Aniridia

Overview

Aniridia is a condition where a part of or the whole iris, the colored part of the eye, is missing. This condition can be present from birth (congenital) or develop later in life (acquired). Being born with aniridia is quite rare, and it usually affects both eyes. Most of the time, this form of aniridia is passed down from parents to their children. However, some people develop it without any family history—these cases are known as sporadic.

Sometimes, spontaneous aniridia is associated with WAGR syndrome. This syndrome includes a combination of conditions: Wilm’s tumor (a type of kidney cancer), aniridia, genitourinary (relating to the organs of reproduction and urination) problems, and intellectual challenges.

A small number of people inherit aniridia in a recessive manner, meaning both parents have to pass on a copy of the faulty gene. This condition, known as Gillespie syndrome, involves aniridia, instability of movements due to issues with a part of the brain called the cerebellum (cerebellar ataxia), and intellectual challenges.

Scientists have discovered that a mutation or change in the PAX6 gene, located on chromosome 11p13, is associated with congenital aniridia.

On the other hand, acquired aniridia happens following an injury or eye surgery.

Causes

Aniridia is a condition where a person is born without the colored part of the eye (iris). Scientists don’t know its exact causes, but a gene called PAX6, which is involved in the development of critical organs like the eye, pancreas, brain and spinal cord, plays a vital role. This gene is situated on chromosome 11p13.

There are various theories about how aniridia occurs. One hypothesis is that it’s a type of iris coloboma, a condition where part of the iris is missing. Another suggests it stems from an anomaly in neuroectodermal development, the process that forms nerve cells in the embryo. This theory is supported by the fact that aniridia often occurs alongside defects in the nerve tissue, like the absence of iris muscles and underdeveloped areas of the retina.

A third theory points to a problem in the development of the mesodermal tissues (middle layer of an embryo from which many organs develop), like the optic nerve. However, this theory does not explain why underdevelopment of the retina often accompanies aniridia.

Aniridia, in reality, comes in various forms:

– Autosomal dominant congenital aniridia: It is the most common form of aniridia and accounts for around two-thirds to 85% of all cases. People with this variant inherit it from a parent, but how severe it is can vary among family members. Some may only experience minor underdevelopment of the iris or iris coloboma.

– Sporadic congenital aniridia: Around 13% to 33% of cases falls under this category where there is a random (not inherited) mutation in the PAX6 gene. It’s important to note that people with this variant of aniridia are at risk of developing a syndrome called WAGR (Wilms tumor, Aniridia, Genitourinary anomalies, and mental Retardation) or Miller syndrome. This includes developing a type of kidney cancer called Wilms tumor, reproductive anomalies, and intellectual disabilities such as learning difficulties, attention deficit hyperactivity disorder, obsessive-compulsive disorder, depression, and anxiety. Facially, there may be deformities. This syndrome occurs due to a partial deletion of chromosome 11, which affects both PAX6 and the Wilms tumor gene (called WT1). Those with WAGR have a 45 to 60% chance of developing kidney cancer, and about 25% to 33% of people with sporadic congenital aniridia can develop a kidney tumor before the age of 3.

– Autosomal recessive congenital aniridia: This is the least common form of aniridia and makes up 1% to 3% of all cases. It usually comes with cerebellar ataxia (difficulty with balance and coordination) and mental retardation, which is known as Gillespie syndrome.

Risk Factors and Frequency

Aniridia, a condition that affects the eye, is relatively rare, occurring in about 1.8 out of every 100,000 births. This condition doesn’t favor any particular gender; it affects both males and females equally.

Signs and Symptoms

Patients with aniridia often have discomfort in bright light, also known as photophobia, and poor eyesight from a young age due to various factors like underdeveloped fovea and optic nerve. This could even lead parents to seek medical attention due to the unusual appearance of their child’s eyes. Other common vision problems in children with aniridia include uncontrollable eye movements (nystagmus) and misalignment of the eyes (strabismus).

In cases of aniridia, the iris may seem partially or entirely missing. This appearance can be confirmed by an exam using light from behind the eye (retroillumination). However, most patients still have small underdeveloped iris tissue. Despite what the term ‘aniridia’ suggests (which means no iris), some researchers argue that ‘iridemia’ is more accurate since it implies a reduced iris. Other symptoms of aniridia may include iris coloboma (a gap in the iris), an off-center pupil, and a loss of intricate patterns in the iris.

