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Uveal Melanoma

Uveal melanoma is a type of eye cancer that originates in the uvea, which includes the iris, choroid, and ciliary body. It is considered the most common primary eye cancer in adults, with an incidence of about 5 cases per million people per year. Males and females are affected equally, and the disease can metastasize, most commonly to the liver.

Iris melanoma
Iris melanoma

Signs and Symptoms

Uveal melanoma may present without any symptoms, depending on the location and size of the tumour. However, when symptoms are present, they can include:

  • Blurred vision
  • Double vision (diplopia)
  • Irritation and pain
  • A perception of flashes of light in the eye (photopsia)
  • Reduction in the total field of vision
  • Sensation of floaters (foreign body in the field of vision)
  • Redness, bulging or displacement of the eye (proptosis)
  • Changes in the shape of the pupil
  • Increased intraocular pressure
  • Metamorphopsia (distorted vision where straight lines appear wavy)

Types

Iris Melanoma

Uveal tumours can originate from melanocytes within the iris. Benign melanocytic tumours, such as iris freckles and nevi, are common and pose no health risks unless they become malignant, at which point they are classified as iris melanomas. Iris melanomas often harbour BRAF mutations and are less likely to metastasize than other uveal melanomas.

Posterior Uveal Melanoma

This type includes choroidal and ciliary body melanomas. Choroidal and ciliary body melanomas often harbour GNAQ/GNA11 mutations. Incidence is highest among individuals with light skin and blue eyes.

Variably pigmented, mushroom-shaped choroidal tumour
Variably pigmented, mushroom-shaped choroidal tumour has ruptured the Bruch membrane and grown into the subretinal space.
Malignant melanoma of the choroid
Malignant melanoma of the choroid

Cause

The exact cause of uveal melanoma is unclear. While uveal nevi are common, they rarely progress to melanoma.

Diagnosis

Diagnosis of uveal melanoma involves clinical examination techniques such as biomicroscopy and indirect ophthalmoscopy. Differential diagnoses vary depending on the tumour's location and include other choroidal, iris, and retinal tumours, as well as inflammatory lesions.

Metastasis

Uveal melanoma metastasizes through local extension or blood-borne dissemination, with the liver being the most common site. Approximately 50% of patients develop metastases within 15 years of initial treatment. Molecular features such as chromosome 3 status and gene expression profiling can help predict the likelihood of metastasis.

Treatment

Treatment varies depending on tumour size and genetic factors. Primary treatments include:

Plaque Brachytherapy

A small disc-shaped shield encasing radioactive seeds is attached to the eye's surface over the tumour for a few days. The risk of metastasis is similar to that of enucleation.

Proton Therapy

Proton therapy delivers high doses of radiation to the tumour while sparing surrounding healthy tissue.

Immunotherapy

Tebentafusp (Kimmtrak) has been approved for HLA-A*2-positive patients with metastatic uveal melanoma.

Other Treatments

Other modalities include transpupillary thermotherapy, tumour resection, gamma knife stereotactic radiosurgery, or a combination of these.

Prognosis

The five-year survival rate for eye melanoma that has spread to distant parts of the body is about 15%. Prognostic factors for metastatic risk include tumour size, ciliary body involvement, and genetic markers such as BAP1 mutations. Gene expression profiling can further refine prognostic predictions.

Surveillance

There is no consensus on the type or frequency of post-treatment surveillance. Techniques often focus on the liver and include MRI, ultrasound, and liver function tests. Regular monitoring is essential due to the high risk of late metastasis.

Epidemiology

Uveal melanomas are the most common primary intraocular tumours in adults with approximately 2500 cases diagnosed annually in the US. The incidence remains stable over time.

History

Uveal melanoma was first described in the literature between 1809-1812 by Scottish surgeons Allan Burns and James Wardrop.


Self-assessment MCQs (single best answer)

What is the most common primary eye cancer in adults?



Which part of the eye does uveal melanoma originate from?



What is the most common site for metastasis of uveal melanoma?



Which type of mutation is commonly found in iris melanomas?



What clinical technique is used for the diagnosis of uveal melanoma?



What is the five-year survival rate for eye melanoma that has metastasized?



Which genetic marker is associated with a higher risk of metastasis in uveal melanoma?



Which treatment involves attaching a radioactive shield to the eye's surface?



What is a common symptom of uveal melanoma?



Who were the first to describe uveal melanoma in the literature?



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Excellent content clearly explained.
SJ

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