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American Journal of Ophthalmology Sep 2023This study aims to characterize foveal vasculature assessed by optical coherence tomography angiography (OCT-A) in congenital aniridia which is hallmarked by foveal...
PURPOSE
This study aims to characterize foveal vasculature assessed by optical coherence tomography angiography (OCT-A) in congenital aniridia which is hallmarked by foveal hypoplasia (FH).
DESIGN
Cross-sectional case-control analysis.
METHODS
At the National Referral Center for congenital aniridia, patients with confirmed PAX6-related aniridia and FH diagnosed on spectral-domain OCT (SD-OCT) with available OCT-A and matched control subjects were included. OCT-A was performed in patients with aniridia and control subjects. Foveal avascular zone (FAZ) and vessel density (VD) were collected. VD in the foveal and parafoveal areas at the level of the superficial and deep capillary plexi (SCP and DCP, respectively) were compared between the 2 groups. In patients with congenital aniridia, correlation between VD and the grading of FH was assessed.
RESULTS
Among 230 patients with confirmed PAX6-related aniridia, high-quality macular B-scans and OCT-A were available in 10 patients. On the foveal area, mean VD was higher in aniridia patients (41.10%, n = 10) than in control subjects (22.65%, n = 10) at the level of the SCP and the DCP (P = .0020 and P = .0273, respectively). On the parafoveal area, mean VD was lower in patients with aniridia (42.34%, n = 10) than in healthy subjects (49.24%, n = 10) at the level of both plexi (P = .0098 and P = .0371, respectively). In patients with congenital aniridia, a positive correlation was found between the grading of FH and the foveal VD at the SCP (r = 0.77, P = .0106).
CONCLUSIONS
Vasculature is altered in PAX6-related congenital aniridia, higher in foveal and lower in parafoveal areas, especially when FH is severe, which is consistent with the concept that the absence of retinal blood vessels is essential for foveal pit development.
Topics: Humans; Tomography, Optical Coherence; Fluorescein Angiography; Cross-Sectional Studies; Macula Lutea; Retinal Vessels; Aniridia; Vision Disorders
PubMed: 37059316
DOI: 10.1016/j.ajo.2023.04.004 -
Biology Dec 2023Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the... (Review)
Review
Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the corneal epithelium, leading to severe conjunctivalization of the cornea. Etiologies for LSCD span from congenital (aniridia), traumatic (chemical or thermal injuries), autoimmune (Stevens-Johnson syndrome) and iatrogenic disease to contact lens (CL) wear. Of these, CL wear is the least understood and is often a subclinical cause of LSCD. Even with recent advances in LSCD research, limitations persist in establishing the pathogenesis and treatment guidelines for CL-induced LSCD. A literature search was conducted to include original articles containing patients with CL-induced LSCD. This review will critically discuss the complex pathophysiology behind CL-induced LSCD, the underlying risk factors and epidemiology of the disease as well as methods to obtain a diagnosis. Various treatment options will be reviewed based on proposed treatment strategies.
PubMed: 38132316
DOI: 10.3390/biology12121490 -
Biomedicines Nov 2023This study assessed the efficacy and safety of Ahmed valve implantation in patients with aniridic glaucoma for three consecutive years.
BACKGROUND
This study assessed the efficacy and safety of Ahmed valve implantation in patients with aniridic glaucoma for three consecutive years.
METHODS
Six adult patients (seven eyes) with Ahmed valve (AV) implants for aniridic glaucoma were enrolled in the study. The primary outcome measures were intraocular pressure reduction, glaucoma medication use, success rates, and visual acuity after AV implantation. A 30% reduction in IOP from baseline without the need for re-intervention was considered an effective treatment. The cessation of antiglaucoma medications was defined as complete success. Intraoperative and postoperative complications were included as secondary outcome measures. Measurements were performed preoperatively, at the first week, and 1, 3, 6, 12, 18, 24, 30, and 36 months postoperatively.
