Approach to leukocoria (pediatrics): Clinical sciences

Leukocoria refers to a white or pale pupillary reflex, and its presence suggests a structural abnormality within the visual axis. It’s important to identify underlying causes of leukocoria promptly, since these conditions can either be lethal or lead to profound visual impairment if left untreated. A thorough ophthalmologic exam can distinguish intraocular masses from other abnormalities involving the lens, retina, or vitreous.

When a pediatric patient presents with leukocoria, first perform a focused history and physical examination, including vision screening and direct ophthalmoscopy.

Now here’s a clinical pearl to keep in mind! You can look for leukocoria by checking your patient’s red reflex. To do so, dim the lights to ensure the pupils are dilated. Then, look through an ophthalmoscope while standing approximately 2 feet away from your patient. View each eye separately and both eyes together. During this test, light from the ophthalmoscope normally reflects back from the illuminated retina, producing a reddish-orange glow. A bilateral red reflex suggests the absence of structural pathology within the visual axis, but a white, pale, or absent reflex requires further examination.

Now back to our patient!

History often reveals visual changes, and in some cases, there’s a family history of retinoblastoma. During vision screening, you may identify vision loss, and the exam will reveal a unilateral or bilateral white pupillary reflex. This confirms leukocoria, so to find out what's causing it, refer your patient urgently for a complete ophthalmologic exam, including a dilated fundoscopic exam with indirect ophthalmoscopy and a slit lamp exam. Keep in mind that patients who cannot tolerate an office evaluation may require an exam under anesthesia.

Here’s a clinical pearl! Although a white reflex raises concern for serious pathology, it can also represent a benign, transient finding called pseudoleukocoria, often seen in a flash photograph, with direct ophthalmoscopy, or in children with asymmetric refraction. It can be difficult to distinguish pseudoleukocoria from true leukocoria, so it’s best to follow up with a complete ophthalmologic evaluation.

Now, whenever a child presents with leukocoria, the first thing to think of is retinoblastoma, so immediately assess for an intraocular mass.

Retinoblastoma is the most common ocular tumor in children, but the exam alone can’t always distinguish this tumor from other intraocular masses like a granuloma caused by ocular larva migrans. This is a manifestation of toxocariasis, which occurs when a patient ingests the eggs of the roundworm Toxocara canis or Toxocara cati, which are shed in dog and cat feces, and can be found in the soil. As the ingested eggs mature into larvae, they travel to various organs, including the eye.

So, if a mass is identified, your patient should be assessed for exposure to cats or dogs, and for a history of a type of pica called geophagia, or eating dirt, since this increases the risk of toxocariasis and subsequent ocular larva migrans.

If there’s no known exposure, consider retinoblastoma. These patients are typically under 5 years of age, and most are younger than 3. History may also reveal strabismus, visual changes, or a family history of retinoblastoma. Vision screening may demonstrate decreased visual acuity. Ocular findings could be either unilateral or bilateral, and may include orbital inflammation, blood in the anterior chamber, retinal detachment, or vitreous inflammation. Often one or more whitish-gray or cream-colored retinal masses will be seen.

These findings are highly suggestive of retinoblastoma, so an orbital ultrasound or MRI is needed for confirmation. Imaging will demonstrate an intraocular mass with calcifications, possibly with extraocular spread or optic nerve involvement. These findings confirm retinoblastoma.

Okay, here’s your first high yield fact! Retinoblastoma occurs when the tumor suppressor gene RB1 is altered either sporadically or through a germline mutation. Compared to children with sporadic retinoblastoma, those with hereditary retinoblastoma are more likely to be diagnosed earlier, have bilateral disease, and develop secondary malignancies, such as sarcoma or melanoma.

Now, on the other hand, if your patient does have a known exposure to cats or dogs, consider ocular larva migrans caused by toxocariasis.

Affected patients are usually young children with a cat or dog in the home, and they may frequently play in a sandbox. Occasionally, history reveals pica. Some patients report visual changes, eye pain, redness, or new-onset strabismus.

Physical exam typically reveals unilateral eye involvement; vision screening may show decreased visual acuity; and fundoscopy may demonstrate tractional retinal detachment. If the patient has visceral larva migrans with other organ involvement, such as hepatitis or pneumonitis, they might also have skin lesions or signs suggesting systemic disease, like fever, wheezing, or hepatomegaly.