Author: Claude (AI), from PubMed abstracts · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Uveal melanoma: diagnosis and primary treatment

Uveal melanoma is the most common primary intraocular tumour in adults [S9]. Untreated choroidal and ciliary body melanoma metastasises in most reported patients, and delay in treatment carries a measurable risk that rises with tumour size [S6] [S11]. Eye-conserving radiotherapy gives survival similar to enucleation in randomised evidence [S1].

Key points - In the COMS randomised trial, survival after iodine-125 brachytherapy did not differ from enucleation, with little difference in quality of life [S1] [S3]. - Each month a melanoma stays untreated is estimated to add 0.3, 1.8 and 4.0 percentage points to the 10-year risk of metastatic death for small, medium and large tumours [S11]. - Charged-particle therapy gives lower local recurrence than brachytherapy, with a possible higher risk of secondary glaucoma; mortality does not differ [S9]. - Surveillance for metastases can be tailored to each patient's prognostic group [S10].

Evidence last checked: 2026-10-17 (PubMed abstracts).

Red flags

• Delay in definitive treatment. Larger melanomas have shorter volume doubling times (717, 421 and 307 days for small, medium and large tumours), so delay matters most for large tumours [S11].
• Untreated melanoma. In the rare published untreated patients, 15 of 17 with choroidal or ciliary body melanoma developed metastases, and disease-specific survival was 29% at 10 years [S6].
• Toxic tumour syndrome after radiotherapy. This aggressive secondary vasculopathy from persisting necrotic tumour usually ends in enucleation if untreated [S4].

Recognise it

• Clinical presentation and the features that separate a melanoma from a naevus are not described in these abstracts (see the choroidal naevus article).
• Growing naevi have a mean volume doubling time of 6392 days, far longer than melanomas (360 days on average) [S11].

Confirm it

• In the COMS, tumours were followed with ophthalmic ultrasound and fundus photography [S3].
• Prognostic biopsy with gene expression profiling (GEP) is used at primary treatment; in a cohort of 347 patients the observed 5-year metastasis-free survival for class 2 tumours (47%) was better than the GEP-predicted 28%, and larger tumour size independently raised metastatic risk [S7].
• The Alberta guideline gives recommendations on genetic prognostic testing and imaging to detect metastases [S8].

Manage it

Before acting on this section, check the national and local guidelines, product information and regulatory approvals that apply where you practise. See the medical disclaimer.

Tier A (primary care / no specialist)

• Refer any suspected intraocular tumour to an eye service (see Refer when). Treatment is not possible at this level.

Tier B (general eye clinic)

• Document the lesion and arrange prompt ocular oncology referral; the cost of delay rises with tumour size [S11].
• Where no ocular oncology service exists, note that enucleation and brachytherapy gave similar survival in the COMS [S1].

Tier C (specialist centre)

1. Plaque brachytherapy. In the COMS (tumours 2.5 to 10.0 mm thick and up to 16.0 mm basal diameter), the 5-year risk of enucleation after iodine-125 brachytherapy was 12.5% and of local treatment failure 10.3% [S3]. Thicker tumours and those close to the fovea had higher risk [S3]. A pooled analysis of 103 studies (21,263 patients) found ruthenium-106 plaques gave high local control while minimising complications, and use of a treatment planning system most influenced outcomes [S5].
2. Charged-particle therapy. A 2024 meta-analysis (2 RCTs, 5 controlled cohorts, 143 case series) found lower local recurrence than brachytherapy (OR 0.38) and no difference in mortality, enucleation or cataract [S9]. The only randomised comparison (184 patients) reported 5-year local control of 100% with helium ions versus 84% with iodine-125 plaque, and 5-year enucleation of 11% versus 22% [S2].
3. Proton beam therapy. Pooled case series (1059 patients) reported 5-year overall survival of 73% and 5-year local control of 94%; glaucoma, optic neuropathy and cataract were the commonest adverse effects [S12].
4. Toxic tumour syndrome. A systematic review suggests endoresection within 3 months of radiotherapy for tumours thicker than 7 mm with basal diameter 8 to 15 mm and post-equatorial location, and endodrainage for eyes with macula-off detachment, diameter above 15 mm or ciliary body involvement [S4].
5. Radiation retinopathy. The Alberta guideline includes recommendations on intravitreal anti-VEGF agents for radiation retinopathy [S8] (see the radiation retinopathy article).
6. Surveillance. Under a "number needed to scan 20" model, patients with disomy 3 tumours need about two examinations while GEP class 2 PRAME-positive patients need up to 17 [S10]. Regimens and intervals are otherwise not detailed in these abstracts.

Refer when

Pitfalls

• Assuming a "watch and wait" delay is harmless for a confirmed medium or large melanoma [S11].
• Telling patients that enucleation improves survival over brachytherapy: the COMS showed no difference [S1].
• Taking a GEP-predicted prognosis as exact: observed survival in class 2 tumours was better than predicted [S7].
• Applying one fixed surveillance schedule to every patient [S10].

Evidence notes

• Most comparative radiotherapy evidence is observational; the level of evidence is limited [S9].
• The doubling-time estimates [S11] and untreated-tumour survival [S6] rest on few patients and modelling.
• The proton beam meta-analysis has no comparator arm [S12].
• Not covered by these sources: symptoms and signs, imaging criteria for diagnosis, radiation doses, enucleation technique, adjuvant therapy, and costs or access in low-resource settings. The Alberta guideline abstract [S8] lists topics but not its recommendations.

Related articles

• Choroidal naevus versus small melanoma
• Metastatic uveal melanoma and tebentafusp
• Radiation retinopathy

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.