Aniridia is a congenital, hereditary, bilateral, extreme form of iris hypoplasia that may be associated with other ocular defects.[1, 2, 3, 4] It describes an extreme form of iris hypoplasia in which the iris appears absent on superficial clinical examination. However, gonioscopy shows the presence of the iris root. Aniridia is not just an isolated defect in iris development but is a panocular disorder with macular and optic nerve hypoplasia, cataract, and corneal changes that are other anomalies that lead to decreased vision and nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.[5]
Patients with aniridia usually lack a foveal reflex, indicating poor macular development. True aplasia of the optic nerve also can occur. All these patients need specialized management of each individual problem. Because of poor visual acuity and nystagmus, low vision aids are very helpful. Lifelong regular follow-up care is necessary for the early detection of any new problems, especially glaucoma, lens, and systemic problems, so that timely treatment is given.[6] Since the condition has a dominant transmission, proper genetic counseling should be obtained.
Aniridia is shown in the images below.
See the list below:
Aniridia alone
Aniridia in association with systemic defects
Wilms tumor (20% of cases)[7, 8, 9]
Genitourinary abnormalities
Mental retardation[10]
Aniridia in association with ocular defects
Albinism
Ectopia lentis (50%)
Spontaneous lens dislocation
Arcus juvenilis
Keratoconus
Cataract (50-85%)
Glaucoma (30-50%)
Nystagmus
Strabismus
Optic nerve hypoplasia (75%)
The pathogenesis of aniridia is attributed to a primary developmental arrest of the neuroectoderm and a secondary alteration of all 3 neural crest waves of the mesenchyme. The functional development of the anterior segment is a complex interrelationship between the neural ectoderm and the neural crest waves of the mesenchyme. The pathogenesis may involve defective formation or excessive regression of various layers of the anterior segment caused by cellular or biochemical aberrations. This explains the combined anterior and posterior segment neural ectodermal and mesenchymal defects. The iris stroma is hypoplastic, indicating an altered third neural crest wave of mesenchyme.
Aniridia occurs as the following:
Autosomal disorder[11]
An identifiable chromosome deletion of the short arm of chromosome 11, including band p13[12]
Sporadic case
The exact defect in iris morphogenesis giving rise to aniridia is unknown. Because the iris pigment epithelium, the iris musculature, the retina, and the optic nerve are derived from neuroectoderm, there may be a common embryologic origin for these anomalies. As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.[13, 14, 15]
Patients with aniridia who have a positive family history are not at an increased risk for Wilms tumor. Two genetic loci for aniridia have been identified: one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.
Patients with aniridia without a positive family history have a 30% chance of developing Wilms tumor, and they represent new mutations for the autosomal dominant gene. About one third of such patients have a mutation that affects the WT and AN2 loci, causing the patient to develop Wilms tumor; the other two thirds of patients have a mutation of just the AN2 locus. Because of the high mortality from Wilms tumor, those patients with the WT and AN2 mutations have a low probability of reproducing, whereas those with just AN2 mutations have normal fertility and, hence, a 50% risk to pass the aniridia gene mutation to each child.
United States
At present, aniridia strikes 1 in 60,000 individuals; in Canada, this would represent only 475 individuals based on a present population of 28.5 million. In the United States, studies have shown the incidence to be 1 in 90,000. Based on a population of 265 million, this would represent 2945 people.
International
Aniridia is rare and has an incidence of 1 per 64,000 to 1 per 96,000 live births. About two thirds of these cases are familial.
All patients with aniridia are visually handicapped for a lifetime. This already reduced vision is threatened further by such complications as cataract and glaucoma. Those patients with Wilms tumor have a reduced span of life.
Aniridia has no racial predisposition.
Congenital glaucoma and aniridia usually are not associated at birth. The glaucoma develops at either the preteen or the teenage level.
Significant cataracts may occur before puberty. The risk for cataract increases with age, with lens opacities observed in 50-85% of patients during the first 2 decades of life.
The prognosis of aniridia varies from patient to patient.
