Leukocoria

What is Leukocoria?

Leukocoria, also known as ‘white pupil,’ is an unusual reflection in the pupil of an eye that can often be more noticeable when the pupil is dilated. This can sometimes signal that there may be severe issues going on inside the eye. Some of the diseases and conditions in which leukocoria can be seen include inborn cataracts (clouding of the eye’s natural lens from birth), Coats disease (a rare condition that leads to vision loss), retinoblastoma (a type of eye cancer in young children), retinopathy of prematurity (an eye problem that occurs in premature babies), toxocariasis (an infection caused by a type of parasitic worm), Norrie disease (a rare genetic disorder), retrolental fibroplasia (a disorder that affects premature babies and may lead to blindness), and others.

It’s crucial to diagnose and treat conditions causing leukocoria as soon as possible because many can pose threats to sight, and diseases like retinoblastoma can even be life-threatening. If leukocoria is noticed, it’s essential to contact an eye doctor immediately. Collaboration with a child eye specialist, an expert who specializes in the retina (the part of the eye that senses light and sends images to your brain), and an eye cancer specialist can help manage and treat the condition efficiently.

What Causes Leukocoria?

When you look at someone’s eyes with a light and see a red glow (called the red reflex), that’s due to light reflecting off blood vessels inside the back of their eyes. This light has to pass through several layers of the eye to get out, including the retina, the vitreous (a jelly-like substance that fills the eye), the lens (which helps focus light), and the cornea (the clear front of the eye). If any of these layers aren’t healthy or normal, it can affect the red reflex and make it look white instead, a condition known as leukocoria.

There are many things that can cause leukocoria. Some of them include:

– Retinoblastoma, which is a type of eye cancer that can occur in children.
– Coats disease, a condition where blood vessels in the eye grow abnormally.
– Retinopathy of prematurity (ROP), a disease that can happen in premature babies where the blood vessels of the retina grow abnormally.
– Persistent fetal vasculature (PFV), a condition where parts of the eye that are supposed to disappear before birth are still there.
– Infections inside the eye called ocular toxocariasis and toxoplasmosis.
– Astrocytic hamartoma, a benign, or noncancerous, tumor that can occur in the eye.
– Familial exudative vitreoretinopathy (FEVR), a genetic disorder that can cause vision loss.
– Vitreous hemorrhage, which is bleeding into the vitreous.
– Retinochoroidal coloboma, a gap in the structure of the eye.
– Endogenous endophthalmitis, an infection inside the eye.
– Incontinentia pigmenti (Bloch-Sulzberger syndrome), a genetic disorder that can affect the skin.
– Retinal detachment, when the retina moves out of its normal position.
– Pediatric uveitis, an inflammation in part of the eye.
– Medullated retinal nerve fibers (MRNF), which happen when certain nerve fibers in the eye get a myelin sheath.
– Medulloepithelioma, a rare tumor in the eye.
– TORCH syndrome, which stands for Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes simplex. These are infections that can pass from a pregnant woman to her baby.

Risk Factors and Frequency for Leukocoria

In a study looking back over ten years, the average age of children with leukocoria, a condition that causes white reflections in the pupils, was about 3.5 years. More than half of these cases were found in both eyes and were slightly more prevalent in males than females. The majority of these children, about 76%, were under six years old.

• In the tested group, 75% of the causes were due to cataracts, while 21% had a form of eye cancer called retinoblastoma.
• Other less common causes included retinal detachment, retinopathy of prematurity, persistent pupillary membrane, and various rare eye conditions.

Based on data from the Third National Cancer survey, 11 new cases of retinoblastoma (a type of eye cancer) happen every year per million children under 5 years old in the United States. It’s the most common type of eye cancer in children, making up 2% of all childhood cancers. The number of new cases can be anywhere from 3 to 42 per million live births. Cancer in the retina occurs equally in both boys and girls, with most cases happening in children under four years old.

Coats disease, another eye condition, occurs in 0.09 per 100,000 people, with boys making up 85% of the cases.

Worldwide, childhood cataracts happen in about 1 per 10,000 to 23 per 10,000 children, and congenital cataracts (that exist at birth) occur in about 0.6% to 9.8% per 10,000 children. Statistics from a study with 602 newborns showed that 34% experienced any stage of retinopathy of prematurity (a potentially blinding eye disorder), and 5% were at a high risk of retinal detachment.

Lastly, neonatal endophthalmitis (inflammation of the internal parts of the eye), happens in about 4.2 cases per million live births in the United States.

