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Survey of Ophthalmology 2023Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive... (Review)
Review
Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.
Topics: Humans; Corneal Diseases; Aniridia; Cornea; Vision Disorders; Forecasting
PubMed: 37146692
DOI: 10.1016/j.survophthal.2023.04.003 -
European Journal of Human Genetics :... Oct 2012Aniridia is a rare congenital disorder in which there is a variable degree of hypoplasia or the absence of iris tissue associated with multiple other ocular changes,... (Review)
Review
Aniridia is a rare congenital disorder in which there is a variable degree of hypoplasia or the absence of iris tissue associated with multiple other ocular changes, some present from birth and some arising progressively over time. Most cases are associated with dominantly inherited mutations or deletions of the PAX6 gene. This article will review the clinical manifestations, the molecular basis including genotype-phenotype correlations, diagnostic approaches and management of aniridia.
Topics: Aniridia; Eye Proteins; Genotype; Homeodomain Proteins; Humans; Intellectual Disability; Mutation; PAX6 Transcription Factor; Paired Box Transcription Factors; Phenotype; Repressor Proteins; Syndrome; Urogenital Abnormalities; WT1 Proteins; Wilms Tumor
PubMed: 22692063
DOI: 10.1038/ejhg.2012.100 -
Indian Journal of Ophthalmology Dec 2022Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently.... (Review)
Review
Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently. Progressive sight loss can arise from cataracts, glaucoma, and aniridia-related keratopathy, which can be managed conservatively or through surgical intervention. The vast majority of patients harbor heterozygous mutations involving the PAX6 gene, which is considered the master transcription factor of early eye development. Over the past decades, several disease models have been investigated to gain a better understanding of the molecular pathophysiology, including several mouse and zebrafish strains and, more recently, human-induced pluripotent stem cells (hiPSCs) derived from aniridia patients. The latter provides a more faithful cellular system to study early human eye development. This review outlines the main aniridia-related animal and cellular models used to study aniridia and highlights the key discoveries that are bringing us closer to a therapy for patients.
Topics: Humans; Animals; Mice; Zebrafish; Aniridia; Iris; Cataract; Glaucoma; PAX6 Transcription Factor
PubMed: 36453299
DOI: 10.4103/ijo.IJO_316_22 -
International Ophthalmology Clinics 2008
Review
Topics: Aniridia; Child; Child, Preschool; Glaucoma; Humans; Infant; Intraocular Pressure
PubMed: 18427263
DOI: 10.1097/IIO.0b013e318169314b -
La Revue Du Praticien Jan 2019Congenital aniridia in children. Congenital aniridia is a genetic rare disease that affects the entire eyeball (pan-ocular disease). The disease is characterized by... (Review)
Review
Congenital aniridia in children. Congenital aniridia is a genetic rare disease that affects the entire eyeball (pan-ocular disease). The disease is characterized by partial or complete absence of iris. Clinical signs in children are essentially photophobia and nystagmus. The prevalence was reported range from 1:40,000 births to 1:100,000 but may be underestimated. It can also be associated with other systemic disorders then constituting a syndromic aniridia. These different syndromes are to be detected rapidly at risk of nephroblastoma in WAGR syndrome (Wilms' tumor, aniridia, genitourinary anomalies, mental retardation) or cerebellar ataxia in Gillespie syndrome. The diagnosis is mostly performed in infants. Congenital aniridia combines several types of ocular disorders, such as aniridia, foveal hypoplasia, glaucoma, cataract, and progressive corneal opacification. Preventive therapies should be instituted and all ocular aspects of the disease should be treated. This disease often leads to major visual impairment or even long-term blindness and requires UV protection optical correction. Clinical research is active with corneal stem cells and gene therapy.
