Aniridia is a rare condition characterized by a progressive fibrotic membrane within the anterior chamber that occurs after ocular surgery or by abnormal development of the iris of the eye. The iris is the circular, colored part in the middle of the eyeball. The center of the iris is known as the pupil. The iris can control the size of the pupil, which regulates the amount of light that enters the eye. Aniridia is a condition in which the iris is either partly or completely missing. Various forms of aniridia have been identified. Each form can be determined by what additional symptoms are present.
Types
The various hypothesis regarding the etiopathogenesis of aniridia include:
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Aniridia may be a subtype of iris coloboma.
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Neuroectodermal theory – Aniridia develops from an anomaly of neuroectodermal development – this theory has support from the association of aniridia with neuroectodermal defects like the absence of iris muscles and foveal hypoplasia. Mesodermal theory suggests that there is an abnormality in the development of mesodermal tissues like optic nerve head hypoplasia; this does not explain foveal hypoplasia which commonly accompanies aniridia.
Classification of congenital aniridia:
- Autosomal dominant congenital aniridia– It consists of at least two-thirds of cases of congenital aniridia and may be present in up to 85% of cases with aniridia. This variant is autosomal dominant and the most common form of aniridia; it has complete penetrance but variable expressivity. Thus family members may have different severity of aniridia, ocular involvement, and visual acuity. Some cases may have subtle iris hypoplasia or iris coloboma.
- Sporadic congenital aniridia– There is a de novo mutation of the PAX6 gene and may consist in 13% to 33% of cases with aniridia. An important fact is that this variant of aniridia correlates with nephroblastoma (Wilms tumor) as a part of WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), also known as Miller syndrome. The genitourinary anomalies include undescended testes in males and streak gonads (nonfunctional ovaries) and/or bicornuate uterus in females. Intellectual disability includes difficulty in learning and processing information. There might be other manifestations, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, depression, and anxiety. There may be craniofacial dysmorphism.
- Autosomal recessive congenital aniridia- It consists of 1% to 3% of all congenital aniridia cases and is the least common variant of congenital aniridia. It has associations with cerebellar ataxia and mental retardation (Gillespie syndrome).
Causes
The exact cause of congenital aniridia is unknown. However, the paired box gene (PAX6) gene at chromosome 11p13 is a crucial factor in pathogenesis. This gene is involved in the development of essential organs, including the eye, pancreas, brain, and spinal cord during embryonic development.
Most forms of isolated aniridia are caused by harmful changes (mutations) in the PAX6 gene causing it to not work normally. This condition typically follows an autosomal dominant pattern. Most people with aniridia have a parent with aniridia. Some patients appear to have a spontaneous, new genetic variant.
Gillespie syndrome is caused by harmful gene changes in the ITPR1 gene. Gillespie syndrome follows an autosomal dominant pattern, or it can occur as a new genetic change.
WAGR syndrome is mainly caused by missing genetic information along chromosome 11. This missing genetic information sometimes encompasses the PAX6 and WT1 genes. WAGR syndrome gene deletions can occur in a dominant pattern. WAGR syndrome gene deletions can also occur for the first time in the affected individual.
We all have two copies of every gene. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a new changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Sometimes a genetic cause for aniridia cannot be identified.
Treatment
Treatment of aniridia is usually directed at improving and preserving vision. Drugs or surgery may be helpful for glaucoma and/or cataracts. Contact lenses may be beneficial in some cases. When a genetic cause cannot be identified, patients should be evaluated for the possibility of the development of Wilms’ tumor. (For more information on this disorder, please choose “Wilms” as your search term in the Rare Disease Database.)
Aniridia-associated keratopathy:
Phase 0 (subclinical limbal stem cell deficiency and phase 1 (slight limbal stem cell deficiency, less than 2 corneal epithelial erosion or ulcer in last 6months, corneal pannus less than 1mm from limbus, mild watering and photophobia, and fluorescein staining abnormality)[rx] The dry eye and keratopathy need frequent artificial tear drops (free of preservatives). Antiglaucoma drops with preservatives may worsen the corneal surface.
Phase 2 (Moderate limbal insufficiency, constant redness, watering, and photophobia, more than three corneal erosions or ulcers in the last six months, constant tear film instability, vascular pannus)[rx] – amniotic membrane transplant or autologous serum is used.
Phase 3 (severe limba insufficiency, corneal vascularization, loss of vision)- Autologous transplant of limbal epithelial cells is not possible due to bilateral involvement. Management options include:
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2 stage surgery involving initial replenishment of the limbal stem cells followed by surgery for visual rehabilitation
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Options for replenishing limbal stem cells include:
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Keratolimbal allografts
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Cultured limbal stem cell transplant
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Cultured oral mucosal epithelial transplantation [rx]
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Options for visual rehabilitation include
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Deep anterior lamellar keratoplasty
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Penetrating keratoplasty
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Simultaneous surgeries for both replenishment of the limbal stem cells and restoration of media clarity by keratoplasty have also been successful.[16]
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Boston keratoprosthesis may be helpful in the visual rehabilitation of patients with severe aniridia-associated keratopathy.[17]
However, the survival of corneal graft is often poor due to multiple causes, including corneal vascularization, limbal stem cell deficiency, severe dry eye, and glaucoma.
The associated squint and ptosis may need correction.
Aniridic fibrosis syndrome needs early surgical intervention to remove the membranes.
Systemic diseases need a collaborative approach of specialists of different subspecialties.
In 2018, the FDA approved the first artificial iris, a surgically implanted device to treat adults and children with aniridia. This device may help to reduce light sensitivity and glare and improve the cosmetic appearance of the eye.
Genetic counseling is recommended. Another treatment is symptomatic and supportive.
References
