Ocular Melanoma

Diagnosis (Ocular)

How is Ocular Melanoma Diagnosed?

Ocular melanoma (OM) is usually diagnosed by an optometrist or an ophthalmologist during a dilated eye exam. Often, OM is asymptomatic until the tumor grows large enough to create visual disturbances. Only OM of the iris can be diagnosed by external – from the outside – examination.

When OM is diagnosed, your doctor may want to take an X-ray, MRI or CT scan of the body to be sure the primary tumor has been diagnosed correctly. And, conversely, your doctor may be sure of the OM diagnosis and may want to take the above scans to be sure that the melanoma hasn’t spread.

Unlike other forms of melanoma, a biopsy is not usually taken to diagnose OM. Rather, OM tends to be a clinical diagnosis – meaning it is often made based on signs and symptoms.

If you or a loved one have been diagnosed with OM, or to learn more about OM research, treatment and support resources, please visit the MRF’s CURE Ocular Melanoma (CURE OM) initiative.

Genetic Testing, Tumor Size and Metastatic Risk

Once ocular melanoma is diagnosed, several items should be discussed with your treatment team that will help everyone learn more about your specific diagnosis. While treating the primary eye tumor remains the most important clinical issue, determining a patient’s risk for developing metastatic disease is also important.

One way that healthcare providers determine a patient’s risk for metastases is to test the genes in the tumor. The results of these genetic tests can help your treatment team develop an appropriate and individualized surveillance plan and, if necessary, a treatment plan. Timing is critical because:

  • These genetic tests come from a biopsy of the tumor.
  • The biopsy must be taken before the tumor is treated with radiation.

Currently, the most common genetic tests in ocular melanoma are:

Genetic Expression Profile (GEP) Testing

This test measures the gene expression profile (GEP), or molecular signature, of the tumor. It is based on a 15-GEP test and groups the tumor into low-, medium- or high-risk for metastases over the next five years.

  • Class 1A tumors have a very low risk of metastasis
  • Class 1B tumors have an intermediate risk of metastasis
  • Class 2 tumors have a high risk of metastasis

Prognostic Genetic Testing

This test examines the DNA of the tumor, tumor histology (how it looks under the microscope) and patient demographic information to produce a personalized prediction of metastatic risk. Results are categorized into low- and high-risk.

  • Low-risk tumors suggest a low risk for the development of metastasis
  • High-risk tumors suggest a high risk for the development of metastasis

Should I have my tumor tested?

Studies have shown that, if given the opportunity, most patients prefer to know their risk. Patients often feel that they can make more informed decisions and have reported that knowing the results of the genetic test were valuable regardless of the results. Ultimately, the hope with genetic testing is that individual clinical follow-up can be tailored to a patient’s risk of metastasis and, perhaps, lead to earlier detection and therapy.

As with any genetic testing, this is a personal decision and many factors must be considered. In addition to your treatment team, speaking with a certified genetic counselor may also be helpful.

Tumor Size

The size of the eye tumor may also impact the prognosis and risk of metastasis. For example, a large tumor has a higher risk of spreading than a small tumor.

  • Small: 1.0-2.5mm in height; greater than 5mm at the base
  • Medium: 2.5-10mm in height; less than or equal to 16mm at the base
  • Large: greater than 10mm in height; greater than 16mm at the base

Genetic Mutations in Ocular Melanoma

Although there are currently no therapies approved by the FDA for the treatment of metastatic OM, several are being studied in clinical trials. Therefore, knowing your mutation status may be helpful.  A variety of genetic mutations have been found in OM. These mutations are thought to “drive” the disease:

  • GNAQ and GNA11  The GNAQ and GNA11 mutations are the most common mutations in ocular melanoma, appearing in more than 80% of all cases. These mutations do not seem to be associated with patient outcomes or risk of metastasis.
  • BAP1  The BAP1 mutation is found in about half of uveal melanoma cases. It is most often associated with older patient age and high risk for metastasis. The BAP1 mutation is strongly associated with a Class 2 gene expression profile (GEP).
  • BRAF – The BRAF mutation is common in cutaneous melanoma but is rare in OM

What does this mean for ocular melanoma treatment?

Currently, this does not impact treatment for primary OM. These results may impact surveillance and/or adjuvant therapy available in clinical trials.