Uveal melanoma – Diagnostics – Overview of Information and Clinical Research

Uveal melanoma is a rare eye cancer that develops in the middle layer of the eye called the uvea, which includes the iris, ciliary body, and choroid. Although it may not cause symptoms in its early stages, proper diagnostic evaluation is essential for identifying the disease, determining its extent, and guiding treatment decisions.

Introduction: Who Should Undergo Diagnostics

Many people with uveal melanoma discover they have this condition without experiencing any symptoms at all. Because this type of eye cancer often develops silently, regular eye examinations become particularly important for early detection. The best way to screen for uveal melanoma is through a routine eye exam with pupil dilation, which is a procedure where the doctor uses special drops to widen the pupil so they can see deep inside the eye.^[1]

If you notice any changes in your vision or eye health, it’s important to see an eye doctor right away. Symptoms that should prompt a visit include blurred vision or sudden loss of vision in one eye, dark spots appearing on the iris (the colored part of your eye), changes in the shape or size of your pupil, flashes of light, floating spots in your vision that look like specks of dust, a bulging eye, or pain and redness in the eye.^[1]^[4] However, these symptoms can also be caused by many other eye conditions that are not cancer, so experiencing them doesn’t necessarily mean you have uveal melanoma.

People with certain characteristics may benefit from more frequent eye examinations. Those with fair skin that freckles and burns easily, light-colored eyes such as blue or green, and those who are White—especially of northern European descent—face higher risk for this disease.^[4]^[6] Older age also increases risk, as uveal melanoma typically affects people in their 60s.^[8] Additionally, individuals with certain pre-existing eye conditions, such as ocular or oculodermal melanocytosis (unusual pigmentation in the eye or surrounding skin), or those with choroidal nevi (sometimes called eye freckles), should be monitored more closely.^[6]

⚠️ Important

Even if you have no symptoms, uveal melanoma can still be present and growing in your eye. Regular comprehensive eye exams with dilation are the most effective way to catch this disease early, when it may be easier to treat. Don’t wait for symptoms to appear before scheduling your routine eye checkup.

Diagnostic Methods for Identifying Uveal Melanoma

When uveal melanoma is suspected, eye doctors use a variety of methods to confirm the diagnosis and understand the characteristics of the tumor. Unlike many other types of cancer, a biopsy—which is the removal of a tissue sample for examination—is rarely needed to diagnose uveal melanoma. Instead, doctors can usually make a confident diagnosis based on a thorough eye examination combined with imaging tests.^[4]^[11]

Eye Examination

The diagnostic process typically begins with a comprehensive eye exam. First, the doctor may examine the outside of the eye, looking for enlarged blood vessels or other unusual features. Then they will use special equipment to look inside your eye after dilating your pupils.^[15] One common technique is called binocular indirect ophthalmoscopy, where the doctor wears a special light on their forehead and uses lenses to see the back of your eye. Another method is slit-lamp biomicroscopy, which uses a microscope with an intense beam of light to examine the eye’s structures in detail.^[4]

During these examinations, the doctor can often see the tumor directly and evaluate its location and appearance. Uveal melanoma can develop in three different parts of the uvea: the iris (the colored front part of the eye), the ciliary body (a ring of tissue behind the iris), or the choroid (the layer of blood vessels at the back of the eye). About 90% of uveal melanomas develop in the choroid, making it the most common location. The ciliary body accounts for about 6% of cases, while the iris is affected in only about 4% of cases.^[1]^[6]

Imaging Tests

Several imaging techniques help doctors see the tumor more clearly and measure its size. Fundus photography takes detailed color pictures of the inside surface of your eye, which can show the melanoma and help doctors track any changes over time.^[14]^[15] Different types of fundus photography exist, including one called fundus autofluorescence, which can provide additional information about the tumor.

Eye ultrasound is another important diagnostic tool that uses high-frequency sound waves to create images of structures inside your eye. During this test, the doctor places a small device that looks like a wand either on your closed eyelid or directly on the front surface of your eye after numbing it. This test is particularly helpful because it can show the tumor’s dimensions—its length, width, and height—which is important for planning treatment.^[15]

Optical coherence tomography (OCT) is an advanced imaging technique that provides detailed cross-sectional images of the eye’s layers. This test can show how the tumor affects the surrounding tissues and is especially useful for examining tumors that affect the macula, which is the central part of the retina responsible for sharp, detailed vision.^[14]

Angiography tests examine the blood vessels in your eye. During these tests, a colored dye is injected into a vein in your arm, and as it travels to the blood vessels in your eye, a special camera takes pictures every few seconds. There are different types of angiography, including fluorescein angiography and indocyanine green angiography, which use different dyes to highlight different aspects of the tumor’s blood supply.^[14]^[15] These tests help doctors understand the tumor’s characteristics and distinguish it from other conditions.

Tumor Sizing and Classification

Once uveal melanoma is identified, doctors measure and classify the tumor based on its size. This process, called staging, helps determine the extent of the disease and guides treatment decisions. Doctors typically categorize tumors into five groups: small, medium, large, extra-large, and a special category for borderline small tumors called atypical nevi.^[14] The size classification is important because it affects which treatment options are most appropriate for each patient.

