What is the most likely diagnosis for a 6-week-old child with leukocoria (white pupillary reflex) in one eye and absent red reflex, who is otherwise developing normally?

Retinoblastoma Until Proven Otherwise

In a 6-week-old infant presenting with unilateral leukocoria and absent red reflex, retinoblastoma must be assumed as the diagnosis until proven otherwise, and this represents an ophthalmologic emergency requiring immediate referral. 1

Why Retinoblastoma is the Primary Diagnosis

• Retinoblastoma is responsible for approximately 50% of leukocoria cases in infants, making it the most critical diagnosis to exclude due to its life-threatening nature. 2

• The American College of Radiology explicitly states that retinoblastoma should be considered the most likely diagnosis in a 6-week-old infant with unilateral leukocoria. 1

• The absence of a red reflex on examination is a critical warning sign that mandates urgent ophthalmologic evaluation to rule out this malignancy. 1

Why Other Diagnoses Are Less Likely

Congenital Cataract (Option D)

• While congenital cataract is the most common cause of leukocoria overall in children, it is less common than retinoblastoma specifically in infants presenting with leukocoria. 1, 3

• Congenital cataracts can present with leukocoria, but the clinical priority is to exclude retinoblastoma first given the mortality implications. 3

• Imaging can differentiate these conditions: absence of calcification on CT helps distinguish cataract from retinoblastoma. 4, 1

Toxocariasis (Option A)

• Ocular toxocariasis is extremely uncommon at 6 weeks of age and typically presents in older children, making it an unlikely diagnosis in this age group. 1

• Toxocariasis (larval granulomatosis) is listed among differential diagnoses for leukocoria but occurs in children who have had environmental exposure to Toxocara larvae, which is developmentally implausible at 6 weeks. 4, 2

Immediate Management Algorithm

1. Urgent ophthalmologic referral - Do not delay while attempting outpatient workup, as leukocoria in an infant is an ophthalmologic emergency. 1

2. Fundoscopic examination and ocular ultrasound by pediatric ophthalmologist are the primary diagnostic tools and may not require additional imaging initially. 4, 1

3. MRI of head and orbits with and without IV contrast is the most useful imaging modality for evaluating malignant intraocular masses (retinoblastoma), demonstrating retrolaminar optic nerve infiltration, choroid-scleral involvement, orbital invasion, and intracranial spread. 4, 1

4. CT of orbits with IV contrast may be helpful for detecting calcifications, which are characteristic of retinoblastoma and help differentiate it from PHPV, Coats disease, and congenital cataract. 4, 1

Critical Pitfalls to Avoid

• Never delay referral while attempting to differentiate between causes - the mortality risk of retinoblastoma demands immediate specialist evaluation. 1

• Avoid corticosteroid treatment before ophthalmologic examination, as this may worsen infectious conditions or mask accurate diagnosis. 1

• Do not be falsely reassured by normal development - retinoblastoma can present in otherwise healthy, normally developing infants. 1