Royal College of Ophthalmologists Guidelines (Focus)

Management of uveal melanoma 

Uveal melanoma threatens the patient with visual deficit, loss of the eye and metastatic death. A healthy controversy surrounds most aspects of care, which continue to evolve. 


Almost all intraocular melanomas can readily be diagnosed by ophthalmoscopy or bio-microscopy; however, the examiner must be aware of every condition that might resemble melanoma and should also be able to recognise any clinical variation of each condition. Some tumours, such as suspicious naevi and melanocytomas, demand life-long monitoring, aided by baseline colour photographs with which ophthalmoscopic appearances can be compared. 

Ultrasonography is useful for measuring tumour dimensions, detecting extraocular extension, and demonstrating whether a tumour is solid or cystic. Special expertise is required to distinguish melanoma from other tumours, according to internal reflectivity. When measuring thickness, care should be taken to measure the thickest part of the tumour, identifying the deep scleral surface, taking account of overlying retinal detachment, and avoiding an oblique cut, which would result in over-estimation. Angiography, computerised tomography, and magnetic resonance imaging are rarely helpful and can be confusing. Occasionally, biopsy is needed to determine the primary source of a metastasis or to exclude melanoma. Both fine needle aspiration biopsy and trans-scleral incisional biopsy require the involvement of a highly skilled cytologist or pathologist. 

Systemic investigation 

Patients with suspected melanoma require a full systematic history, complete medical examination, full blood count, serum biochemistry and liver function tests. If these give rise to any suspicion of extraocular malignancy then further investigations are performed as appropriate. There is debate as to whether pre-operative liver scans should be performed routinely or only if there is an increased chance of metastatic disease (ie, tumour diameter >17mm or extraocular extension.) 

Ocular treatment 

Plaque radiotherapy is the first choice of treatment in most centres. The ruthenium applicator is effective for tumours up to 5.5mm thick. Iodine plaques destroy tumours up to 9mm thick but are more likely to cause radiational side-effects. 

Proton beam radiotherapy is relatively expensive. It requires suturing of tantalum markers to sclera, treatment planning at Clatterbridge Centre for Oncology (Wirral) two weeks later, and a four-day course of radiotherapy at Clatterbridge after another fortnight. Unlike plaque treatment, proton beam radiotherapy often damages superficial tissues, causing permanent discomfort. It is therefore reserved for some small, posterior melanomas that are difficult to treat with plaque. Some centres select proton beam radiotherapy for large tumours, accepting the high incidence of persistent exudative retinal detachment and neovascular glaucoma. Proton beam radiotherapy has been applied to iris tumours, as an alternative to local resection, with encouraging initial results (Damato et al, unpublished data). 

Trans-scleral local resection of choroidal and ciliary body melanomas is technically difficult and requires hypotensive anaesthesia to lower the systemic blood pressure to 44 mm Hg. Local tumour recurrence has become less of a problem since the introduction of adjunctive plaque radiotherapy, but about 25% of all patients require subsequent vitreoretinal surgery. For these reasons, resection is performed only in a few centres, where it is reserved for tumours deemed too large for radiotherapy. 

Photocoagulation using argon, xenon or krypton applications has largely been superseded by low-energy, long exposure trans-pupillary thermotherapy delivered with a 3 mm diode laser. Some centres would rely entirely on trans-pupillary thermotherapy to destroy a juxtapapillary tumour; however, such a policy is opposed by those who have seen patients return with orbital recurrence many years after apparently successful photocoagulation. Long-term studies are required to determine (1) whether phototherapy is indeed as effective as is suggested by early results and, (2) whether it can safely be used to reduce radiational safety margins and tumour dose when administering plaque or proton beam radiotherapy. 

Trans-retinal 'endoresection' has been developed for small, juxtapapillary melanomas as a means of avoiding radiational complications. It is controversial because of fears about tumour seeding. Although this complication has not yet occurred in a series of more than 50 primary endoresections, initial phototherapy is now administered as a precaution. The main complications are silicone cataract and retinal detachment, mostly cause by entry-site tears. Further studies are needed to determine the scope of endoresection. 

Enucleation is indicated when none of the methods above can conserve what the patient considers to be a useful eye. It is performed in the standard fashion, with an orbital implant. Pre-enucleation radiotherapy is now known to be useless. If there is extra-ocular extension the patient is either monitored or given prophylactic external beam radiotherapy, according to individual preference. 

