Retinoblastomas are the most common primary intraocular malignancy in children. They are caused by sporadic or inherited mutations in the retinoblastoma gene (Rb). While sporadic retinoblastomas tend to occur unilaterally, hereditary retinoblastomas usually occur bilaterally and may be associated with other malignancies (e.g., osteosarcoma). The characteristic clinical features of retinoblastomas are leukocoria (white fundal reflex instead of the usual red) and strabismus. All children who present with leukocoria should undergo funduscopic examination. Enucleation of the affected eye is the treatment of choice if the eye is not salvageable. A more conservative approach that spares vision may be attempted in the case of small, localized retinoblastomas. The prognosis is favorable if the tumor is diagnosed and treated early. If left untreated, retinoblastomas are almost always fatal.
The retinoblastoma gene (Rb) is a found on chromosome 13.
(autosomal dominant inheritance) 
- Two-hit hypothesis: A germline mutation occurs in one of the alleles of the Rb gene; , which renders this allele non-functional in all cells of the affected individual → The presence of the second functional allele prevents the development of a retinoblastoma → However, a spontaneous somatic mutation in the second allele in any retinal cell results in a non-functioning Rb gene and the development of a retinoblastoma.
- Inherited retinoblastomas tend to be bilateral.
- A child born to a parent who has had a heritable retinoblastoma has a 50% chance of acquiring the mutated Rb allele! 
Sporadic retinoblastomas: due to spontaneous mutation →
- Two spontaneous mutations must occur in the same retinal cell, affecting both Rb alleles.
- Sporadic retinoblastomas tend to be unilateral
Evaluation of the retinoblastoma
- Fundus examination: grayish white, vascularized retinal tumor
- Following fundus examination:
- Ocular ultrasound
- Contrast-enhanced MRI of the cranium: identify optic nerve involvement and extent of tumor
Molecular genetic testing of leukocytes for mutations in the Rb1 gene is recommended for all patients with retinoblastomas. If the patient has a germline mutation, genetic testing and tumor surveillance of the patient's siblings and parents are necessary.
Metastatic evaluation is not done routinely but is indicated if the choroidal layer and/or optic layer is involved.
- See “Differential diagnosis of leukocoria.”
- For the differential diagnosis of strabismus in childhood see “ .”
The differential diagnoses listed here are not exhaustive.
- If the eye is potentially salvageable
- If the eye is not salvageable (either anatomically or functionally)
- In the case of metastatic disease: high-dose chemotherapy with/without radiotherapy