Signs and Symptoms of Leukocoria

To identify and diagnose the cause of leukocoria, which is a condition that causes the pupil to appear white, doctors will ask for a comprehensive medical history. This includes details about the current health issue, any past eye problems, general health concerns, and any related issues in the family’s health history. A family photo might also be used to help determine if the leukocoria was present since birth or developed during childhood.

For example, if there’s a history of premature birth, doctors may look into conditions like retinopathy of prematurity, which can cause leukocoria due to a detached retina and abnormal growth of blood vessels in the eye. Birth trauma could result in bleeding in the eye, which can also change the color of the pupil. Family health history is particularly important in cases of retinoblastoma, a rare type of eye cancer, FEVR, which affects the development of the retina, and coloboma, a hole in one of the structures of the eye.

The color of the pupil when light shines on it can also give a clue about what is causing the condition. Retinoblastoma usually causes the pupil to look white, while congenital cataracts can give the pupil a blue-grey color. Coats disease, which causes abnormal blood vessel development in the eye, and retinal detachment can both make the pupil look yellowish. It’s important to note that in about 20% of cases, retinoblastoma can cause strabismus, or misalignment of the eyes. Conditions that generally affect one eye include retinal detachments, bleeding in the eye, Coats disease, and about 60% of retinoblastomas. Conditions that typically affect both eyes include FEVR, endophthalmitis (inflammation inside the eye), astrocytic hamartomas (a benign tumor in the eye), and about 40% of retinoblastomas.

Testing for Leukocoria

If your child shows signs of leukocoria, which is an abnormal white reflection from the retina of the eye, there are several tests a doctor would want to conduct to establish a clear diagnosis. These can include checking your child’s vision, light reflexes in the eyes, performing a detailed look at your child’s eyes using a device called a slit-lamp, along with numerous imaging tests such as Fluorescein Angiography (FFA) and Optical Coherence Tomography (OCT) of the retina, and ultrasonography.

Your doctor might also consider other methods like Neuroimaging, blood tests, genetic testing, and a procedure known as fine-needle aspiration cytology which involves getting a sample of cells from suspicious areas. These add-on tests help to give a more comprehensive understanding of what might be causing the Leukocoria.

When it comes to examining the eye reflexes, this is typically done in a dark room using something called a direct ophthalmoscope. This can help the doctor see if the light reflected from the eye is normal or if it’s white or has dark spots. If there is uncertainty, doctors can use eye drops to enlarge the pupil and get a closer look.

Ultrasonography is highly recommended for all patients with signs of leukocoria. This test can help to identify unusual solid masses in the retina, fluid under the retina, or any other signs of disease like inflammation or tumors. Fundus Fluorescein Angiography (FFA), essentially a sort of photography of the eye with a special dye, helps doctors to see the blood vessels in the retina to identify any abnormalities.

Optical Coherence Tomography (OCT), another imaging tool, provides detailed images of the eye, which helps to identify fluid, swelling, or scarring in the retina. However, while CT scans can be useful, they are generally avoided in children because they expose the patient to relatively high levels of radiation.

If there are suspicions of a spread of tumors to the brain, a Magnetic Resonance Imaging (MRI) scan might be needed. Some blood tests can help differentiate between infections or inflammation. And while fine-needle aspiration cytology can be helpful in diagnosing infections or inflammation, this procedure is typically avoided in cases of suspected eye cancer, as it can cause the spread of cancer cells.

Finally, genetic testing can be useful for diagnosing conditions linked to leukocoria as well as providing insights for genetic counselling. In particular, this can help identify if a harmful mutation is present in the patient’s genes, which could have led to the development of the disease.

Treatment Options for Leukocoria

Leukocoria, or having a white eye reflex, is linked to eye conditions that require treatment. Here’s how the most frequent conditions that cause leukocoria are treated:

Retinoblastoma (eye cancer in children): Doctors usually use a method called chemoreduction which involves giving medicines to reduce the size of the cancer. This is followed by other treatments, such as shooting the tumor with a laser (laser photocoagulation), or using freezing temperatures (cryotherapy). Surgery to remove the eye (enucleation) is also an option, especially for severe cases or those where the eye is already blind and painful. More recently, the injection of cancer-fighting drugs directly into the blood vessel that leads to the eye (intra-arterial chemotherapy) has been successfully used in some cases.

Coats disease (an eye disorder leading to vision loss or detachment of the retina): In some mild cases, this disease can simply be observed. In other cases, laser treatment can help to reduce abnormal vessels, and medicine may be injected into the eye to slow down the growth of new, leaky vessels. Surgery may be needed if the retina detaches.