RESULTS
A total of seven eyes (6 patients) were evaluated 36 months after AV implantation. The mean ± SD values of IOP preoperatively at 1 day, 1 week, and 1, 3, 6, 12, 18, 24, 30, and 36 months postoperatively were 30.4 ± 4.0 mmHg, 14.6 ± 4.6 mmHg, 16.1 ± 4.6 mmHg, 20.7 ± 7.0 mmHg, 14.5 ± 2.7 mmHg, 16.5 ± 5.9 mmHg, 16.2 ± 4.0 mmHg, 16.3 ± 4.3 mmHg, 17.2 ± 10.1 mmHg, 17.6 ± 6.9 mmHg, and 18.2 ± 5.5 mmHg, respectively. At the last follow up, the mean IOP was reduced by 40.2%. The qualified success rate was 85.7%. One patient (one eye) at the last follow-up visit did not require antiglaucoma medications, resulting in a complete success rate of 14.3%. Intra- and postoperative mild or moderate subconjunctival bleeding was observed in all the patients. No other major/minor intraoperative or postoperative complications were noted.
CONCLUSIONS
In long-term follow up, the AV implantation procedure is well-tolerated and relatively safe for reducing IOP in adult aniridia patients with glaucoma. These results should be validated through studies involving a larger patient cohort.
PubMed: 38001995
DOI: 10.3390/biomedicines11112996 -
Ophthalmology and Therapy Aug 2023Aniridia is a rare congenital vision-loss disease caused by heterozygous variants in the PAX6 gene. There is no vision-saving therapy, but one exciting approach is to...
INTRODUCTION
Aniridia is a rare congenital vision-loss disease caused by heterozygous variants in the PAX6 gene. There is no vision-saving therapy, but one exciting approach is to use CRISPR/Cas9 to permanently correct the causal genomic variants. Preclinical studies to develop such a therapy in animal models face the challenge of showing efficacy when binding human DNA. Thus, we hypothesized that a CRISPR gene therapy can be developed and optimized in humanized mouse embryonic stem cells (ESCs) that will be able to distinguish between an aniridia patient variant and nonvariant chromosome and lay the foundation for human therapy.
METHODS
To answer the challenge of binding human DNA, we proposed the "CRISPR Humanized Minimally Mouse Models" (CHuMMMs) strategy. Thus, we minimally humanized Pax6 exon 9, the location of the most common aniridia variant c.718C > T. We generated and characterized a nonvariant CHuMMMs mouse, and a CHuMMMs cell-based disease model, in which we tested five CRISPR enzymes for therapeutic efficacy. We then delivered the therapy via lipid nanoparticles (LNPs) to alter a second variant in ex vivo cortical primary neurons.
RESULTS
We successfully established a nonvariant CHuMMMs mouse and three novel CHuMMMs aniridia cell lines. We showed that humanization did not disrupt Pax6 function in vivo, as the mouse showed no ocular phenotype. We developed and optimized a CRISPR therapeutic strategy for aniridia in the in vitro system, and found that the base editor, ABE8e, had the highest correction of the patient variant at 76.8%. In the ex vivo system, the LNP-encapsulated ABE8e ribonucleoprotein (RNP) complex altered the second patient variant and rescued 24.8% Pax6 protein expression.
CONCLUSION
We demonstrated the usefulness of the CHuMMMs approach, and showed the first genomic editing by ABE8e encapsulated as an LNP-RNP. Furthermore, we laid the foundation for translation of the proposed CRISPR therapy to preclinical mouse studies and eventually patients with aniridia.
PubMed: 37210469
DOI: 10.1007/s40123-023-00729-6 -
PLoS Biology Oct 2023The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on...
The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity.
Topics: Humans; Limbus Corneae; Cornea; Epithelium, Corneal; Transcription Factors; Cell Differentiation; Corneal Opacity
PubMed: 37856539
DOI: 10.1371/journal.pbio.3002336 -
Journal of AAPOS : the Official... Aug 2023To report on the incidence, characteristics, and treatment of glaucoma in association with aniridia in a population of Egyptian children.
PURPOSE
To report on the incidence, characteristics, and treatment of glaucoma in association with aniridia in a population of Egyptian children.
METHODS
A retrospective chart review was conducted of children (<18 years of age) presenting with aniridia between 2007 and 2022. Diagnosis of glaucoma was based on cup:disk ratio (>0.3) and IOP (>16 mm Hg). Success of glaucoma surgery was defined as IOP ≤16 mm Hg and stable or regressing cup:disk ratio.
