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Aniridia: for professionals


  • Autosomal dominant
  • de novo sporadic
Genes involved
(OMIM no.)
  • Reduced visual acuity
  • Photophobia
Ocular features
Systemic features
Key investigations
  • OCT: foveal and iris hypoplasia
  • UBM: to detect iris hypoplasia if corneal oedema is present
  • USS B-scan: to measure axial length and document microphthalmia
  • Renal USS to detect for Wilms tumour
Molecular diagnosis
  • Chromosomal microarray: exclude WT1 and PAX6 deletion
  • Direct sequencing: detect variants in PAX6 for isolated aniridia
  • Supportive
  • Correct refractive errors, prevent amblyopia
  • Monitor for complications and treat accordingly
  • Serial 3 monthly renal USS till age 8 for confirmed WT1 deletions
  • Multidisciplinary approach to other associated systemic issues
Therapies under researchNonsense suppression therapy (phase 2)

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Clinical phenotype

Presenting features

Aniridia is a pan-ocular disorder with iris hypoplasia being most characteristic. Most children present at birth with an obvious iris or pupillary abnormality or during infancy with nystagmus. Visual acuity is usually impaired due to foveal hypoplasia but the severity can vary between and within families, with some displaying subtle changes to the iris architecture, good vision, and normal foveal structure. Affected individuals tend to have symmetrical ocular findings. 

A patient with no iris, typical of aniridia and some catarac
Iris hypoplasia with lens opacities

Other ocular features

Apart from iris hypoplasia, aniridia can be associated with the following features[2] :

  • Microphthalmia, anophthalmia, coloboma (MAC) spectrum
  • Strabisumus
  • Aniridia-related keratopathy leading to progressive corneal opacification 
  • Secondary glaucoma but congenital glaucoma can rarely occur[3] 
  • Cataract
  • Lens subluxation
  • Exudative vascular retinopathy
  • Choroidal degeneration 
  • Optic nerve hypoplasia
The usually transparent cornea is now covered with blood vessels from the conjunctiva, causing it to be opaque.
Aniridia-related keratopathy

Associated extraocular features

Contiguous deletion of PAX6 and the adjacent WT1 gene causes WAGR syndrome. However, mutations in PAX6 alone can be associated with the following systemic features[2],[4-6]:

  • Central auditory processing deficits
  • Behavioural problems
  • Sleep disorders
  • Obesity 
  • Glucose intolerance 

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1) Gene: PAX6 (11p13)

OMIM no.: #607108

Protein: Paired Box 6

Location of expression: Ubiquitously expressed, mainly in the brain and eye

Function: A highly conserved transcription regulator that is involved in the early development of the eye, brain, olfactory bulb, neural tube, pancreas and gutin the embryo[1] 99%[2] of isolated aniridia are due to mutations in PAX6.

2) Gene: ELP4 (11p13)

OMIM no.: #606985

Protein: Elongator acetyltransferase complex subunit 4

Location of expression: Ubiquitously expressed throughout body

Function: An ultra-conserved PAX6 cis-regulatory element (SIMO) that is critical in maintaining the transcription of the PAX6 gene during embryonic development.[2] 

3) Gene: WT1 (11p13)

OMIM no.: #607102

Protein: Wilms tumour 1

Location of expression: Developing kidneys and gonads

Function: Development of kidneys and gonads before birth. Postnatally, the WT1 protein regulates renal cell division, differentiation and apoptosis. Deletion of the WT1 gene leads to unregulated cell cycle and thus increases the risk Wilms tumour formation.[7] 

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Key investigations


1) Optical coherence tomography (OCT)

OCT can be used to detect fovea hypoplasia and support a clinical diagnosis especially where iris defects may be subtle. Anterior segment OCT is able to help delineate anterior segment structures even in the presence of corneal opacity.[8]

OCT scan of the macula showing the absence of a pit which is normally present in normal individuals.
OCT scan of the left macula of a PAX6 aniridia patient showing foveal hypoplasia

2) High-frequency ultrasound biomicroscopy (UBM)

This is usually performed in infants (under general anaesthesia) presenting with corneal opacity or corneal oedema associated with congenital glaucoma. It is able to assess for iris hypoplasia and/or absence.

3) Ultrasound B-scan

This should be performed routinely to assess axial length (AL) due to the association with microphthalmia. It is defined as AL < 19mm in infants at 1 year of age or <21mm in adults. 

