Uveal Melanoma: Causes, Types, Symptoms, Diagnosis, Staging, Treatment, Management and Prognosis

Uveal Melanoma: Causes, Symptoms, Diagnosis, Treatment, and Prognosis

Uveal Melanoma is a rare but aggressive form of eye cancer that develops from melanocytes within the uveal tract of the eye. Although it represents a small fraction of all melanoma cases, uveal melanoma is the most common primary intraocular malignancy in adults. Due to its subtle early symptoms and potential for distant metastasis—especially to the liver—early detection and specialized care are critical.

This article provides an in-depth, SEO-optimized overview of uveal melanoma, covering its causes, risk factors, symptoms, diagnosis, staging, treatment options, prognosis, and recent advances in research.

~What Is Uveal Melanoma?

Uveal melanoma is a malignant tumor that arises from pigment-producing cells (melanocytes) in the uvea, the middle layer of the eye. The uvea consists of three parts:

1. Iris – the colored front part of the eye

2. Ciliary body – produces aqueous humor and helps focus the lens

3. Choroid – a vascular layer supplying blood to the retina

Among these, choroidal melanoma accounts for approximately 85–90% of uveal melanoma cases, making it the most common subtype.

~How Common Is Uveal Melanoma?

Uveal melanoma is considered rare, with an incidence of approximately 5–6 cases per million people per year. It is more commonly diagnosed in:

• Adults between 50 and 70 years of age

• Individuals of Caucasian descent

• People with lighter eye color (blue or green)

Unlike cutaneous melanoma, uveal melanoma is not strongly linked to ultraviolet (UV) light exposure, though research is ongoing.

~Causes and Risk Factors of Uveal Melanoma

The exact cause of uveal melanoma remains unclear, but several risk factors have been identified.

Key Risk Factors

• Light eye color (blue, green, or gray)

• Fair skin

• Older age

• Genetic mutations, particularly in the GNAQ and GNA11 genes

• Ocular melanocytosis (increased pigmentation in the eye)

• Dysplastic nevus syndrome

• Family history of uveal melanoma (rare but possible)

Unlike skin melanoma, uveal melanoma is not commonly associated with BRAF mutations or sunburn history.

~Types of Uveal Melanoma

Uveal melanoma is classified based on its location within the uveal tract:

1. Choroidal Melanoma

• Most common subtype

• Often asymptomatic in early stages

• Detected during routine eye exams

2. Ciliary Body Melanoma

• Less common but more aggressive

• Often diagnosed at a later stage

• Higher risk of metastasis

3. Iris Melanoma

• Least aggressive form

• Usually detected early due to visible changes

• Better prognosis compared to other types

~Signs and Symptoms of Uveal Melanoma

Many patients with uveal melanoma experience no symptoms in early stages, which is why regular eye examinations are essential.

Common Symptoms

• Blurred or decreased vision

• Flashes of light

• Floaters (dark spots or squiggly lines)

• Visual field loss

• Change in pupil shape

• Dark spot on the iris (in iris melanoma)

• Eye pain or redness (less common)

Symptoms typically appear when the tumor grows large enough to affect the retina or optic nerve.

~Diagnosis of Uveal Melanoma

Uveal melanoma is usually diagnosed by an ophthalmologist or ocular oncologist through a combination of clinical examination and imaging studies.

Diagnostic Methods

1. Dilated Eye Examination

Allows visualization of the retina and choroid using specialized lenses.

2. Ultrasound (B-scan)

Measures tumor thickness and internal reflectivity.

3. Optical Coherence Tomography (OCT)

Provides high-resolution images of retinal layers.

4. Fundus Photography

Documents tumor size and appearance.

5. Fluorescein Angiography

Assesses tumor blood supply.

6. Fine-Needle Aspiration Biopsy (FNAB)

Used selectively for genetic and prognostic testing.