RESULTS
A total of 93 eyes of 47 children were included. The mean patient age at presentation was 41.2 ± 44.7 months. The mean intraocular pressure (IOP), corneal diameter, cup:disk ratio, and axial length on presentation were 16.4 ± 10.3 mm Hg, 11.4 ± 1.3 mm, 0.4 ± 0.3, and 22.43 ± 2.6 mm Hg. Of eyes with IOP and cup:disk ratio data at presentation, 23 (30%) were diagnosed with glaucoma. Fourteen eyes underwent surgery after presentation; follow-up data were available for half the remaining eyes. At the final follow-up, glaucoma was present in 20 eyes (49%). Glaucoma surgery was performed in 17 eyes, with a complete or qualified success rate of 82.4% at final follow-up, with 15 eyes having at least 12 months' follow-up.
CONCLUSIONS
In this study cohort, children with aniridia presented at around 3 years of age, with glaucoma at presentation in almost one-third of the cases.
Topics: Humans; Child; Child, Preschool; Retrospective Studies; Egypt; Glaucoma; Intraocular Pressure; Aniridia; Treatment Outcome; Follow-Up Studies; Trabeculectomy
PubMed: 37499898
DOI: 10.1016/j.jaapos.2023.06.005 -
Medical Hypothesis, Discovery &... 2023The most accurate method of intraocular lens (IOL) power calculation in cataract surgery has not been determined, and further studies are needed to reach a consensus....
BACKGROUND
The most accurate method of intraocular lens (IOL) power calculation in cataract surgery has not been determined, and further studies are needed to reach a consensus. The aim of this study was to assess publications related to IOL power calculation formulas, mapping their yearly trends, most productive authors, top publishing countries and institutions, and areas of specialization for IOL power formulas.
METHODS
We conducted a comprehensive analysis of research articles published on the topic of IOL power calculation formulas. Using PubMed, we employed appropriate search terms and filtered the results for the period of January 1, 1946, to June 28, 2023. Data were analyzed using CiteSpace, VOSviewer, and Microsoft Excel programs. The visual representations of the collected data through the use of figures was provided to demonstrate the aspects of IOL power calculation research.
RESULTS
We retrieved 5475 documents in the initial search. Analysis of these documents revealed an increase in the number of publications, from one publication in 1946 to 201 publications in 2023. The top three countries contributing to these publications were the United States, China, and Japan, collectively accounting for over 27% of the total articles. However, the two institutions with the highest contributions were located in the United Kingdom and Hungary, neither of which was among the top 10 countries in overall contributions. Overall 15 326 authors contributed to publications pertaining to IOL power calculation formulas. Among these authors, the most prolific contributors included Achim Langenbucher from Saarland University (Germany), Giacomo Savini from G.B. Bietti Foundation I.R.C.C.S. (Italy), and Kenneth J Hoffer from the University of California (United States). Saarland University emerged as the most productive institution, contributing equally to two distinct departments: the Dr. Rolf M. Schwiete Center for Limbal Stem Cell Research and Congenital Aniridia, as well as the Department of Experimental Ophthalmology. The School of Physical Science at the Open University in the United Kingdom engaged in partnership with various institutions including Eye & Laser Clinic Castrop Rauxel in Germany and Johannes Kepler University Linz in Austria. Among the top 10 keywords found in the publications were "cataract", "cataract surgery", and "intraocular lens".
CONCLUSIONS
This study represents the first scientometric analysis of publications related to IOL power calculation formulas. The study offers valuable insights into the geographic distribution, contributing authors, and emphasis of research on the IOL power calculation formulas. Further cooperation is essential to pinpoint the most suitable formula and to address gaps in our current understanding.
PubMed: 38476575
DOI: 10.51329/mehdiophthal1477 -
Survey of Ophthalmology 2023Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular...
Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular morbidities such as cataract, keratopathy, optic nerve and foveal hypoplasia, and nystagmus. The iris abnormality, however, often leads to symptoms such as photophobia, glare, and decreased visual acuity, as well as cosmetic dissatisfaction. Current management options for the iris deficit include colored iris contact lenses, corneal tattooing, and tinted contact lenses. Symptoms arising from small iris defects can be resolved with surgical management using micro-tying suture techniques such as McCannel or Siepser. Currently, larger iris defects can be treated with artificial iris implants. New prosthetic options range from colored intraocular lenses to flexible custom-made silicone iris implants. With a range of therapeutic options available and given the challenges of multiple comorbidities in aniridia, we evaluate the literature relating to the use of artificial iris implants in congenital aniridia, with a focus on the different surgical implantation techniques, the clinical outcomes achieved, complications occurred, and risk of bias of the studies included.
Topics: Humans; Visual Acuity; Aniridia; Iris; Lenses, Intraocular; Prosthesis Implantation; Vision Disorders
PubMed: 36379301
DOI: 10.1016/j.survophthal.2022.11.001 -
Journal of Clinical Medicine Jun 2023Given the various ocular manifestations of limbal stem cell insufficiency, an awareness of the genetic, acquired, and immunological causes and associated additional... (Review)
Review
Given the various ocular manifestations of limbal stem cell insufficiency, an awareness of the genetic, acquired, and immunological causes and associated additional treatments of limbal stem cell deficiency (LSCD) is essential for providers. We performed a comprehensive review of the literature on the various etiologies and specific therapies for LSCD. The resources utilized in this review included Medline (PubMed), Embase, and Google Scholar. All English-language articles and case reports published from November 1986 through to October 2022 were reviewed in this study. There were collectively 99 articles on these topics. No other exclusion criteria were applied. Depending on the etiology, ocular manifestations of limbal stem cell deficiency range from dry eye syndrome and redness to more severe outcomes, including corneal ulceration, ocular surface failure, and vision loss. Identifying the source of damage for LSCD is critical in the treatment process, given that therapy may extend beyond the scope of the standard protocol, including artificial tears, refractive surgery, and allogeneic stem cell transplants. This comprehensive review of the literature demonstrates the various genetic, acquired, and immunological causes of LSCD and the spectrum of supplemental therapies available.
PubMed: 37445454
DOI: 10.3390/jcm12134418 -
Indian Journal of Ophthalmology Aug 2023Aniridia is defined as missing iris tissue which can be partial, subtotal, or total. Characteristic clinical symptoms include photophobia and decreased visual acuity due...
BACKGROUND
Aniridia is defined as missing iris tissue which can be partial, subtotal, or total. Characteristic clinical symptoms include photophobia and decreased visual acuity due to an increased light perception. In addition to this, disturbing cosmetic problems are prevalent. Even after implantation of an intraocular lens, patients often tend to be unsatisfied.
PURPOSE
The answer to this problem lies in the implantation of an aniridic scleral fixation of intraocular lens (SFIOL), which has a central optical axis that acts as the refractive lens and a peripheral rim of a hyperpigmented area that mimics the iris and hence reduces photophobia. The purpose of the video was to demonstrate the use of black diaphragm intraocular lens (BDIOL) implantation, its surgical steps, and its outcomes.
SYNOPSIS
We report one such case where a young patient presented with post-traumatic aniridia with subluxated total cataract and spillover vitreous hemorrhage. He was subjected to a vitrectomy, cataract removal, and placement of an aniridic SFIOL with prolene 9-0 using the four-point fixation method. This gave an extremely gratifying outcome and solved both problems, that is, vision and photophobia. Highlight: Before implantation of the SFIOL, the patients had reduced visual acuity from aphakia and intolerable glare from aniridia. In this case-based approach and with relevant example, we tried to provide a solution for tricky scenarios like co-existing traumatic cataract and traumatic aniridia. The patient showed improved visual acuity and marked glare reduction after black diaphragm SFIOL implantation.
VIDEO LINK
https://youtu.be/atl60WetFsM.
Topics: Male; Humans; Lens Implantation, Intraocular; Photophobia; Lenses, Intraocular; Iris; Aniridia; Vision Disorders; Eye Injuries; Cataract
PubMed: 37530301
DOI: 10.4103/IJO.IJO_775_23