4) Electrophysiology

To assess level of vision and exclude other causes of nystagmus such as ocular or oculocutaneous albinism


Children should be referred to a paediatrician for investigation of systemic features which include:

  • Serial 3 monthly renal ultrasound for children under the age of 8 whilst awaiting genetic results
  • Audiology
  • MRI brain imaging
  • Endocrine assessment (if indicated)
  • Sleep assessment (if indicated)

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New patients should be under joint care with a paediatrician and have genetic testing done urgently either by a clinical geneticist or an ophthalmologist specialising in genetic eye disease as follows:

  • Chromosomal microarray to exclude deletions of PAX6 and WT1 (WAGR syndrome)
  • Direct sequencing of PAX6 and rarely ELP4 if a chromosomal deletion is not detected
  • Whole genome sequencing to identify novel mutations in genes or non-coding regulatory elements

Related links

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Supportive management:

  • Observe visual development, treat amblyopia if present
  • Regular refraction
  • Advise tinted/photochromic lenses. Contact lens might not be suitable due to ARK
  • Regular monitoring by glaucoma specialists
  • Cataract surgery if indicated
  • Referral to corneal specialists if evidence of limbal stem cell deficiency
  • Referral to low vision services
  • Direct patients to supporting organisations
  • Consider registration if criteria met
This shows an aniridia patient who has undergone cataract surgery. A clear artificial lens is seen inside the eye.
An aniridia patient after cataract surgery with a clear IOL


Children diagnosed with WAGR syndrome require serial 3 monthly renal ultrasound monitoring by paediatricians until the age of 8 due to the increased risk of developing Wilms tumour (90% of patients develop by age 4 and 98% develop by 7 years old).[9] They will need to be managed by the appropriate multidisciplinary team due to other systemic issues.

For children that did not receive genetic testing or refused to, they need to be monitored similarly as children with confirmed WT1 deletion until the age of 8. If WT1 deletion is negative, regular renal ultrasound monitoring is not required.[2]

Visual impairment can have a negative impact on a child’s early general development. Therefore, timely referral to practitioners familiar with developmental surveillance and intervention for children with visual impairment (VI), such as developmental paediatricians as well as a Qualified Teacher of children and young people with Visual Impairment (QTVI) is crucial to optimise their developmental potential.

The Developmental Journal for babies and young children with visual impairment (DJVI) is a structured early intervention programme designed to track developmental and vision progress from birth to three years of age. It is mainly used by qualified healthcare professionals working in services providing support to babies and young children with VI in conjunction with the child’s parents.

Children with VI may be referred to specialist services such as the developmental vision clinic in the Great Ormond Street Hospital for Children or other specialist developmental services for further management.

Family management and counselling

  • Proband with positive family history

It will be inherited in an autosomal dominant pattern.[2]

  • Proband with negative family history (sporadic aniridia)

Careful examination of both parents is required due to phenotypic variability among family members. Genetic testing of both parents is recommended to confirm a sporadic case.

Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients in clinic. They provide emotional and practical support to help patients deal with their diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist service

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research.

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Current research in aniridia

1) Nonsense suppression therapy

Nonsense suppression therapy is a new drug-based treatment targeting conditions caused by nonsense mutations. A nonsense mutation introduces an abnormal “stop” signal into a gene that halts protein production prematurely, resulting in a protein which is too short and not functional. A drug called ataluren (TranslarnaTM) modifies the affected cell to “ignore” these abnormal “stop” signals and produce normal full-length functional protein.

Up to 40%[6] of patients with aniridia are due to nonsense mutations. Animal studies have shown that ataluren eye drops is able to reverse the developmental defects associated with aniridia when given at a specific time frame after birth.[7][8]

In a pre-clinical study conducted by Professor Moosajee’s team, 3D optic cups and 2D limbal epithelial stem cell (LESC) models were created using induced pluripotent stem cells to accurately replicate reduced PAX6 protein levels. Amlexanox, identified as a promising translational readthrough-inducing drug (TRID), and effectively increased full-length PAX6 levels in both models, normalizing disease-specific abnormalities. This highlights iPSC-derived cells as a valuable model and suggests amlexanox as a potential treatment for aniridia with PAX6 nonsense mutations.Top of Form

A clinical trial called Study of Ataluren in Participants With Nonsense Mutation Aniridia (STAR) was conducted to assess the safety and effectiveness of oral ataluren in patients with aniridia due to nonsense mutations, however, the trial failed to meet its primary endpoints.

