Overview
Ocular melanoma (also called uveal melanoma) is a malignant tumor that originates from melanocytes, the pigment‑producing cells, within the eye. It most commonly arises in the uvea—the pigmented middle layer of the eye that includes the iris, ciliary body, and choroid. Although it accounts for only about 5% of all melanomas and less than 1% of all eye cancers, ocular melanoma is the most common primary intra‑ocular malignancy in adults.
- Who it affects: Primarily adults between the ages of 40 and 70. Men are slightly more likely than women to develop the disease (approximately 1.3 : 1 ratio).
- Prevalence: In the United States, an estimated 2,500 new cases are diagnosed each year, translating to an incidence of about 0.5–0.7 per 1 million people.1 Rates are higher in people of Caucasian descent with light eye color and are less common among Asian, African, and Hispanic populations.
Symptoms
Early ocular melanoma often produces no noticeable signs, which is why routine eye examinations are crucial. When symptoms do appear, they can involve one or both eyes and may mimic more benign conditions.
- Visual disturbances – sudden or gradual blurring, decreased visual acuity, or a central “spot” in the line of sight (scotoma).
- Flashes of light (photopsia) especially when looking at a bright background.
- Floaters – dark spots or cobweb‑like shapes that move with eye movement.
- Change in eye color – a subtle darkening of the iris or a visible dark patch on the sclera.
- Pain or pressure – uncommon, but may occur if the tumor grows large enough to affect intra‑ocular pressure.
- Redness or irritation – usually mild; can be mistaken for conjunctivitis.
- Bulging of the eye (proptosis) – rare; suggests orbital extension of the tumor.
- Double vision (diplopia) – when the tumor invades structures that control eye movement.
Causes and Risk Factors
Unlike cutaneous melanoma, which is strongly linked to UV exposure, the exact cause of ocular melanoma remains unclear. Several genetic and environmental factors appear to increase risk.
Genetic factors
- Mutations in the BAP1 gene (BRCA1‑associated protein 1) significantly raise the lifetime risk of uveal melanoma and other cancers.2
- GNAQ and GNA11 somatic mutations are found in >80% of tumors, driving uncontrolled cell growth.
- Family history of melanoma (cutaneous or uveal) modestly increases risk.
Phenotypic risk factors
- Light eye color (blue, gray, green) – less melanin provides less protection.
- Freckles or a high number of cutaneous nevi.
- Presence of a congenital ocular nevus (a pigmented birthmark of the eye).
Environmental & lifestyle factors
- Chronic exposure to ultraviolet or visible light may play a contributory role, although evidence is weaker than for skin melanoma.
- Occupational exposure to welding arcs or intense infrared radiation has been associated with a small increased risk.
Demographic factors
- Age > 40 years (median age at diagnosis ≈ 58).
- Male sex.
- Caucasian ethnicity.
Diagnosis
Prompt, accurate diagnosis relies on a combination of clinical examination and imaging studies. The goal is to confirm malignancy, determine tumor size and location, and rule out metastasis.
Clinical eye exam
- Slit‑lamp biomicroscopy – provides a magnified view of the anterior segment (iris, ciliary body).
- Indirect ophthalmoscopy – visualizes the posterior segment (choroid, retina). The tumor often appears as a raised, pigmented, dome‑shaped lesion.
Imaging modalities
- Ultrasound B‑scan – measures thickness, internal reflectivity, and vascularity; a hallmark is low to medium internal reflectivity. <
- Optical Coherence Tomography (OCT) – high‑resolution cross‑sectional images; useful for lesions affecting the macula.
- Fundus fluorescein angiography (FFA) – highlights abnormal blood vessels.
- Magnetic Resonance Imaging (MRI) – assesses extra‑ocular extension and detects orbital or brain involvement.
Pathology
Fine‑needle aspiration biopsy (FNAB) or trans‑scleral biopsy may be performed when imaging is inconclusive. Cytology and molecular testing (e.g., BAP1 immunostaining) guide prognosis and therapy.
Systemic staging
Because 15–20% of patients present with metastasis (most often to the liver), baseline staging includes:
- Contrast‑enhanced CT of the chest, abdomen, and pelvis.
- MRI of the liver or a dedicated hepatic ultrasound.
Treatment Options
Treatment is individualized based on tumor size, location, visual potential, and the patient’s overall health. Options range from eye‑preserving therapies to enucleation (removal of the eye).
