What is the likely diagnosis for a 6-week-old infant presenting with unilateral leukocoria (white pupillary reflex)?

Unilateral Leukocoria in a 6-Week-Old Infant: Diagnosis

Retinoblastoma is the most likely diagnosis and must be assumed until proven otherwise in a 6-week-old infant presenting with unilateral leukocoria. 1, 2

Primary Diagnosis: Retinoblastoma

This is an ophthalmologic emergency requiring immediate referral to a pediatric ophthalmologist—do not delay for outpatient workup or additional imaging. 1, 2

Why Retinoblastoma is Most Likely

• Retinoblastoma accounts for approximately 50% of all childhood leukocoria cases and is the most critical diagnosis to exclude due to its life-threatening nature 3, 4
• At 6 weeks of age, retinoblastoma presents as the dominant concern, as it can manifest this early and requires urgent intervention to prevent vision loss, metastasis, or death 1
• The unilateral presentation is consistent with sporadic retinoblastoma, which tends to be more aggressive than bilateral cases associated with hereditary forms 5

Key Clinical Features to Assess

• Absence of red reflex on Brückner testing is the critical warning sign that mandates urgent ophthalmologic evaluation 1
• The affected eye should be normal-sized (not microphthalmic), as retinoblastoma typically presents in a normal-sized globe 3
• Look for any family history of retinoblastoma, though most cases at this age are sporadic 4

Differential Diagnoses (Less Likely at This Age)

Congenital Cataract

• While congenital cataract is the most common cause of leukocoria overall, it is less common than retinoblastoma in the differential for leukocoria requiring urgent evaluation 1, 6
• Cataract causes leukocoria by blocking light transmission through an opaque lens, preventing the normal red reflex 7
• Critical distinction: Absence of calcification on imaging helps differentiate cataract from retinoblastoma 1

Persistent Hyperplastic Primary Vitreous (PHPV)

• PHPV accounts for 28% of leukocoria cases but typically presents with microphthalmia (small eye), which should be clinically apparent 3, 8
• Appears as a dense tubular mass extending from lens to retina along the hyaloid canal 3
• Absence of calcification on imaging distinguishes PHPV from retinoblastoma 2

Ocular Toxocariasis

• Extremely uncommon at 6 weeks of age and typically presents in older children (toddlers to school-age) 1
• Requires exposure to Toxocara canis larvae, usually from contaminated soil or puppies 3
• This diagnosis can be safely excluded based on age alone 1

Immediate Diagnostic Approach

Urgent Ophthalmologic Evaluation

• Fundoscopic examination under dilation by a pediatric ophthalmologist is the primary diagnostic tool 1, 7
• Ocular ultrasound (B-scan) is the imaging modality of choice when media opacity prevents direct visualization of the posterior segment 7
• Ultrasound can detect characteristic calcifications within retinal lesions, which are pathognomonic for retinoblastoma 2

Advanced Imaging (After Ophthalmologic Consultation)

• MRI of head and orbits with and without IV contrast is the most useful imaging for evaluating malignant intraocular masses, demonstrating retrolaminar optic nerve infiltration, choroid-scleral involvement, and intracranial spread 1
• CT of orbits with IV contrast may detect calcifications characteristic of retinoblastoma but should be avoided as initial imaging due to radiation exposure concerns 1, 7

Critical Pitfalls to Avoid

• Never delay referral while attempting outpatient workup—leukocoria in an infant is an ophthalmologic emergency 1, 2
• Do not assume the diagnosis is benign simply because the child appears to be developing normally; both retinoblastoma and congenital cataract can present with normal systemic development while causing severe unilateral visual impairment 7
• Avoid corticosteroid treatment before ophthalmologic examination, as this may worsen infectious conditions or mask accurate diagnosis 1
• Do not order CT scan as initial imaging due to radiation exposure, which is particularly concerning in retinoblastoma patients 7