Approximately 2-4 % of adult onset and 10 % of juvenile onset cases of primary open angle glaucoma can be attributed to non-synonymous coding mutations in MYOC. One of the key characteristics of a pathogenic MYOC mutant is the inability of the resulting protein to be secreted from trabecular meshwork cells. Instead, pathogenic myocilin variants accumulate in the endoplasmic reticulum. Typically, localization of MYOC mutants is compared to wild-type myocilin in cellular secretion assays that use immunoblot to detect myocilin in extracellular media, alongside intracellular soluble and insoluble (aggregated) fractions. Here, we implement a new method that utilizes a complement-based luminescence method in which an 11-residue HiBiT tag is appended to myocilin and complements a truncated nanoluciferase. The method allows for highly sensitive luminescence detection and does not require immunoblot. We tested non-synonymous coding variants T377R, D384G, D395ins, C433Y, T455K, and L486F, in an established immortalized trabecular meshwork cell line. Secretion was tested in 96-well plate format, revealing poor secretion for these mutants compared to wild-type myocilin. For assays conducted in 6-well plates, myocilin mutants were accumulated in intracellular fractions. HiBiT luminescence signals correlated well with immunofluorescence as well as immunoblot but is more sensitive than the latter. Overall, our study demonstrates that complement-based detection of mutant myocilin using luminescence allows for facile and sensitive detection of myocilin localization and has confirmed secretion defects for six variants.

The aim of this study is to describe the visual, refractive, functional, and patients' satisfaction outcomes of the AcrySof™ IQ Vivity™ extended depth-of-focus intraocular lens (EDOF IOL) in patients with mild primary open-angle glaucoma (POAG).

This is an ambispective, multicenter, and descriptive study. Patients with mild and stable POAG for at least 6 months, as well as patients who had the AcrySof™ IQ Vivity™ EDOF IOL implanted were included. Humphrey Field Analyzer III (Carl Zeiss Meditec, Dublin, CA, USA) and Triton optical coherence tomography (Topcon, Japan) were used to evaluate the inclusion criteria. In all cases, the formula used to calculate IOL power was Barrett Universal II. Refractive outcomes and visual acuity at distance, intermediate, and near were evaluated from 3 months postoperatively onward. In addition, monocular and binocular defocus curve and contrast sensitivity (CSV-1000, VectorVision, Greenvile, OH, USA) were assessed. Patient satisfaction was assessed through the Intraocular Lens Satisfaction (IOLSAT) and Questionnaire for Visual Disturbances (QUVID) questionnaires .

In total, 72 AcrySof™ IQ Vivity™ lenses from 36 patients were enrolled, of which 28 were women. The mean age was 71.61 ± 7.68 years, the mean thickness of the retinal nerve fiber layer (RNFL) was 79.24 ± 14.96 µm, the mean intraocular pressure (IOP) was 16.88 ± 3.09 mmHg, and the mean number of topical anti-glaucoma medication was 0.89 ± 0.95. Binocular corrected distance visual acuity (CDVA), binocular corrected intermediate visual acuity (CIVA), and binocular corrected near visual acuity (CNVA) were 0.00 ± 0.12, 0.16 ± 0.14, and 0.24 ± 0.11 LogMAR, respectively. Spherical equivalent was -0.27 ± 0.33 diopters (D). In addition, 86.11% of eyes were within ± 0.5 D and 95.83% were within ± 1.0 D. The binocular defocus curve shows a peak of maximum visual acuity (VA) at 0 D (0.00 ± 0.11 LogMAR) and smooth curve at intermediate (66 cm/-1.5 D) 0.11 ± 0.09 LogMAR and near distance (40 cm/-2.5 D) 0.36 ± 0.18 LogMAR. Binocular contrast sensitivity showed a decrease in high spatial frequencies compared with low spatial frequencies. The IOLSAT revealed that in bright light conditions, 88.89%, 91.67%, and 63.89% of patients "never" or "rarely" need glasses at far, arm's length, and near distances, respectively. In addition, according to the QUVID, 97.06% of patients "never" report shadow areas.

The new AcrySof™ IQ Vivity™ EDOF IOL seems to provide good visual outcomes at distance, intermediate, and near vision, with an adequate contrast sensitivity, defocus curve, a low rate of visual disturbances and high visual satisfaction in patients with mild and stable POAG.

Genetic variants in apolipoprotein E (APOE) are reported as risk factors for glaucoma in different ethnic populations, however, there is a scarcity of data from North India. Therefore, the present study aimed to investigate the association of APOE promoter region variants c.-219T > G, c.-427T > C, and c.-491A > T with glaucoma in the North Indian population.

286 primary glaucoma patients and 300 healthy controls were included in the present study. Promoter region variants (c.-219T > G, c.-427T > C, c.-491A > T) of APOE were genotyped by Sanger sequencing followed by statistical analyses.

Present case-control association analysis indicated that the GG genotype of the c.-219T > G variant is more common in glaucoma patients (18.53 %) than in controls (11.33 %) and conferred a 1.9-fold increased risk of glaucoma (OR = 1.92, 95 % CI 1.16-3.16, p = 0.010). This risk is particularly higher in females, showing a 2.7-fold increase (OR = 2.66, 95 % CI 1.10-6.41, p = 0.028). In the recessive model, the GG genotype also exhibited a 1.8-fold increased risk of glaucoma development (OR = 1.78, 95 % CI 1.12-2.83, p = 0.014). During sub-group analysis, GG genotype was more prevalent in POAG group compared to controls, with a 2.3-fold increased risk (OR = 2.27, 95 % CI 1.32-3.89, p = 0.002). However, no significant differences in genotype distribution were found between PACG and PCG vs. controls. Additionally, the genotype and allele frequency distributions for the c.-427T > C and c.-491A > T variants were not statistically significant between cases and controls.

Our study shows the association of the c.-219T > G variant in the development of glaucoma in the analyzed Indian population. The present study analyzed the genotype-phenotype correlation between APOE promoter region variants and glaucoma characteristics in the Indian population.

The pathophysiology of primary open-angle glaucoma (POAG), the most prevalent glaucoma type, is poorly understood. Although it is well known that epigenetic factors affect the progression of POAG, the impact of β-hydroxybutyrylation (Kbhb) on POAG remains unknown. Based on POAG-related datasets (GSE27276, GSE4316, and GSE231749) retrieved from the Gene Expression Omnibus (GEO) database, four biomarkers (FABP5, GLS, PDLIM1, and TAGLN) with a diagnostic value for POAG were identified by combining differential expression analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Immune infiltration analysis demonstrated significant differences in the infiltration abundances of 10 immune cells between POAG and controls, including regulatory T cells, monocytes, and macrophages, with notable positive correlations between TAGLN expression and these immune cells. Subsequently, single-cell analysis revealed that GLS, PDLIM1, and TAGLN were higher expressed in chondrocytes, smooth muscle cells, and endothelial cells. In addition, in vitro cellular experiments and animal models revealed that the TAGLN expression trend was consistent with the data from GSE27276 and GSE4316. In conclusion, TAGLN may play an important role in understanding of the molecular mechanisms of POAG and exploration of therapeutic targets.

