Aniridia in the Newborn
Article Last Updated: Aug 4, 2008
AUTHOR AND EDITOR INFORMATION
Author: Sophie Bakri, MD, Assistant Professor of Ophthalmology, Vitreoretinal
Diseases and Surgery, Mayo Clinic of Rochester
Sophie Bakri is a member of the following medical societies: American Academy
Coauthor(s): John W Simon, MD, Chair, Department of Ophthalmology,
Professor, Departments of Ophthalmology and Pediatrics, Albany Medical
Editors: Gerhard W Cibis, MD, Clinical Professor, Director of Pediatric
Ophthalmology Service, Department of Ophthalmology, University of Kansas,
Kansas City; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor,
eMedicine; J James Rowsey, MD, Former Director of Corneal Services, St
Luke's Cataract and Laser Institute, Florida; Lance L Brown, OD, MD,
Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital,
Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical
Professor, Department of Ophthalmology, University of Arkansas for Medical
Author and Editor Disclosure
Synonyms and related keywords: aniridia, congenital aniridia, aniridia in
newborn, iris hypoplasia, absence of iris, iris absence, Wilms tumor, Wilm's
tumor, nephroblastoma, WAGR complex, Miller syndrome, pediatric glaucoma,
In 1818, Barratta first described aniridia (Greek for absence of the iris). Aniridia is
a rare, bilateral, panophthalmic disorder, of which iris hypoplasia is the most
striking feature. Aniridia also has corneal, lens, optic nerve, and retinal
manifestations. Foveal and optic nerve hypoplasia are often present, causing a
reduction in visual acuity and congenital sensory nystagmus. Progressive
worsening of vision may occur later in life as a result of cataracts, glaucoma, and
Aniridia may be familial or sporadic. It is caused by a mutation in the PAX6 gene
on chromosome 11.
Approximately 85% of cases are familial (designated AN1) with autosomal
dominant inheritance with complete penetrance but variable expressivity. These
familial cases usually have isolated ocular involvement.
The 15% of cases that are sporadic have a deletion or mutation on the short arm
of chromosome 11. The same deletion is responsible for the development of
Wilms tumor (nephroblastoma).
The exact pathogenesis of aniridia is unknown. After early reports of ocular
colobomas in patients with aniridia, some authors proposed that it is a
colobomatous disorder. Others attributed it to a failure of mesodermal
development with involvement of the rim of the optic cup, causing iris hypoplasia.
Still others advocated the neuroectodermal theory, which links the presence of
retinal anomalies and iris muscular hypoplasia to a developmental failure of
Aniridia is a very rare disorder. According to a population-based study in
Michigan, it has been estimated to affect approximately 1 per 61,000 newborns.
A more recent study from Denmark reported the incidence as 1 per 96,000 live
Aniridia itself is not a lethal disorder. However, miscarriages and a stillborn child
have been the only results of a consanguineous mating between individuals with
aniridia. A homozygous mutation of the aniridia gene may possibly be lethal. The
morbidity of aniridia is significant because of the decreased vision and
No racial predilection has been described.
The incidence of aniridia is equal in males and females.
Aniridia is a congenital disorder apparent at birth. It is never acquired.
An infant may come to medical attention with nystagmus or photophobia.
Patients may present with strabismus and amblyopia. The family may notice an
abnormal pupil, or they may describe a fixed, dilated pupil.
Visual acuity is reduced, usually to around the 20/100 level. Pendular nystagmus,
strabismus, and amblyopia may be present. Nystagmus occurs in 85-92% of
patients. Ocular examination reveals absence of the irides or dilated
unresponsive pupils. Other findings may include small anterior polar cataracts,
pupillary membrane remnants, ectopia lentis (in 18-35%), corneal pannus,
progressive keratopathy, and optic nerve or foveal hypoplasia.
Poor vision in infancy often is due to foveal or optic nerve hypoplasia and
secondary nystagmus. Acquired vision loss may be due to cataract (present in
85% of cases), glaucoma (present in 70%), keratopathy, or amblyopia.