Eye‑saving procedures
- Plaque brachytherapy – a small radioactive disc (usually I‑125 or Ru‑106) is sutured to the sclera over the tumor for 3–7 days. Provides excellent local control (≈ 95% at 5 years) while preserving the eye in most cases.3
- External beam radiation therapy (EBRT) – includes proton beam or stereotactic radiosurgery (Gamma Knife, CyberKnife). Particularly useful for tumors near critical structures where plaque placement is difficult.
- Transpupillary thermotherapy (TTT) – uses infrared laser to deliver heat directly to the tumor; usually combined with brachytherapy.
- Local surgical resection – “partial lamellar sclerouvectomy” removes the tumor through the sclera. Reserved for select, accessible lesions.
Enucleation
Complete removal of the globe is indicated for very large tumors (> 15 mm thickness), those causing painful blind eye, or when there is extra‑ocular extension. Cosmetic rehabilitation with an orbital implant and prosthesis follows.
Systemic therapies for metastatic disease
- Immunotherapy – checkpoint inhibitors (nivolumab, pembrolizumab) have shown activity, though response rates are lower than in cutaneous melanoma.
- Targeted therapy – agents against the MAPK pathway (MEK inhibitors such as trametinib) are under investigation.
- Clinical trials – enrollment in trials exploring novel agents (e.g., adoptive T‑cell therapy) is encouraged.
Lifestyle & supportive care
- Smoking cessation – improves overall health and may enhance response to systemic therapy.
- Balanced diet rich in antioxidants (berries, leafy greens) to support ocular health.
- Regular ophthalmology follow‑up to monitor for radiation‑induced cataract, glaucoma, or recurrence.
Living with Ocular Melanoma
Adapting to life after diagnosis involves physical, emotional, and practical considerations.
Vision rehabilitation
- Low‑vision aids (magnifiers, high‑contrast reading glasses) can maximize remaining sight.
- Occupational therapy helps with daily tasks such as driving, computer use, and reading.
Psychological support
- Joining support groups (e.g., Melanoma Research Foundation) reduces isolation.
- Consider counseling or cognitive‑behavioral therapy to manage anxiety about recurrence.
Follow‑up schedule
After definitive treatment, most specialists recommend:
- Every 3–4 months for the first 2 years (clinical exam + ocular imaging).
- Every 6–12 months thereafter, plus annual liver imaging (MRI or ultrasound) for at least 10 years because metastasis can appear late.
Practical tips
- Wear UV‑blocking sunglasses with 100% UVA/UVB protection to reduce photo‑damage.
- Use a hat with a wide brim when outdoors.
- Maintain good control of systemic conditions (diabetes, hypertension) that may affect eye health.
Prevention
Because many risk factors (age, genetics) are non‑modifiable, prevention focuses on reducing environmental exposures and promoting early detection.
- Sun protection – broad‑spectrum sunglasses and hats; avoid looking directly at the sun.
- Regular eye examinations – at least once every 2 years after age 40, or annually for high‑risk individuals (light‑colored eyes, family history).
- Self‑monitoring – note any new visual changes and report them promptly.
- Genetic counseling – for families with known BAP1 mutations or multiple melanoma cases.
Complications
If left untreated or inadequately managed, ocular melanoma can lead to serious outcomes.
- Local complications – loss of vision, cataract, radiation‑induced optic neuropathy, secondary glaucoma, and, in advanced cases, painful blind eye.
- Metastatic spread – the liver is the most common site (up to 95% of metastases), followed by lungs and bone. Metastatic disease carries a 5‑year survival of ~15% despite modern therapy.4
- Psychosocial impact – anxiety, depression, and reduced quality of life are reported in up to 30% of patients.
When to Seek Emergency Care
- Sudden, severe eye pain or pressure that does not improve with rest.
- Rapid loss of vision in one eye (e.g., “blackout” or “curtain” effect).
- Sudden appearance of flashes, floaters, or a large dark spot accompanied by headache.
- Signs of orbital cellulitis – swelling, redness, fever, and limited eye movement.
- Any trauma to the eye that results in bleeding, discharge, or vision change.
Sources:
- SEER Cancer Statistics Review, National Cancer Institute. Uveal Melanoma Statistics. Accessed 2024.
- Carvajal RD, et al. “Frequent mutation of BAP1 in metastasizing uveal melanoma.” Science. 2015;348(6230):1459‑1463. PMCID: PMC4471887.
- Cleveland Clinic. “Uveal (Ocular) Melanoma.” 2023. Link.
- American Cancer Society. “Uveal Melanoma Survival Rates.” 2023. Link.
- Mayo Clinic. “Uveal melanoma (eye cancer).” Updated 2024. Link.