This study investigated the baseline systemic features that predict rapid thinning of the retinal nerve fiber layer (RNFL) in patients with primary open-angle glaucoma (POAG). A database drawn from electronic medical records (EMRs) was searched for patients diagnosed with POAG between 2009 and 2016 who had been followed up for > 5 years with the annual evaluation of global RNFL thickness using spectral-domain optical coherence tomography. The rate of change in global RNFL thickness for each eye was determined by linear regression analysis over time. Systemic data obtained within 6 months from the time of glaucoma diagnosis were extracted from the EMRs and incorporated into a model to predict the rate of progressive RNFL thinning. The predictive model was trained and tested using a random forest (RF) method and interpreted using Shapley additive explanation plots (SHAP). The features able to explain the rate of progressive RNFL thinning were identified and interpreted. Data from 1256 eyes of 696 patients and 1107 eyes of 607 patients were included in the training and test sets, respectively. The R2 value for the RF model was 0.88 and mean absolute error of the model was 0.205 μm/year. The prediction model identified higher serum levels of aspartate aminotransferase, lower blood glucose, lower systolic blood pressure, and higher high-density lipoprotein as the four most important systemic features predicting rapid RNFL thinning over 5 years. Among the ophthalmic features, a higher global RNFL thickness and a higher intraocular pressure were the most important factors predicting rapid RNFL thinning. The study revealed baseline systemic features from the EMRs that were of predictive value for progression rate of POAG patients.

Approximately 2-4% of adult onset and 10% of juvenile onset cases of primary open angle glaucoma can be attributed to non-synonymous coding mutations in MYOC. One of the key characteristics of a pathogenic MYOC mutant is the inability of the resulting protein to be secreted from trabecular meshwork cells. Instead, pathogenic myocilin variants accumulate in the endoplasmic reticulum. Typically, localization of MYOC mutants is compared to wild-type myocilin in cellular secretion assays that use immunoblot to detect myocilin in extracellular media, alongside intracellular soluble and insoluble (aggregated) fractions. Here, we implement a new method that utilizes a complement-based luminescence method in which an 11-residue HiBiT tag is appended to myocilin and complements a truncated nanoluciferase. The method allows for highly sensitive luminescence detection and does not require immunoblot. We tested non-synonymous coding variants T377R, D384G, D395ins, C433Y, T455K, and L486F, in an established immortalized trabecular meshwork cell line. Secretion was tested in 96-well plate format, revealing poor secretion for these mutants compared to wild-type myocilin. For assays conducted in 6-well plates, myocilin mutants were accumulated in intracellular fractions. HiBiT luminescence signals correlated well with immunofluorescence as well as immunoblot but is more sensitive than the latter. Overall, our study demonstrates that complement-based detection of mutant myocilin using luminescence allows for facile and sensitive detection of myocilin localization and has confirmed secretion defects for seven variants.

The visualization of circle of Zinn-Haller (CZH) on optical coherence tomography angiography (OCTA) or its pattern does not have a clear effect on glaucoma, whereas the location of CZH is associated with axial length (AXL) in highly myopic eyes.

To investigate the association between the CZH and the presence of glaucoma using swept-source optical coherence tomography angiography (SS-OCTA) images of the optic nerve of patients with high myopia (HM).

This retrospective case series included 227 eyes with HM, comprising 134 and 93 eyes with and without glaucoma, respectively. The characteristics of CZH, including visualization, pattern, and location, were assessed using SS-OCTA. Vascular parameters, such as vessel density and microvascular dropout (MvD), were quantified. The factors affecting the presence of glaucoma and the correlations between the CZH distance and AXL were identified using logistic regression analysis and Pearson correlation analysis, respectively.

CZH was detected more frequently in HM patients with glaucoma (71.6%) than in patients without glaucoma (51.6%) ( P <0.002). However, the visualization of CZH was not related to the presence of glaucoma in multivariate regression analysis (odds ratio [OR], 0.688; 95% confidence interval [CI], 0.328-1.444; P =0.322). Moreover, compared with the annular pattern used as a reference, triangular and irregular patterns were not associated with the presence of glaucoma (OR: 1.043, 95% CI: 0.101-10.763, P =0.971; OR: 0.527, 95% CI: 0.255-1.092, P =0.085, respectively). MvD was significantly higher in patients with glaucoma (61.2%) than that in patients without glaucoma (2.2%) ( P <0.001) and was identified as a significant factor affecting the presence of glaucoma (OR, 42.120; 95% CI, 9.416-188.413; P <0.001). AXL showed a significant correlation with CZH distance in all patients (R=0.399; P <0.001).

CZH was more commonly detected in HM patients with glaucoma. However, no clear associations of glaucoma with the visualization, pattern, or location of CZH were observed in the present study. The correlation between AXL and CZH distance in eyes with HM warrants further investigation. These results may offer insights into the pathogenesis of glaucoma in eyes with HM as OCTA technology advances.

The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and inner wall endothelium of Schlemm's canal (SC) and its basement membrane, plays a significant role in regulating intraocular pressure (IOP) by controlling aqueous humor outflow resistance. Despite its significance, the biomechanical and hydrodynamic properties of this region remain inadequately understood. Fluid-structure interaction (FSI) and computational fluid dynamics (CFD) modeling using high-resolution microstructural images of the outflow pathway provides a comprehensive method to estimate these properties under varying conditions, offering valuable understandings beyond the capabilities of current imaging techniques.

In this study, we utilized high-resolution 3D serial block-face scanning electron microscopy (SBF-SEM) to image the TM/JCT/SC complex of a normal human donor eye perfusion-fixed at an IOP of 7 mm Hg. We developed a detailed 3D finite element (FE) model of the pathway using SBF-SEM images to simulate the biomechanical environment. The model included the TM/JCT/SC complex (structure) with interspersed aqueous humor (fluid). We employed a 3D, inverse FE algorithm to calculate the unloaded geometry of the TM/JCT/SC complex and utilized FSI to simulate the pressurization of the complex from 0 to 15 mm Hg.

Our simulations revealed that the resultant velocity distribution in the aqueous humor across the TM/JCT/SC complex is heterogeneous. The JCT and its deepest regions, specifically the basement membrane of the inner wall of SC, exhibited a volumetric average velocity of ∼0.011 mm/s, which is higher than the TM regions, with a volumetric average velocity of ∼0.007 mm/s. Shear stress analysis indicated that the maximum shear stress, based on our FE code criteria, was 0.5 Pa starting from 10 µm into the TM from the anterior chamber and increased to 0.95 Pa in the JCT and its adjacent SC inner wall basement membrane. Also, the tensile stress and strain distributions showed significant variations, with the first principal stress reaching up to 57 Pa (compressive volumetric average) and the first principal strain reaching up to 3.5 % in areas of high mechanical loading. The resultant stresses, strains, and velocities exhibited relatively similar average values across the TM, JCT, and SC regions, primarily due to the uniform elastic moduli assigned to these components. Our computational fluid dynamics (CFD) analysis revealed that while the velocity of the aqueous humor remained consistent, the maximum shear stress was reduced by a factor of thirty.

