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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 -
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 -
Der Ophthalmologe : Zeitschrift Der... Jun 2021A 53-year-old female patient presented with increased light sensitivity 3 weeks after oral intake of moxifloxacin tablets for an upper respiratory tract infection. The...
A 53-year-old female patient presented with increased light sensitivity 3 weeks after oral intake of moxifloxacin tablets for an upper respiratory tract infection. The symptoms were anisocoria and the pupils did not react to light or accommodation. The examination of the anterior segment of the eye revealed extensive bilateral iris transillumination defects (ITD). We diagnosed a bilateral acute iris transillumination (BAIT) syndrome. The BAIT syndrome is a rare disorder associated with massive depigmentation of the iris and atrophy of the iris musculature. A risk factor for BAIT syndrome seems to be the oral intake of antibiotics, in particular moxifloxacin after an upper respiratory tract infection but cases of spontaneous occurrence have also been described. Middle-aged women are particularly affected. The exact cause of BAIT syndrome is so far unknown but a potential mechanism involves the concentration of the antibiotic in the vitreous body. Differential diagnoses include other causes for ITD, such as albinism, intraocular inflammation, pseudoexfoliation syndrome and pigment dispersion syndrome. To date there is no specific treatment for BAIT syndrome. Possible complications include increased light sensitivity and post-BAIT glaucoma. Knowledge of the rare BAIT syndrome can be useful in the clinical routine for the differential diagnostic classification of an anisocoria and can possibly contribute to avoidance of unnecessary diagnostic steps.
Topics: Anisocoria; Female; Glaucoma, Open-Angle; Humans; Iris; Iris Diseases; Middle Aged; Moxifloxacin
PubMed: 32588124
DOI: 10.1007/s00347-020-01153-y -
Indian Journal of Ophthalmology Aug 2021
Topics: Humans; Iris; Iris Diseases
PubMed: 34304164
DOI: 10.4103/ijo.IJO_2619_20 -
Turkish Journal of Ophthalmology Aug 2023Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular... (Review)
Review
Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.
Topics: Humans; Cataract; Exfoliation Syndrome; Glaucoma; Glaucoma, Open-Angle; Lens Subluxation
PubMed: 37602651
DOI: 10.4274/tjo.galenos.2023.76300 -
Indian Journal of Ophthalmology Aug 2022Surgeons often notice unexplained dilation of the pupil following an uncomplicated intra-ocular surgery. No definite line of treatment has been proposed for managing...
BACKGROUND
Surgeons often notice unexplained dilation of the pupil following an uncomplicated intra-ocular surgery. No definite line of treatment has been proposed for managing Urrets-Zavalia syndrome (UZS). The authors have previously documented the results of surgical pupilloplasty and have outlined this modality of treatment for cases with UZS.
PURPOSE
To highlight the aspect of development of UZS post-operatively in the eyes following an intra-ocular surgery.
SYNOPSIS
The video highlights the aspect of prevalence of the persistently dilated pupil that is non-responsive to topical miotics. Apart from associated glare, these cases often have raised intra-ocular pressure because of appositional closure of the anterior chamber angle. Surgical pupilloplasty pulls the iris tissue centrally, eventually releasing the mechanical blockage and often breakage of the peripheral anterior synechias as demonstrated by intra-operative gonioscopy and anterior segment optical coherence tomography.
HIGHLIGHTS
Performing a surgical pupilloplasty can resolve the UZS, and timely intervention can also prevent the development of secondary glaucoma because of fallback of the iris tissue on the structures of the anterior chamber angle.
ONLINE VIDEO LINK
https://youtu.be/IF_w8dVk5_w.
Topics: Glaucoma; Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Iris; Iris Diseases; Pupil Disorders; Tomography, Optical Coherence
PubMed: 35919013
DOI: 10.4103/ijo.IJO_896_22 -
Indian Journal of Ophthalmology Sep 2022Disinsertion of iris leads to debilitating sequelae like diplopia and glare. Hence, iridodialysis repair is essential to optimize the visual quality. Iris base repair...
BACKGROUND
Disinsertion of iris leads to debilitating sequelae like diplopia and glare. Hence, iridodialysis repair is essential to optimize the visual quality. Iris base repair often leads to corectopia that necessitates an additional procedure to optimize the pupil shape and size. Twofold technique helps to achieve both the aspects.
PURPOSE
To highlight the technique of twofold iridodialysis repair.
SYNOPSIS
The video highlights the method of twofold iridodialysis repair, wherein nonappositional repair is followed by single-pass four-throw (SFT) pupilloplasty that allows adequate closure of varied degrees of iridodialysis along with centration of eccentric pupil.
