until significant macular or optic disc involvement occurs. Iris melanomas cause iris discoloration, unilateral pupil distortion, and secondary glaucoma. Many are detected incidentally during routine fundoscopy.

Fundoscopic examination with indirect ophthalmoscopy is primary. B-scan ultrasonography confirms choroidal mass with intrinsic vascularity and acoustic hollowness. CT and MRI orbits assess extraocular extension. Fine needle aspiration biopsy (FNAB) for molecular prognostication: BAP1 IHC, chromosome 3 monosomy, chromosome 8q gain, SF3B1 mutation, and gene expression profiling (GEP Class 1 vs Class 2) for metastatic risk stratification.

Local tumor treatment: plaque brachytherapy (iodine-125 or ruthenium-106) is the most common organ-preserving treatment. Proton beam radiotherapy for larger tumors. Stereotactic radiosurgery (Gamma Knife/CyberKnife). Enucleation for very large tumors, blind painful eyes, or failure of primary treatment. Systemic treatment for metastatic disease: tebentafusp (gp100xCD3 bispecific, HLA-A*02:01 patients only) — first immunotherapy to improve OS in uveal melanoma. Ipilimumab plus nivolumab; clinical trials preferred.

Local treatment is effective for primary tumor control in over 95% of patients. However, 25-50% develop distant metastasis, almost exclusively to the liver. Class 2 GEP or monosomy 3 tumors: 5-year metastatic risk approximately 70-80%. Metastatic uveal melanoma: historically median OS 6-9 months; tebentafusp improved median OS to approximately 21 months in HLA-A*02:01 positive patients, representing a significant therapeutic advance.