Some have considered aniridia a misnomer because a rudimentary stump of
tissue usually can be found behind the limbal sclera by gonioscopy. The
diagnosis can be very difficult to make in patients with a substantial amount of iris
tissue. However, characteristic absence of the pupillary rim, iris sphincter muscle,
and central iris tissue is noted.
Syndromes associated with aniridia
o Miller syndrome (WAGR complex, 11p- syndrome)
Approximately 30% of patients with sporadic aniridia develop
Wilms tumor, usually before age 5 years. The association
between aniridia and Wilms tumor is referred to as Miller
syndrome, after his 1964 report of 6 cases of aniridia among
440 cases of Wilms tumor. It was reported that 1.4% of
patients with Wilms tumor have aniridia compared to 1 in
64,000 to 1 in 100,000 of the general population.
Affected children have other genitourinary abnormalities,
craniofacial dysmorphism, hemihypertrophy, and severe
mental retardation. They also may have poorly lobulated
low-set ears, prominent noses, and long narrow facies. The
acronym WAGR (Wilms tumor, aniridia, genitourinary
anomalies, and mental retardation) describes some of the
features of Miller syndrome.
Miller syndrome has been attributed to a deletion of band
11p13. Patients with sporadic aniridia should undergo a
thorough physical examination and workup by a family
practitioner or pediatrician.
o Gillespie syndrome
Gillespie syndrome is the association of aniridia, cerebellar
ataxia, and mental retardation. It is autosomal recessive,
occurring in approximately 2% of patients with aniridia.
These patients have anatomical defects in the cerebellum
and other parts of the brain, and they are not predisposed to
developing Wilms tumor.
A study of the PAX6 gene in Gillespie syndrome failed to find
a mutation, suggesting that abnormalities in the PAX6 gene
are not responsible for this syndrome.
Glaucoma is one of the major causes of visual loss in
patients with aniridia, with a reported incidence of 6-75%.
This variation is explained by the referral patterns of the
various institutions, the variable phenotypic expression of
aniridia, and the definitions of glaucoma. Glaucoma in
aniridia is rare in infants and newborns and typically is
acquired in early adulthood. As a result of its delayed onset,
the clinical findings of megalocornea, buphthalmos, and
Haab striae typically are not found.
Progressive apposition of the rudimentary stump of iris to the
trabecular meshwork is believed to occur during the first 2
decades of life. In patients without glaucoma, the structures
of the anterior chamber angle appear normal by gonioscopy.
In older patients with aniridic glaucoma, the severity of the
glaucoma is related to the proportion of the filtration angle
covered by the iris stump. The periphery of the hypoplastic
stump of iris may insert anteriorly, and even where it is more
open, the scleral spur and ciliary body band may be defined
poorly. In the rare cases of infants with aniridic glaucoma,
filtration-angle defects are present at birth. In these cases,
the angle usually is covered by vascularized sheets
extending from the iris, rather than being blocked by the iris
Cataracts occur in 50-85% of patients with aniridia, usually
acquired during the first 2 decades of life. At birth, small lens
opacities may be noted, but these typically are not visually
significant. Types of cataracts described include anterior
polar, pyramidal, nuclear, lamellar, and cortical.
Visually significant cataracts in neonates require prompt
surgical extraction to prevent amblyopia. However, in
patients whose cataracts develop later, the factor most
strongly limiting visual acuity is the presence of foveal
hypoplasia, not the cataract. Areas of clear space may be
present in the cataractous lens, which allows for relatively
good vision. In these patients, surgery is best delayed, since
the risks of glaucoma developing or progressing in aniridic
eyes outweighs the small potential for visual improvement.
o Ectopia lentis: Some investigators have reported lens subluxations
in as many as 56% of eyes with aniridia, while others have reported
none. This finding may be due to failure to detect mild cases. The
zonules are believed to be histologically normal, but their molecular
structure is not understood clearly.
o Corneal defects
Progressive corneal opacification and pannus occur in most
patients, developing as early as age 2 years. Initially, fine
radial vessels invade the superficial layers of the peripheral
cornea at the 6- and 12-o'clock positions and, then, involve
the whole circumference. This process may progress to
involve the entire cornea, requiring corneal transplantation.
