Uveal melanoma is a rare but serious form of eye cancer that develops in the middle layer of the eye, known as the uvea. Though it accounts for only a small fraction of all melanoma cases, it remains the most common type of primary eye cancer in adults, affecting roughly 5 people per million each year.
Epidemiology
Uveal melanoma is not a common disease, but it holds the distinction of being the most frequent primary eye cancer diagnosed in adults. Across the United States, approximately 2,000 new cases are identified each year. The incidence, which refers to the number of new cases occurring in a given population, has remained relatively stable over the past three decades. This consistency has been observed not only in the United States but also in countries around the world, suggesting that the factors contributing to this disease have not changed dramatically in recent years.[1][6][8]
Globally, the mean age-adjusted incidence is about 5.1 cases per million people per year. However, these numbers vary significantly depending on geographic location and ethnic background. People of northern European descent, particularly those with fair skin, face a much higher risk compared to individuals from other ethnic groups. For instance, the incidence is notably low among Black populations, whether in Africa or among African Americans in the United States. Similarly, Asian populations and those of Hispanic descent show lower rates of uveal melanoma. In Europe, there is a north-to-south decreasing gradient in incidence, which suggests that lighter skin pigmentation, more common in northern regions, plays a protective role against this type of cancer.[6][8]
The disease typically affects middle-aged and older adults. Most cases are diagnosed in people during their sixth decade of life, with the median age at diagnosis being around 55 years. Incidence rates progressively increase with age, peaking around 70 to 75 years, after which they tend to reach a plateau. Both men and women are affected in roughly equal numbers, though some studies have reported a slight male predominance. When sex differences do appear, the age of diagnosis tends to be slightly older in women compared to men.[2][8]
Causes
The exact cause of uveal melanoma remains unclear in the vast majority of cases. Unlike skin melanoma, which is strongly linked to ultraviolet (UV) light exposure from the sun or tanning beds, uveal melanoma does not appear to have a direct association with environmental factors such as sun exposure. This distinction is important because it means that many of the lifestyle changes that reduce the risk of skin melanoma may not have the same protective effect against eye melanoma.[14][17]
However, recent advances in genetics have revealed that nearly all cases of uveal melanoma involve mutations in specific genes. The most commonly mutated genes are GNAQ (G protein subunit alpha Q) and GNA11 (G protein subunit alpha 11). These genetic changes appear to play a central role in the development of the tumor. Despite this knowledge, scientists still do not fully understand what triggers these mutations in the first place.[11]
A small percentage of uveal melanoma cases—approximately 2 to 3 percent—are linked to inherited genetic mutations. The most notable of these is a mutation in the BAP1 gene. Individuals who inherit this mutation may develop uveal melanoma at a younger age than the general population. Although these hereditary cases are rare, they highlight the importance of genetic factors in some families. It is important to note, however, that uveal melanoma does not typically “run in families,” and children, siblings, or parents of patients are almost always free from the condition.[8][14]
Risk Factors
Certain characteristics and conditions increase the likelihood that a person will develop uveal melanoma. Understanding these risk factors can help individuals and their doctors remain vigilant, though having one or more risk factors does not guarantee that the disease will occur.
The most significant risk factor is having a fair complexion. This includes fair skin that freckles and burns easily, as well as light-colored eyes such as blue, green, or gray. People who have difficulty tanning or who tan poorly are also at higher risk. These features are more common among individuals of northern European ancestry, which explains the higher incidence rates observed in these populations. Being White, in general, increases the risk of developing uveal melanoma compared to people of other racial or ethnic backgrounds.[4][10]
Age is another important factor. Uveal melanoma is rare in children and young adults. The risk increases steadily as people grow older, with most cases occurring in individuals aged 50 or above. This age-related pattern suggests that cumulative factors over a lifetime may contribute to the disease, even if the exact triggers remain unknown.[2][8]
Certain pre-existing conditions in the eye can also raise the risk. People with ocular melanocytosis—a condition where extra pigment cells are present in the eye, leading to a darker appearance or heterochromia (different-colored eyes)—are at increased risk. Similarly, individuals with choroidal nevi, which are benign moles or freckles on the inside of the eye, may see those lesions transform into melanoma over time. Other risk factors include cutaneous or iris nevi and a rare genetic condition involving the BAP1 gene.[6][8]
While smoking has been identified as a risk factor that increases the likelihood of developing ocular melanoma, the relationship between lifestyle habits and uveal melanoma remains less clear than for other cancers.[14]
Symptoms
One of the most challenging aspects of uveal melanoma is that it often does not cause any noticeable symptoms, especially in the early stages. Many people discover they have the disease only during a routine eye examination, when an eye doctor dilates the pupil and examines the inside of the eye. This makes regular eye check-ups especially important for individuals with risk factors.[1][4][13]
When symptoms do occur, they can vary depending on the size and location of the tumor. Common symptoms include blurred vision or other changes in vision. Some people experience a gradual loss of vision in one eye, which may be partial or, in advanced cases, complete. Others notice a dark spot appearing on the iris, which is the colored part of the eye visible when looking in a mirror. This dark spot may grow over time.[1][4]
