Ocular Melanoma

Ocular melanoma, or melanoma of the eye, is the most common primary eye tumor in adults and the 2nd most common melanoma (after cutaneous melanoma) with around 2,000 new cases diagnosed each year in the United States. Like other melanomas, it begins in melanocytes – the cells that produce the pigment melanin that colors the skin, hair, and eyes, as well as forms moles. 

Although sometimes these terms are used synonymously, they are, in fact, different. Here is a brief explanation: 

  • Uveal melanoma: The uvea is a three-layered part of the back of the eye. It is made up of the choroid, iris and ciliary body. Uveal melanoma can form in any of the three layers and is named for where it forms. Melanoma in the iris occurs in the front, colored part of the eye. Iris melanomas usually grow slowly and do not typically metastasize, or spread, to other parts of the body outside the eye. Ciliary body melanomas occur in the back part of the eye and are grouped by the size of the tumor. Melanomas in the ciliary body tend to grow and metastasize to the liver more quickly than iris melanomas. 
  • Choroidal melanoma: Choroidal melanoma is the most common subtype of uveal melanoma. Choroidal melanoma begins in the layer of blood vessels – the choroid – beneath the retina. You may be interested in 2012 article by the American Academy of Ophthalmology discussing the differences between choroidal nevi and choroidal melanoma.  

  • Conjunctival melanoma: Conjunctival melanoma is very rare. It often appears as a raised tumor and may contain little or even no pigment, or color. Conjunctival melanoma most commonly occurs in the bulbar conjunctiva – the mucous membrane that covers the outer surface of the eyeball. Unlike other forms of eyemelanoma that spread most often to the liver, when conjunctival melanoma spreads, it most often spreads to the lungs. 

Frequency, Incidence & Risk Factors

Melanoma of the skin increased in frequency over the last several decades, while such a trend is less evident with ocular melanoma. About 6 people per 1 million are diagnosed with eye melanoma in the U.S. every year, while invasive melanoma of the skin occurs in approximately 1 in 50 Americans each year. The incidence is similar in other Caucasian populations worldwide. According to a 2017 article published in Clinical Ophthalmology, melanoma of the eye accounts for approximately 3-5% of all melanomas.

A variety of risk factors have been identified, including light eyes, fair skin type, dysplastic nevus syndrome and the BAP1 mutation. The role of sun exposure as a risk factor for ocular melanoma remains unclear.

Melanoma of the eye tends to occur slightly more often in males than in females and overall risk tends to increase with age. 

Genetic Mutations in Ocular Melanoma

Melanoma is typically classified by clinical characteristics, such as depth, ulceration and site of origin. However, in the past several years, mutations in certain proteins are allowing scientists to further define the melanoma at the molecular level.

Ocular melanoma generally lacks the BRAF, NRAS and KIT mutations common in cutaneous melanoma. In addition to genetic profiling of the primary tumor, additional genes have recently been identified in ocular melanoma as being mutated. The most common mutations currently described in ocular melanoma are the GNAQ and GNA11 genes. About 50% of people will have the GNAQ mutation and around another 23% will have the GNA11 mutation.

BAP1 is also a common mutation. BAP1 is a tumor-supressor gene located on chromosome 3 and a 2010 study suggests that the BAP1 gene is mutated in almost half (47%) of ocular melanomas. The BAP1 mutation is strongly correlated with the development of metastases.

Researchers and specialists are currently working to fully understand the implications of these genetic mutations, and clinical trials are ongoing to identify systemic treatments to impact these mutated genes. Ocular melanoma has distinct genetic alterations and a strong tendency to metastasize (spread) to the liver.

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