What is the diagnostic approach for a 2-year-old (two-year-old) with leukocoria (white pupil) instead of a normal red reflex?

Diagnostic Approach for Leukocoria in a 2-Year-Old

Immediate ophthalmologic referral is mandatory, as retinoblastoma must be assumed until proven otherwise in any child presenting with leukocoria. 1

Initial Clinical Evaluation

The diagnostic workup begins with:

• Fundoscopic examination by a pediatric ophthalmologist is the primary diagnostic tool, ideally performed with pharmacologic pupillary dilation using 0.5% cyclopentolate and 2.5% phenylephrine, as dilation increases detection of leukocoria from 30% to 100% in retinoblastoma cases 2
• Ocular ultrasound performed by the ophthalmologist to characterize intraocular masses and detect calcifications 3
• Examination under anesthesia (EUA) if the child is uncooperative, to allow detailed fundus examination 4

Differential Diagnosis Considerations

The most common causes of leukocoria in children include:

• Retinoblastoma (responsible for 50% of leukocoria cases in infants and 12.5% overall in pediatric series) 5, 4
• Congenital cataract (most common overall at 79.76% in one series, though less common than retinoblastoma in infants) 4, 1
• Persistent hyperplastic primary vitreous (PHPV) 3
• Coats disease 3
• Retinopathy of prematurity 3
• Ocular toxocariasis (extremely uncommon at age 2) 1, 5

Imaging Algorithm

When retinoblastoma is suspected (which it must be in all leukocoria cases), proceed directly to advanced imaging:

First-Line Imaging: MRI

MRI of the head and orbits with and without IV contrast is the most useful imaging modality for evaluating malignant intraocular masses. 3, 1, 6

MRI provides critical staging information:

• Retrolaminar optic nerve infiltration (determines extraocular extension) 3, 6
• Choroid-scleral infiltrations and orbital invasion (upstages disease and changes management) 3, 6
• Concurrent intracranial tumors in sellar or pineal regions (trilateral retinoblastoma in hereditary cases) 3, 6
• Intracranial spread of tumor 3, 6
• Postcontrast enhancement patterns help differentiate retinoblastoma from benign mimics like PHPV, Coats disease, or retinopathy of prematurity 3

Adjunctive Imaging: CT

CT of the orbits with IV contrast may be helpful for detecting calcifications, which are characteristic of retinoblastoma and help differentiate it from other causes 3, 1, 6

• CT can also evaluate extension along optic nerves and intracranially, though it provides less soft tissue detail than MRI 3
• Absence of calcification on CT helps differentiate PHPV and Coats disease from retinoblastoma 3, 1

Key Imaging Distinctions

• Retinoblastoma: Normal-sized globe, calcifications present, postcontrast enhancement 3
• PHPV and retinopathy of prematurity: Microphthalmia, no calcification 3
• Coats disease: Normal-sized globe, no calcification 3

Critical Pitfalls to Avoid

• Never delay referral while attempting outpatient workup—leukocoria is an ophthalmologic emergency 1
• Do not attempt to examine through an undilated pupil, as this misses 70% of retinoblastoma cases 2
• Avoid corticosteroid treatment before ophthalmologic examination, as this may worsen infectious conditions or mask accurate diagnosis 1
• Do not assume benign etiology based on age or unilateral presentation—retinoblastoma remains the most critical diagnosis to exclude 1, 5

Diagnostic Sequence Summary

1. Immediate pediatric ophthalmology referral 1, 7
2. Dilated fundoscopic examination and ocular ultrasound 3, 2
3. MRI head and orbits with and without IV contrast for complete staging if retinoblastoma suspected 3, 1, 6
4. CT orbits with IV contrast as adjunct for calcification detection 3, 1