Retinoblastoma

Retinoblastoma is a cancer of the retina, the light-sensitive tissue at the back of the eye, usually arising in early childhood. A white reflection in the pupil, sometimes noticed in photographs, or a new squint can be an early sign. Reduced vision, a painful red eye or swelling may also occur.

These signs also have other causes, but should not be dismissed or monitored at home while waiting for repeated photographs. Prompt pediatric ophthalmology assessment can identify the cause and arrange referral to a retinoblastoma team.

A specialist examines both eyes, often under anesthesia in young children, and maps tumor size, location, retinal detachment and tumor seeds. Ultrasound can help identify characteristic calcification. High-resolution MRI of the orbits and brain assesses the optic nerves, extension beyond the eye and intracranial lesions; current European guidance favors MRI rather than CT for this work-up.

Direct biopsy of the retinal tumor is generally avoided because it can spread tumor cells outside the eye. This is different from carefully controlled aqueous-humor sampling at expert centers. Neither a routine needle biopsy nor a blood cancer-marker panel is a substitute for the specialist eye examination.

The International Intraocular Retinoblastoma Classification groups eyes from A to E to describe disease within the eye and help plan eye salvage. The precise classification version should be stated. AJCC TNM and other staging systems also assess local invasion, nodes or distant spread; an eye-group letter is not a whole-body stage.

Vitreous or subretinal seeds are small deposits in different compartments and can require different local treatment. A tumor near the macula or optic disc may severely limit vision even if controlled. With bilateral disease, one eye may be suitable for conservation while the other requires removal.

Hereditary disease usually involves a constitutional pathogenic RB1 variant, which may be inherited or arise newly in the child. Bilateral and truly multifocal disease strongly raise this possibility, but unilateral disease does not exclude it. Testing should include appropriate variant and deletion analysis, with attention to mosaicism and what older tests may have missed.

Genetic counseling links results to surveillance of the unaffected eye, siblings and future children. Do not wait for symptoms in an infant known to be at risk: the AACR update recommends eye assessment promptly after birth and age-adapted surveillance. A tumor-only molecular result does not by itself establish the family's inherited risk.

Small accessible tumors may be treated with focal laser or cryotherapy; larger or multifocal disease often needs chemotherapy followed by local consolidation. The plan depends on each eye's anatomy, seeding, visual potential, prior treatment and the child's age. Preserving an eye that cannot provide useful vision is a different goal from preserving vision.

Intravenous chemotherapy treats through the circulation; intra-arterial chemotherapy delivers medicine through the ophthalmic artery; intravitreal treatment targets disease in the vitreous. These routes are not interchangeable. Plaque or external-beam radiation has a role in selected situations, with particular caution about late effects in hereditary disease.

A randomized trial at six Chinese hospitals compared intra-arterial and intravenous chemotherapy in selected newly diagnosed unilateral group D or E disease without high-risk clinical features. Two-year progression-free globe salvage favored intra-arterial treatment, 53% versus 27%. This endpoint measured avoiding progression or eye removal, not normal vision, and overall survival did not differ.

The procedure requires experienced interventional and pediatric anesthesia teams. Eye-artery narrowing or occlusion and retinal injury are relevant risks even when systemic toxicity is lower. The result does not justify transferring every bilateral, very young or extraocular case to the same approach.

Vitreous seeds can persist despite treatment of the main retinal mass. Intravitreal chemotherapy can place medicine directly in this compartment using safety measures intended to prevent spread along the injection tract. COG ARET2121 is a phase II study of incorporating intravitreal melphalan into systemic treatment; the trial asks how this combination performs, rather than establishing a universal schedule.

A small 2026 retrospective series explored intravitreal topotecan with focal treatment for recurrent solid retinal tumors. Ten treated eyes showed regression during limited follow-up, but the study had no randomized comparator. It is a specialist salvage signal, not proof of long-term safety or a reason to postpone necessary enucleation.

For an eye with advanced disease, little useful visual potential or unsafe persistent activity, enucleation can be the treatment that best protects life. Repeated attempts at salvage need explicit reassessment criteria. Choosing removal when indicated is not a failure by the child or family.

The removed eye provides a full pathology assessment. Extensive choroidal invasion, invasion beyond the optic-nerve lamina and involvement of the surgical cut end have different implications. Expert review determines whether adjuvant systemic chemotherapy or further staging is needed; not every removed eye needs the same additional treatment. Prosthesis fitting and visual rehabilitation should be discussed early.

Orbital extension, distant disease outside the brain and central nervous system involvement are different treatment situations. They require pediatric oncology-led systemic care; eye-directed chemotherapy alone cannot address them. Evaluation may include marrow or cerebrospinal-fluid testing when the extent and risk justify it.

COG ARET0321 used chemotherapy and radiation for locoregional extraocular disease, and intensive chemotherapy with autologous stem-cell support for selected metastatic groups. Results were substantially less favorable with CNS involvement. The approach illustrates why eye-salvage percentages from intraocular studies cannot predict outcomes after dissemination.

Aqueous humor is the clear fluid at the front of the eye. Tumor DNA in this fluid can provide eye-specific molecular information without directly sampling the retinal mass. A 2026 prospective single-center report evaluated a clinically validated platform in 60 patients with suspected intraocular disease, including 41 with retinoblastoma, and found molecular changes that tracked clinical disease.

A separate multicenter safety study examined 1,203 sampling procedures. These findings support carefully selected specialist use, but do not make sampling risk-free or replace eye examination, MRI or constitutional RB1 testing. Availability, laboratory validation and whether the result would actually change care must be established for the individual child.

Follow-up examines treated eyes for recurrence and at-risk eyes for new tumors. The frequency changes with age, findings and inherited risk. Hereditary disease also carries a risk of a separate midline brain tumor, called trilateral retinoblastoma. Baseline brain MRI is recommended; repeat screening is a specialist discussion rather than one schedule applied to every child.

Long-term care includes vision testing, amblyopia management, protection of the better-seeing eye, school support and prosthesis review when needed. Hereditary survivors need lifelong attention to other cancers and prompt assessment of concerning symptoms. Whole-body MRI screening has not reached universal consensus; follow-up should also reflect chemotherapy, radiation and hearing-related exposures.