Eye Cancer: A Plain-Language Overview

"Eye cancer" mostly means one of two conditions, and they have almost nothing in common.

Uveal melanoma is a disease of adults. NCI calls it the most common primary cancer that starts inside the adult eye. Retinoblastoma is a disease of young children, driven by a specific gene. The tests, the treatments, and the follow-up are separate. Find out which one is being discussed before you read anything else.

How common it is. NCI reports about 4.3 new cases per million people each year in the United States, at 4.9 per million in males and 3.7 per million in females. Incidence peaks around age 70.

Who gets it. Listed susceptibility factors are white race or ethnicity, light eye color, fair skin, and the way skin tans. NCI notes that sunlight exposure shows only a weak link to risk, which surprises many people.

Where it starts. The uvea has three parts, and location drives outcome.

• Iris melanomas are the smallest and slowest growing. They rarely spread, with more than 95% five-year survival.
• Ciliary body melanomas sit in the middle for aggressiveness and are less common.
• Choroid melanomas are the most common and the most likely to spread.

How it is found. Exam by an experienced ophthalmologist does most of the work. Direct ophthalmoscopy, meaning looking into the eye with a light, may show orange pigment on the tumor surface. Ultrasonography measures the tumor and checks for extrascleral extension, meaning growth outside the white of the eye. Fluorescein angiography and fine-needle aspiration biopsy fill in the rest.

How size is classified. The Collaborative Ocular Melanoma Study, or COMS, set the size groups still used today. Small is 1.0 to 3.0 mm in height with a 5.0 to 16.0 mm base. Medium is 3.1 to 8.0 mm in height with a base of 16.0 mm or less. Large is over 8.0 mm in height, or over 16.0 mm across when height is at least 2.0 mm.

Observation is used for iris melanomas and some small choroidal lesions. NCI reports a 31% chance of growth within five years for small tumors, so this is active watching with repeat imaging, not doing nothing.

Plaque brachytherapy places a small radioactive disc on the outside of the eye over the tumor. Iodine-125 is the isotope NCI describes as probably the most commonly used, delivering 85 Gy at a rate of 0.42 to 1.06 Gy per hour. For medium-sized melanomas, survival matched removal of the eye in the COMS trial, and 85% of patients still had their eye at five years.

Proton-beam radiation gives a sharper dose edge, which helps when the tumor sits near the optic disc or fovea. One large single-center series reported 95% local control at 15 years; another reported 92% local control and 87% eye preservation at 10 years.

Enucleation, removal of the eye, is reserved for large tumors. The COMS trial tested giving external-beam radiation before enucleation and found no effect on overall survival.

Transpupillary thermotherapy uses an 810 nm infrared laser to heat and kill tumor tissue. NCI limits it to small tumors and notes relatively high local recurrence, especially near the optic disc.

Ask about them by name. Both are done on tissue from a fine-needle aspiration, a biopsy, or a removed eye.

Chromosome 3 status. Loss of one copy of chromosome 3, called monosomy 3, is linked to worse prognosis.

Gene-expression profile, or GEP. Class 1 predicts a favorable course, Class 2 a poorer one.

These change surveillance, not the eye treatment itself. Uveal melanoma spreads through the bloodstream, not the lymph system, because the uvea has no lymphatic vessels. The liver is the dominant target: NCI reports it as the only site in 46% of patients who develop metastasis. Lung, bone, and tissue under the skin follow. Only 2% to 3% of patients have detectable spread at diagnosis, yet five-year melanoma-specific mortality is roughly 30% for choroid and ciliary body tumors, against 2% to 3% for iris tumors. That gap is why liver imaging continues for years after the eye is treated.

Retinoblastoma makes up about 3% of childhood cancers, with roughly 3 cases per million children under 20. Among children aged 0 to 4, the rate is 18.4 per million. Two-thirds are diagnosed before age 2, and disease in both eyes usually shows up in the first 12 months of life.

The two signs parents notice. Leukocoria, a white reflex in the pupil, is the most common. It is often first spotted in a flash photograph, where one pupil glows white instead of red. Strabismus, an eye that turns in or out, is second most common and tends to mean the tumor involves the macula. Advanced tumors can cause pain, glaucoma, orbital swelling, or buphthalmos, an enlarged eyeball.

The genetics. Retinoblastoma comes from loss of both working copies of the RB1 gene. NCI reports heritable forms in 25% to 30% of cases and nonheritable forms in 70% to 75%. About 15% of children with disease in only one eye are still presumed to carry the heritable form, so genetic testing is offered even then. Children with the heritable form face trilateral retinoblastoma, a midline brain tumor, in 5% to 15% of cases, typically between 20 and 36 months of age.

How eyes are grouped. The International Classification of Retinoblastoma sorts eyes A through E. Group A is small intraretinal tumors 3 mm or less, away from the fovea and optic disc. Group B covers other discrete retinal tumors. Group C has limited seeding, Group D has widespread seeding, and Group E has features such as neovascular glaucoma or lens involvement.

Treatment. Options include systemic chemotherapy for chemoreduction, intra-arterial chemotherapy delivered by catheter, intravitreal chemotherapy injected into the eye, cryotherapy, laser photocoagulation, plaque brachytherapy, radiation, and enucleation. NCI states the goal directly: save the child's life and preserve useful vision.

• A white pupil in a photo, or a pupil that never shows the red reflex. Ask for a pediatric ophthalmology exam, not a wait-and-see.
• A new eye turn in an infant or toddler.
• A dark spot on the iris that is growing, or new flashes, floaters, or a shadow in your side vision.

Go to an emergency department, or an eye casualty unit if your area has one, for sudden loss of vision in one eye, or for severe eye pain with a red eye, haloes around lights, or vomiting. Raised pressure inside the eye can damage sight within hours, so this is not something to hold until the next clinic slot.

• Is this uveal melanoma, retinoblastoma, or something else entirely?
• What is the tumor height and base diameter in millimeters?
• Has chromosome 3 or GEP testing been done, and what class?
• What is my liver surveillance schedule, and for how many years?
• For a child: has RB1 testing been ordered for the child and for siblings?
• Is an ocular oncology center reviewing this case?

For related reading, see Pathology Reports, Getting a Second Opinion, and Imaging Tests.

• National Cancer Institute — Intraocular (Uveal) Melanoma Treatment (PDQ), Health Professional Version
• National Cancer Institute — Retinoblastoma Treatment (PDQ), Health Professional Version