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

Diagnostic Approach for Leukocoria in a 2-Year-Old

This child requires immediate urgent referral to a pediatric ophthalmologist without delay for comprehensive examination, as leukocoria (white pupil) is an absolute indication for specialist evaluation and may represent life-threatening retinoblastoma or vision-threatening congenital cataract. 1, 2

Immediate Action Required

• Do not delay referral to obtain additional testing or imaging, as postponing specialist evaluation for conditions like retinoblastoma or dense congenital cataract can result in permanent vision loss or death 3, 2
• The combination of squint (strabismus) with absent red reflex suggests the strabismus may be secondary to severe visual impairment in the affected eye, making urgent evaluation critical 2
• Any opacity in the red reflex, markedly diminished reflex, white or dull reflex, or asymmetry between eyes mandates referral to an ophthalmologist experienced in examining children 1

Initial Office Evaluation Before Referral

Perform a red reflex test properly to document the finding:

• Use a direct ophthalmoscope set at lens power "0" held close to your eye 1
• In a darkened room, direct the light toward both eyes simultaneously from 18-30 inches (45-75 cm) away 1
• Adjust lens power to ensure pupillary reflexes are sharply focused 1
• A normal red reflex should be symmetric, bright reddish-yellow (varies by race/ethnicity based on retinal pigmentation), and identical in both eyes 1
• Document whether the white reflex is unilateral or bilateral, and assess ocular alignment using cross-cover test 1

Differential Diagnosis Considerations

The most common causes of leukocoria in this age group, in order of frequency:

• Congenital cataract (79.76% of cases): Lens opacity blocks light transmission through the eye, preventing normal red reflex 3, 4
• Retinoblastoma (12.5% of cases): Life-threatening malignancy that cannot be excluded without specialist examination including fundoscopy and ocular ultrasound 3, 4, 5
• Persistent hyperplastic primary vitreous (PHPV) (1.1%), Coats disease (3.5%), and retinal detachment (2.9%) are less common causes 4, 5

What the Pediatric Ophthalmologist Will Perform

The specialist evaluation will include:

• Cycloplegic refraction to accurately determine refractive error and assess for media opacities 3, 2
• Detailed funduscopic examination under dilation to evaluate the posterior segment and definitively rule out retinoblastoma 3, 2
• Ocular ultrasound (B-scan) to characterize intraocular pathology when direct visualization is blocked by media opacity 3, 4
• Examination under anesthesia (EUA) if the child is uncooperative for detailed fundus examination 4
• Binocular alignment testing in multiple fields of gaze to fully characterize the strabismus 2

Critical Clinical Pitfalls to Avoid

• Never assume the diagnosis is benign simply because the child appears to be developing normally systemically, as both congenital cataract and retinoblastoma can present with normal systemic development while causing severe unilateral visual impairment 3
• Do not dismiss parental concerns about abnormal pupillary appearance—family members are most likely to detect the first signs, and delayed diagnosis due to dismissing parental observations has resulted in worse outcomes 6, 5, 7
• The exception to urgent referral is only a transient opacity from mucus in the tear film that is mobile and completely disappears with blinking 1

Prognostic Considerations

• Leukocoria as a presenting sign correlates with excellent patient survival (>86% at 5 years) but poor ocular survival in the affected eye (4% for unilateral cases at 5 years), emphasizing that early detection before leukocoria develops would improve visual outcomes 7
• Strabismus as a presenting sign also correlates with excellent patient survival (90% at 5 years) but poor ocular survival (17% at 5 years), though slightly better than leukocoria alone 7