-
Journal of Vitreoretinal Diseases 2023To assess the impact of retinal thickness variability (RTV) control on visual and treatment burden outcomes in patients with diabetic macular edema (DME) who received...
To assess the impact of retinal thickness variability (RTV) control on visual and treatment burden outcomes in patients with diabetic macular edema (DME) who received the 0.19 mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien, Alimera Sciences). This post hoc analysis examined the outcomes of a 3-year, phase 4, nonrandomized, open-label observational study. Retinal thickness was measured as central subfield thickness (CST). RTV was quantified by CST area under the curve (CST-AUC), retinal thickness amplitude (RTA), and retinal thickness standard deviation (RTSD). Visual outcomes were measured as best-corrected visual acuity (BCVA), and treatment burden was measured as the number of yearly supplemental DME treatments. The percentage of eyes with a CST ≤300 µm fluctuated throughout the study but was significantly increased relative to baseline at 36 months (baseline: 32.9% vs 36 months: 46.8%; < .05). FAc significantly reduced RTV in all measures more than 36 months ( < .0001). When divided into quartiles, eyes with the best RTV control post FAc had the greatest BCVA gains and improved disease control (ie, reduced need for supplemental therapy). The last-observed BCVA letter score exhibited linear correlations with CST-AUC ( = -0.100), RTA ( = -0.125), and RTSD ( = -0.162). A multivariate linear regression with baseline BCVA as a covariate displayed improved correlations with the last-observed BCVA, CST-AUC ( = -0.448), RTA ( = -0.432), and RTSD ( = -0.436). The sustained corticosteroid release of the 0.19 mg FAc implant reduced RTV in patients with DME, which directly correlated with significantly improved vision and a reduced supplemental treatment burden.
PubMed: 37974917
DOI: 10.1177/24741264231201314 -
Movement Disorders : Official Journal... Jan 2024The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP ) receptor type 1 (IP R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic...
BACKGROUND
The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP ) receptor type 1 (IP R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.
OBJECTIVES
We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy.
METHODS
Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction.
RESULTS
We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression.
CONCLUSIONS
This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Cerebellar Ataxia; Mutation, Missense; Movement Disorders; Atrophy; Inositol 1,4,5-Trisphosphate Receptors; Carbonic Anhydrases; Intracellular Signaling Peptides and Proteins; Intellectual Disability; Spinocerebellar Degenerations; Aniridia
PubMed: 37964426
DOI: 10.1002/mds.29651 -
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 -
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 -
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