Other eye conditions they may have include:

• Bilateral ptosis (droopy eyelids on both sides)
• Meibomian gland dysfunction (gland disorder causing dry eyes)

In cases of aniridia associated keratopathy (AAK), there is a deficiency in limbal stem cells, irregular epithelial cells of the cornea, and the cornea’s conjunctivalization. This condition leads to various other problems like corneal opacity, corneal scarring, and vascularization. It also causes issues like dryness of the eye and instability of the tear film, which makes the surface of the eye poor and unstable, increasing the risk of an epithelial defect and eye infection.

Glaucoma, a condition where high pressure inside the eye damages the optic nerve, may arise. This pressure could be influenced by the thickness of the cornea. Though the angle of the anterior chamber is typically open in early life, angle closure due to a peripheral anterior synechia could be noted, increasing intraocular pressure.

Another common finding among these patients is a reduced size of the optic nerve, which leads to hypoplasia. This condition is found in 75% of aniridia patients according to a study that included 12 participants. One measure used to confirm hypoplasia is a reduced diameter of the optic disc.

Another condition common in aniridia patients is foveal hypoplasia, which is when the region responsible for sharp and central vision doesn’t properly develop. This condition is characterized by a lack of an avascular zone, an absence of pigmentation in that area, and the tendency of blood vessels to course through it.

Some patients also show progressive signs of fibrosis, which is a topic of ongoing clinical research. It involves the appearance of fibrous tissue in the front part of the eyes, which might occur after multiple surgical procedures.

Other conditions that patients with aniridia might have:

• Sensory deficiency, which may cause an impaired sense of smell and hearing loss
• AGR triad, which includes aniridia, abnormalities in the urinary tract, and cognitive impairment
• Missing or underdeveloped kneecap (patella), which can run in the family

Testing

A fundus fluorescein angiogram is a test that uses a dye to light up the blood vessels in the back of your eye. This test can show if there is an area in your eye’s fovea, the part responsible for sharp central vision, that lacks blood vessels. In other words, this test showed there was no well-defined area without blood vessels in your eye’s fovea.

Optical coherence tomography, an imaging test that uses light waves to take cross-section pictures of your retina (the back part of your eye), was done to examine the fovea. Normally, there is a slight dip or depression in the fovea, but this test shows it is missing in your case. The test also shows the presence of inner retinal layers, indicating additional layers of tissue in your eye.

If a condition called sporadic congenital aniridia, an eye disorder that involves a partially or completely missing iris (the colored part of your eye), is suspected, it’s important to screen for a type of kidney cancer called Wilms tumor. This can be done by regular ultrasound scans of your abdomen. Doctors can also look at your genes (the body’s blueprint for development) to see if there are changes in the PAX6 and WT1 genes, as these are commonly involved in this specific eye condition.

It’s also very important to examine the eyes of your family members. This is because some eye conditions can be hereditary, meaning they can be passed down from parent to child. By checking your family members’ eyes, doctors can get a better idea of any potential genetic influences on your eye health.

Treatment

In early childhood, the treatment of eye conditions involves prescription glasses or contact lenses, patching therapy for lazy eye, and straightening any misaligned eyes. Special tinted or painted contact lenses can also be used to reduce light sensitivity, improve appearance, and improve vision. These lenses can also help manage involuntary eye movements. Glasses that change color in response to light can also be beneficial.

A synthetic iris implant, which has been approved by the Food and Drug Administration, can be used to enhance eye appearance, reduce light sensitivity, and improve vision quality. This artificial iris can be especially helpful for individuals born without an iris or those who’ve suffered iris damage due to injuries or conditions like albinism. But, there’s also a risk that this artificial iris might increase the chances of getting glaucoma or damage to limbal stem cells at the edge of the cornea.

Glaucoma, an eye condition that causes pressure on the optic nerve, is often hard to manage with medications and may require surgery. This is particularly true for glaucoma diagnosed before a child’s first birthday or in individuals born without an iris. The success of these surgical interventions can vary, and some may have side effects. If eye pressure isn’t controlled through regular methods, more aggressive treatments might be needed.