HIGHLIGHTS
The twofold technique is a combination of nonappositional iris repair and SFT procedure. It can be clinically applied in all cases of iridodialysis with varied degrees of severity.
ONLINE VIDEO LINK
https://youtu.be/OncBdz2UIBY.
Topics: Humans; Iris; Iris Diseases; Pupil Disorders; Suture Techniques; Sutures
PubMed: 36018147
DOI: 10.4103/ijo.IJO_952_22 -
PloS One 2014Many studies have assessed the association between ocular pseudoexfoliation syndrome (PEX) and vascular disease and produced controversial results. We performed a... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Many studies have assessed the association between ocular pseudoexfoliation syndrome (PEX) and vascular disease and produced controversial results. We performed a meta-analysis of epidemiologic studies to evaluate this relationship.
METHODS
Eligible studies that reported the incidence of vascular disease among PEX and control groups were identified via computer searches and reviewing the reference lists of the key articles. The summary odds ratio (OR) and 95% confidence interval (CI) were pooled using a random-effects model. Meta-regression to assess heterogeneity by several covariates and a subgroup analysis on study design and population were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test.
RESULTS
Sixteen eligible studies involving 8,533 PEX patients and 135,720 control patients were included in the meta-analysis. All studies were performed primarily in whites with a mean age between 54.7 and 77.1 years. The overall combined ORs for patients with PEX compared with the reference group were 1.72 (95% CI: 1.31 to 2.26) for any vascular disease, 1.61 (95% CI: 1.22 to 2.14) for coronary heart disease, 1.59 (95% CI: 1.12 to 2.23) for cerebrovascular disease, and 2.48 (95% CI: 1.30 to 4.72) for aortic aneurysm. There was evidence of statistical heterogeneity; however, subgroup and sensitivity analyses showed this result to be robust. No evidence of publication bias was observed.
CONCLUSIONS
The overall current literature suggests that PEX was associated with increased risk of vascular disease. Because of the limitations of the included studies and meta-analysis, the findings need to be confirmed in future research via well-designed cohort studies.
Topics: Exfoliation Syndrome; Female; Humans; Male; Models, Biological; Risk Factors; Vascular Diseases
PubMed: 24667689
DOI: 10.1371/journal.pone.0092767 -
The New England Journal of Medicine Apr 2019
Topics: Eye Injuries; Humans; Iris; Iris Diseases; Male; Middle Aged
PubMed: 30970191
DOI: 10.1056/NEJMicm1812087 -
Journal of Glaucoma Jul 2018Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (exfoliation material) at extracellular matrices in... (Review)
Review
Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (exfoliation material) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where exfoliation material accumulations form on the surface of the ciliary body, iris, and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies. Progress in understanding the cellular bases for XFS/XFG has been slowed by a lack of experimental models. Working with primary human tenon fibroblasts (TF) derived from trabeculectomies of XFG patients and age-matched primary open-glaucoma controls, we found that TF from XFG cells display many of the functional features observed in cells from other protein aggregate diseases, such as Parkinson, Alzheimer, Huntington, and age-related macular degeneration. We have documented defects in lysosomal positioning, microtubule organization, autophagy processing rate, and mitochondrial health. In regard to failure of lysosomal and autophagosome positioning in XFG cells, we have found that XFG TF are unable to establish the transnuclear microtubule organizing center that is required for efficient centripetal vesicular locomotion along microtubules. In regard to potential sources of the autophagy malfunction, we have directed our attention to a potential role of the lysyl oxidase-like 1 protein (LOXL1), the elastic fiber catalyst that displays variant-dependent association with risk for XFG. Our experiments show that (a) in XFG cells, a substantial fraction of LOXL1 is processed for degradation by the autophagic system; (b) most of the LOXL1 N-terminus domain exists in a highly disordered state, a condition known to greatly increase the frequency of polypeptide misfolding; (c) that maximum misfolding occurs at amino acid position 153, the location of the high risk variant G153D; and (d) that replacement of glycine (G) by aspartate (D) there results in a substantial decrease in disorder within the 20 amino acid surrounding domain. Finally, we show that clusterin, a protein that can be induced by the presence of intracellular, or extracellular aggregates, is uniformly overexpressed in XFG TF. The implications of our results for a theory relating XFG to cellular aggregopathy are discussed.
Topics: Amino Acid Oxidoreductases; Anterior Eye Segment; Autophagy; Exfoliation Syndrome; Extracellular Matrix; Glaucoma, Open-Angle; Humans; Protein Aggregates
PubMed: 29547474
DOI: 10.1097/IJG.0000000000000919