Dr Gregory-Evans speaking about her research in using nonsense suppression therapy to treat aniridia

2) Limbal stem cell transplant

(a) Role of limbal stem cells

Limbal stem cells reside in a specialised microenvironment called the limbal niche. It is characterised by extracellular matrix, signalling molecules and various supporting cells (fibroblasts, melanocytes and vascular cells).[13] The stem cells are dependent on the limbal niche to function optimally and maintain corneal epithelium homeostasis.

(b) Role of PAX6 mutation in ARK

PAX6 mutation causes dysfunction of the limbal stem cells, its associated niche and the limbal barrier.[13][14] Consequently, this affects corneal epithelial healing, corneal epithelial integrity and conjuntivalisation of the cornea. Patients with ARK may require surgery if the central corneal opacity is severely impacting vision.

(c) Types of transplant

  • Allografts

Penetrating keratoplasty alone usually results in graft failure as limbal stem cell deficiency is not addressed.[1] As a result, limbal stem cell allografts (due to bilateral nature of aniridia), either in the form of cultured stem cell sheet or direct tissue transplant are indicated.[15]However, these therapies have variable long term results[16][17] and lifelong systemic immunosuppression might be required to prevent rejection.

  • Cultivated oral mucosal epithelial transplantation (COMET)

To avoid systemic immunosuppression use, COMET has been used instead to achieve ocular surface stability. However, the associated visual outcomes are sub-optimal as the transplanted epithelium does not convert to a corneal phenotype, producing a thicker and more opaque epithelium.[18] The long term outcome of this technique is not available yet.

The variable outcomes associated with the above treatment strategies is in part due to the failure of restoring the dysfunctional limbal niche.[18] In addition, the amniotic membranes used as limbal stem cell scaffolds are biologically variable and carries a small risk of infectious disease transmission.[19] Due to these challenges, RAFT was developed as an alternative extracellular matrix scaffold. It is a type 1 collagen hydrogel based substrate cast moulded to mimic the limbal niche architecture.Proper alignment of the niche was demonstrated with the detection of corneal epithelium on the surface, limbal stem cell markers in the basal layer and limbal fibroblasts in the stroma.[19] While amniotic membranes rely on suitable donors, RAFT plates can be manufactured consistently with low risk of infection. Its success in pre-clinical studies led to the planning of a phase 1/2 clinical trial for ARK which is due to start in 2020.

3) Anti-inflammatory and tear film treatment

Inflammatory responses, including lymph- and angiogenesis, can lead to the rejection of transplanted cells or tissues. Pharmaceutical strategies targeting dendritic cells and T-cells, such as co-receptor blocking agents like CTLA4-Ig, show promise in managing inflammation and have been used in ocular inflammatory conditions. Additionally, optimizing the ocular surface using artificial tears with anti-inflammatory properties is suggested as an initial step in AAK management. Autologous serum eye drops, containing growth factors and immunoglobulins, have been effective in treating inflammatory and angiogenic factors in AAK. Early intervention with topical pharmacotherapy using these approaches is proposed to prevent or delay AAK progression, requiring careful patient selection and long-term monitoring due to the condition’s slowly progressive nature.

An ongoing phase 1 clinical trial (NCT05400590) is investigating the safety and efficacy of growth factor-enriched plasma (GFP) and autologous serum (AS) in patients with aniridia.

4) Anti-angiogenic treatment

A potential treatment for aniridia-associated keratopathy (AAK) involves anti-angiogenic therapy, specifically using topical anti-VEGF compounds like bevacizumab. Other agents, such as ranibizumab and aflibercept, also show promise but are off-label for corneal application. GS-101 (Aganirsen), targeting insulin receptor substrate-1 (IRS-1), inhibits VEGF activity and is under clinical investigation. These antiangiogenic agents not only hinder AAK progression but may also enhance graft survival post limbal stem cell transplantation (LSCT). Physical methods like photodynamic therapy and fine-needle diathermy, along with UVA-based corneal collagen crosslinking, are being explored. Achieving a vessel-free limbal transplant region for optimal long-term limbal epithelial stem cell survival remains a focus.

