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International Journal of Molecular... Oct 2023This study aims to present a clinical case involving the unique co-occurrence of congenital aniridia and Down syndrome in a young girl and to analyze the combined impact...
This study aims to present a clinical case involving the unique co-occurrence of congenital aniridia and Down syndrome in a young girl and to analyze the combined impact of these conditions on the patient's phenotype. The investigation involved comprehensive pediatric and ophthalmological examinations alongside karyotyping and Sanger sequencing of the gene. The patient exhibited distinctive features associated with both congenital aniridia and Down syndrome, suggesting a potential exacerbation of their effects. Cytogenetic and molecular genetic analysis revealed the presence of trisomy 21 and a known pathogenic nonsense variant in exon 6 of the gene (c.282C>A, p.(Cys94*)) corresponding to the paired domain of the protein. The observation of these two hereditary anomalies offers valuable insights into the molecular pathogenetic mechanisms underlying each condition. Additionally, it provides a basis for a more nuanced prognosis of the complex disease course in this patient. This case underscores the importance of considering interactions between different genetic disorders in clinical assessments and treatment planning.
Topics: Female; Humans; Child; Down Syndrome; PAX6 Transcription Factor; Chromosomes, Human, Pair 21; Trisomy; Aniridia; Eye Proteins; Homeodomain Proteins; Pedigree; Mutation
PubMed: 37958513
DOI: 10.3390/ijms242115527 -
Frontiers in Physiology 2023Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms... (Review)
Review
Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut performance, which is why there is a need for further research into the pathophysiology and countermeasures. As an in-flight countermeasure, neurostimulation seems to be among the most promising options.
PubMed: 37929210
DOI: 10.3389/fphys.2023.1281327 -
Current Eye Research Feb 2024To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor β1...
PURPOSE
To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) expression in healthy and keratoconus human corneal fibroblasts (HCFs and KC-HCFs), 24 h after Rose Bengal photodynamic therapy (RB-PDT).
METHODS
HCFs were isolated from healthy human corneal donors ( = 5) and KC-HCFs from elective penetrating keratoplasties ( = 5). Both cell cultures underwent RB-PDT (0.001% RB concentration, 0.17 J/cm fluence) and 24 h later collagen I, collagen V, NF-κB, LOX, TGF-β1 and IL-6 mRNA and protein expression have been determined using qPCR and Western blot, IL-6 concentration in the cell culture supernatant by ELISA.
RESULTS
TGF-β1 mRNA expression was significantly lower ( = 0.02) and IL-6 mRNA expression was significantly higher in RB-PDT treated HCFs ( = 0.01), than in HCF controls. COL1A1, COL5A1 and TGF-β1 mRNA expression was significantly lower ( = 0.04; = 0.02 and = 0.003) and IL-6 mRNA expression was significantly higher ( = 0.02) in treated KC-HCFs, than in KC-HCF controls. TGF-β1 protein expression in treated HCFs was significantly higher than in HCF controls ( = 0.04). IL-6 protein concentration in the HCF and KC-HCF culture supernatant after RB-PDT was significantly higher than in controls ( = 0.02; = 0.01). No other analyzed mRNA and protein expression differed significantly between the RB-PDT treated and untreated groups.
CONCLUSIONS
Our study demonstrates that RB-PDT reduces collagen I, collagen V and TGF-β1 mRNA expression, while increasing IL-6 mRNA and protein expression in KC-HCFs. In HCFs, RB-PDT increases TGF-β1 and IL-6 protein level after 24 h.
Topics: Humans; Transforming Growth Factor beta; Interleukin-6; NF-kappa B; Rose Bengal; Transforming Growth Factor beta1; Protein-Lysine 6-Oxidase; Collagen; Collagen Type I; Fibroblasts; RNA, Messenger
PubMed: 37921272
DOI: 10.1080/02713683.2023.2276057 -
Korean Journal of Ophthalmology : KJO Dec 2023
Topics: Humans; Cataract Extraction; Eye Injuries; Cataract; Wounds, Nonpenetrating; Aniridia; Iris
PubMed: 37899280
DOI: 10.3341/kjo.2023.0091 -
Journal Francais D'ophtalmologie Dec 2023To evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure.
BACKGROUND/PURPOSE
To evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure.
METHODS
Single surgeon retrospective cohort study including 85 eyes of 74 patients who underwent KPro implantation to treat severe ocular surface disease, including limbal stem cell deficiency, postinfectious keratitis, aniridia and chemical burns. Procedures were performed at the Centre hospitalier de l'Université de Montréal from October 2008 to May 2012. All patients with at least 5 years of follow-up were included in the analysis, including eyes with repeated KPro. Main outcome measures were visual acuity (VA), visual failure, defined as a sustained VA worse than the preoperative VA, postoperative complications, and device retention.
