Snapshot A 2-year-old boy presents to his pediatrician for strabismus. Family history is notable for osteosarcoma in his father. Physical examination is notable for strabismus and bilateral leukocoria. He is referred to a pediatric ophthalmologist for further evaluation. Introduction Overview a primary intraocular malignancy arising from the retina 2 forms heritable retinoblastoma (Rb) associated germline mutations in the RB1 gene or de novo germline mutations typically leads to bilateral disease nonheritable Rb associated with somatic mutations in the RB1 gene typically leads to unilateral disease Epidemiology Incidence most commonly affects children (< 5 years of age) ETIOLOGY Pathophysiology RB1 gene encodes a nuclear protein, retinoblastoma, that serves as a tumor suppressor located in chromosome 13 does not allow the cell cycle to proceed from the G1 to the S phase via its binding to E2F, a transcription factor loss of the RB1 gene dysregulates the cell cycle and results abnormal cellular proliferation "2-hit hypothesis" there are 2 Rb alleles that encode the tumor suppressor Rb mutation is inherited, affecting the allele of the RB1 gene a second, acquired mutation that affects the second RB1 allele, leads to the development of retinoblastoma Associated conditions osteosarcoma Presentation Symptoms visual loss Physical exam leukocoria loss of/abnormal red reflex strabismus nystagmus Imaging Ocular ultrasonography indication may be performed prior or during ophthalmologic examination under anesthesia can find echogenic soft-tissue mass with variable shadowing Optical coherence tomography indication performed during ophthalmologic examination under anesthesia provides high-resolution images that can detect small tumors, can serve as a screening tool, and identify tumor recurrence MRI Brain and orbit indication imaging study of choice helps determine potential optic nerve involvement, determine the size of the tumor, and if there is an associated intracranial tumor Studies Ophthalmic evaluation under anesthesia indication newly diagnosed leukocoria in a child component of evaluation of retinoblastoma findings chalky and off-white retinal mass has a friable consistency Biopsy contraindicated because of the risk of tumor seeding Genetic testing performed in all cases Differential Cataract differentiating factor ophthalmologic examination will demonstrate opacification of the lens Treatment Medical local and systemic chemotherapy indication a first-line therapeutic option Surgical laser photoablation indication a first-line therapeutic option radioactive plaques indication a first-line therapeutic option cryotherapy indication a first-line therapeutic option enucleation indication a first-line therapeutic option Complications Metastatic disease Blindness Prognosis Deadly if not treated the tumor expands to fill the eye and destroy the globe > 95% survival with treatment