Persistent Fetal Vasculature (PFV) (an eye disorder present from birth): For less severe instances, observation and treatment of related issues like cataracts or high pressure in the eye (glaucoma) may be all that’s needed. More severe cases may require surgery to remove the lens and other abnormal tissues from the eye.

Pediatric cataract: Surgery performed between 2 and 6 months of age usually gives good results. Unilateral cataracts should be operated on before six weeks, and bilateral cataracts before eight weeks of age. Surgery is advised for cataracts causing serious visual disturbance.

Pediatric uveitis (inflammation within the eye): Doctors primarily use corticosteroids for treatment. In severe cases, more powerful immunomodulatory drugs or anti-TNF agents might be needed. Risks of this treatment are glaucoma and cataracts.

Toxocariasis (an eye infection caused by a parasitic worm): Corticosteroids are often used to control inflammation. Antiparasitic medicines may sometimes be used as well, but their role in treatment is controversial. Surgery might be needed in severe cases.

Retinopathy of prematurity (ROP): This eye disorder primarily affects premature babies. Available treatments include observation, the use of laser or freezing temperatures (cryotherapy) to treat the abnormal vessels, or potentially surgery if the retina detaches.

Endogenous endophthalmitis (an infection inside the eye): Treatment involves using different types of antibiotics depending on the bacteria causing the infection. If the infection is severe, surgery might be needed.

Retinochoroidal coloboma (a gap in parts of the eye’s structure): Treatment solutions might include lasers, surgery, or observation depending on the specifics of the case.

Familial exudative vitreoretinopathy (FEVR): Treatment may include observation, laser treatment or potentially surgery, depending on how advanced the condition is.

Retinal Detachment: Treatment typically involves surgery to repair the retina.

Medulloepithelioma (a rare type of eye cancer): Surgery to remove part or all of the eye is the standard treatment. More extensive surgery may be required if the cancer has spread beyond the eye.

Incontinentia pigmenti (a rare genetic disorder affecting the skin, hair, teeth, and central nervous system): Treatment may involve lasers or freezing treatments (cryotherapy).

What else can Leukocoria be?

Leukocoria is when there’s a whitish or greyish change in the reflection from the pupil, unlike the usual bright red or orange one. There are several conditions that could appear similar to leukocoria, but they don’t actually change the pupil’s reflex. These conditions could make the eye look different and may cause parents to take their child to the doctor. They include:

• Glaucoma in children
• An eye alignment issue called strabismus and a certain type of reflex called Bruckner reflex
• Hypopyon, a condition where pus builds up in the front part of the eye
• Hyphema, or bleeding in the front part of the eye
• Clouding of the cornea
• A foreign object in the eye

There are also several conditions that result in the accumulation of calcium inside the eye, including:

• Cataracts that are hardened with calcium
• A condition called asteroid hyalosis
• A type of eye cancer called retinoblastoma
• Hardened deposits in the eye called drusen
• Tumors related to cells in the retina called astrocytic hamartomas
• A benign type of eye tumor called retinocytoma
• Certain types of brain tumors including astrocytomas and optic nerve meningioma
• Another type of hardened deposit in the optic nerve called optic nerve head drusen
• A condition defined by the shrinking or scarring of the eye, called phthisis

What to expect with Leukocoria

Retinoblastoma (RB), a form of eye cancer, usually has a survival rate of 90% to 95%, along with a generally positive prognosis, although it often results in vision loss in the affected eye. The prognosis can be negatively impacted by various factors, such as the cancer spreading to the optic nerve, the presence of multiple tumors, late diagnosis, and the level of tumor differentiation. The prognosis generally isn’t affected by whether both eyes have the disease or not and also doesn’t depend on the presence of dead tissue or calcification. Interestingly, the prognosis hinges most significantly on the condition of the more severely affected eye. If the cancer has spread to the optic nerve, involves the choroid (a part of the eye that contains blood vessels and connective tissue), extended to the orbit (eye socket), or involves the anterior segment and uveal tissue (middle layer of the eye), there is a higher risk of the cancer coming back.

Congenital cataract, which is a clouding of the lens present at birth, has a good prognosis if it is diagnosed early and treated before the baby reaches six weeks. The prognosis is better for those with developmental cataract, which occurs later during infancy or childhood. If cataracts are present in both eyes, the prognosis is better than for those with a cataract in just one eye. However, even a small clouding of the lens can significantly impact vision. Unilateral cataracts, which are present in only one eye, also pose a higher risk of anisometropia (a difference in refractive power between the two eyes).