RESULTS
Mean follow-up was 7.2±1.3 years (±SD). Mean VA was 2.1±0.7 (logarithm of minimal angle resolution) preoperatively and 1.9±1.2 at last follow-up. In total, 2.4% of patients had VA better than 20/200 preoperatively vs. 36.5% at last follow-up. Maintenance of improved postoperative VA was seen in 61.8% of eyes at 7 years. Preoperative factors associated with visual failure were known history of glaucoma (HR=2.7 [1.2 to 5.9], P=0.02) and Stevens-Johnson syndrome (HR=7.3 [2.5 to 21.4], P<0.01). Cumulative 8-year complication rates were 38.8% retroprosthetic membrane formation, 25.9% hypotony, 23.5% new onset glaucoma, 17.6% retinal detachment, 8.2% device extrusion and 5.9% endophthalmitis. The majority (91.8%) of eyes retained the device 8 years after implantation.
CONCLUSION
Nearly two-thirds of patients exhibited improved VA 7 years after KPro implantation. Preoperative risk factors for visual failure were known glaucoma and Stevens-Johnson syndrome.
Topics: Humans; Cornea; Prostheses and Implants; Corneal Diseases; Retrospective Studies; Stevens-Johnson Syndrome; Artificial Organs; Canada; Glaucoma; Prosthesis Implantation; Postoperative Complications; Follow-Up Studies
PubMed: 37867123
DOI: 10.1016/j.jfo.2023.07.014 -
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 -
Klinische Monatsblatter Fur... Dec 2023Congenital aniridia is a severe malformation of almost all eye segments. Aniridia-associated keratopathy (AAK) and secondary glaucoma, which occur in more than 50% of...
BACKGROUND
Congenital aniridia is a severe malformation of almost all eye segments. Aniridia-associated keratopathy (AAK) and secondary glaucoma, which occur in more than 50% of affected individuals, are typically progressive and pose a high risk of blindness for patients with congenital aniridia. Our aim was to investigate the effect of glaucoma treatment on AAK in patients of the Homburg Aniridia Center.
METHODS
Our retrospective monocentric study included patients who underwent a comprehensive ophthalmological examination at the Homburg Aniridia Center between June 2003 and January 2022.
RESULTS
There were 556 eyes of 286 subjects (20.1 ± 20.1 years; 45.5% males) included. In 307 (55.2%) eyes of 163 subjects (27.5 ± 16.3 years; 43.1% males), glaucoma was present at the time of examination. The mean intraocular pressure in the glaucoma group was 19.0 mmHg (± 8.0), while in the non-glaucoma group, it was 14.1 mmHg (± 3.6) (p < 0.001). In the glaucoma group, 68 patients used antiglaucomatous topical monotherapy, 51 patients used 2 agents, 41 patients used 3 agents, 7 patients used quadruple therapy, and 140 did not use topical therapy (e.g., after pressure-lowering surgery, pain-free end-stage glaucoma, or incompliance). Patients were classified according to the following stages of AAK: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). The mean stage of AAK was 1.4 (1.2 - 1.5) in the group without eye drops, 1.9 (1.5 - 2.2) in the group with monotherapy, 1.8 (1.5 - 2.1) in the group with 2 drugs, 1.9 (1.5 - 2.2) in the group with 3 drugs, 3.4 (2.3 - 4.6) in the group with 4 drugs, and 3.3 (3.1 - 3.6) after antiglaucomatous surgery. The stage of AAK was significantly positively correlated with the number of pressure-lowering eye drops (p < 0.05) and prior pressure-lowering surgery (p < 0.05). Prostaglandin analogues were not correlated with a higher AAK stage compared to the other drug groups.
CONCLUSIONS
At the Homburg Aniridia Center, patients using topical antiglaucomatous quadruple therapy or who had previously undergone antiglaucomatous surgery had by far the highest AAK stage. The different drug groups had no influence on the AAK stage.
PubMed: 37852284
DOI: 10.1055/a-2194-1580 -
Journal of Cataract and Refractive... Mar 2024To investigate the effect of formula constants on predicted refraction and limitations of constant optimization for classical and modern intraocular lens (IOL) power...
PURPOSE
To investigate the effect of formula constants on predicted refraction and limitations of constant optimization for classical and modern intraocular lens (IOL) power calculation formulae.
SETTING
Tertiary care center.
DESIGN
Retrospective single-center consecutive case series.
METHODS
This analysis is based on a dataset of 888 eyes before and after cataract surgery with IOL implantation (Hoya Vivinex). Spherical equivalent refraction predSEQ was predicted using IOLMaster 700 data, IOL power, and formula constants from IOLCon ( https://iolcon.org ). The formula prediction error (PE) was derived as predSEQ minus achieved spherical equivalent refraction for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulae. The gradient of predSEQ (gradSEQ) as a measure for the effect of the constants on refraction was calculated and used for constant optimization.
