eMedicine Specialties > Ophthalmology > Iris & Ciliary Body

Aniridia

Daljit Singh, MBBS, MS, DSc, Professor Emeritis, Department of Ophthalmology, Guru Nanak Dev University, Amritsar, India; Director, Daljit Singh Eye Hospital
Arun Verma, MD, Senior Consultant, Department of Ophthalmology, Daljit Singh Eye Hospital, Amritsar, India

Updated: Jan 17, 2008

Introduction

Background

Aniridia is a congenital, hereditary, bilateral, extreme form of iris hypoplasia that may be associated with other ocular defects. 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.

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. Since the condition has a dominant transmission, proper genetic counseling should be obtained.

Clinical manifestation

Aniridia alone
Aniridia in association with systemic defects
- Wilms tumor (20% of cases)
- Genitourinary abnormalities
- Mental retardation
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%)

Pathophysiology

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
An identifiable chromosome deletion of the short arm of chromosome 11, including band p13
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.

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.

Frequency

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.

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

No racial predisposition exists.

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.

Clinical

History

The history 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
- Specific inquiry about any ocular abnormality and/or low vision
- Dental anomaly
- Protruding umbilicus
- Genitourinary abnormalities (Wilms tumor)
- Mental retardation
Thorough systemic examination of the patient

Physical

A detailed ocular examination 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.

The patient might show the following findings:

Nystagmus
Strabismus
Photophobia
Cornea

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

Vitreous - Usually normal
Fundus

Optic nerve hypoplasia
Macular reflex dull
Glaucomatous cupping

Intraocular pressure

Normal
Increased

Vision - Usually about 20/200 or less

Causes

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.

Differential Diagnoses

Workup

Laboratory Studies

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.

Histologic Findings

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.

Treatment

Medical Care

Prophylaxis is directed toward the prevention of glaucoma, which includes the following:
- Medical treatment with miotics
- Surgical separation of the iris from the trabecular meshwork in selected cases
The medical treatment is directed toward control of intraocular pressure, which includes the topical use of the following:
- Miotics
- Beta-blockers
- Sympathomimetics
- Carbonic anhydrase inhibitors
- Prostaglandin analogues
The chances of failure with local antiglaucoma treatment are high.
Treatment of photophobia and nystagmus
- Tinted or iris contact lenses
- Tinted spectacle lenses
- Tinted intraocular lenses (IOLs)
- By the above measures, reducing the amplitude and frequency of nystagmus is possible.
Treatment of refractive errors - Careful refraction and complete correction
Treatment of amblyopia and strabismus
- Usually, the potential visual acuity in both eyes should be symmetrical.
- When the vision is unequal without structural difference, vigorous amblyopia exercises should be performed in the worst eye.
- Binocularity can be achieved if macular hypoplasia is not severe.
- Strabismus surgery is indicated at an early age.

Surgical Care

Management of corneal opacification
- Keratoplasty
- Keratoprosthesis
Management of cataract
- 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 contact lens correction, if the lens is grossly out of place
Management of glaucoma
- Goniotomy
  - Prophylactic
  - Early surgical therapy - Some risk to the crystalline lens and the zonules exists because the surgery is performed from the anterior approach.
- 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.

Consultations

Banded chromosome analysis on the patient and both parents
Linkage analysis when large families are available
Genetic counseling

Follow-up

Further Outpatient Care

Lifelong, regular, and careful follow-up care is essential.

Deterrence/Prevention

Patients should have proper genetic counseling.
Patients should have thorough lifelong follow-up care to determine whether glaucoma is present.

Complications

Aniridia can be complicated by the presence or association of other problems, mainly cataract and glaucoma.

Prognosis

Prognosis 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.

Patient Education

Thoroughly educating the patient and parents about this condition and the associated ocular anomalies and systemic problems is mandatory.

Miscellaneous

Medicolegal Pitfalls

Failure to detect glaucoma
Failure to educate the patient regarding all aspects of the disease, including the genetic aspects
Failure to refer for a thorough systemic checkup

Special Concerns

Structural iris defects: These defects may present as full-thickness holes through the iris with or without sphincter involvement. A more extensive defect with most of the iris absent is seen in aniridia.
Other associated ocular anomalies and systemic problems are as follows:
- Wilms tumor
- Mental retardation
- WAGR (Wilms tumor, aniridia, genitourinary abnormalities, mental retardation) syndrome

Multimedia

Media file 1: Aniridia with superiorly dislocated cataract.

Media file 2: Aniridia. Close-up of the superior limbus of same patient as in Media file 1, to show pannus.

Media file 3: Aniridia with a vascularized corneal opacity in a young patient.

Media file 4: Centrally placed cataractous lens and aniridia in a pediatric patient.

Media file 5: 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.

Media file 6: Aniridia and aphakia following perforating injury.

Media file 7: Single piece intraocular lens inside the bag, in a case of aniridia.

Media file 8: Multipiece intraocular lens inside the bag, in a case of aniridia.

Media file 9: In-the-bag intraocular lens. The lens has been displaced superiorly.

