What Is Uveal Melanoma?

Overview 

Uveal melanoma, often referred to as intraocular melanoma, is a type of cancer that develops in melanocytes. Melanocytes are the group of cells responsible for pigment in the skin, hair and eyes - specifically in this case, they are responsible for the colour of the iris.¹ 

The American Academy of Ophthalmology states that although uveal melanoma is the most common eye cancer in adults, the incidence rate is still very low and is a rare form of cancer. Evidence throughout the years has shown that populations with  fair skin and older age are at an increased risk of developing intraocular melanoma.² 

Intraocular melanomas form in the middle section of the eye that cannot be seen without optical equipment. This makes it difficult for early diagnosis as the first signs and symptoms of cancer in the eye may not be reported by the patient.¹

Background and Incidence

Uveal melanoma is the most common form of cutaneous malignancy in adults caused by melanocytes after skin melanoma, accounting globally for 5% of melanoma cases. Overall, the incidence rate of uveal melanoma across Europe and North America has shown a steadily low rate. A recent meta-analysis analysed trends of diagnosis across North America and Europe demonstrating an incidence rate of 6 cases per million per year in both continental regions.³  Most cases of uveal melanoma in the US affect the white population at 97.8%.⁴ 

Studies have shown that uveal melanoma can develop in any age group, though only 1% of cases are in patients under the age of 18. Trends in incidence rates have shown that there is an increased risk of developing uveal melanoma with increasing age up to the age of 70.⁴ 

Ocular outcomes for uveal melanoma are generally positive in cases where the tumour is deemed small. However, it is estimated that around 50% of uveal melanoma cases develop distant metastatic disease spreading to the liver, resulting in fatality within 1 year.³ 

The exact causes of most cancers worldwide are generally unknown. However, it is widely accepted that cellular changes or transformations at a cellular level can lead to the development of neoplasms. Specifically with uveal melanoma, most cases demonstrate monosomy within chromosome 3. Monosomy is the presence of one chromosome from a pair in contrast to the two chromosomes that form a pair in diploid cells.⁴  Amplification of chromosome 8q is also accepted as being a precursor to the development of uveal melanoma. Over-expression of this chromosome promotes oncogenicity. Both cytogenetic aberrations are predictors of metastatic behaviour and generally lead to poor prognosis.⁴

Clinical presentation

Typically, uveal melanoma can be asymptomatic in the early stages. Due to its asymptomatic nature, uveal melanoma is often diagnosed during routine optical examinations. Uveal melanoma also occurs in the uvea - the middle lining of the eye which cannot be seen without using optical equipment. However, signs and symptoms of uveal melanoma also will need differential diagnoses as they can be caused by other conditions.

The list below contains some common signs and symptoms as identified by the National Cancer Institute (US):

• Change in vision - blurred/distorted vision or blind spots
• Dark spots on the iris
• Changes in the pupil’s size or shape
• Floaters in field of vision
• A sensation of flashing lights in field of vision

As aforementioned, these signs and symptoms can also be typical of other conditions so it is important to get any of these assessed by a doctor or health professional. 

Diagnostic evaluation

Due to the non-specific nature of the clinical presentation of uveal melanoma, diagnosis solely relies on ophthalmic examination by dilating the eye. According to the American Academy of Ophthalmology, if uveal melanoma is suspected, the recommendation is to order an ultrasound examination of the eye. The ultrasound will produce an image of the internal eye, which is then used to determine the size of the melanoma. 

A fluorescein angiography is another diagnostic tool which is used to determine if there is any leakage from the uveal melanoma into the surrounding regions, or if it has caused any blockage. 

An optical coherence tomography may also be ordered (more commonly known as an OCT scan) - which produces a highly detailed image of the internal eye. This is most commonly used in routine eye examinations with an optician. A biopsy may be considered but is not typically necessary to diagnose uveal melanoma.

Treatment options

After uveal melanoma is diagnosed, the stage of disease is determined using various diagnostic tools. The staging process is important as it aids in treatment decision-making. The size of the melanoma is an important factor that is also used to determine the treatment option. Thus, overall treatment depends on the size and location of the uveal melanoma.¹ Overall, treatment options for uveal melanoma generally fall into two categories: surgery or radiotherapy. In some cases, a combination of treatments may be used.

Typically, a small tumour will be treated by radiotherapy methods. The National Cancer Institute defines a small tumour as anywhere between 5 to 16 millimetres in diameter and 1 to 3 millimetres in thickness.  For smaller tumours, a type of radiation therapy is used to only target the site of the melanoma whilst preserving the surrounding tissue. This is referred to as ruthenium plaque radiotherapy and has a high success rate.

For the smallest tumours, a local resection i.e. surgical removal of the melanoma is possible. In such cases, ruthenium plaque radiotherapy is used after the surgical removal of the melanoma. Enucleation is the complete removal of the eye. This option is only considered if the melanoma has shown metastatic growth into surrounding tissues and if it is too large to treat with radiotherapy. For uveal melanomas on the surface of the eye, it is possible to treat this with chemotherapy eye drops or radiotherapy. Generally, these tumours tend to be quite small thus can be treated with no to slight complications.¹

Prognosis and follow-up

The long-term prognosis of uveal melanoma with malignancy is poor, with over 50% of cases resulting in fatality. Improved prognosis is observed with early detection of uveal melanoma, as it allows for early treatment and control over metastasis whilst it is still small in size. This type of tumour is associated with a high risk for metastasis, with the most common sites affected being the liver, lung and bone respectively. Thus, the survival rate for malignant uveal melanoma is estimated between 6 to 12 months.²

Summary

Although rare in incidence, it is still important to report any changes within the eye whether it is vision changes or sudden pain. Despite poor prognostic factors, if symptoms are reported early then early detection and treatment can lead to a long-term survival rate. Symptoms related to uveal melanoma can also be non-specific and can be the cause of other underlying conditions thereby it is very important to keep up with regular optical tests as it is during these visits that some cases of uveal melanoma have been reported early in its disease progression.