Pathologically, the pannus seen in aniridic keratopathy is
quite unusual; the corneal epithelium may harbor ectopic
conjunctival goblet cells, and inflammatory cells are usually
present. The pathogenesis is uncertain, but many theories
have been proposed. It has been attributed to a total
absence of the limbal girdles of Vogt and corneal epithelial
limbal stem cells. PAX6 has been found in corneal and
conjunctival epithelia, and it is believed that this gene may
play a role in the activity of corneal stem cells.
Microcornea also has been found in most cases of aniridia.
o Optic nerve and foveal hypoplasia
Posterior segment abnormalities include both macular and
optic nerve hypoplasia. Approximately 75% of patients with
aniridia have some degree of optic nerve hypoplasia. The
macula and optic nerve are usually normal in patients with
Gillespie syndrome. Mild cases may be difficult to detect
because of nystagmus and corneal or lens opacities. Poor
macular or retinal development may be responsible for the
optic nerve hypoplasia. Because the retina is derived from
neuroectoderm, as are the iris epithelium and musculature,
foveal hypoplasia often is associated with aniridia.
Decreased vision and nystagmus in patients with aniridia
result from faulty development of the macula, not the iris.
There appears to be no correlation between the degree of
iris hypoplasia and foveal hypoplasia. In some patients,
foveal hypoplasia may be so subtle that fluorescein
angiography may be necessary to demonstrate lack of the
foveal avascular zone.
o Strabismus: This is a common finding in patients with aniridia, and
esotropia most frequently is found. A full cycloplegic refraction is
warranted because amblyopia may occur from anisometropia or
o Nystagmus: This is commonly pendular secondary to poor vision
from foveal hypoplasia. It may improve with visual maturation.
o Peripheral retinal lipoidal deposits have been reported in at least 3
o Electroretinogram (ERG) amplitudes are low in patients with worse
than 20/60 vision, while patients with better vision may have high
a:b wave ratios.
See related CME at Neuro-ophthalmology and Pediatric Ophthalmology.
Aniridia may be familial or sporadic. It is caused by a mutation in the PAX6 gene
on chromosome 11.
Glaucoma, Complications and Management of Glaucoma Filtering
Histopathologic examination of advanced cases of aniridia reveals only stubs of
iris tissue that lack dilator and sphincter muscles, both neuroectodermal
Medical management of glaucoma associated with aniridia
o Medical therapy of the glaucoma is the initial treatment of choice. It
initially may be efficacious in reducing intraocular pressure, but
most patients with aniridia who have glaucoma eventually require
o Miotics often are tried first; they improve aqueous outflow by
contracting the ciliary muscle. However, the induced myopia may
not be well tolerated by young patients. Adrenergic agonists, beta-
blockers, and carbonic anhydrase inhibitors also may be tried, but
they often are ineffective long term as the patient becomes
refractory to them. Whenever a new medication is to be instituted, a
trial should be performed, adding and removing only one
medication at a time.
o Patients with aniridia may be emmetropic, myopic, or hyperopic.
Spectacle or contact lens correction of significant refractive errors
should begin in the newborn. In cases of lens subluxation, the
refractive error should be corrected through the aphakic portion of
o To lessen photophobia, patients may be fitted with tinted or iris
contact lenses or with tinted spectacle lenses at any age.
Treatment of amblyopia and strabismus: In cases of strabismus, patching
of the favored eye is indicated to treat amblyopia. Cycloplegic refraction
should be performed, and appropriate correction should be given.
