Choroidal Melanoma

Melanoma arising from melanocytes of the choroid, the posterior uveal tract. It accounts for about 90 percent of uveal melanomas and is the form most likely to cause visual loss and metastatic death.

• Usually unilateral, arises from a pre-existing naevus (the transformation risk of a choroidal naevus is about 1 in 8,000 per year in the general population but rises with risk features).
• Associated: ocular melanocytosis, germline BAP1 variants, fair complexion, age above 50 years, and rarely neurofibromatosis type 1.
• Tumour behaviour: growth through Bruch membrane giving the mushroom shape, extension to the sclera and orbit along emissary canals, and haematogenous spread to the liver.

• Painless blurred vision, scotoma, flashes and floaters, metamorphopsia, or incidental discovery; large tumours cause field loss, exudative retinal detachment (inferior), and secondary glaucoma.
• Fundus: pigmented (grey brown), amelanotic (yellow orange) or mixed mass with overlying orange pigment, subretinal fluid, retinal pigment epithelial changes, drusen over old naevi, haemorrhage, and tumour vessels.
• Differential diagnosis: choroidal naevus, congenital hypertrophy of the retinal pigment epithelium, choroidal metastasis, choroidal haemangioma, haemorrhagic retinal pigment epithelial detachment, neovascular age related macular degeneration with haemorrhage, osteoma, choroidal detachment, and posterior scleritis.
• Features favouring a naevus: thickness under 2 mm, drusen, halo, no fluid or symptoms; features favouring melanoma: thickness above 2 mm, subretinal fluid, symptoms, orange pigment, margin within 3 mm of the disc.

• Dilated fundus examination with indirect ophthalmoscopy and scleral depression, fundus photographs, and clinical drawing with measurements (base and thickness).
• B-scan ultrasound: acoustic hollowness, choroidal excavation, shadowing of the orbit, and measurement of thickness; A-scan with internal vascularity; follow up ultrasound for growth (increase of thickness by 0.5 mm or base by 1 mm suggests melanoma).
• Optical coherence tomography with enhanced depth imaging (subretinal fluid, retinal pigment epithelial changes, shaggy photoreceptors), fundus autofluorescence, fluorescein angiography (mottled hyperfluorescence, double circulation), and indocyanine green angiography.
• MRI of the orbit for extraocular extension; biopsy (fine needle aspiration, 25 to 27 gauge) for prognostic genetic testing or diagnostic doubt.
• Staging: liver imaging and function tests; systemic examination.

• Treat at an ocular oncology centre. Observation for small suspicious lesions with documented stability and review at 3 to 6 months.
• Eye preserving radiotherapy:
  • Plaque brachytherapy: ruthenium-106 (apical height up to 5 to 6 mm; dose 100 Gy to apex or 80 to 100 Gy at 5 mm), iodine-125 (apical height up to 10 mm, dose 85 Gy to apex at 0.6 to 1.05 Gy/hour; implanted for 5 to 7 days), palladium-103; with notched plaques for juxtapapillary tumours.
  • Proton beam therapy 56 to 60 Gy (cobalt Gray equivalent) in 4 fractions over 4 days, with tantalum clip localisation, for large, posterior, or juxtapapillary tumours.
  • Stereotactic radiosurgery (gamma knife, CyberKnife): 35 to 45 Gy in 1 to 5 fractions.
  • Adjuvant transpupillary thermotherapy for small thin tumours, with caution.
• Enucleation for very large tumours (thickness above 10 mm or base above 18 mm), blind painful eyes, optic nerve invasion, extraocular extension (orbital exenteration rare), and failed local therapy.
• Complications and care: radiation retinopathy and maculopathy (prophylactic and treatment intravitreal anti-VEGF every 2 to 3 months, triamcinolone, laser), vitreous haemorrhage (vitrectomy), neovascular glaucoma (anti-VEGF, cycloablation, drainage devices, enucleation), cataract surgery after radiation, dry eye, and optic neuropathy.
• Regular ocular follow up every 3 to 6 months for 5 years then yearly, plus liver surveillance every 6 months (MRI or ultrasound) for at least 10 years.
• Metastatic disease: tebentafusp 20 micrograms IV on day 1, 30 micrograms on day 8, then 68 micrograms weekly for HLA-A*02:01 positive patients; liver perfusion with melphalan 3 mg/kg; checkpoint inhibitors (ipilimumab 3 mg/kg with nivolumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab maintenance); referral to a medical oncology team.
• Prognosis: 5-year melanoma-specific survival about 95 percent for small tumours, 80 to 85 percent for medium, and 65 to 70 percent for large; metastasis risk is predicted by size, chromosome 3 loss, 8q gain, and gene expression class.