Leukocoria differential including retinoblastoma

Leukocoria means a white pupillary appearance. Light normally enters through transparent ocular structures and returns from the fundus as a reddish reflex. An opacity, abnormal tissue or detached retina can alter that returning light. The abnormality may be apparent only from a particular direction or in a photograph. It can also be discovered during a routine examination before a parent has noticed anything unusual. The immediate clinical task is to establish an appropriate specialist assessment, not to choose a benign explanation from appearance alone.

Retinoblastoma must be considered because it is potentially fatal and can initially remain confined to the eye. It usually presents in early childhood, but age does not provide an absolute exclusion. A tumour may cause leukocoria, squint or poor visual behaviour; pain and systemic illness need not be present. A child with one well-seeing eye can continue to play and navigate normally despite substantial disease in the other eye. Reassurance based on apparent wellness therefore addresses the wrong question.

The differential is anatomically useful. A cataract lies within the lens and may be congenital or develop later. Persistent fetal vasculature represents retained developmental tissue and vessels, often in a smaller eye, with cataract or a stalk extending towards the optic disc. Coats disease produces abnormal retinal vessels, lipid-rich exudation and sometimes exudative retinal detachment. Advanced retinopathy of prematurity, other retinal detachments and intraocular inflammation can also change the reflex. None of these alternatives can be safely diagnosed solely from a family photograph.

Obtain a careful history of onset, laterality and progression, including photographs if available, pregnancy and neonatal history, prematurity and previous eye examinations. Ask about an eye turning, new visual behaviours, ocular redness or discomfort, trauma and relevant infection exposure. Establish whether there is retinoblastoma or unexplained childhood eye removal in the family. A previously normal newborn eye check does not exclude a later-developing tumour or cataract. Conversely, an isolated photographic reflection can be an optical artefact, but uncertainty or a persisting same-eye concern deserves a sufficiently thorough assessment.

Examine both eyes, using a direct ophthalmoscope in suitable lighting to compare the reflexes. Describe colour, symmetry, brightness and any focal dark or pale area, together with the child's cooperation. Assess fixation, pupils, alignment, corneal transparency and external appearance. Do not claim a normal posterior segment examination when only a brief reflex was obtained. If the result is abnormal or genuinely uncertain, obtain urgent specialist advice. Photographs can accompany the referral but should not replace direct communication about serious findings.

NICE NG12 advises considering a suspected cancer pathway referral for an absent fundal red reflex. NICE NG127 specifies immediate ophthalmology referral when new-onset squint accompanies that finding. Moorfields separately advises urgent telephone referral for an abnormal reflex. These are related but not identical instructions: urgency should reflect the actual combination of signs, the child's condition and the receiving service's triage. Initial clinicians should not postpone the referral to arrange ultrasound, MRI or genetic blood testing themselves.

The retinoblastoma team assesses both eyes, often under general anaesthesia, with detailed fundus examination and ultrasound. The 2025 European specialist imaging guidance recommends MRI for pretreatment staging, including local extension and intracranial disease, rather than routinely using CT to demonstrate calcification. Diagnostic needle biopsy of a suspected intraocular retinoblastoma is contraindicated because opening a route outside the eye can spread tumour cells. Specialist research involving aqueous biomarkers is not permission for an unsupervised diagnostic tap.

Treatment depends on tumour burden, location, seeding, visual potential and disease beyond the eye. Options include focal laser or cryotherapy, chemotherapy delivered through specialist routes, selected radiotherapy and enucleation when necessary. Preserving an eye must not compromise control of the malignancy. The family also needs genetic counselling, assessment of relatives at risk and continuing follow-up. Heritable disease can occur without a previously affected relative, and unilateral disease does not by itself prove that the RB1 change is confined to the tumour.