A 2-year-old boy is brought to the pediatrician’s office for a well-child visit. The parents have no concerns at this time and note he is starting to run around and speak in 3-word sentences. He has no remarkable medical history and his mother had an uncomplicated full-term pregnancy and delivery. He is appropriately meeting the developmental milestones for his age. The patient’s temperature is 98.4°F (36.9°C), blood pressure is 96/52 mmHg, pulse is 102/min, and respirations are 25/min. He is in the 55th percentile for height and 62nd percentile for weight, which is consistent with his documented growth curves. Fundoscopic exam shows the finding in Figure A. His pediatrician continues the ocular examination and further notes that the pupils are equal, round, and reactive, extraocular movements are full, and ocular alignment appears normal. Which of the following is the most appropriate next step in management?
Reevaluation at the next well-child visit
Biopsy
Genetic testing
Ophthalmology referral
Ophthalmology referral
This otherwise healthy patient presents with leukocoria, or a white pupillary reflex, and requires an urgent referral to ophthalmology for further evaluation given the concern for retinoblastoma.

The differential diagnosis for leukocoria includes retinoblastoma, cataract, vitreous hemorrhage, retinal detachment, and other intraocular/systemic disease processes. Newly diagnosed leukocoria should be urgently referred to ophthalmology to exclude retinoblastoma. Retinoblastoma is the most common intraocular cancer of childhood caused by mutations in the RB1 tumor suppressor gene that encodes the retinoblastoma protein. Retinoblastoma typically presents as leukocoria in a child under the age of 3 with other signs including strabismus, nystagmus, or a red, inflamed eye. Treatment options include chemotherapy, laser photocoagulation, radiation, cryotherapy, and enucleation. Prompt diagnosis and treatment are important for optimal visual outcome and survival.

Francis et al. study the risk of extraocular extension in eyes with retinoblastoma that received intravitreous chemotherapy injections. The authors find that the risk of extraocular extension is small. The authors recommend the regular use of precautionary injection methods including lowering of intraocular pressure, cryotherapy, ocular surface irrigation, and ultrasonic biomicroscopy surveillance of the injection site.

Figure/Illustration A shows a child with leukocoria (blue circle) in the left eye.

Incorrect Answers:
Answer A: Biopsy of the eye is contraindicated in retinoblastoma due to the risk of tumor seeding.

Answer B: Genetic testing can be used to determine if a patient has the hereditary form of retinoblastoma, characterized by germline RB1 mutations, as opposed to the nonheritable form, which is associated with somatic RB1 mutations. An ophthalmological evaluation is required first to confirm the diagnosis.

Answer C: While magnetic resonance imaging of the brain and orbits should be performed in all children with suspected retinoblastoma to assess disease extent, an ophthalmological evaluation should be completed first.

Answer E: Reassurance or reevaluation at the next well-child visit is not appropriate management of newly diagnosed leukocoria given that undiagnosed retinoblastoma can be vision- and life-threatening.

Bullet Summary:
Leukocoria, or a white pupillary reflex, in a child requires urgent ophthalmologic referral to rule out retinoblastoma.