What is the most likely diagnosis for a 6-week-old child presenting with leukocoria (absent red reflex) in one eye?

Diagnosis: Retinoblastoma

In a 6-week-old infant presenting with unilateral leukocoria (absent red reflex), retinoblastoma is the most likely diagnosis and must be assumed until proven otherwise. 1

Clinical Reasoning

Why Retinoblastoma is Most Likely

• Retinoblastoma accounts for approximately 50% of leukocoria cases in infants, making it the single most important diagnosis to exclude in this age group 2
• Leukocoria is the most common presenting sign of retinoblastoma (occurring in over 50% of cases), followed by strabismus 3, 4
• The absence of a red reflex on Brückner testing is a critical warning sign that requires urgent ophthalmologic evaluation to rule out this life-threatening malignancy 1, 5
• Early detection is vital as untreated retinoblastoma leads to blindness and death from metastases 4

Why Other Diagnoses are Less Likely

Congenital cataract (Option D):

• While congenital cataracts can present with leukocoria at 6 weeks, they are less common than retinoblastoma in this specific presentation 1
• Congenital cataracts would typically be bilateral in hereditary cases, though unilateral presentations occur 1
• The key distinction is that absence of calcification on imaging helps differentiate cataract from retinoblastoma 1

Toxocariasis (Option A):

• Ocular toxocariasis (larval granulomatosis) is listed as a cause of leukocoria but is extremely uncommon at 6 weeks of age 1
• Toxocariasis typically presents in older children (ages 2-10 years) who have had exposure to contaminated soil or puppies 2
• The clinical timeline makes this diagnosis highly unlikely in a 6-week-old infant

Diagnostic Approach

Immediate Actions Required

• All cases of leukocoria require immediate evaluation by a pediatric ophthalmologist experienced in examining children—this is not optional 5
• The only exception that does not require referral is a transient opacity from mucus in the tear film that completely disappears with blinking 5
• Referral should occur within 1 week to exclude retinoblastoma 4

Initial Ophthalmologic Evaluation

• Fundoscopic examination and ocular ultrasound performed by the ophthalmologist are the primary diagnostic tools and may not require additional imaging initially 1
• Clinical history and examination can often establish the diagnosis without advanced imaging 1

Advanced Imaging When Indicated

If retinoblastoma is suspected:

• MRI of head and orbits with and without IV contrast is the most useful imaging modality for evaluating malignant intraocular masses 1
• MRI demonstrates retrolaminar optic nerve infiltration, choroid-scleral involvement, orbital invasion, and intracranial spread 1
• CT of orbits with IV contrast may be helpful for detecting calcifications, which are characteristic of retinoblastoma and help differentiate it from other causes 1
• Avoid CT when possible to reduce radiation exposure in children at risk for second malignancies 6

Key Imaging Distinctions

• Presence of calcification on CT strongly suggests retinoblastoma and helps differentiate it from persistent hyperplastic primary vitreous (PHPV), Coats disease, and congenital cataract 1
• Normal-sized globe favors retinoblastoma or Coats disease, while microphthalmia suggests PHPV or retinopathy of prematurity 1
• Postcontrast enhancement on MRI helps differentiate retinoblastoma from non-enhancing lesions like PHPV or Coats disease 1

Critical Pitfalls to Avoid

• Never delay referral while attempting outpatient workup—leukocoria in an infant is an ophthalmologic emergency 5, 4
• Do not start corticosteroid treatment before ophthalmologic examination, as this may worsen infectious conditions or mask accurate diagnosis 5
• Do not assume a benign cause based on normal development—retinoblastoma can present in otherwise healthy, normally developing infants 3
• Do not rely on bilateral presentation to rule out retinoblastoma—unilateral disease is common and may be the initial presentation 3, 6