Non-treatment is not advised, unless the patient is moribund, because (1) an opportunity for preventing metastatic disease might be missed, (2) the eye might become acutely painful, necessitating urgent enucleation, perhaps when the patient is unfit for general anaesthesia, and (3) the scope for preserving vision might diminish. 

Factors reducing the chances of ocular retention include: (1) tumour diameter > 15 mm; (2) thickness > 5.5 mm; (3) posterior margin < 1 mm from disc; (4) involvement of more than a third of ciliary body, iris, or angle; (5) retinal perforation; (6) extraocular extension; and (7) diffuse spread. Good visual acuity can be expected if the tumour does not extend within 3 mm of fovea and if pre-operative acuity is normal. 

Management of systemic disease 

The most valuable predictive factors for metastatic death are (1) intra-tumoral chromosomal abnormality, such as monosomy 3, (2) large basal tumour diameter (i.e., > 15 mm), (3) epithelioid cells, (4) closed vascular loops, and (5) old age (i.e., > 60 years) at treatment. These allow patients with approximately an 80% chance of surviving 10-15 years to be distinguished from those with only a 30% chance of surviving five years. 

Metastatic disease usually presents with hepatic problems and is invariably fatal. Chemotherapy for established disease only rarely prolongs life significantly, whether delivered systemically or by hepatic perfusion. Partial hepatectomy can be beneficial in the few patients having only a few metastases. 

It is not yet known whether screening for metastatic disease should be recommended to all patients or just high risk cases or not at all. 

Interferon-alpha, vaccination, and intra-hepatic chemotherapy are under investigation as adjuvant therapies aimed at preventing any micro-metastases from developing into clinical disease. 

The European Organisation for Research and Treatment of Cancer (EORTC) has established the Ophthalmic Oncology Group so that these questions can be addressed by multi-centre studies. 

Ocular Oncology Centres 

A few ocular oncology centres exist around Britain. Some (i.e., in Glasgow, Liverpool, London and Sheffield) are funded supra-regionally, removing financial obstacles imposed by the extra-contractual referral system. The routine treatment of many patients at specialist units allows patients to be managed by multi-disciplinary teams, enables investment in special equipment, and enhances opportunities for research and teaching. It also becomes easier to address psychological problems, for example, by providing expert counselling, getting patients in touch with others who have had a similar experience, and providing a telephone help-line. 

Shared Care 

Special precautions are necessary when referring a patient to an oncology centre. The patient should be informed of the suspected diagnosis and advised to get in touch if an appointment letter is not received within a specified time. The referral should not be delayed unduly because investigations are being performed. 

When monitoring is required, some oncologists alternate visits with the referring ophthalmologist to facilitate the eventual discharge of the patient from the oncology centre. For this strategy to work, referring ophthalmologists and other associates need to be kept informed on the patient's progress, reassured about signs that might cause undue concern, and alerted to any problems that can arise. Conversely, the referring ophthalmologist should develop the habit of sending the oncologist a copy of the GP letter after each visit, explicitly stating the visual acuity in each eye and mentioning any ocular or systemic conditions that develop. This would facilitate audit, which forms an essential part of ocular oncology. 


Many patients with uveal melanoma have a reasonable chance of surviving and retaining the eye with good vision. Sadly all too often, they are referred with a large tumour, usually because their condition was missed when they presented with blurred vision, metamorphopsia, or photopsia. Ophthalmologists should teach optometrists and general practitioners not to assume that such symptoms are due to cataract or macular degeneration without performing full ophthalmoscopy with mydriasis. Such simple measures might do more to prevent visual loss and metastasis than any marvellous developments in microsurgery, immunotherapy or chemotherapy. 

Bertil Damato PhD FRCOphth,
Ocular Oncology Centre,
St Paul's Eye Unit,
Royal Liverpool University Hospital,
Prescot St,
L7 8XP 


1 Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet 1996; 347: 1222-1225.

2 Char DH. Clinical ocular oncology. Philadelphia: Lippincott-Raven, 1997: 2 edn.

3 Leyvraz S, Spataro V, Bauer J, et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol. 1997; 15: 2589-2595.

4 Ryan SJ, Ogden TE and Schachat AP. Retina, Vol. 1 St. Louis: Mosby, 1994: 2 edn.

5 Shields JA and Shields CL. Intraocular tumours. A text and atlas. Philadelphia: W.B. Saunders Company, 1992.

More Guidelines