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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 -
Investigative Ophthalmology & Visual... Apr 2023To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia.
PURPOSE
To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia.
METHODS
Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment.
RESULTS
The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less.
CONCLUSIONS
The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.
Topics: Male; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Dark Adaptation; Retina; Retinal Cone Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Vision Disorders; Corneal Diseases; Aniridia; Tomography, Optical Coherence
PubMed: 37067366
DOI: 10.1167/iovs.64.4.18 -
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 -
Investigative Ophthalmology & Visual... Apr 2018To assess color vision and its association with retinal structure in persons with congenital aniridia.
PURPOSE
To assess color vision and its association with retinal structure in persons with congenital aniridia.
METHODS
We included 36 persons with congenital aniridia (10-66 years), and 52 healthy, normal trichromatic controls (10-74 years) in the study. Color vision was assessed with Hardy-Rand-Rittler (HRR) pseudo-isochromatic plates (4th ed., 2002); Cambridge Color Test and a low-vision version of the Color Assessment and Diagnosis test (CAD-LV). Cone-opsin genes were analyzed to confirm normal versus congenital color vision deficiencies. Visual acuity and ocular media opacities were assessed. The central 30° of both eyes were imaged with the Heidelberg Spectralis OCT2 to grade the severity of foveal hypoplasia (FH, normal to complete: 0-4).
RESULTS
Five participants with aniridia had cone opsin genes conferring deutan color vision deficiency and were excluded from further analysis. Of the 31 with aniridia and normal opsin genes, 11 made two or more red-green (RG) errors on HRR, four of whom also made yellow-blue (YB) errors; one made YB errors only. A total of 19 participants had higher CAD-LV RG thresholds, of which eight also had higher CAD-LV YB thresholds, than normal controls. In aniridia, the thresholds were higher along the RG than the YB axis, and those with a complete FH had significantly higher RG thresholds than those with mild FH (P = 0.038). Additional increase in YB threshold was associated with secondary ocular pathology.
CONCLUSIONS
Arrested foveal formation and associated alterations in retinal processing are likely to be the primary reason for impaired red-green color vision in aniridia.
Topics: Adolescent; Adult; Aged; Aniridia; Child; Color Perception Tests; Color Vision; Color Vision Defects; Female; Fovea Centralis; Humans; Male; Middle Aged; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 29801149
DOI: 10.1167/iovs.17-23047 -
Acta Ophthalmologica Nov 2008Aniridia is a rare panocular disorder affecting the cornea, anterior chamber, iris, lens, retina, macula and optic nerve. It occurs because of mutations in PAX6 on band... (Review)
Review
Aniridia is a rare panocular disorder affecting the cornea, anterior chamber, iris, lens, retina, macula and optic nerve. It occurs because of mutations in PAX6 on band p13 of chromosome 11. It is associated with a number of syndromes, including Wilm's tumour, bilateral sporadic aniridia, genitourinary abnormalities and mental retardation (WAGR) syndrome. PAX6 mutations result in alterations in corneal cytokeratin expression, cell adhesion and glycoconjugate expression. This, in addition to stem-cell deficiency, results in a fragile cornea and aniridia-associated keratopathy (AAK). It also results in abnormalities in the differentiation of the angle, resulting in glaucoma. Glaucoma may also develop as a result of progressive angle closure from synechiae. There is cataract development, and this is associated with a fragile lens capsule. The iris is deficient. The optic nerve and fovea are hypoplastic, and the retina may be prone to detachment. Aniridia is a profibrotic disorder, and as a result many interventions--including penetrating keratoplasty and filtration surgery--fail. The Boston keratoprosthesis may provide a more effective approach in the management of AAK. Guarded filtration surgery appears to be effective in glaucoma. Despite our increasing understanding of the genetics and pathology of this condition, effective treatment remains elusive.
Topics: Abnormalities, Multiple; Animals; Aniridia; Cataract; Cornea; Corneal Diseases; Embryonic Development; Eye Proteins; Glaucoma; Homeodomain Proteins; Humans; Optic Nerve; PAX6 Transcription Factor; Paired Box Transcription Factors; Prosthesis Implantation; Repressor Proteins; Retina; WAGR Syndrome
PubMed: 18937825
DOI: 10.1111/j.1755-3768.2008.01427.x -
Indian Journal of Ophthalmology Jul 2022Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of... (Review)
Review
Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of ocular findings, including foveal hypoplasia, optic nerve hypoplasia, nystagmus, late-onset cataract, glaucoma, and keratopathy. The latter three are reasons for further visual compromise in such patients. This entity is often due to mutations in the PAX6 (Paired box protein Pax-6) gene. Recently, aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis. In this review, we describe the various clinical features of classic aniridia, the comorbidities and their management, the mutation spectrum of the genes involved, genotype-phenotype correlation of PAX6 and non-PAX6 mutations, and the genetic testing plan. The various systemic associations and their implications in screening and genetic testing have been discussed. Finally, the future course of aniridia treatment in the form of drugs (such as ataluren) and targeted gene therapy has been discussed.