The uneven distribution of shear stress and velocity within the TM/JCT/SC complex highlights the complex biomechanical environment that regulates aqueous humor outflow.

Juvenile onset open-angle glaucoma (JOAG) manifests in individuals under the age of 40, resulting in elevated intraocular pressure and significant optic nerve damage. To broaden the spectrum of mutations associated with JOAG and to determine their specific structural implications, we examined Myocilin and Cytochrome P450 1B1 gene in a cohort of 111 unrelated North Indian patients diagnosed with JOAG.

A clinical and experimental study.

PCR-DNA sequencing screened the coding exons and intron-exon junctions of the MYOC and CYP1B1 genes in 111 unrelated JOAG patients and 100 controls. Identified sequence variations were searched in the ClinVar database, HGMD, and dbSNP. Six different online available algorithms including rare exome variant ensemble learner (REVEL), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, SNAP2, IMutant2.0, and MutPred2 were used for the pathogenicity prediction of missense variations. The Structural consequences of detected possible pathogenic variations were predicted by using PyMol, Chimera and MD simulation of these changes.

Potentially-pathogenic variations were observed in thirty patients (27.02%) within the MYOC and CYP1B1 genes, encompassing both novel and previously documented variants. Structural predictions of novel potentially-pathogenic mutations indicate altered stability and flexibility.

Analysis reveals a higher prevalence of CYP1B1 gene variants (22.5%) relative to MYOC gene variants (4.5%), suggesting that CYP1B1 is the predominant gene implicated in JOAG among Indian patients. Our findings enhance the understanding of mutation spectra and frequencies of MYOC and CYP1B1gene in JOAG among the North Indian population. Structural predictions of novel pathogenic mutations could enhance the understanding of JOAG pathogenesis and support subsequent functional analysis.

This study provides a bibliometric and bibliographic review of emerging applications of micro- and nanotechnology in treating ocular diseases, with a primary focus on glaucoma. We aim to identify key research trends and analyze advancements in devices and drug delivery systems for ocular treatments. The methodology involved analyzing 385 documents indexed on the Web of Science using tools such as VOSviewer and Bibliometrix. The results show a marked increase in scientific output, highlighting prominent authors and institutions, with England leading in the field. Key findings suggest that nanotechnology holds the potential to address the limitations of conventional treatments, including low ocular bioavailability and adverse side effects. Nanoparticles, nanovesicles, and polymer-based systems appear promising for prolonged and controlled drug release, potentially offering enhanced therapeutic efficacy. In conclusion, micro- and nanotechnology could transform ocular disease treatment, although challenges remain concerning the biocompatibility and scalability of these devices. Further clinical studies are necessary to establish these innovations within the therapeutic context of ophthalmology.

Endothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology. In this study, aqueous humor from patients undergoing ocular surgery was assayed for ET-1 abundance and related to the presence of glaucoma.

Open angle glaucoma patients (n=62 total) from the ophthalmology clinics of the University of Iowa Hospitals and Clinics were enrolled in this study and organized into three distinct cohorts based on their diagnostic criteria, including those with primary open angle glaucoma (POAG, n=25 patients), normal tension glaucoma (NTG, n=17 patients), exfoliation glaucoma (XFG, n=8 patients), and normal controls (n=12 patients).

Aqueous humor was collected intraoperatively from patients undergoing surgeries for glaucoma (including minimally invasive glaucoma surgeries, trabeculectomy, or glaucoma drainage device implantation) for samples in the glaucoma cohorts and cataract extraction for those in the control cohort. Aqueous humor was assayed by ELISA to measure and compare ET-1 abundance between the glaucoma cohorts and control cohort. ET-1 levels were also analyzed with linear regression to control for the covariates of age and sex.

ET-1 was significantly elevated in the aqueous humor of patients in the POAG (mean ± SD: 7.8 ± 5.1 pg/mL; p = 0.002) and NTG cohorts (6.1 ± 3.0 pg/mL; p = 0.030) compared to the control (4.0 ± 1.9 pg/mL). No significant difference in aqueous ET-1 was detected in the XFG cohort (6.2 ± 4.5 pg/mL; p = 0.230) compared to the control. Significantly higher ET-1 levels were detected in a merged grouping of all glaucoma cohorts (POAG, NTG, XFG) relative to controls (p = 0.021). Analysis of covariance indicated neither age nor sex was associated with ET-1 level (p = 0.60 and p = 0.27), respectively. Controlling for age and sex had minimal influence on the comparison of ET-1 levels in the POAG versus control cohort (p = 0.018) and nominal influence on the comparisons between the NTG (p = 0.089) or XFG cohort (p = 0.15) relative to the control.

Elevated ET-1 in aqueous humor was associated with POAG and NTG compared to controls amongst cohorts of patients at the University of Iowa. These data suggest that dysregulation of vascular perfusion may have a role in the pathophysiology of POAG. The analyses of NTG and XFG samples were limited by the relatively small sample sizes.

Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction, leading to neurodegeneration, is the pathological hallmark of primary open-angle glaucoma (POAG). Impaired axonal transport is an early and critical feature of glaucomatous neurodegeneration. However, a robust mouse model that accurately replicates these human POAG features has been lacking. We report the development and characterization of a new Cre-inducible mouse model expressing a DsRed-tagged Y437H mutant of human myocilin (Tg.CreMYOCY437H). A single intravitreal injection of HAd5-Cre induced selective MYOC expression in the TM, causing TM dysfunction, reducing the outflow facility, and progressively elevating IOP in Tg.CreMYOCY437H mice. Sustained IOP elevation resulted in significant loss of retinal ganglion cells (RGCs) and progressive axonal degeneration in Cre-induced Tg.CreMYOCY437H mice. Notably, impaired anterograde axonal transport was observed at the optic nerve head before RGC degeneration, independent of age, indicating that impaired axonal transport contributes to RGC degeneration in Tg.CreMYOCY437H mice. In contrast, axonal transport remained intact in ocular hypertensive mice injected with microbeads, despite significant RGC loss. Our findings indicate that Cre-inducible Tg.CreMYOCY437H mice replicate all glaucoma phenotypes, providing an ideal model for studying early events of TM dysfunction and neuronal loss in POAG.

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms. Targeting NETs in the elderly as an anti-aging therapy seems to be a very attractive therapeutic approach. Therapeutic apheresis with a specific filter to remove NETs could be a promising strategy worth considering.

To evaluate the incidence and to describe the characteristics of the intrableb pigmentation (IBP) following XEN63 implantation.