Topics: Aniridia; Cerebellar Ataxia; Glaucoma; Humans; Infant, Newborn; Intellectual Disability; Syndrome
PubMed: 30983291
DOI: No ID Found -
Archivos de La Sociedad Espanola de... Nov 2021This review updates the knowledge about the morphological assessment of the foveal hypoplasia in congenital aniridia and resumes the reported genotype-phenotype... (Review)
Review
This review updates the knowledge about the morphological assessment of the foveal hypoplasia in congenital aniridia and resumes the reported genotype-phenotype correlations known to date. Congenital aniridia is a pan ocular disease. Although iris absence is considered the hallmark of this entity, foveal hypoplasia is present in 94.7%-84% of patients. A foveal morphology assessed by optical coherence tomography in which external retina structures can be identified, with presence of the lengthening of photoreceptors outer segment and a greater external retinal thickness, is associated with a better visual outcome, regardless a foveal pit is identified or not. This analysis can be performed once the external retina has completed its differentiation, by 6 years old. PAX6 mutations that introduce premature termination codon, C terminal extension or PAX6 involving deletions have been related to lesser foveal differentiation. Better foveal differentiation has been associated to non-coding PAX6 mutations.
Topics: Aniridia; Child; Fovea Centralis; Humans; Iris; PAX6 Transcription Factor; Tomography, Optical Coherence
PubMed: 34836590
DOI: 10.1016/j.oftale.2020.11.006 -
The Ocular Surface Oct 2021Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated... (Review)
Review
Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease.
Topics: Aniridia; Cornea; Corneal Diseases; Humans; Scleral Diseases; Stem Cells
PubMed: 34520870
DOI: 10.1016/j.jtos.2021.09.001 -
Survey of Ophthalmology 2021Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in... (Review)
Review
Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in the PAX6 gene, leading to involvement of most eye structures. Hypoplasia of the fovea is usually present and is associated with reduced visual acuity and nystagmus. Aniridia-associated keratopathy, glaucoma, and cataract are serious and progressive complications that can further reduce visual function. Treatment of the ocular complications of aniridia is challenging and has a high risk of side effects. New approaches such as stem cell therapy may, however, offer better prognoses. We describe the various ocular manifestations of aniridia, with a special focus on conditions that commonly require treatment. We also review the growing literature reporting systemic manifestations of the disease.
Topics: Aniridia; Cataract; Corneal Diseases; Glaucoma; Humans; Iris
PubMed: 33675823
DOI: 10.1016/j.survophthal.2021.02.011 -
Progress in Retinal and Eye Research Jul 2023Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities... (Review)
Review
Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of PAX6-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated. Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the PAX6 gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options. Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.
Topics: Humans; PAX6 Transcription Factor; Aniridia; Eye Abnormalities; Mutation; Phenotype; Eye Proteins
PubMed: 36280537
DOI: 10.1016/j.preteyeres.2022.101133 -
Archivos de La Sociedad Espanola de... Nov 2021Congenital aniridia is a rare genetic disease associated with mutations in the PAX6 gene. Changes in the lens in aniridia can be alterations of size and shape, of... (Review)
Review
Congenital aniridia is a rare genetic disease associated with mutations in the PAX6 gene. Changes in the lens in aniridia can be alterations of size and shape, of position - which generally reveal zonular weakness and determines subluxation of the lens - and mainly changes in transparency, cataracts, with variable morphology of polar, cortical, subcapsular, lamellar, and more rarely, nuclear cataract. Visual acuity and quality of vision in patients with congenital aniridia complicated by cataracts can be improved by carefully planned surgery, when lack of media transparency justifies surgical indication. Most patients have some improvement in visual acuity and quality of retinal image. Cataract surgery with aniridia is complicated by pathological changes due to the underlying cause of the aniridia. Challenges include corneal opacification, friable capsule and, above all, iris and pupil reconstruction. It can also determine late complications, such as secondary glaucoma or deterioration of pre-existent glaucoma, and corneal endothelial decompensation. After crystalline lens surgery in these patients, either by cataract or dislocation, for visual rehabilitation there are various techniques such as keratopigmentation, prosthetic iris devices or Morcher intraocular lenses with a black diaphragm. An appropriate individualised surgical plan should be selected depending on patient and surgical experience, in order to minimise complications and give the best chance of postoperative success.
Topics: Aniridia; Humans; Lens Implantation, Intraocular; Lens, Crystalline; Lenses, Intraocular; Retrospective Studies
PubMed: 34836587
DOI: 10.1016/j.oftale.2020.12.008