Strabismus surgery may be indicated at an early age to enhance
No convincing opinion exists as to which surgical procedure is the treatment of
choice for aniridic glaucoma; none has been considered reliable and predictable
in efficacy. Surgical procedures for the treatment of aniridic glaucoma include the
o Although goniotomy has been suggested early in the management
of aniridic glaucoma, reported series have shown disappointing
results. The procedure is hazardous in these eyes, since the
Barkan goniotomy knife is passed over the vulnerable lens and
zonules in the anterior chamber. However, results of prophylactic
goniotomy have been encouraging.
o Two separate surgeries on each eye may be performed to strip the
tissue extending over the trabecular meshwork, working on 180° of
the angle each time. The benefit of this prophylactic procedure is
not yet proven, and it should be delayed until after the first year of
life. Because of the shallow anterior chamber angle, patients with
aniridia should have gonioscopy performed yearly. If the iris
processes are becoming more prominent, strong consideration
should be given to performing a prophylactic goniotomy.
Trabeculotomy: This procedure is considered safer than goniotomy, since
it relies on the posterior approach (ab externo), which avoids the lens and
zonules. However, it is not without risk and has been associated with the
need for repeat surgery.
Trabeculectomy: Most surgeons opt for trabeculectomy after a few
attempts at goniotomy or trabeculotomy. However, the risk of vitreous loss
is increased in aniridia, and cataract formation or progression may occur
with inadvertent damage to the lens during surgery. Nelson et al reported
that 5 of 14 patients needed reoperation or had failure with
trabeculectomy1; others have reported initial success rates from 0-9%.
Setons: The success rate of the Molteno implant has been reported as
83% of 6 eyes. This device cannot be recommended as the initial
operation of choice because of the higher risk of complications.
Cyclophotocoagulation and cyclocryotherapy: Both these modalities are
designed to destroy part of the ciliary body. Cyclophotocoagulation is
performed with the yttrium-aluminum-garnet (YAG) laser. Both methods
must be split into multiple treatment sessions to avoid complications, such
as uveitis, phthisis bulbi, uveal effusion, vitreous hemorrhage, and
prolonged hypotony. Cryotherapy may accelerate peripheral corneal
opacification or cataract progression. Therefore, these procedures must
be approached with extreme caution, and they have been associated with
hypotony and vitreous hemorrhage.
Cataract extraction: When the cataract is dense, removal may result in
some improvement in visual acuity. Lensectomy performed with an
aspiration-cutting instrument has been recommended. Capsule-supported
intraocular lenses are not appropriate for patients with ectopia lentis.
Penetrating keratoplasty: This may be indicated for corneas that have
opacified from pannus. However, the prognosis is guarded because of
rejection and underlying amblyopia or other structural defects.
o All patients with aniridia should be referred for genetic counseling.
A full family history should be sought, with specific attention to
ocular abnormalities, low vision, genitourinary abnormalities, Wilms
tumor, and mental retardation.
o A full physical examination should be performed concentrating on
the genitourinary system. Imaging of the abdomen and brain,
preferably MRI, is indicated.
o Chromosome analysis of the patient and family members and
genetic analysis of the PAX6 gene should be performed.
o Parents and close relatives should have a careful ocular
o Fluorescein angiography of the iris and fundus may reveal subtle
abnormalities not found clinically, for example, abnormalities of the
iris collarette and foveal avascular zone.
Currently, no medications are approved by the US Food and Drug Administration
(FDA) for the treatment of pediatric glaucoma. Medications, such as miotics,
topical beta-blockers, and topical carbonic anhydrase inhibitors, have been tried;
however, these medications must be prescribed only after a full discussion of
their risks and benefits with the parents. The doses are not discussed here since
the medications are not approved by the FDA.
Further Outpatient Care
Patients should be observed by the ophthalmologist as indicated,
depending on the complications and their severity.
In/Out Patient Meds
Available medications are discussed in Medical Care and Medication.
The complications of aniridia are discussed throughout this article.
The prognosis and visual acuity level varies depending on the
complications of aniridia. Generalizations cannot be made.
The parents of the patient should be educated about the disease.
Education should be geared toward maintaining careful follow-up care of
the specific ocular complications of aniridia being experienced by the
Medical/legal pitfalls relate to mismanagement of the specific
complications of aniridia.