Retrospective case series of three eyes presenting a pigment dispersion in the filtering bleb after a XEN63 implantation for uncontrolled IOP. Demographic, clinical and imaging data were obtained from medical records.

Three out of 40 patients who underwent XEN implantation (average age 70.67 years) showed an IBP during the 12 months postoperative period. The mean time of IBP onset was 50 days (range, 15-90). The slit lamp examination showed two IBP patterns: a "diffuse" pattern (2 patients) with multiple spots of pigmentation inside the bleb; a "punctiform" pattern (1 patient), with a single spot at the distal end of the device. The AS-OCT imaging confirmed the presence of IBP appearing as a hyperreflective spot/s in the context of the filtering bleb. The patient with the punctiform IBP experienced a distal XEN ostium obstruction with a decrease in bleb function. In one case the diffuse IBP occurred after a successful needling procedure. All the patients' IOP reported at the end of the follow-up was below 21 mmHg.

The development of IBP might occur after XEN implantation in various times and with different patterns. The IBP pattern can provide meaningful clues on the bleb filtering function. A proper follow-up based on slit lamp biomicroscopy, IOP measurement, and AS-OCT imaging is recommended to manage potential complications related to IBP.

Primary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.

To evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.

This was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023.

Three PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS).

Odds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components.

A total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs.

In this cross-sectional study, despite some improvements in OR-based risk stratification using the Gharahkhani PRSs, Han PRSs, and Craig PRSs, consistently lower improvements in AUROC and R2 for African-ancestry compared with European-ancestry groups highlight the need for risk prediction models tailored to diverse populations.

This study aims to examine ferroptosis-associated genes in primary open-angle glaucoma (POAG) and offer new insights into the underlying disease mechanisms and potential therapeutic approaches. Differentially expressed genes (DEGs) between the POAG and control groups were identified using bioinformatics analysis and subsequently intersected with a ferroptosis gene set to isolate ferroptosis-related DEGs (Ferr DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to examine their biological functions. Core genes were identified through protein-protein interaction (PPI) network and Friends analysis. The diagnostic potential of core Ferr DEGs was assessed using receiver operating characteristic (ROC) curve analysis, while immune cell infiltration was examined using the CIBERSORT algorithm. Additionally, Spearman correlation analysis was used to examine the relationships between the identified genes and immune cell populations. A total of 25 Ferr DEGs were identified, with DDIT4, GDF15, NAMPT, HBA1, and IGFBP7 recognized as key core genes. ROC analysis demonstrated that these genes exhibited high diagnostic accuracy, with an AUC > 0.7. Additionally, the infiltration levels of memory B cells and macrophage_M2 were significantly elevated in POAG tissues compared to the control group. Notably, the core genes revealed significant correlations with various immune cell types. Our findings underscore the involvement of ferroptosis-related genes in POAG pathogenesis and highlight their potential as diagnostic biomarkers and therapeutic targets. Future research should focus on validating these findings in clinical settings and exploring the therapeutic modulation of ferroptosis in POAG management.

This study aimed to explore anatomical differences in the aqueous humor (AH) outflow pathway between male and female dogs using ultrasound biomicroscopy (UBM).

Clinical data were collected from 30 eyes of 30 dogs (15 males: 10 right eyes, 5 left eyes; and 15 females: 7 right eyes, 8 left eyes) treated at the Veterinary Medical Teaching Hospital of Chungbuk National University, South Korea, between August 2018 and February 2024.

The study conducted an in-depth UBM examination, specifically observing peripheral anterior chamber depth (ACD), geometric iridocorneal angle (ICA), and angle-opening distance (AOD) alongside measurements of ciliary cleft width (CCW), length (CCL), and area (CCA), and assessed the longitudinal fibers of ciliary muscle thickness (Lf-CMT) and the longitudinal and radial fibers of ciliary muscle thickness (LRf-CMT) for gender-based differences.

The study identified a significant sex difference in peripheral ACD, with females displaying shallower depths compared to males, potentially clarifying the higher incidence of glaucoma in female dogs. No significant gender differences were found in ICA, AOD, CC parameters, or ciliary muscle parameters measurements.

This research uncovered that peripheral ACD is significantly shallower in females than in males, potentially indicating a risk factor that could contribute to the development of primary angle-closure glaucoma.

In myocilin-associated glaucoma, pathogenic missense mutations accumulate mainly in the olfactomedin domain (mOLF) of myocilin. This makes the protein susceptible to aggregation, where mOLF-mOLF dimerization is possibly an initial stage. Nevertheless, there are no molecular level studies that have probed the nature of interactions occurring between two mOLF domains and the key characteristics of the resulting dimer complex. In this work, we used AlphaFold2 to obtain an I477N mutant mOLF structure with high quality followed by a stable I477N mOLF-mOLF homodimer model using molecular docking combined with molecular dynamics simulations. Moreover, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods coupled with per-residue energy decomposition studies are carried out to identify the key residues involved in the binding interaction. Based on these results, we provide insights into the molecular level understanding of the intermolecular interaction between two mOLF domains in an I477N homodimer. Hydrogen bonds, salt bridges, and favorable van der Waals interactions are observed in the binding interface of the homodimer. Additionally, our results suggest that I477N mutant mOLF aggregation could be a multistep process, beginning with an initial mOLF-mOLF dimerization mainly mediated by residues such as Asp395 and Arg681. Also, the peptides P1 (residues 326-337) and P3 (residues 426-442) of the mOLF domain, previously identified as pertinent for myocilin aggregation, could potentially contribute to a subsequent stage of myocilin aggregation, the first step being mOLF-mOLF dimerization.

Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction, leading to neurodegeneration, is the pathological hallmark of primary open-angle glaucoma (POAG). Impaired axonal transport is an early and critical feature of glaucomatous neurodegeneration. However, a robust mouse model that replicates these human POAG features accurately has been lacking. We report the development and characterization of a novel Cre-inducible mouse model expressing a DsRed-tagged Y437H mutant of human myocilin (Tg.CreMYOCY437H). A single intravitreal injection of HAd5-Cre induced selective MYOC expression in the TM, causing TM dysfunction, reducing outflow facility, and progressively elevating IOP in Tg.CreMYOCY437H mice. Sustained IOP elevation resulted in significant retinal ganglion cell (RGC) loss and progressive axonal degeneration in Cre-induced Tg.CreMYOCY437H mice. Notably, impaired anterograde axonal transport was observed at the optic nerve head before RGC degeneration, independent of age, indicating that impaired axonal transport contributes to RGC degeneration in Tg.CreMYOCY437H mice. In contrast, axonal transport remained intact in ocular hypertensive mice injected with microbeads, despite significant RGC loss. Our findings indicate that Cre-inducible Tg.CreMYOCY437H mice replicate all glaucoma phenotypes, providing an ideal model for studying early events of TM dysfunction and neuronal loss in POAG.

