Aniridia - Symptoms, Causes, Diagnosis and Treatment

Introduction

According to the National Organization for Rare Disorders and the European consortium for rare diseases, aniridia is a rare severe disease. It is a rare bilateral condition of the eye characterized by deformity in the iris. Aniridia is also called absent iris, congenital aniridia, or irideremia. The complete or partial absence of a colored part of the iris. Iris controls the pupil's size and regulates the amount of light entering the eyes. As a result, the pupil becomes abnormal, or there is a change in shape. It can lead to a reduction of visual acuity that decreases the sharpness of the vision and leads to photophobia, which increases sensitivity to light. It is seen around late childhood or early adolescence. Patients with aniridia have eye problems.

Aniridia affects males and females equally. Clouding in the eye lens is seen in nearly 50% of the population. The severity of symptoms is usually the same in both eyes. Various forms of aniridia have been identified. Patients may also have behavioral problems and problems in detecting the odor.

What About the Epidemiology of Aniridia?

It occurs in 1:50,000 live births. Two third of cases are dominantly transmitted, meaning an abnormal gene from one parent can cause disease. The other third of cases are sporadic, which occur at irregular intervals. For example, one-fifth of sporadic aniridia patients may develop a Wilm's tumor (kidney cancer seen during childhood).

What Are the Causes of Aniridia?

• Mutations in the PAX-6 Gene - Aniridia is caused due to mutations in the PAX-6 gene. The PAX-6 gene is responsible for developing the eye, brain, spinal cord, and pancreas. This gene is responsible for developing olfactory cells that produce a smell—mutation in the PAX-6 gene results in non -functional PAX-6 protein formation. Due to the lack of functional PAX-6 protein, there is a disruption in the eyes' formation during the embryo's development. PAX-6 protein is also called a transcription factor.

• Gillespie Syndrome - Characterized by aniridia, intellectual disability, and ataxia. Mutations in the ITPR1 gene cause it.

• WAGR Syndrome - WAGR syndrome stands for Wilms tumor, aniridia, genitourinary abnormalities, and retardation. It is caused by missing genetic information on chromosome no.11. It is also associated with obesity.

What Is the Classification of Aniridia?

1. Aniridia Type-1 - It can be transferred from a parent to a child and is caused by mutations in the PAX-6 gene on chromosome 11.

2. Aniridia Type-2 - It is a sporadic form not inherited from either parent. Two conditions are associated with this type, i.e., Miller syndrome and WAGR syndrome.

3. Gillespie Syndrome Type 3 - This follows autosomal recessive inheritance traits.

What Are the Symptoms Associated With Aniridia?

• Patients suffer from increased pressure in the eye, that is, glaucoma.

• A cataract (cloudy lens) is seen in almost 50 % of the population.

• Patients with albinism (a rare genetic condition that affects melanin) suffer from aniridia.

• Under the development of the optic nerve.

• Nystagmus (eyes make repetitive, uncontrolled movements).

• Progressive loss of vision.

• Superficial clouding of the cornea.

• Bilateral ptosis (when the upper eyelid droops over the eye).

• Choroidal degeneration (a hereditary disorder that affects the retina of the eyes).

• Pain in eyes.

• Microcornea (cornea less than 10 mm in diameter).

• Meibomian gland dysfunction (when the gland is not secreting enough oil).

• Underdeveloped fovea area of retina.

• Hearing difficulty.

• Strabismus (also called crossed eyes, when eyes do not look at an object at the same point of time).

• Abnormal olfaction (smell).

How About the Diagnosis of Aniridia?

1. Ophthalmic Examination - Optic examination of family members and genetic diagnosis may help diagnose aniridia.

2. Slit-Lamp Examination - Careful slit-lamp examination is recommended for iris defects. In this examination, the doctor looks around your eye using a special microscope and light.

3. Ultrasonogram - Ultrasonogram of the abdomen is done to rule out Wilms tumor.

4. Fundus Fluorescein Angiogram - It lacks a well-defined foveal avascular zone.

5. Optical Coherence Tomography - It shows a lack of foveal depression and the presence of the inner retinal layers.

6. High-Frequency Ultrasound Biomicroscopy - Useful in infants with corneal opacity or severe corneal edema, as it can demonstrate complete or partial iris hypoplasia.

7. Electrophysiology - Electrophysiology is used to assess the level of vision.

What Is the Treatment of Aniridia?

• Treatment aims to improve visual acuity, and refractive errors are corrected using spectacles.

• Medicines or surgery is done in case of glaucoma or cataracts, and prophylactic goniotomy effectively manages patients suffering from glaucoma.

• Artificial tears or lubricating topical substitutes can help with corneal problems.

• In some conditions, contact lenses can also be used for cosmetic purposes.

• Antimetabolites such as 5-Fluorouracil or Mitomycin C are used to treat the condition.

• Drainage tube surgery or cyclodiode laser treatment can also be performed.

• Surgical implanted artificial iris can also be placed, and it is made up of medical-grade silicone, but it is a challenging treatment.

• Limbal stem cell transplantation can be performed and have a better prognosis.

• Corneal grafting is required in progressive corneal opacification.

• Vitamin A ointment and topical Bevacizumab drops can be used.

What Is the Differential Diagnosis of Aniridia?

• Congenital Cataract - Defined as clouding of the lens present at birth.

• Congenital Nystagmus - Defined as involuntary rhythmic movements at birth.

• Ectopia Lentis - Dislocation of the natural crystalline lens.

• Iris Coloboma - Defect in the iris of the eye.

• Juvenile Glaucoma - Uncommon and severe form.

• Rieger and Peters Anomalies - Thinning and clouding of the cornea.

What Are the Complications Associated With Aniridia?

• Glaucoma (a group of eye diseases that cause vision loss and blindness by damaging the optic nerve).

• Aniridic fibrosis syndrome (rare anomaly occurring because of intraocular surgery).

• Painful or painless blind eye.

• Wilms tumor(childhood cancer that starts in the kidneys).

Conclusion

Aniridia occurs in some patients suffering from Gillespie syndrome and WAGR syndrome. It is a severe life-threatening genetic disorder that may cause Aniridia-related keratopathy, glaucoma, cataract, problems with the optic nerve, and retinal tearing. Genetic testing and counseling play an important role in confirming the mutations of PAX-6. Treatment aims at improving the vision of the patient. Other treatments are symptomatic and supportive. New approaches, such as stem cell therapy, offer a better prognosis. Long follow-ups are required to monitor the systemic problems associated with this condition. Patients should have regular eye examinations. When genetic causes are not identified, patients should be ruled out for Wilms tumor.