Endogenous endophthalmitis, an inflammation of the interior of the eye usually caused by an infection from elsewhere in the body, typically has a poor prognosis. It often leads to retinal detachment (when the light-sensitive layer of tissue lining the inside of the eye pulls away from the supportive tissue beneath it) and an uncontrollable infection, sometimes requiring the surgical removal of the eye.

FEVR (Familial Exudative Vitreoretinopathy) is a lifelong condition where blood vessels supplying the retina at the back of the eye do not develop correctly. It can become active again at any time. After treatment, patients with FEVR should have examinations of the back part of their eye and a test called fluorescein angiography, which uses a dye to check the blood vessels in the retina, every six months. When these patients undergo surgery for retinal detachment, the prognosis is typically poor, as children often present with poor visual acuity (how good their vision is) and a higher chance of the macula (the part of the eye responsible for sharp, central vision) being involved. The children also have a lifelong risk of getting cataracts, glaucoma (a group of eye conditions that cause damage to the optic nerve), and having another retinal detachment.

Medulloepithelioma, a rare eye tumor, has an excellent prognosis if the tumor hasn’t spread beyond the eye. In such cases, a 5-year survival rate of 90-95% can be expected post enucleation (surgical removal of the eye).

The prognosis for retinochoroidal coloboma, a gap in some of the layers of the eye, is quite good if amblyopia (lazy eye) is timely managed and preventative measures are taken to avoid retinal detachment. The involvement of the fovea, the central focus point of the retina, can lead to significant vision loss.

Possible Complications When Diagnosed with Leukocoria

There are multiple disorders that can lead to Leukocoria, a condition causing a white pupil, and each one has its own set of potential complications.

When it comes to Retinoblastoma, possible complications may include:

• Invasion of the tumor into the choroid (a layer of blood vessels in the eye) and sclera (outer layer of the eye)
• Spread of the cancer to other parts of the body (metastasis)
• Seeding of the vitreous humor (jelly-like substance in the eye) by the tumor
• Tumor spreading into the front part of the eye
• Development of new blood vessels causing glaucoma
• The recurrence of the tumor and the potential for other new tumors
• Increased pressure inside the skull
• Shrunken and non-functioning eye
• Death

For Pediatric Uveitis, the complications might involve:

• Lazy eye (also known as amblyopia)
• Cloudiness in the lens of the eye (cataracts)
• A build-up of calcium on the cornea (band-shaped keratopathy)
• Increased eye pressure (glaucoma)
• Swelling in the macula (part of the retina)

Retinochoroidal Coloboma could potentially cause:

• Cataracts
• Retinal detachment
• Lazy eye
• Weakness of the zonules (tiny fibers that suspend the eye’s lens)

Possible complications of Cataracts and Cataract Surgery include:

• Lazy eye
• Abnormal vision due to unequal refractive power (anisometropia)
• Clouding of the posterior lens capsule after cataract surgery
• Secondary glaucoma
• Inflammation inside the eye and infection of the inner layers of the eye following surgery
• Retinal detachment

And Coats Disease may result in complications such as:

• Glaucoma due to new blood vessel growth
• Infection in the tissues surrounding the eye (orbital cellulitis)
• Cholesterol deposits in the anterior segment of the eye
• Bleeding in the vitreous humor
• New blood vessel network on the optic disc and retina
• Microscopic cysts in the retina
• Tumor stimulated by an abnormal increase in blood vessels

Preventing Leukocoria

Leukocoria, which causes a white color in the pupil, often appears in children. As the symptoms can suggest a wide range of conditions – from harmless variations in the eye’s reaction to light (known as the Bruckner reflex) to a serious eye cancer called retinoblastoma – it’s very important to thoroughly examine any child showing this symptom. This examination is usually performed by the family doctor, pediatrician, or primary care physician who first notices the leukocoria.

If your child’s pupil appears white, don’t panic, but do take it seriously. Understand that a complete examination may take some time and may involve scanning the brain and eyes (neuroimaging). If you have other children, it could be necessary to check them as well, because some conditions linked to leukocoria can run in families.

When it comes to retinoblastoma, genetic counseling is important. Even though only 5 percent of people with this eye cancer have a family history of the disease, genetics can play a significant role. For example, a parent who survived retinoblastoma in both eyes has a 45 percent chance of having a child with the same illness. If retinoblastoma was present in only one eye, the risk drops to 7 percent. Parents of a child with retinoblastoma in both eyes have less than a 5 percent chance of having another child with the disease. However, if two or more children in a family have retinoblastoma, the likelihood of another child being affected increases to 45 percent.