Media file 10: Aniridia. A single piece nonfoldable lens has been implanted after placing an endocapsular ring. An endocapsular ring provides better chances of centration.

Media file 11: 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.

References

Akpek EK, Harissi-Dagher M, Petrarca R, Butrus SI, Pineda R 2nd, Aquavella JV, et al. Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter study. Am J Ophthalmol. Aug 2007;144(2):227-231. [Medline].
Dharmaraj N, Reddy A, Kiran V, Mandal A, Panicker S, Chakrabarti S. PAX6 gene mutations and genotype-phenotype correlations in sporadic cases of aniridia from India. Ophthalmic Genet. Sep 2003;24(3):161-5. [Medline].
Elsas FJ, Maumenee IH, Kenyon KR, Yoder F. Familial aniridia with preserved ocular function. Am J Ophthalmol. May 1977;83(5):718-24. [Medline].
Fantes JA, Bickmore WA, Fletcher JM, Ballesta F, Hanson IM, van Heyningen V. Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization. Am J Hum Genet. Dec 1992;51(6):1286-94. [Medline].
François J, Coucke D, Coppieters R. Aniridia-Wilms' tumour syndrome. Ophthalmologica. 1977;174(1):35-9. [Medline].
Friedman AL. Wilms' tumor detection in patients with sporadic aniridia. Successful use of ultrasound. Am J Dis Child. Feb 1986;140(2):173-4. [Medline].
Glaser T, Walton DS, Maas RL. Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet. Nov 1992;2(3):232-9. [Medline].
Grant WM, Walton DS. Progressive changes in the angle in congenital aniridia, with development of glaucoma. Am J Ophthalmol. Nov 1974;78(5):842-7. [Medline].
Green DM, Breslow NE, Beckwith JB, Norkool P. Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study. Med Pediatr Oncol. 1993;21(3):188-92. [Medline].
Hittner HM. Aniridia. In: Robert ED, Shields MB, et al, eds. The Glaucomas. St. Louis: Mosby; 1989:869-884.
Jastaneiah S, Al-Rajhi AA. Association of aniridia and dry eyes. Ophthalmology. Sep 2005;112(9):1535-40. [Medline].
Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L. Aniridia. A review. Surv Ophthalmol. May-Jun 1984;28(6):621-42. [Medline].
Nevin NC, Lim JH. Syndrome of partial aniridia, cerebellar ataxia, and mental retardation--Gillespie syndrome. Am J Med Genet. Apr 1990;35(4):468-9. [Medline].
Pearce WG. Variability of iris defects in autosomal dominant aniridia. Can J Ophthalmol. Feb 1994;29(1):25-9. [Medline].
Pilling GP. Wilms' tumor in seven children with congenital aniridia. J Pediatr Surg. Feb 1975;10(1):87-96. [Medline].
Riccardi VM, Sujansky E, Smith AC, Francke U. Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. Pediatrics. Apr 1978;61(4):604-10. [Medline].
Roy FH. Ocular Differential Diagnosis. 7^th ed. Lippincott Williams & Wilkins; 2002.
Roy FH. Ocular Syndromes and Systemic Disease. 3^rd ed. Lippincott Williams & Wilkins; 2002.
Schroeder HW, Orth U, Meyer-König E, Gal A. [Hereditary foveal hypoplasia - clinical differentiation]. Klin Monatsbl Augenheilkd. Aug 2003;220(8):559-62. [Medline].
Vincent MC, Pujo AL, Olivier D, Calvas P. Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. Eur J Hum Genet. Feb 2003;11(2):163-9. [Medline].
Walton DS. Aniridic glaucoma: the results of gonio-surgery to prevent and treat this problem. Trans Am Ophthalmol Soc. 1986;84:59-70. [Medline].
Wong VW, Lam PT, Lai TY, Lam DS. Black diaphragm aniridia intraocular lens for aniridia and albinism. Graefes Arch Clin Exp Ophthalmol. May 2005;243(5):501-4. [Medline].

Keywords

absence of iris, partial or complete absence of iris, congenital aniridia, iridemia, iris hypoplasia, panocular disorder, cataract

Contributor Information and Disclosures

Author

Daljit Singh, MBBS, MS, DSc, Professor Emeritis, Department of Ophthalmology, Guru Nanak Dev University, Amritsar, India; Director, Daljit Singh Eye Hospital
Daljit Singh, MBBS, MS, DSc is a member of the following medical societies: All India Ophthalmological Society, American Society of Cataract and Refractive Surgery, Indian Medical Association, International Intraocular Implant Club, and Intraocular Implant and Refractive Society, India
Disclosure: Nothing to disclose.

Coauthor(s)

Arun Verma, MD, Senior Consultant, Department of Ophthalmology, Daljit Singh Eye Hospital, Amritsar, India
Disclosure: Nothing to disclose.

Medical Editor

Richard W Allinson, MD, Associate Professor, Division of Ophthalmology, Texas A&M University Health Science Center, Associate Professor, Department of Surgery, Scott and White Clinic
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Further Reading