~Staging of Uveal Melanoma

Uveal melanoma is staged using the American Joint Committee on Cancer (AJCC) TNM system, which evaluates:

• T (Tumor size)

• N (Lymph node involvement)

• M (Metastasis)

Metastatic Spread

• Liver (most common, >90%)

• Lungs

• Bone

• Skin

Once metastasis occurs, prognosis significantly worsens, making early detection vital.

~Genetic and Molecular Features

Unlike cutaneous melanoma, uveal melanoma has a distinct genetic profile.

Key Genetic Mutations

• GNAQ and GNA11 – early driver mutations

• BAP1 loss – associated with high metastatic risk

• SF3B1 – intermediate prognosis

• EIF1AX – favorable prognosis

Gene Expression Profiling (GEP)

Tumors are classified into:

• Class 1 – low metastatic risk

• Class 2 – high metastatic risk

This molecular classification plays a crucial role in treatment planning and surveillance.

~Treatment Options for Uveal Melanoma

Treatment depends on tumor size, location, visual potential, and metastatic risk.

Eye-Preserving Treatments

1. Plaque Brachytherapy

• Most common treatment

• Radioactive plaque placed on the eye

• Effective for small to medium tumors

2. Proton Beam Therapy

• Highly precise radiation

• Preserves surrounding tissues

3. Stereotactic Radiotherapy

• Delivers focused radiation in fewer sessions

4. Transpupillary Thermotherapy (TTT)

• Laser-based treatment for small tumors

• Often combined with radiation

Surgical Treatment

Enucleation

• Removal of the entire eye

• Reserved for large tumors or severe pain

• Does not improve survival but may relieve symptoms

~Management of Metastatic Uveal Melanoma

Metastatic uveal melanoma is challenging to treat, particularly due to liver involvement.

Treatment Options Include:

• Liver-directed therapies (embolization, radiofrequency ablation)

• Systemic immunotherapy

• Targeted therapy

• Clinical trials

Unlike cutaneous melanoma, checkpoint inhibitors show limited effectiveness, though newer therapies are improving outcomes.

~Prognosis and Survival Rates

Prognosis depends on tumor size, location, genetic profile, and metastatic status.

Key Prognostic Factors

• Tumor thickness and diameter

• Ciliary body involvement

• BAP1 mutation status

• Gene expression class

Survival Statistics

• 5-year survival (localized disease): ~80%

• 10-year risk of metastasis: up to 50%

• Median survival after metastasis: 6–12 months

Early diagnosis and molecular risk stratification significantly influence outcomes.

~Follow-Up and Surveillance

Long-term monitoring is essential due to the risk of delayed metastasis.

Recommended Surveillance

• Liver imaging (MRI or ultrasound)

• Liver function tests

• Chest imaging

• Frequency based on genetic risk

High-risk patients may require imaging every 3–6 months.

~Advances and Research in Uveal Melanoma

Recent advances are reshaping the treatment landscape:

• Tebentafusp – first FDA-approved therapy shown to improve survival in metastatic uveal melanoma

• Personalized immunotherapy

• Novel liver-directed treatments

• Genetic risk-based surveillance strategies

Ongoing clinical trials offer hope for improved long-term outcomes.

~Living With Uveal Melanoma

A diagnosis of uveal melanoma can be emotionally and physically challenging.

Supportive Care Includes:

• Vision rehabilitation

• Psychological counseling

• Support groups

• Regular communication with oncology and ophthalmology teams

Early intervention and holistic care improve quality of life.

~Conclusion

Uveal melanoma is a rare but serious eye cancer with unique biological behavior and clinical challenges. While early-stage disease can often be managed with eye-preserving treatments, the risk of metastasis—especially to the liver—remains a major concern. Advances in genetic testing, targeted therapy, and immunotherapy are improving prognostic accuracy and survival outcomes.

Regular eye examinations, early diagnosis, and personalized treatment strategies remain the cornerstone of effective uveal melanoma management.