5) Artificial iris prosthesis

These devices aim to improve visual acuity, alleviate photophobia and improve cosmetic appearance. Although studies have demonstrated functional and anatomic improvement in patients (mainly traumatic aniridia), we do not advocate implanting these devices in congenital aniridia patients due to the following reasons[20]:

  • Variable visual outcome—associated ocular co-morbidities might limit visual improvement
  • Development/progression of glaucoma and ARK
  • Prolonged anterior uveitis
  • Hypotony
  • Retinal/choroidal detachment, vitreous haemorrhage, cystoid macular oedema development
  • Endophthalmitis
  • Implant malposition—Surgical repositioning of implant is rare but can lead to aniridic fibrosis syndrome

The three main types of prosthesis are:

The prosthesis can be broadly categorised into three groups:

  • Iris-lens diaphragm (Morcher and Ophtec)
  • Endocapsular tension ring-based (Morcher)
  • Customised artificial iris (HumanOptics)

These devices are inserted into aphakic or pseudophakic eyes, either as a separate procedure or combined with cataract surgery. They are mainly inserted either into the capsule or in the sulcus with transcleral fixation sutures.

Related links

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Further information and support

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  1.  Hingorani M, Hanson I, Van Heyningen V. Aniridia. European Journal of Human Genetics. 2012;20(10):1011.
  2.  Moosajee M, Hingorani M, Moore AT. PAX6-Related Aniridia. In: GeneReviews®[Internet]. University of Washington, Seattle; 2018.
  3.  Gramer E, Reiter C, Gramer G. Glaucoma and frequency of ocular and general diseases in 30 patients with aniridia: a clinical study. Eur J Ophthalmol. 2012;22(1):104-110.
  4.  Bamiou DE, Free SL, Sisodiya SM, et al. Auditory inter-hemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations. Arch Pediatr Adolesc Med. 2007;161(5):463-469
  5.  Yasuda T, Kajimoto Y, Fujitani Y, et al. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes. 2002;51(1):224-230.
  6.  Lim HT, Kim DH, Kim H. PAX6 aniridia syndrome: clinics, genetics, and therapeutics. Curr Opin Ophthalmol. 2017;28(5):436-447.
  7.  US National Library of Medicine. WT1 gene. https://ghr.nlm.nih.gov/gene/WT1. Published 2019. Updated September 2018. Accessed 30/10/19.
  8.  Majander AS, Lindahl PM, Vasara LK, Krootila K. Anterior segment optical coherence tomography in congenital corneal opacities. Ophthalmology. 2012;119(12):2450-2457
  9.  Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998;79(4):268-273.
  10.  Lee H, Khan R, O’Keefe M. Aniridia: current pathology and management. Acta Ophthalmol. 2008;86(7):708-715.
  11.  S Gregory-Evans CY, Wang X, Wasan KM, Zhao J, Metcalfe AL, Gregory-Evans K. Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects. J Clin Invest. 2014;124(1):111-116
  12.  Wang X, Gregory-Evans K, Wasan KM, Sivak O, Shan X, Gregory-Evans CY. Efficacy of Postnatal In Vivo Nonsense Suppression Therapy in a Pax6 Mouse Model of Aniridia. Mol Ther Nucleic Acids. 2017;7:417-428.
  13.  Shortt AJ, Secker GA, Munro PM, Khaw PT, Tuft SJ, Daniels JT. Characterization of the limbal epithelial stem cell niche: novel imaging techniques permit in vivo observation and targeted biopsy of limbal epithelial stem cells. Stem Cells. 2007;25(6):1402-1409.
  14.  Ramaesh K, Ramaesh T, Dutton GN, Dhillon B. Evolving concepts on the pathogenic mechanisms of aniridia related keratopathy. Int J Biochem Cell Biol. 2005;37(3):547-557.
  15.  Fernandez-Buenaga R, Aiello F, Zaher SS, Grixti A, Ahmad S. Twenty years of limbal epithelial therapy: an update on managing limbal stem cell deficiency. BMJ Open Ophthalmol. 2018;3(1):e000164.
  16.  Baylis O, Figueiredo F, Henein C, Lako M, Ahmad S. 13 years of cultured limbal epithelial cell therapy: a review of the outcomes. J Cell Biochem. 2011;112(4):993-1002.
  17.  Shortt AJ, Secker GA, Notara MD, et al. Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol. 2007;52(5):483-502.
  18.  Yazdanpanah G, Haq Z, Kang K, Jabbehdari S, Rosenblatt ML, Djalilian AR. Strategies for reconstructing the limbal stem cell niche. Ocul Surf. 2019;17(2):230-240.
  19.  Levis HJ, Kureshi AK, Massie I, Morgan L, Vernon AJ, Daniels JT. Tissue Engineering the Cornea: The Evolution of RAFT. J Funct Biomater. 2015;6(1):50-65.
  20.  Srinivasan S, Ting DS, Snyder ME, Prasad S, Koch HR. Prosthetic iris devices. Can J Ophthalmol. 2014;49(1):6-17

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Updated on January 31, 2024
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