This focused review highlights the importance of yes-associated protein (YAP)/transcriptional coactivator with PDZ binding motif (TAZ) mechanosignaling in human trabecular meshwork and Schlemm's canal cells in response to glaucoma-associated extracellular matrix stiffening and cyclic mechanical stretch, as well as biochemical pathway modulators (with signaling crosstalk) including transforming growth factor beta 2, glucocorticoids, Wnt, lysophosphatidic acid, vascular endothelial growth factor, and oxidative stress. We provide a comprehensive overview of relevant literature from the last decade, highlight intriguing research avenues with translational potential, and close with an outlook on future directions.

To investigate associations between statin use and glaucoma in the 2017 to 2022 All of Us (AoU) Research Program.

Cross-sectional, population-based.

79 742 adult participants aged ≥40 years with hyperlipidemia and with electronic health record (EHR) data in the AoU database.

Hyperlipidemia, glaucoma status, and statin use were defined by diagnoses and medication information in EHR data collected by AoU. Logistic regression analysis was performed to evaluate the association between statin use and glaucoma likelihood. Logistic regression modeling was used to examine associations between glaucoma and all covariates included in adjusted analysis. Serum low-density lipoprotein cholesterol (LDL-C) was used to assess hyperlipidemia severity. Analyses stratified by LDL-C level and age were performed.

Any glaucoma as defined by International Classification of Diseases codes found in EHR data.

Of 79 742 individuals with hyperlipidemia in AoU, there were 6365 (8.0%) statin users. Statin use was associated with increased glaucoma prevalence when compared with statin nonuse (adjusted odds ratio [aOR]: 1.13, 95% confidence interval [CI]: 1.01-1.26). Higher serum levels of LDL-C were associated with increased odds of glaucoma (aOR: 1.003, 95% CI: 1.003, 1.004). Statin users had significantly higher LDL-C levels compared to nonusers (144.9 mg/dL versus 136.3 mg/dL, P value < 0.001). Analysis stratified by LDL-C identified positive associations between statin use and prevalence of glaucoma among those with optimal (aOR = 1.39, 95% CI = 1.05-1.82) and high (aOR = 1.37, 95% CI = 1.09-1.70) LDL-C levels. Age-stratified analysis showed a positive association between statin use and prevalence of glaucoma in individuals aged 60 to 69 years (aOR = 1.28, 95% CI = 1.05-1.56).

Statin use was associated with increased glaucoma likelihood in the overall adult AoU population with hyperlipidemia, in individuals with optimal or high LDL-C levels, and in individuals 60 to 69 years old. Findings suggest that statin use may be an independent risk factor for glaucoma, which may furthermore be affected by one's lipid profile and age.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

This research confirms and further establishes that pathogenic variants in a fourth gene, METTL23, are associated with autosomal dominant normal-tension glaucoma (NTG).

To determine the frequency of glaucoma-causing pathogenic variants in the METTL23 gene in a cohort of patients with NTG from Iowa.

This case-control study took place at a single tertiary care center in Iowa from January 1997 to January 2024, with analysis occurring between January 2023 and January 2024. Two groups of participants were enrolled from the University of Iowa clinics: 331 patients with NTG and 362 control individuals without glaucoma. Patients with a history of trauma; steroid use; stigmata of pigment dispersion syndrome; exfoliation syndrome; or pathogenic variants in MYOC, TBK1, or OPTN were also excluded.

Detection of an enrichment of METTL23 pathogenic variants in individuals with NTG compared with control individuals without glaucoma.

The study included 331 patients with NTG (mean [SD] age, 68.0 [11.7] years; 228 [68.9%] female and 103 [31.1%] male) and 362 control individuals without glaucoma (mean [SD] age, 64.5 [12.6] years; 207 [57.2%] female and 155 [42.8%] male). There were 5 detected instances of 4 unique METTL23 pathogenic variants in patients with NTG. Three METTL23 variants-p.Ala7Val, p.Pro22Arg, and p.Arg63Trp-were judged to be likely pathogenic and were detected in 3 patients (0.91%) with NTG. However, when all detected variants were evaluated with either mutation burden analysis or logistic regression, their frequency was not statistically higher in individuals with NTG than in control individuals without glaucoma (1.5% vs 2.5%; P = .27).

This investigation provides evidence that pathogenic variants in METTL23 are associated with NTG. Within an NTG cohort at a tertiary care center, pathogenic variants were associated with approximately 1% of NTG cases, a frequency similar to that of other known normal-tension glaucoma genes, including optineurin (OPTN), TANK-binding kinase 1 (TBK1), and myocilin (MYOC). The findings suggest that METTL23 pathogenic variants are likely involved in a biologic pathway that is associated with glaucoma that occurs at lower intraocular pressures.

Glaucoma, a prevalent and potentially blinding eye disease, is linked to a variety of factors, including elevated intraocular pressure, optic nerve damage, and oxidative stress. In recent years, dietary habits, as a controllable lifestyle factor, have received increasing attention in the prevention and treatment of glaucoma. The purpose of this review was to investigate the effects of dietary factors on glaucoma, with a particular emphasis on two common dietary patterns: the high-salt diet and the Mediterranean diet. In addition, we investigated the association between many particular nutrients (including omega-3 fatty acids, vitamins, caffeine, and minerals) and glaucoma to fully assess the potential involvement of dietary variables in glaucoma pathogenesis, prevention, and treatment. This article reveals the importance of dietary components in glaucoma prevention and explores prospective possibilities for future research by conducting a comprehensive review of previous scientific studies.

Systemic hypertension (HT) is associated with the development of increased intraocular pressure (IOP), a risk factor for glaucoma. However, it remains unclear whether high IOP is a risk factor for HT.

We investigated 7,487 Japanese individuals (4,714 men, 2,773 women; mean [±SD] age 49±9 years) who underwent annual health checkups in 2006. Over the 10-year follow-up period, 1,232 (24.3%) men and 370 (11.5%) women developed new-onset HT, defined as initiation of antihypertensive drug treatment or blood pressure ≥140/90 mmHg. After dividing IOP into tertiles (T1-T3), Cox proportional hazards analysis (adjusted for age, sex, systolic blood pressure, obesity, current smoking, alcohol consumption, family history of HT, estimated glomerular filtration rate, and diabetes and dyslipidemia diagnoses at baseline) revealed a significantly higher risk of newly developed HT in T3 (IOP ≥14 mmHg; hazard ratio 1.14; 95% confidence interval 1.01-1.29; P=0.038) using T1 (IOP ≤11 mmHg) as the reference group. There was no significant interaction between sex and IOP tertile (P=0.153). A restricted cubic spline model showed a gradual but robust increase in the hazard ratio for new-onset HT with increasing IOP.

High IOP is an independent risk factor for the development of HT over a 10-year period.

To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT).

A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups.

In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05).

The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG.