RESULTS
Using initial formula constants, the mean PE was -0.1782 ± 0.4450, -0.1814 ± 0.4159, -0.1702 ± 0.4207, -0.1211 ± 0.3740, and -0.1912 ± 0.3449 diopters (D) for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulas, respectively. gradSEQ for all formula constants (except gradSEQ for the Castrop R) decay with axial length because of interaction with the effective lens position (ELP). Constant optimization for a zero mean PE (SD: 0.4410, 0.4307, 0.4272, 0.3742, 0.3436 D) results in a change in the PE trend over axial length in all formulae where the constant acts directly on the ELP.
CONCLUSIONS
With IOL power calculation formulae where the constant(s) act directly on the ELP, a change in constant(s) always changes the trend of the PE according to gradSEQ. Formulae where at least 1 constant does not act on the ELP have more flexibility to zero the mean or median PE without coupling with a PE trend error over axial length.
Topics: Humans; Lenses, Intraocular; Lens Implantation, Intraocular; Visual Acuity; Retrospective Studies; Biometry; Refraction, Ocular; Optics and Photonics; Phacoemulsification; Axial Length, Eye
PubMed: 37847110
DOI: 10.1097/j.jcrs.0000000000001337 -
Journal of Clinical Medicine Sep 2023Childhood glaucoma is one of the most common causes of corneal opacity in childhood and is associated with various pathological corneal changes, including corneal...
BACKGROUND
Childhood glaucoma is one of the most common causes of corneal opacity in childhood and is associated with various pathological corneal changes, including corneal enlargement, corneal clouding, and edema. Congenital glaucoma (CG) may cause a decrease in vision outcomes due to corneal opacity or clouding, which is often associated with stimulus deprivation amblyopia. Therefore, to create a balance between preventing amblyopia and sustaining corneal clearance, patients with CG can be managed with early penetrating corneal transplantation surgery along with advanced glaucoma management.
AIM
To investigate the graft survival rate and factors affecting graft survival in patients with congenital glaucoma who underwent penetrating keratoplasty (PKP).
STUDY DESIGN
Cross-sectional.
MATERIALS AND METHODS
Patients with congenital glaucoma who underwent PKP were retrospectively evaluated. The associations between age, corneal diameter, presence of ocular comorbidities, concurrent ocular surgeries with corneal graft, and visual outcomes were assessed.
RESULTS
Among the 30 eyes enrolled in the study, 6 (20%) had aniridia, 6 (20%) had Axenfeld-Rieger syndrome, and 18 (60%) were diagnosed with primary congenital glaucoma. Graft survival rates were 66.6% and 63.33% at 12 and 24 months, respectively. At the end of the follow-up, the overall graft survival rate was 60%. Statistical significance was observed between patient age at the time of surgery and graft failure ( = 0.02). Graft failure was associated with a younger patient age. Functional vision was achieved in 53.3% of patients.
CONCLUSIONS
The management of congenital glaucoma and its corneal complications is a delicate issue that requires great effort. PKP in congenital glaucoma was moderately successful in the present study. To provide functional vision, PKP could be the treatment of choice.
PubMed: 37834920
DOI: 10.3390/jcm12196276 -
Health Psychology and Behavioral... 2023Congenital aniridia is a rare genetic disorder of the eye characterized by visual impairment and progressive vision loss. While prior research has focused on ocular...
BACKGROUND
Congenital aniridia is a rare genetic disorder of the eye characterized by visual impairment and progressive vision loss. While prior research has focused on ocular manifestations in individuals with aniridia, there is a dearth of research on impacts on cognition and mental health. The aims of this study were to describe subjective symptoms of everyday executive functioning, fatigue and sleepiness in adults with aniridia and to compare self-reported health status with that of a normative reference group.
METHODS
Twenty-nine adults (aged 18-79 years) with congenital aniridia were included in this online survey, of whom 52% were females. Participants completed self-report measures of executive functioning (The Behavior Rating Inventory of Executive Function-Adult Version), sleepiness, fatigue, and health status (EQ-5D-5L).
RESULTS
Participants reported relatively few problems in everyday executive functioning, with only 14% experiencing impaired executive functioning. Scores on the five EQ-5D-5L domains (mobility, self-care, usual activities, pain, and anxiety/depression) did not differ from those of the normative reference group. The frequencies of excessive daytime sleepiness and severe fatigue were 17% and 38%, respectively. Ocular pain was experienced by 62% of participants.
CONCLUSIONS
The findings show that cognitive problems are related to and reflect self-reported health status and extent of fatigue. Moreover, those who suffered from ocular pain reported more difficulties with executive functioning, sleepiness and fatigue. These findings are important for understanding this disorder and supporting patients.
PubMed: 37811316
DOI: 10.1080/21642850.2023.2263534