Retinoblastoma is a rare cancer of the eye that develops in young children, typically before age 5. It starts in immature cells of the retina, the light-sensitive tissue at the back of the eye, and occurs in roughly 1 in every 16,000 to 24,000 live births. It accounts for about 3% of all cancers diagnosed in children under 15. Despite being a serious diagnosis, survival rates for cases caught while the tumor is still inside the eye are high, and many children retain useful vision in at least one eye.
How Retinoblastoma Develops
Retinoblastoma traces back to a single gene called RB1, located on chromosome 13. This gene acts as a brake on cell division. When it’s working normally, the protein it produces latches onto a key molecule that would otherwise push cells to multiply, holding them in check. When both copies of the RB1 gene are damaged or missing, that brake fails, and immature retinal cells begin dividing uncontrollably.
Both copies of the gene must be knocked out for a tumor to form. In some children, the first mutation is inherited and present in every cell of the body from birth. Only a single additional hit to the remaining copy in a retinal cell is needed to trigger cancer. In other children, both mutations happen by chance in a single retinal cell after birth, with no inherited component at all.
Heritable vs. Non-Heritable Cases
About 25% to 35% of retinoblastoma cases are heritable, meaning the child carries an RB1 mutation in their germline (every cell in the body). Some of these children have a parent who had the disease, but many are the first in their family: the mutation arose spontaneously in the egg, sperm, or early embryo. The remaining 65% to 75% of cases are non-heritable, caused by two random mutations occurring in a single retinal cell.
Heritable retinoblastoma tends to affect both eyes and is usually diagnosed earlier. Non-heritable retinoblastoma almost always appears in one eye only. The distinction matters beyond childhood, because children who carry the germline mutation face a meaningfully higher lifetime risk of developing other cancers later in life.
Signs Parents Notice First
The most common sign of retinoblastoma is leukocoria, a white glow in the pupil. Parents often spot it in photographs taken with a flash: instead of the typical red-eye effect, one pupil appears white or yellowish. This happens because light reflects off the surface of the tumor inside the eye.
The second most common sign is strabismus, where one eye appears to turn inward or outward. Other possible signs include decreased vision (especially when both eyes are affected), eye redness, swelling, or pain. Because the children affected are infants and toddlers, they rarely complain about vision changes, so visual cues like the white pupil reflex are often the first clue.
How It’s Diagnosed
Diagnosis starts with a dilated eye exam. The ophthalmologist uses drops to widen the child’s pupils and then examines the retina with a bright light. Very young children or those who can’t hold still often need general anesthesia so the doctor can get a thorough look. A small wire device holds the eye open during the exam.
If the exam reveals a suspicious mass, several imaging tools help confirm the diagnosis and assess the tumor’s size and spread:
- Ultrasound uses sound waves to measure the tumor and identify the type of tissue it contains.
- MRI provides detailed images of the brain and the area surrounding the eye, checking whether the tumor has extended beyond the eyeball.
- Fundus photography captures detailed images of the retina to map the tumor’s location.
- Fluorescein angiography involves injecting a dye into the arm that travels to the eye, highlighting abnormal blood vessels around the tumor.
Unlike many other cancers, retinoblastoma is generally not biopsied before treatment. Inserting a needle into the eye risks spreading tumor cells. Doctors rely on the characteristic appearance and imaging findings to make the diagnosis.
Staging: Groups A Through E
Doctors classify intraocular retinoblastoma into five groups that reflect how advanced the tumor is and how likely it is that the eye can be saved.
- Group A: Small tumors (3 mm or less), located away from the center of vision and the optic nerve, with no seeding into surrounding tissue.
- Group B: Larger tumors, possibly near the center of vision or optic nerve, but still without seeding.
- Group C: Tumors with localized seeding, meaning small clusters of cancer cells have spread into the gel of the eye or beneath the retina, but remain close to the main tumor.
- Group D: Large tumors with widespread seeding throughout the eye’s interior.
- Group E: The most advanced stage, where the tumor occupies more than half the eye and may involve complications like elevated eye pressure or damage to the cornea. There is typically no remaining useful vision.
Treatment Options
Treatment depends on the group, whether one or both eyes are involved, and whether the cancer has spread beyond the eye. The overall goal is to eliminate the cancer, preserve the eye when possible, and maintain as much vision as possible.
Focal Therapies
For smaller tumors (groups A and B), doctors can often destroy the cancer using laser therapy (which heats the tumor) or cryotherapy (which freezes it). These treatments are delivered directly to the tumor through the pupil and can be repeated over several sessions. When combined with chemotherapy, they successfully save nearly all group A, B, and C eyes.
Chemotherapy
Chemotherapy can be delivered in two main ways. Systemic (intravenous) chemotherapy circulates drugs through the entire body to shrink the tumor, often followed by focal therapies to finish off remaining cancer cells. Intra-arterial chemotherapy delivers drugs directly into the artery supplying the eye through a tiny catheter threaded from the leg. This approach concentrates the medication at the tumor site while sparing most of the body, resulting in fewer side effects and shorter treatment courses. It’s typically given once every four weeks for three sessions.
Intra-arterial chemotherapy has become a primary treatment for moderate to advanced intraocular tumors (groups B through D) and has proven effective as a second-line option for tumors that didn’t respond to initial treatment, saving eyes that would otherwise need to be removed.
Eye Removal
When the tumor is too advanced to treat safely, particularly in group E eyes or when there’s evidence the cancer has extended into the optic nerve or surrounding bone, surgical removal of the eye (enucleation) is the most reliable way to ensure the cancer doesn’t spread. This is more common in unilateral cases where the other eye is healthy and vision is unaffected.
After removal, children are fitted with a custom prosthetic eye. A conformer (placeholder) is typically worn for the first six weeks while the socket heals, though early fitting of the prosthesis has been shown to improve quality of life. The prosthetic is hand-painted to match the remaining eye and can be worn day and night, cleaned once daily with soap and water.
Survival Rates
For tumors caught while they’re still inside the eye, the outlook is very good. Eye salvage rates exceed 80% for early-stage disease, even without radiation. When the cancer has spread to the eye socket or nearby tissue, 60% to 85% of patients are cured with chemotherapy and radiation. The prognosis drops significantly for metastatic disease that reaches the brain and spinal fluid, where three-year survival falls to around 12%.
Early detection makes an enormous difference. Tumors caught through routine pediatric eye exams or early recognition of the white pupil reflex are far more likely to be treated successfully and with less aggressive methods.
Long-Term Risks for Survivors
Children who carry the heritable form of retinoblastoma face an elevated risk of developing other cancers later in life. In a study following 199 hereditary retinoblastoma survivors for a median of 30 years, 44 developed a second, unrelated cancer. The most common types were sarcomas (cancers of bone or soft tissue), melanomas, and epithelial cancers (cancers of the skin, breast, lung, or other organs).
The level of risk depends partly on the specific type of RB1 mutation. Certain common mutations carried more than three times the average risk of a second cancer, while others, particularly low-penetrance mutations, carried significantly lower risk. Survivors with the heritable form benefit from lifelong cancer surveillance tailored to their specific genetic profile.