The sympathetic nervous responses to cold stress are known; however, concurrent cardiovascular and ocular parameter alterations in the responses are poorly characterized. The aim of this study was to examine the influence of the cold pressor test (CPT) on cardiovascular and ocular parameters in young adult subjects. There was a total of 86 participants. The CPT was conducted by submerging each participant's left hand in cold water (3-5 °C) for 3 min. During the CPT, systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), and heart rate were found to be significantly increased compared to the baseline and significantly decreased compared to recovery, including the mean of the standard deviations of all normal-to-normal intervals (SDNN). In the recovery phase, the SDNN continued to decrease statistically significantly compared to the baseline and the CPT. Furthermore, the findings of this study show that the CPT impacted intra-ocular pressure (IOP), ACD, and pupil size parameters. There was a positive correlation between the MAP and IOP in both eyes during the CPT. The cold stress stimulates a sympathetic response, leading to an increase in the MAP. The pupil size increased in response to the CPT in both eyes, indicating that ocular function was increased in response to the CPT in young adults compared to baseline. In conclusion, our results suggest that in young adults, cardiovascular and ocular parameters respond to the sympathetic nervous system during the CPT.

Myocilin-associated glaucoma is a protein-conformational disorder associated with formation of a toxic amyloid-like aggregate. Numerous destabilizing single point variants, distributed across the myocilin olfactomedin β-propeller (OLF, myocilin residues 245-504, 30 kDa) are associated with accelerated disease progression. In vitro, wild type (WT) OLF can be promoted to form thioflavin T (ThT)-positive fibrils under mildly destabilizing (37°C, pH 7.2) conditions. Consistent with the notion that only a small number of residues within a protein are responsible for amyloid formation, 3D 13C-13C solid-state NMR spectra show that OLF fibrils are likely to be composed of only about one third of the overall sequence. Here, we probe the residue composition of fibrils formed de novo from purified full-length OLF. We were able to make sequential assignments consistent with the sequence S331-G-S-L334. This sequence appears once within a previously identified amyloid-prone region (P1, G326AVVYSGSLYFQ) internal to OLF. Since nearly half of the pairs of adjacent residues (di-peptides) in OLF occur only once in the primary structure and almost all the 3-residue sequences (tri-peptides) are unique, remarkably few sequential assignments are necessary to uniquely identify specific regions of the amyloid core. This assignment approach could be applied to other systems to expand our molecular comprehension of how folded proteins undergo fibrillization.

Parasympathetic activation in the anterior eye segment regulates various physiological functions. This process, mediated by muscarinic acetylcholine receptors, also impacts intraocular pressure (IOP) through the trabecular meshwork. While FDA-approved M3 muscarinic receptor (M3R) agonists exist for IOP reduction, their systemic cholinergic adverse effects pose limitations in clinical use. Therefore, advancing our understanding of the cholinergic system in the anterior segment of the eye is crucial for developing additional IOP-reducing agents with improved safety profiles. Systems genetics analyses were utilized to explore correlations between IOP and the five major muscarinic receptor subtypes. Molecular docking and dynamics simulations were applied to human M3R homology model using a comprehensive set of human M3R ligands and 1,667 FDA-approved or investigational drugs. Lead compounds from the modeling studies were then tested for their IOP-lowering abilities in mice. Systems genetics analyses unveiled positive correlations in mRNA expressions among the five major muscarinic receptor subtypes, with a negative correlation observed only in M3R with IOP. Through modeling studies, rivastigmine and edrophonium emerged as the most optimally suited cholinergic drugs for reducing IOP via a potentially distinct mechanism from pilocarpine or physostigmine. Subsequent animal studies confirmed comparable IOP reductions among rivastigmine, edrophonium, and pilocarpine, with longer durations of action for rivastigmine and edrophonium. Mild cholinergic adverse effects were observed with pilocarpine and rivastigmine but absent with edrophonium. These findings advance ocular therapeutics, suggesting a more nuanced role of the parasympathetic system in the anterior eye segment for reducing IOP than previously thought.

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 μM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.

Excessive levels of glutamate activity could potentially damage and kill neurons. Glutamate excitotoxicity is thought to play a critical role in many CNS and retinal diseases. Accordingly, glutamate excitotoxicity has been used as a model to study neuronal diseases. Immune proteins, such as major histocompatibility complex (MHC) class I molecules and their receptors, play important roles in many neuronal diseases, while T-cell receptors (TCR) are the primary receptors of MHCI. We previously showed that a critical component of TCR, CD3ζ, is expressed by mouse retinal ganglion cells (RGCs). The mutation of CD3ζ or MHCI molecules compromises the development of RGC structure and function. In this study, we investigated whether CD3ζ-mediated molecular signaling regulates RGC death in glutamate excitotoxicity. We show that mutation of CD3ζ significantly increased RGC survival in NMDA-induced excitotoxicity. In addition, we found that several downstream molecules of TCR, including Src (proto-oncogene tyrosine-protein kinase) family kinases (SFKs) and spleen tyrosine kinase (Syk), are expressed by RGCs. Selective inhibition of an SFK member, Hck, or Syk members, Syk or Zap70, significantly increased RGC survival in NMDA-induced excitotoxicity. These results provide direct evidence to reveal the underlying molecular mechanisms that control RGC death under disease conditions.

Recent advancements in deep learning have significantly impacted ophthalmology, especially in glaucoma, a leading cause of irreversible blindness worldwide. In this study, we developed a reliable predictive model for glaucoma detection using deep learning models based on clinical data, social and behavior risk factor, and demographic data from 1652 participants, split evenly between 826 control subjects and 826 glaucoma patients.

We extracted structural data from control and glaucoma patients' electronic health records (EHR). Three distinct machine learning classifiers, the Random Forest and Gradient Boosting algorithms, as well as the Sequential model from the Keras library of TensorFlow, were employed to conduct predictive analyses across our dataset. Key performance metrics such as accuracy, F1 score, precision, recall, and the area under the receiver operating characteristics curve (AUC) were computed to both train and optimize these models.

The Random Forest model achieved an accuracy of 67.5%, with a ROC AUC of 0.67, outperforming the Gradient Boosting and Sequential models, which registered accuracies of 66.3% and 64.5%, respectively. Our results highlighted key predictive factors such as intraocular pressure, family history, and body mass index, substantiating their roles in glaucoma risk assessment.

This study demonstrates the potential of utilizing readily available clinical, lifestyle, and demographic data from EHRs for glaucoma detection through deep learning models. While our model, using EHR data alone, has a lower accuracy compared to those incorporating imaging data, it still offers a promising avenue for early glaucoma risk assessment in primary care settings. The observed disparities in model performance and feature significance show the importance of tailoring detection strategies to individual patient characteristics, potentially leading to more effective and personalized glaucoma screening and intervention.

Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide. Understanding the molecular aetiology is key to improving diagnosis, prognosis and unlocking the potential for optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families of diverse ethnic backgrounds, recruited into the Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, to improve the genetic diagnostic yield. Using the Genomics England/Genomic Medicine Centres (GE/GMC) diagnostic pipeline, 13 unrelated families were solved (13/78, 17%). Further interrogation using an expanded gene panel yielded a molecular diagnosis in 7 more unrelated families (7/78, 9%). This analysis effectively raises the total number of solved CG families in the GE100KGP to 26% (20/78 families). Twenty-five percent (5/20) of the solved families had primary congenital glaucoma (PCG), while 75% (15/20) had secondary CG; 53% of this group had non-acquired ocular anomalies (including iris hypoplasia, megalocornea, ectopia pupillae, retinal dystrophy, and refractive errors) and 47% had non-acquired systemic diseases such as cardiac abnormalities, hearing impairment, and developmental delay. CYP1B1 was the most frequently implicated gene, accounting for 55% (11/20) of the solved families. We identified two novel likely pathogenic variants in the TEK gene, in addition to one novel pathogenic copy number variant (CNV) in FOXC1. Variants that passed undetected in the GE100KGP diagnostic pipeline were likely due to limitations of the tiering process, the use of smaller gene panels during analysis, and the prioritisation of coding SNVs and indels over larger structural variants, CNVs, and non-coding variants.

This study presents a 3D in vitro cell culture model, meticulously 3D printed to replicate the conventional aqueous outflow pathway anatomical structure, facilitating the study of trabecular meshwork (TM) cellular responses under glaucomatous conditions. Glaucoma affects TM cell functionality, leading to extracellular matrix (ECM) stiffening, enhanced cell-ECM adhesion, and obstructed aqueous humor outflow. Our model, reconstructed from polyacrylamide gel with elastic moduli of 1.5 and 21.7 kPa, is based on serial block-face scanning electron microscopy images of the outflow pathway. It allows for quantifying 3D, depth-dependent, dynamic traction forces exerted by both normal and glaucomatous TM cells within an active fluid-structure interaction (FSI) environment. In our experimental design, we designed two scenarios: a control group with TM cells observed over 20 hours without flow (static setting), focusing on intrinsic cellular contractile forces, and a second scenario incorporating active FSI to evaluate its impact on traction forces (dynamic setting). Our observations revealed that active FSI results in higher traction forces (normal: 1.83-fold and glaucoma: 2.24-fold) and shear strains (normal: 1.81-fold and glaucoma: 2.41-fold), with stiffer substrates amplifying this effect. Glaucomatous cells consistently exhibited larger forces than normal cells. Increasing gel stiffness led to enhanced stress fiber formation in TM cells, particularly in glaucomatous cells. Exposure to active FSI dramatically altered actin organization in both normal and glaucomatous TM cells, particularly affecting cortical actin stress fiber arrangement. This model while preliminary offers a new method in understanding TM cell biomechanics and ECM stiffening in glaucoma, highlighting the importance of FSI in these processes. STATEMENT OF SIGNIFICANCE: This pioneering project presents an advanced 3D in vitro model, meticulously replicating the human trabecular meshwork's anatomy for glaucoma research. It enables precise quantification of cellular forces in a dynamic fluid-structure interaction, a leap forward from existing 2D models. This advancement promises significant insights into trabecular meshwork cell biomechanics and the stiffening of the extracellular matrix in glaucoma, offering potential pathways for innovative treatments. This research is positioned at the forefront of ocular disease study, with implications that extend to broader biomedical applications.

Primary open angle glaucoma (POAG) is a leading cause of blindness globally. Characterized by progressive retinal ganglion cell degeneration, the precise pathogenesis remains unknown. Genome-wide association studies (GWAS) have uncovered many genetic variants associated with elevated intraocular pressure (IOP), one of the key risk factors for POAG. We aimed to identify genetic and morphological variation that can be attributed to trabecular meshwork cell (TMC) dysfunction and raised IOP in POAG.

62 genes across 55 loci were knocked-out in a primary human TMC line. Each knockout group, including five non-targeting control groups, underwent single-cell RNA-sequencing (scRNA-seq) for differentially-expressed gene (DEG) analysis. Multiplexed fluorescence coupled with CellProfiler image analysis allowed for single-cell morphological profiling.

Many gene knockouts invoked DEGs relating to matrix metalloproteinases and interferon-induced proteins. We have prioritized genes at four loci of interest to identify gene knockouts that may contribute to the pathogenesis of POAG, including ANGPTL2, LMX1B, CAV1, and KREMEN1. Three genetic networks of gene knockouts with similar transcriptomic profiles were identified, suggesting a synergistic function in trabecular meshwork cell physiology. TEK knockout caused significant upregulation of nuclear granularity on morphological analysis, while knockout of TRIOBP, TMCO1 and PLEKHA7 increased granularity and intensity of actin and the cell-membrane.

High-throughput analysis of cellular structure and function through multiplex fluorescent single-cell analysis and scRNA-seq assays enabled the direct study of genetic perturbations at the single-cell resolution. This work provides a framework for investigating the role of genes in the pathogenesis of glaucoma and heterogenous diseases with a strong genetic basis.

This review aims to evaluate the therapeutic potential of green tea (GT), scientifically named Camellia sinensis, in treating eye diseases. We provide an overview of the ingredients and traditional use of Camellia sinensis, followed by a detailed discussion of its therapeutic uses in various eye diseases, including ocular surface diseases (allergic diseases, dry eye, pterygium, and infections), cataract, glaucoma, uveitis, retinal diseases, and optic nerve diseases. The pharmacologic activities related to ocular diseases, such as anti-vascular endothelial growth factor, aldose reductase inhibitor activity, anti-bacterial, anti-inflammatory, and antioxidant effects are also explored in this review. The dose and route of administration of GT in various studies are discussed. Safety issues related to the use of GT, such as the side effects associated with high doses and long-term use, are also addressed. The review highlights the potential of GT as a natural therapeutic agent for a variety of ocular diseases. Its various pharmacologic activities make it a promising treatment option. However, more well-designed studies are needed to determine the optimal dose and route of administration and to assess its long-term safety and efficacy. Overall, GT appears to be a promising adjunct therapy for various ocular diseases.

Self-treatment with glaucoma medication (eye drops) has been associated with adherence challenges. Poor adherence results in worse outcomes in terms of visual field loss.

To investigate patterns in medication adherence among Danish patients with glaucoma in relation to selected predictors of adherence, long-term adherence patterns, and long-term societal economic consequences of poor adherence.

This register-based study included 30 100 glaucoma patients followed for 10 years between 2000 and 2018. Glaucoma was identified from the Danish national registers by diagnosis of Open Angle Glaucoma and/or by redeemed prescriptions of glaucoma medication. Logistic regression models were applied to estimate patient characteristics related to medical adherence. Diagnosis-related group fees were applied to estimate healthcare costs.