Topics: Aniridia; Eye Abnormalities; Glaucoma; Humans; Intracellular Signaling Peptides and Proteins; PAX6 Transcription Factor; Phenotype; Tripartite Motif Proteins
PubMed: 35791108
DOI: 10.4103/ijo.IJO_2255_21 -
Taiwan Journal of Ophthalmology 2023Congenital aniridia is a rare genetic eye disorder characterized by the complete or partial absence of the iris from birth. Various theories and animal models have been... (Review)
Review
Congenital aniridia is a rare genetic eye disorder characterized by the complete or partial absence of the iris from birth. Various theories and animal models have been proposed to understand and explain the pathogenesis of aniridia. In the majority of cases, aniridia is caused by a mutation in the gene, which affects multiple structures within the eye. Treating these ocular complications is challenging and carries a high risk of side effects. However, emerging approaches for the treatment of aniridia-associated keratopathy, iris abnormalities, cataract abnormalities, and foveal hypoplasia show promise for improved outcomes. Genetic counseling plays a very important role to make informed choices. We also provide an overview of the newer diagnostic and therapeutic approaches such as next generation sequencing, gene therapy, silencing, and miRNA modulation.
PubMed: 38249501
DOI: 10.4103/tjo.TJO-D-23-00140 -
The Ocular Surface Jul 2023The inaugural Aniridia North America (ANA) Symposium was held on the first weekend in November 2021 in Charlottesville, VA, at the University of Virginia. The purpose of... (Review)
Review
The inaugural Aniridia North America (ANA) Symposium was held on the first weekend in November 2021 in Charlottesville, VA, at the University of Virginia. The purpose of this meeting was to bring together an international group of scientists, physicians, patient advocacy groups, and individuals with aniridia to discuss recent advances in knowledge about aniridia and other congenital eye diseases and the development of potential treatments for congenital eye disorders using personalized medicine. Leaders in several areas of eye research and clinical treatment provided a broad perspective on new research advances that impact an understanding of the causes of the damage to the eye associated with aniridia and the development of novel treatments for this and related disorders. Here we summarize the research discussed at the symposium.
Topics: Humans; PAX6 Transcription Factor; Aniridia; North America
PubMed: 37247841
DOI: 10.1016/j.jtos.2023.05.010 -
Der Ophthalmologe : Zeitschrift Der... Jan 2022Patients with iris defects suffer from severe visual impairment, especially increased glare sensitivity, and cosmetic disturbances. This can constitute a great... (Review)
Review
BACKGROUND
Patients with iris defects suffer from severe visual impairment, especially increased glare sensitivity, and cosmetic disturbances. This can constitute a great psychological strain for patients. In the recent past the treatment consisted of iris print contact lenses, sunglasses and simple iris prostheses. The indications for surgical treatment are colobomas of the iris, aniridia, traumatic iris defects and persistent mydriasis. The aim of this review article is to investigate the surgical approaches, complications, functional and aesthetic outcome after implantation of an individual artificial iris prosthesis made from silicone.
OBJECTIVE
Analysis of the literature on the topic of surgical iris reconstruction with an artificial iris in combination with the own experience in more than 120 patients treated by the author in the last 10 years.
MATERIAL AND METHODS
The custom-made flexible silicone iris prosthesis ArtificialIris (HumanOptics, Erlangen, Germany) assessed in this review is an innovative and versatile option for surgical treatment of iris defects. Patients were examined before and after iris reconstruction with respect to feasibility, complications and outcome.
RESULTS
Change of best corrected visual acuity, intraocular pressure, pupillary opening, glare, contrast sensitivity, endothelial cell count, anterior chamber depth, anterior chamber angle and patient satisfaction were assessed. Furthermore, complications and color match to the residual and fellow iris were assessed.
CONCLUSION
The implantation of an artificial iris is an effective option for the treatment of extensive traumatic iris defects and leads to an individual aesthetically appealing and good functional outcome as well as high patient satisfaction; however, this is an intervention that should not be underestimated because of a flat learning curve and various complications that can occur.
Topics: Aniridia; Contrast Sensitivity; Glare; Humans; Iris; Lenses, Intraocular; Pupil
PubMed: 34181062
DOI: 10.1007/s00347-021-01406-4