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.
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Aniridia with a vascularized corneal opacity in a young patient.
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Centrally placed cataractous lens and aniridia in a pediatric patient.
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.
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.
Mortality/Morbidity
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.
Race
Aniridia has no racial predisposition.
Age
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 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
Cornea
Pannus (shown in the images below)
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Aniridia with superiorly dislocated cataract.
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Aniridia. Close-up of the superior limbus of same patient as in the image above to show pannus.
Epithelial ulcers
Aniridic keratopathy
Arcus juvenilis
Microcornea
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.
Crystalline lens
Transparent or opaque
Ectopia lentis
Completely dislocated lens (shown in the image below)
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In-the-bag intraocular lens. The lens has been displaced superiorly.
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.
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.
Management of corneal opacification in patients with aniridia is as follows:
Limbal stem cell transplantation
Keratoplasty
Keratoprosthesis[20]
Management of cataract in patients with aniridia is as follows:
In-the-bag lens implantation in cases without lens dislocation
Use of opaque intracapsular rings to produce an artificial pupil or use of a large intraocular lens with a clear central optic and an opaque periphery
In-the-bag IOL placement with intracapsular rings, when there is slight lens displacement
Lens extraction followed by tinted/artificial pupil scleral-fixated posterior chamber lens
Lens extraction followed by contact lens correction, if the lens is grossly out of place
Management of glaucoma in patients with aniridia is as follows:
Goniotomy: This includes prophylactic and early surgical therapy. In early surgical therapy, some risk to the crystalline lens and the zonules exists because the surgery is performed from the anterior approach.[21]
Trabeculotomy is safer than goniotomy. The tissues can be defined more clearly, and accurate surgery can be performed. However, failures are common.
Filtering procedures: Greater danger of injury to the crystalline lens and disturbance of the vitreous exists because the iris is absent. Nonperforating filtration surgery techniques are safer, because the anterior chamber remains undisturbed. Since glaucoma develops in young patients with aniridia, the intraoperative use of mitomycin is justified. Fugo blade can be used to produce a transconjunctival microfiltration track of 200-300 µm in any part of the angle, away from the lens and the vitreous.
Laser therapy to angle abnormalities
Cyclocryotherapy: Endocyclophotocoagulation in selected cases
Glaucoma valve procedure: The choice of the techniques and the order in which they are used depends upon the peculiarities of the case and the perception of the surgeon.
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.
Michael Ross, MD, Clinical Instructor, University of British Columbia Faculty of Medicine, Canada
Disclosure: Nothing to disclose.
Coauthor(s)
Jean Deschênes, MD, FRCSC, Professor, Research Associate, Director, Uveitis Program, Department of Ophthalmology, McGill University Faculty of Medicine; Senior Ophthalmologist, Clinical Director, Department of Ophthalmology, Royal Victoria Hospital, Canada
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute
Disclosure: Nothing to disclose.
Chief Editor
Michael Taravella, MD, Director of Cornea and Refractive Surgery, Rocky Mountain Lions Eye Institute; Professor, Department of Ophthalmology, University of Colorado School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: J&J Vision (Consultant)/Proctor<br/> for: Coronet Surgical (Consultant), no income received.
Additional Contributors
Arun Verma, MD, Senior Consultant, Department of Ophthalmology, Dr Daljit Singh Eye Hospital, India
Disclosure: Nothing to disclose.
Daljit Singh, MBBS, MS, DSc, † Professor Emeritus, Department of Ophthalmology, Guru Nanak Dev University; Director, Daljit Singh Eye Hospital, India
Disclosure: Nothing to disclose.
Richard W Allinson, MD, Associate Professor, Department of Ophthalmology, Texas A&M University Health Science Center; Senior Staff Ophthalmologist, Scott and White Clinic
Disclosure: Nothing to disclose.
References
Hittner HM. Aniridia. Robert ED, Shields MB, et al, eds. The Glaucomas. St. Louis: Mosby; 1989. 869-884.
Aniridia with a vascularized corneal opacity in a young patient.
Centrally placed cataractous lens and aniridia in a pediatric patient.
Aniridia with superiorly dislocated cataract.
Aniridia. Close-up of the superior limbus of same patient as in the image above to show pannus.
In-the-bag intraocular lens. The lens has been displaced superiorly.
Aniridia with superiorly dislocated cataract.
Aniridia. Close-up of the superior limbus of same patient as in the image above to show pannus.
Aniridia with a vascularized corneal opacity in a young patient.
Centrally placed cataractous lens and aniridia in a pediatric patient.
Aniridia. 3-D image showing absence of the inferior half of the iris and absence of most of the anterior leaf of the iris in the upper half. In the less affected area, the iris is represented mostly by the posterior pigment epithelium. No choroidal coloboma was present.
Aniridia and aphakia following perforating injury.
Single piece intraocular lens inside the bag, in a case of aniridia.
Multipiece intraocular lens inside the bag, in a case of aniridia.
In-the-bag intraocular lens. The lens has been displaced superiorly.
Aniridia. A single piece nonfoldable lens has been implanted after placing an endocapsular ring. An endocapsular ring provides better chances of centration.
Partial traumatic aniridia. The lost iris gap has been covered by the use of a lens optic that is clear in the center and is opaque at the periphery. A scleral fixated lens has been used in this case.
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