High adherence in the first year(s) of treatment was less likely among men (ORfirst year: 0.78, 95% CI: 0.75 to 0.82), younger individuals and among those with a positive Charlson Comorbidity Index (CCI) score (ORfirst year/CCI≥3: 0.71, 95% CI: 0.63 to 0.80). Adherence in the first year and in the first two years was associated with adherence in the fifth (ORfirst year: 4.55, 95% CI: 4.30 to 4.82/ORfirst two years: 6.47, 95% CI: 6.10 to 6.86) as with adherence in the 10th year with slightly lower estimates. Being medical adherent was related to higher costs related to glaucoma medication after 5 and 10 years comparing with poor adherence, whereas poor adherence was associated with a marked increase in long-term costs for hospital contacts.

Increasing age, female sex and low comorbidity score are correlated with better adherence to glaucoma treatment. Adherence in the first years of treatment may be a good predictor for future adherence. In the long term, patients with poor adherence are overall more expensive to society in terms of hospital contacts.

This cross-sectional study investigated the association between glaucoma and B vitamin dietary intake. A total of 5025 enrolled individuals participated in self-reported glaucoma questionnaire and 3264 participated in International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria. In self-reported glaucoma, the risk of having self-reported glaucoma was lower in the third quartile of vitamin B1 intake (odds ratio [odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40-0.97), and P trend (P trend = 0.004) for vitamin B12 was significant; in males, the third quartile of vitamin B1 intake (OR 0.44, 95% CI 0.24-0.83) and the fourth quartile of vitamin B2 intake (OR 0.39, 95% CI 0.17-0.89) were associated with a lower risk. In glaucoma based on ISGEO criteria, the increase of niacin intake (OR 0.94, 95% CI 0.89-0.99) was negatively associated with the odds of self-reported glaucoma. After sex-stratified analysis, the third quartile of vitamin B6 intake (OR 0.21, 95% CI 0.08-0.60) in males were associated with reduced odds of glaucoma. The restricted cubic spline analysis revealed a nonlinear association of vitamin B2 (p for nonlinearity = 0.04) and B9 (p for nonlinearity = 0.024) intake with glaucoma diagnosed by ISGEO criteria in females.

Given its increasing prevalence, aging is of great concern to researchers worldwide. Cellular senescence is a physiological or pathological cellular state caused by aging and a prominent risk factor for the interruption of the integrity and functionality of human biological barriers. Health barriers play an important role in maintaining microenvironmental homeostasis within the body. The senescence of barrier cells leads to barrier dysfunction and age-related diseases. Cellular senescence has been reported to be a key target for the prevention of age-related barrier diseases, including Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, and preeclampsia. Drugs such as metformin, dasatinib, quercetin, BCL-2 inhibitors, and rapamycin have been shown to intervene in cellular senescence and age-related diseases. In this review, we conclude that cellular senescence is involved in age-related biological barrier impairment. We further outline the cellular pathways and mechanisms underlying barrier impairment caused by cellular senescence and describe age-related barrier diseases associated with senescent cells. Finally, we summarize the currently used anti-senescence pharmacological interventions and discuss their therapeutic potential for preventing age-related barrier diseases.

Glaucoma is a complex neurodegenerative disease characterized by optic nerve damage and visual field loss, and remains a leading cause of irreversible blindness. Elevated intraocular pressure (IOP) is a critical risk factor that requires effective management. Emerging research underscores dual roles of bioactive lipid mediators in both IOP regulation, and the modulation of neurodegeneration and neuroinflammation in glaucoma. Bioactive lipids, encompassing eicosanoids, specialized pro-resolving mediators (SPMs), sphingolipids, and endocannabinoids, have emerged as crucial players in these processes, orchestrating inflammation and diverse effects on aqueous humor dynamics and tissue remodeling. Perturbations in these lipid mediators contribute to retinal ganglion cell loss, vascular dysfunction, oxidative stress, and neuroinflammation. Glaucoma management primarily targets IOP reduction via pharmacological agents and surgical interventions, with prostaglandin analogues at the forefront. Intriguingly, additional lipid mediators offer promise in attenuating inflammation and providing neuroprotection. Here we explore these pathways to shed light on their intricate roles, and to unveil novel therapeutic avenues for glaucoma management.

To evaluate the effect of uneventful cataract surgery on Schlemm's canal (SC) and the trabecular meshwork (TM) in cases with pseudoexfoliation (PX).

In this prospective study, 37 PX and 37 normal eyes, who underwent cataract surgery, were included. The PX group was further divided into two subgroups: PX syndrome (PXS) and PX glaucoma (PXG). Preoperative complete ophthalmologic examination, anterior segment (AS) imaging using a Scheimpflug camera, and measurements of SC length and area and TM thickness and length using AS optical coherence tomography (AS-OCT) were performed in all cases. All measurements were repeated at the first and third months after surgery.

Preoperative intraocular pressure (IOP), AS parameters, SC, and TM values showed no significant differences between the groups (p > 0.05). After surgery, there was a significant increase in AS parameter values and a significant decrease in IOP values in both the PX and control groups (p < 0.05). The nasal and temporal SC area showed a significant increase in the PX group after surgery (p = 0.007, p = 0.003, respectively). In the subgroup analysis, the only significant change in the nasal and temporal SC area was in the PXS group (p = 0.006, p = 0.003, respectively).

Cataract surgery resulted in an increase in the SC area in patients with PXS. This increase may be due to multiple mechanisms including the IOP-lowering effect of cataract removal, change in AS, and removal of intraocular PX material after surgery.

This study evaluated the utility of incorporating deep learning into the relatively novel imaging technique of wide-field optical coherence tomography angiography (WF-OCTA) for glaucoma diagnosis. To overcome the challenge of limited data associated with this emerging imaging, the application of few-shot learning (FSL) was explored, and the advantages observed during its implementation were examined. A total of 195 eyes, comprising 82 normal controls and 113 patients with glaucoma, were examined in this study. The system was trained using FSL instead of traditional supervised learning. Model training can be presented in two distinct ways. Glaucoma feature detection was performed using ResNet18 as a feature extractor. To implement FSL, the ProtoNet algorithm was utilized to perform task-independent classification. Using this trained model, the performance of WF-OCTA through the FSL technique was evaluated. We trained the WF-OCTA validation method with 10 normal and 10 glaucoma images and subsequently examined the glaucoma detection effectiveness. FSL using the WF-OCTA image achieved an area under the receiver operating characteristic curve (AUC) of 0.93 (95% confidence interval (CI): 0.912-0.954) and an accuracy of 81%. In contrast, supervised learning using WF-OCTA images produced worse results than FSL, with an AUC of 0.80 (95% CI: 0.778-0.823) and an accuracy of 50% (p-values < 0.05). Furthermore, the FSL method using WF-OCTA images demonstrated improvement over the conventional OCT parameter-based results (all p-values < 0.05). This study demonstrated the effectiveness of applying deep learning to WF-OCTA for glaucoma diagnosis, highlighting the potential of WF-OCTA images in glaucoma diagnostics. Additionally, it showed that FSL could overcome the limitations associated with a small dataset and is expected to be applicable in various clinical settings.