Cataracts in the context of absent iris can also need removal. The operation can be challenging because of weak structures within the eye. After cataract removal, the patient might be left without a natural lens in the eye, which could require prescription glasses or contact lenses. Special artificial lenses colored to resemble the iris are also available. These lenses can reduce light sensitivity. However, surgery could increase the chances of glaucoma or damage to the cornea.

Aniridia-associated keratopathy, a cornea condition associated with absent iris, can be managed using artificial tear drops for treating dry eyes and corneal damage. For more severe cases, treatments may involve grafting of tissue or cells to repair the damaged cornea.

A keratoprosthesis, an artificial cornea, can also be useful for patients with severe aniridia-associated keratopathy, although the survival of artificial cornea may be challenged due to multiple reasons including blood vessel growth in the cornea, limbal stem cell deficiency, severe dry eye, and glaucoma.

Other conditions associated with aniridic, such as squint or droopy eyelids, may also need surgical correction. Aniridic fibrosis syndrome, a condition that can lead to scarring on the eye’s surface, also requires early surgery to remove the scar tissue.

To manage systemic diseases related to aniridia, a team of specialists in various fields may be required.

Related Conditions

Here are some conditions that could be present from birth or develop in young children:

• Congenital Cataract (cloudy lens present at birth)
• Congenital Nystagmus (uncontrollable eye movements)
• Ectopia Lentis (displacement of the eye’s lens)
• Iris Coloboma (a hole in part of the eye)
• Juvenile Glaucoma (increased pressure in the eye that can cause vision loss)

Prognosis

Typically, the outlook for vision is not very good in people with aniridia, a condition where the iris (colored part of the eye) is partially or completely missing. In fact, up to 86% of patients with this condition might have a visual acuity (sharpness of vision) of 20/100 or worse in their better eye. This means that what a person with normal vision can see clearly from 100 feet away, they can only see from 20 feet away.

There are several reasons why the vision may deteriorate in these patients. These include:

– Foveal hypoplasia, a condition where the part of the eye responsible for sharp vision is underdeveloped.
– Optic nerve head hypoplasia, a condition in which the nerve that sends vision signals from the eye to the brain is underdeveloped.
– Glaucoma, a group of eye conditions that damage the optic nerve, typically due to high pressure in the eye.
– Cataract, a clouding of the lens inside the eye that leads to a decrease in vision.
– Keratopathy, a disease or injury affecting the cornea (the outermost layer of the eye) which may cause pain, redness, and vision loss.

However, it’s worth noting that in some families with a history of aniridia, members retain fairly good vision, with visual acuity of at least 20/30 in up to 61% of individuals. This means they can see objects at 30 feet away that a person with normal vision can see clearly from 20 feet away.

Possible Complications

Aniridia, a condition resulting in the absence or partial absence of the iris of the eye, can lead to several complications.

• Glaucoma: This is a condition where pressure builds up in the eye and can cause blindness. Approximately half to three-quarters of individuals with Aniridia develop glaucoma, but it generally does not show up at birth. Instead, it usually begins to occur between ages 10 and 20. This is likely due to the iris strands blocking the part of the eye that drains fluid, or due to a poorly developed angle in the front part of the eye. Glaucoma is the main cause of blindness in individuals with Aniridia and treating it can be complex. Often, both medication and surgery are not effective in controlling the condition. Overall, it has an uncertain outcome.
• Aniridic Fibrosis Syndrome: This is another possible complication.
• Blind Eye: This may occur with or without pain.
• Associated health conditions: There can also be a relationship between Aniridia and other health issues, such as Wilms tumor, a type of kidney cancer that primarily affects children.

Pearls and Other Issues

Patients experiencing aniridia, a condition that is characterized by a complete or partial absence of the iris in the eye, should regularly undergo abdominal ultrasonography. This is because this condition has been linked the possibility of developing Wilms tumor, which is a type of kidney cancer that primarily affects children. However, if it is discovered through genetic testing that the patient does not have a mutation or deletion of WT1, a gene associated with this tumor, then this screening might not be necessary.

The proposed schedule for the ultrasound screening is as follows:

– For children up to 5 years of age: every 3 months

– For children between 5 to 10 years of age: every 6 months

– For individuals between 10 to 16 years of age: once a year (every 12 months)