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 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.
Diagnosis
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.
Conclusions
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,
Liverpool
L7 8XP
References
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2
Char DH. Clinical ocular oncology. Philadelphia: Lippincott-Raven,
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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,
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Shields JA and Shields CL. Intraocular tumours. A text and atlas.
Philadelphia: W.B. Saunders Company, 1992.
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