Uveal melanoma is a type of eye cancer in the uvea of the eye.[ Symptoms include blurred vision, loss of vision, and photopsia, but there may be no symptoms.]
Tumors arise from the melanocyte that reside within the uvea and give color to the eye. These melanocytes are distinct from the retinal pigment epithelium cells underlying the retina that do not form melanomas. When eye melanoma is spread to distant parts of the body, the five-year survival rate is about 15%.[ Eye Cancer Survival Rates, American Cancer Society, Last Medical Review: December 9, 2014 Last Revised: February 5, 2016]
It is the most common type of primary eye cancer.[ Males and females are affected equally.][
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Signs and symptoms
Ocular melanoma may present without symptoms depending upon the location and size of the tumor. When symptoms do occur, they can include:
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blurred vision
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double vision (diplopia)
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irritation
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pain
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a perception of flashes of light in the eye (photopsia)
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a reduction in the total field of vision
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loss of vision
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a sensation of a foreign body in the field of vision (floaters)
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redness, bulging or displacement of the eye (proptosis)
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a change in the shape of the pupil
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pressure within the eye
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metamorphopsia (a distortion of vision where, when a person looks at a grid of straight lines, the lines appear wavy and parts of the grid appears blank).
Types
Uveal melanomas, often referred to by the media and in the general population as ocular melanomas, may arise from any of the three parts of the uvea, and are sometimes referred to by their location, choroidal melanoma, ciliary body melanoma, or iris melanoma. Large tumors often encompass multiple parts of the uvea and can be named accordingly. True iris melanomas, originating from within the iris as opposed to originating elsewhere and invading the iris, are distinct in their etiology and prognosis, such that the other tumors are often referred to collectively as posterior uveal melanomas.
Iris melanoma
Uveal tumors can originate from melanocytes residing within the iris. Benign melanocytic tumors, such as iris freckles and moles (nevi), are common and pose no health risks, unless they show signs of malignancy, in which case they are classified as iris melanomas. Though derived from uveal melanocytes, iris melanomas share more in common with cutaneous (skin) melanomas in that they frequently harbor BRAF mutations associated with ultraviolet damage.
Posterior uveal melanoma
Benign melanocytic tumors of the choroid, such as choroidal freckles and nevi, are very common and pose no health risks, unless they show signs of malignancy, in which case they are considered melanomas.
Cause
The cause of uveal melanoma is unclear. Uveal nevi are common (5% of Caucasians),
Metastasis
Because there are no lymphatic channels to the uveal tract, metastasis occurs through local extension and/or blood-borne dissemination.
The average survival time after diagnosis of liver metastases depends on the extent of systemic spread. The disease-free interval, the performance status, the liver substitution by metastases and the serum level of lactic dehydrogenase are the most important prognostic factors for metastatic uveal melanoma.
Treatment
The treatment protocol for uveal melanoma has been directed by many clinical studies, the most important being The Collaborative Ocular Melanoma Study (COMS).
Plaque brachytherapy
The most common radiation treatment is plaque brachytherapy, in which a small disc-shaped shield (plaque) encasing radioactive seeds (most often iodine-125, though ruthenium-106 and palladium-103 are also used) is attached to the outside surface of the eye, overlying the tumor. The plaque is left in place for a few days and then removed. The risk of metastasis after plaque radiotherapy is the same as that of enucleation, suggesting that micrometastasis spread occurs prior to treatment of the primary tumor.
Proton therapy
Proton therapy delivers powerful doses of radiation to the tumor while sparing surrounding healthy eye tissue. The treatment is also effective at controlling tumor growth and maintaining a patient's natural eye.
Immunotherapy
On January 25, 2022, the FDA approved tebentafusp (Kimmtrak) for adult HLA-A*2-positive patients with metastatic uveal melanoma. Approval was based on the IMCgp100-202 trial ( NCT03070392), which compared tebentafusp with investigator's choice of either dacarbazine, pembrolizumab or ipilimumab. Patients lived a median of 16 months when treated with investigator's choice of therapy, compared to a median 21.7 months with tebentafusp. This translated in a 49% reduction in the risk of death. Overall survival after one year of treatment was 59% in the control group, versus 73% in the tebentafusp group.
Other
Other modalities of treatment include transpupillary thermotherapy, resection of the tumor, gamma knife stereotactic radiosurgery, or a combination of different modalities. Different surgical resection techniques can include trans-scleral partial choroidectomy and transretinal endoresection.
A 2017 analysis of genomic data led to a new analysis of clinical subtyping in uveal melanoma.
Prognosis
When eye melanoma is spread to distant parts of the body, the five-year survival rate is about 15%.
Several clinical and pathological prognostic factors have been identified that are associated with higher risk of metastasis of uveal melanomas. These include large tumor size, ciliary body involvement, presence of Lipofuscin overlying the tumor, and older patient age.
The most important genetic alteration associated with poor prognosis in uveal melanoma is inactivation of BAP1, which most often occurs through mutation of one allele and subsequent loss of an entire copy of chromosome 3 (monosomy 3) to unmask the mutant copy.
The most accurate prognostic factor is molecular classification by gene expression profiling of uveal melanomas. This analysis has been used to identify two subclasses of uveal melanomas: class 1 tumors that have a very low risk of metastasis, and class 2 tumors that have a very high risk of metastasis.
Surveillance
Currently, there is no consensus regarding type or frequency of scans following diagnosis and treatment of the primary eye tumor.
Of the 50% of patients who develop metastatic disease, more than 90% of patients will develop liver metastases. As such, the majority of surveillance techniques are focused on the liver. These include abdominal magnetic resonance imaging (MRI), abdominal ultrasound and liver function tests. The scientific community is currently working to develop guidelines, but until then, each patient must take into consideration their individual clinical situation and discuss appropriate surveillance with their doctors.
Some ophthalmologists have also found promise with the use of intravitreal avastin injections in patients with radiation-induced retinopathy, a side effect of plaque brachytherapy treatment, as well as imaging surveillance with SD-OCT.
Epidemiology
Uveal melanomas are the most common primary intraocular tumor in adults.
There are about 2500 patients with UM diagnosed annually in the US.[Masoomian B, Shields JA, Shields CL (2018) Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. J Curr Ophthalmol 30(2):102-109]
Apparent clustering
In 2018, it was reported that two clusters of cases have been identified in Huntersville, North Carolina, and Auburn, Alabama. Cases involved alumni of Auburn University who were acquainted with each other. Health officials investigated and found that the "cluster" is an artifact of social networking.
History
Uveal melanoma was first described in the literature in 1809-1812 by two Scottish surgeons, Allan Burns and James Wardrop.
See also
External links