Unmonitored and untreated elevated intraocular pressure may damage vision.
Cataract may require surgery.
Progressive corneal opacification may need corneal grafting.
Thoroughly educating the patient and parents about aniridia and the associated ocular anomalies and systemic problems is mandatory.
The history of aniridia is straightforward. The condition is discovered early in life, especially in whites. In blacks, the condition might remain undiscovered for a long time until an ophthalmologist examines the eyes for visual problems. The patient presents with the following problems:
Absence of iris
Nystagmus
Strabismus
Reduced vision
Thorough family history includes the following:
Specific inquiry about any ocular abnormality and/or low vision
Dental anomaly
Protruding umbilicus
Genitourinary abnormalities (Wilms tumor)
Mental retardation
Perform a thorough systemic examination of the patient.
A detailed ocular examination in patients with aniridia is sometimes difficult because of photophobia and nystagmus. If slit lamp flash pictures are taken, they can provide detailed information on corneal opacities and blood vessels, the depth of the anterior chamber, the edge of a transparent dislocated lens, the presence or absence of zonular fibers, and the presence of lenticular opacities. Photographs are useful to observe changes in the tissues with the passage of time. A picture session is especially important in children.[16]
The patient might show the following findings:
Nystagmus
Strabismus
Photophobia
Anterior chamber
Best judged with a slit lamp microscope
Configuration dependent upon the position of the crystalline lens
Iris
Complete absence of iris on oblique illumination
Hypoplasia with irregular pupillary margins (atypical coloboma of pupil)
Root of the iris visible on gonioscopy
Angle of the anterior chamber - Trabecular meshwork may be partially or completely covered by the iris stump.
Vitreous - Usually normal
Fundus
Optic nerve hypoplasia
Macular reflex dull
Glaucomatous cupping
Intraocular pressure
Normal
Increased
Vision - Usually about 20/200 or less
Aniridia is caused by the following:
An identifiable chromosome deletion of the short arm of chromosome 11, including band p13
Patients with aniridia who have a positive family history: Two genetic loci for aniridia have been identified, one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.
As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.
Aniridia can be complicated by the presence or association of other problems, mainly cataract and glaucoma.
Chromosomal deletion is detected by cytogenetic testing with the use of high-resolution banding.
Submicroscopic deletions of the Wilms tumor gene are recognized with a fluorescent in situ hybridization (FISH) technique.
High-resolution chromosome studies are obtained in sporadic cases to determine if there is a deletion of band 11p13.
Serial renal ultrasound examinations are indicated in patients through age 7 years, especially for those with a deletion of band 11p13 or for those with a negative family history of aniridia and normal chromosomes.[17]
Histologically, small portions of the iris are always present; the ciliary body is usually hypoplastic; and the anterior chamber angle may be normal, immature (ie, incompletely developed), or malformed. In eyes enucleated from older patients, extensive peripheral anterior synechiae that cause the iris stump to adhere to the posterior corneal surface have been observed.
Prophylaxis in patients with aniridia is directed toward the prevention of glaucoma, which includes the following:
Limbal stem cell deficiency associated with aniridia can be treated with the following:
The medical treatment of aniridia is directed toward control of intraocular pressure, which includes the topical use of the following:
The chances of failure with local antiglaucoma treatment are high.
Treatment of photophobia and nystagmus in patients with aniridia is as follows:
Refractive errors are treated with careful refraction and complete correction.
Treatment of amblyopia and strabismus in patients with aniridia is as follows:
Management of corneal opacification in patients with aniridia is as follows:
Management of cataract in patients with aniridia is as follows:
Management of glaucoma in patients with aniridia is as follows:
See the list below:
Banded chromosome analysis on the patient and both parents
Linkage analysis when large families are available
Genetic counseling
Patients with aniridia should have proper genetic counseling.
Patients should have thorough lifelong follow-up care to determine whether glaucoma is present.
Lifelong, regular, and careful follow-up care of aniridia is essential with an ophthalmologist, with particular attention to the ocular surface and glaucoma monitoring and treatment.