Common causes of leukocoria in children

The common causes of leukocoria in children include.

Retinoblastoma (47 percent of cases in one series)

Persistent fetal vasculature

Retinopathy of prematurity

Cataract

Coloboma (fissure or cleft) of choroid or optic disc

Uveitis

Toxocariasis

Coats disease

Vitreous hemorrhage

Retinal dysplasia

Retinoblastoma  — Retinoblastoma is the most common intraocular tumor of childhood, occurring in approximately 1 in 15,000 live births .The annual incidence is 11 per million in children from birth to four years of age and 0.6 per million in children five years and older .The average age at the time of diagnosis is two years in unilateral cases and one year in bilateral cases

Leukocoria is the most common presenting finding . Other findings may include strabismus, decreased vision, ocular inflammation, family history of retinoblastoma, vitreous hemorrhage, hyphema, orbital cellulitis, proptosis, glaucoma, eye pain, and fever . The diagnosis of retinoblastoma is usually made on the basis of clinical examination and the presence of calcification on computed tomography (CT) or ocular ultrasonography.

Persistent fetal vasculature  — Persistent fetal vasculature (PFV, formerly called persistent hyperplastic primary vitreous [PHPV]) results from a failure of the embryonic primary vitreous and hyaloid vascular system to involute during gestation. The posterior form is characterized by the presence of a rudimentary vascular stalk in the vitreous that usually extends to the optic nerve and is associated with a plaque-like opacity in the posterior lens. It is typically unilateral; bilateral lesions may be associated with trisomy 13. The involved eye is usually mildly microphthalmic with a shallow anterior chamber, prominent vessels on the iris, elongated ciliary processes, and vascularized white retrolental tissue.Children with PFV may go on to develop glaucoma, cataract, intraocular hemorrhage, or retinal detachment

Retinopathy of prematurity  — Retinopathy of prematurity (ROP) is a developmental vascular proliferative disorder that occurs in the incompletely vascularized retina of premature infants and can lead to retinal detachment. ROP affects a substantial number of premature infants, and its incidence increases with decreasing gestational age and birth weight. Other risk factors for ROP include assisted ventilation for longer than one week, surfactant therapy, high blood transfusion volume, sepsis, fluctuations in blood gas measurements, intraventricular hemorrhage, bronchopulmonary dysplasia, and elevated arterial oxygen tension ROP causes leukocoria only when ROP is severe and results in retinal detachment.

Cataract  — A cataract is an opacity of the lens of the eye that can cause partial or total blindness if not diagnosed and treated promptly. Congenital cataracts may be present at birth or appear in early infancy .

Autosomal dominant inheritance is the most commonly identified cause of cataracts in children. Cataracts may be associated with congenital infections (eg, rubella, toxoplasmosis, herpes simplex virus, cytomegalovirus [CMV]). Cataracts also can develop in children who have various systemic, genetic, or metabolic conditions (eg, diabetes mellitus, Turner syndrome, Down syndrome, galactosemia, peroxisomal disorders) or who are exposed to high-dose, long-term systemic corticosteroid therapy . In addition, cataracts may develop in children who have uveitis or sustain ocular trauma.

Optic disc abnormalities  — Congenital and acquired abnormalities of the optic disc, such as optic disc coloboma , morning glory disc ( picture 5), myelinated nerve fibers and malignant infiltration also can produce leukocoria. These disorders are discussed separately.

Uveitis  — Inflammation of the iris, ciliary body, and/or choroid can cause leukocoria due to abnormal retinal reflection, the presence of inflammatory cells and debris in the vitreous, or the development of secondary cataract . Uveitis is an occasional cause of leukocoria in patients with inflammatory or infectious retinal diseases such as toxocariasis, toxoplasmosis, or CMV retinitis. A more common mechanism is the abnormal white or off-white reflection of the lesion itself (eg, toxocariasis).

Toxocariasis  — Toxocariasis, or visceral larva migrans, is an infection caused by the dog ascarid 

Toxocara canis or, less commonly, the cat ascaridToxocara catis . It occurs most commonly in children one to five years of age. Ocular involvement may be the sole manifestation of disease, often presenting in those without an antecedent history of symptomatic visceral larva migrans. The ocular lesion is caused by the inflammatory response to the second-stage larva, which may localize in the eye. Two characteristic lesions may result:

A whitish subretinal granuloma measuring one to two disc diameters and located anywhere in the retina; this lesion can cause leukocoria even in the absence of significant uveitis

A large inflammatory mass (nematode endophthalmitis) with prominent vitreous inflammation

Either of these lesions may be confused with retinoblastoma, particularly if there is associated calcification. Common presenting signs are strabismus and poor vision.

Coats disease  — Coats disease is characterized by idiopathic retinal telangiectasias and retinal exudation that can cause retinal detachment . It is usually unilateral and has a bimodal distribution, primarily affecting males less than 18 years of age and middle-aged men . Presenting complaints include decreased visual acuity, strabismus, or leukocoria. Coats disease appears to be caused by somatic mutation in the NDP gene, resulting in a deficiency of norrin (the protein product of the NDP gene) within the developing retina .

Vitreous hemorrhage  — Vitreous hemorrhage causes leukocoria when there is extensive organization of the blood into a clot before degradation . Vitreous hemorrhage can occur in a number of conditions, including :

Hemorrhagic disease of the newborn

Advanced ROP

Persistent fetal vasculature

Trauma

Leukemia or other blood dyscrasias

Trauma, including intentional trauma (eg, nonaccidental head injury) is the most common cause of vitreous hemorrhage in young children. In the appropriate clinical context, vitreous hemorrhage may be diagnostic of nonaccidental injury.

Retinal dysplasia  — Retinal dysplasia refers to the abnormal development of retinal tissue or cells with retention of some features resembling normal structures. It implies aberrant differentiation in any of the cellular layers and is often associated with the formation of rosettes of circular or oval groupings of dysplastic retinal cells. The rosettes are highly variable in shape and size (unlike those in retinoblastoma, which are uniform in size). In many cases, retinal dysplasia is associated with retinal detachment .

Retinal dysplasia may be caused by intrauterine insults or infection. In addition, it occurs in some genetic diseases such as trisomy 13, trisomy 18, and Norrie disease. Norrie disease is an X-linked disorder associated with microcephaly, congenital blindness, deafness, and progressive neuropsychiatric illness.Ocular findings include bilateral retinal detachment without anterior segment abnormalities, features that help to distinguish it from PFV or cataract .