Visual disturbances are another key symptom. Patients may see flashes of light, even when no light source is present, or they may notice floaters—small specks or threads that appear to drift across their field of vision. These floaters are caused by changes inside the eye that affect how light is processed. Some individuals report seeing a curtain or shadow that blocks part of their peripheral (side) vision, which can be alarming and interfere with daily activities such as driving or reading.[2][5]
In certain cases, the tumor causes changes in the shape of the pupil, the dark circle at the center of the eye. The pupil may become irregular or distorted. If the tumor is large or located near the front of the eye, it can cause the eye to bulge outward, a condition known as proptosis. Less commonly, patients experience redness, irritation, or pain in the affected eye. However, most cases of uveal melanoma are not painful, which is why many people do not realize anything is wrong until an eye doctor detects the tumor.[1][2][5]
It is important to remember that these symptoms can also be caused by other, less serious eye conditions. However, if you notice any sudden or persistent changes in your vision or eye appearance, it is essential to see an eye care professional as soon as possible. Early detection can make a significant difference in the outcome of treatment.[1][13]
Prevention
Because the exact cause of uveal melanoma is not well understood and the disease is not directly linked to environmental factors like sun exposure, there are no guaranteed ways to prevent it. Unlike skin melanoma, where avoiding UV light and using sunscreen can significantly reduce risk, uveal melanoma develops inside the eye where such protective measures have little to no effect.[17]
That said, reducing exposure of the eyes to UV light may still offer some benefit. Wearing sunglasses that block UV rays when outdoors, especially in bright sunlight, is a sensible precaution that also protects against other eye conditions such as cataracts and macular degeneration. However, it is important to understand that this step alone will not eliminate the risk of uveal melanoma.[4]
The most effective form of prevention is early detection through regular eye examinations. For individuals with fair skin, light-colored eyes, or a history of ocular melanocytosis or choroidal nevi, routine eye exams with pupil dilation are especially important. During these exams, an eye doctor can look inside the eye and spot any suspicious changes before symptoms develop. Early detection allows for earlier treatment, which may improve outcomes and reduce the risk of the cancer spreading to other parts of the body.[1][13]
For the small number of individuals who have an inherited BAP1 gene mutation, genetic counseling and regular monitoring are recommended. Family members of patients with uveal melanoma may also benefit from screening, although the disease rarely runs in families.[8][14]
Pathophysiology
To understand how uveal melanoma affects the body, it helps to know a bit about the structure of the eye. The eye has three main layers. The outer layer includes the white part of the eye, called the sclera, and the clear front surface known as the cornea. The inner layer contains the retina, a thin sheet of nerve tissue that senses light and sends visual signals to the brain via the optic nerve. The middle layer, where uveal melanoma develops, is called the uvea or uveal tract.[4][10]
The uvea has three main parts. The iris is the colored portion at the front of the eye that controls the size of the pupil and regulates how much light enters. Behind the iris is the ciliary body, a ring of tissue with muscles that adjust the shape of the lens to help the eye focus. The ciliary body also produces the clear fluid that fills the space between the cornea and the iris. The third part, the choroid, is a layer of blood vessels that supplies oxygen and nutrients to the eye. Most uveal melanomas—about 90 percent—develop in the choroid. The remaining cases occur in the ciliary body (about 6 percent) or the iris (about 4 percent).[1][2][4]
Uveal melanoma begins when melanocytes, the pigment-producing cells in the uvea, undergo genetic changes that cause them to grow and divide uncontrollably. These cells form a tumor that can grow larger over time. Tumors in the iris tend to be smaller and grow more slowly. They are also less likely to spread to other parts of the body. In contrast, tumors in the ciliary body or choroid are often larger and carry a higher risk of metastasis, which is the spread of cancer cells to distant organs.[2][4][10]
As the tumor grows, it can cause physical and biochemical changes inside the eye. The tumor may push against the retina, causing it to detach or distort, which leads to vision problems. The blood vessels in the choroid can become damaged, affecting the eye’s ability to receive nutrients and oxygen. If the tumor is large enough, it may block light from reaching the retina or interfere with the shape of the pupil. These mechanical disruptions explain many of the symptoms that patients experience, such as blurred vision, floaters, and changes in pupil appearance.[1][5]
One of the most concerning aspects of uveal melanoma is its tendency to spread to other parts of the body. More than 50 percent of patients eventually develop metastases, most commonly in the liver. This spread often occurs even before the primary tumor in the eye is detected, a phenomenon known as micrometastasis. Cancer cells break away from the tumor and travel through the bloodstream to distant organs, where they begin to grow. Once the cancer has spread, it becomes much more difficult to treat, and the prognosis becomes significantly more guarded. Despite advances in treating the tumor inside the eye, long-term survival rates remain a concern due to this high risk of metastasis.[2][6][8]
Recent research has shed light on the genetic and molecular mechanisms that drive uveal melanoma. Mutations in genes such as GNAQ and GNA11 are present in nearly all cases. These mutations cause abnormal signaling pathways inside the cells, leading to uncontrolled growth. Additionally, changes in chromosomes and other genetic markers can help predict which tumors have a high risk of spreading. Tumor biopsy and genetic testing are now being used to classify tumors into low-risk and high-risk categories, which helps guide treatment decisions and monitoring plans.[6][11]