It’s worth noting that many people have small, flat pigmented spots in their eyes called choroidal nevi, which are like freckles inside the eye. These occur in approximately 20% of the population and are typically harmless. However, certain characteristics—such as increasing thickness—may suggest that a nevus has a higher chance of developing into melanoma, which is why doctors monitor them over time.^[14]

Distinguishing Uveal Melanoma from Other Conditions

Because several other eye conditions can look similar to uveal melanoma, doctors must carefully distinguish the cancer from other possibilities. For tumors in the choroid, other conditions to consider include benign choroidal nevi, tumors that have spread to the eye from cancer elsewhere in the body (metastatic tumors), choroidal hemangioma (a benign blood vessel tumor), bleeding conditions, and inflammatory diseases.^[2] For iris tumors, the doctor must rule out iris nevi, various types of cysts, and other conditions. This is why a thorough examination using multiple diagnostic techniques is so important.

Diagnostics for Clinical Trial Qualification

For patients considering participation in clinical trials, additional diagnostic procedures may be required beyond those used for standard diagnosis. Clinical trials are research studies that test new treatments or approaches to managing uveal melanoma, and they often have specific criteria that patients must meet to enroll.

Tumor Biopsy and Genetic Testing

While a biopsy is rarely needed to diagnose uveal melanoma initially, it may be performed during or after treatment to obtain tumor tissue for genetic analysis. This tissue sample allows scientists to study the tumor’s genetic mutations—changes in the DNA of cancer cells that can affect how the disease behaves.^[11]^[14] Research has shown that nearly every case of uveal melanoma involves mutations in certain genes, most commonly GNAQ or GNA11.^[11]

Genetic testing of the tumor can reveal important information about the risk of the cancer spreading (metastasizing) to other parts of the body. Tumors can be classified into different risk categories based on their genetic characteristics. For example, tumors are sometimes divided into “class I” (lower metastatic risk) and “class II” (higher metastatic risk) based on their genetic profile.^[2] This information helps patients and doctors understand the likely behavior of the disease and can influence decisions about monitoring and treatment.

Some clinical trials specifically require genetic testing results as part of their enrollment criteria. The genetic characteristics of a tumor may determine whether a patient is eligible for trials testing treatments that target specific molecular pathways. This means that understanding your tumor’s genetic makeup not only provides information about prognosis but may also open doors to innovative treatment options through clinical trial participation.

Metastatic Screening

Before enrolling in certain clinical trials, especially those involving surgery or testing treatments for advanced disease, patients typically need screening tests to determine whether the cancer has spread beyond the eye. Uveal melanoma most commonly spreads to the liver, so imaging tests of the liver and other organs may be required.^[14] These screening procedures help doctors fully understand the extent of disease and ensure that the clinical trial is appropriate for each patient’s situation.

Additional Assessments

Clinical trials may require additional tests to ensure patient safety during the study. For instance, if surgery is planned as part of the trial, patients might need tests to confirm they are healthy enough for the procedure. Blood tests, heart function tests, and other general health assessments may be part of the pre-enrollment evaluation. Each clinical trial has its own specific requirements, and the research team will clearly explain what tests are needed and why.

⚠️ Important

Participating in a clinical trial is a personal decision that should be made carefully with your medical team. While clinical trials offer access to cutting-edge treatments and contribute to advancing medical knowledge, they also involve additional testing and monitoring. Your doctors can help you understand whether a clinical trial might be right for your specific situation.

Prognosis and Survival Rate

Prognosis

The outlook for patients with uveal melanoma depends on several factors. One of the most important is the location and size of the tumor. Melanomas of the iris tend to grow slowly and rarely spread to other parts of the body, which generally means a better prognosis. In contrast, melanomas of the ciliary body and choroid are more likely to spread and therefore carry a more serious prognosis.^[4]^[10] Available treatments for the eye tumor itself—including radiation therapy and surgical removal of the eye—are usually successful at controlling the cancer in the eye. However, the major challenge with uveal melanoma is that in many patients, microscopic cancer cells have already begun to spread through the bloodstream before the eye tumor is diagnosed, even though they cannot yet be detected by standard tests.^[2]

More than 50% of patients with uveal melanoma will eventually develop metastatic disease, meaning the cancer spreads to distant organs, most commonly the liver.^[2]^[6] Several factors help predict the risk of metastasis. These include the tumor’s size (larger tumors carry higher risk), its genetic characteristics (certain gene mutations indicate higher metastatic potential), and the specific cells that make up the tumor when examined under a microscope. Understanding these risk factors helps doctors develop appropriate monitoring plans for each patient and may identify candidates for clinical trials testing new approaches to prevent or treat metastatic disease.

Survival Rate

Despite advances in treating the eye tumor itself, long-term survival rates for uveal melanoma patients have remained relatively unchanged over the past three decades.^[6]^[8] This is primarily because the development of metastases significantly affects survival. When uveal melanoma spreads to distant parts of the body, particularly the liver, the five-year survival rate drops to approximately 15%.^[2] This sobering statistic highlights an important unmet medical need: while doctors can effectively treat the tumor in the eye, preventing or treating metastatic disease remains a major challenge. Researchers continue working to develop better treatments for metastatic uveal melanoma and to find ways to prevent the cancer from spreading in the first place. There is growing evidence that early detection through regular screening and prompt treatment of small tumors may lead to better outcomes, offering hope that survival rates could improve as more tumors are caught and treated at earlier stages.^[6]