The choroid is a highly vascularized tissue that provides the main blood flow supply, mostly oxygen and nutrients, to the retina. The choroid is thought to play an important role in the progression of glaucoma because of its special structure and rich blood flow. However, the exact mechanism remains unclear due to limitations in research techniques. In this review, the pathophysiology of glaucoma is elucidated by combining swept-source optical coherence tomography (SS-OCT) results with noninvasive angiography data to comprehensively assess the anatomy and blood flow in the choroids of glaucoma patients. Our analyses suggest that functional and structural changes in the choroid are evident in glaucoma patients as the disease progresses and that the action mechanism varies across different types of glaucoma. This review highlights the potential of SS-OCT to improve the early diagnosis and monitoring of glaucoma. Understanding the role of the choroid in glaucoma may lead to the development of new therapeutic approaches and thus facilitate the early detection, diagnosis and treatment of glaucoma.

We conducted a systematic review and meta-analysis to estimate the prevalence of all types of glaucoma in Latin America (LATAM) and evaluate potential demographic associations. This study followed PRISMA guidelines and was registered in PROSPERO (CRD42024506330). A comprehensive search of PubMed, SciELO, and Web of Science was conducted to identify population-based or cross-sectional studies reporting glaucoma prevalence in LATAM. Studies were categorized into two groups: Group 1 included general population studies without selection based on visual acuity (VA), and Group 2 included studies limited to individuals with VA < 20/60. Data from five studies in Group 1 (25,288 individuals) and eight studies in Group 2 (29,882 individuals) were analyzed using R software. The pooled prevalence of glaucoma was 4% (95% CI: 1-3%) in Group 1 and 1% (95% CI: 0-1%) in Group 2. No statistically significant associations were found between glaucoma prevalence and sex (p = 0.08) or age (p = 0.5669). Although our findings highlight the relevance of glaucoma as a public health concern in LATAM, the limited number of available studies and methodological variability reduce the certainty of the estimates.

To determine the impact of progression of central visual field (VF) and global VF on vision-related quality of life (VRQOL).

Retrospective cohort study.

This study included 364 eyes of 235 primary open-angle glaucoma (POAG) participants who had at least five 24-2 VF tests over a minimum of 2-year follow-up. The slopes of global mean deviation (MD) and central mean total deviation (MTD10) (12 test points within the central 10° of 24-2) were calculated. Analyses were conducted using different slope thresholds to define VF-based progression and mean composite National Eye Institute Visual Function Questionnaire (NEI-VFQ) Rasch-calibrated scores associated with these progression thresholds were quantified using linear mixed-effects models.

The baseline 24-2 VF MD of all participants was -5.6 (95% CI, -6.4, -4.9) dB. At baseline, eyes with MTD10 progression had significantly worse 24-2 VF MD compared to those without MTD10 progression. When fast progression was defined as MTD10 slope < -0.50 dB/year, fast progressors had a mean baseline 24-2 MD of -9.71 dB (95% CI: -11.89, -7.53) compared to -5.24 dB (95% CI: -6.02, -4.46) in slow progressors (p < 0.001). Eyes exhibiting MTD10 progression consistently displayed worse mean composite VRQOL scores across various thresholds compared to global MD. Notably, a similar level of VRQOL impairment was observed at a lower threshold for MTD10 compared to MD, consistent across all glaucoma severity groups. In the overall cohort, eyes progressing at a rate of -0.5 dB/year or faster for MTD10 had a mean composite VRQOL score comparable to those progressing at -1.0 dB/year or faster for global MD.

Central VF change had a greater impact on VRQOL compared to global VF change. Conventional assessments based on global MD may underestimate the effect of central VF changes. Refining progression detection strategies to include central VF is necessary to better reflect changes in patient-centered outcomes like VRQOL.

To assess the cost-effectiveness of Hydrus Microstent combined with cataract surgery (CS) vs. CS alone for treating patients with mild to moderate primary open-angle glaucoma (POAG).

Cost-utility analysis using efficacy and safety results of a pivotal randomized clinical trial.

Modeled cohort of patients with mild to moderate POAG and visually significant cataract.

A semi-Markov model was developed to model effects and costs over a 15-year time horizon from the Canadian public health care payer perspective for patients with mild or moderate POAG receiving Hydrus Microstent during CS vs. CS alone. The model utilizes the Hydrus Microstent for Lowering IOP in Glaucoma Patients Undergoing Cataract Surgery (HORIZON) trial patient cohort. Progression was guided using the annualized rate of progression derived from a post hoc analysis of 5-year visual field loss data from the HORIZON trial. The amount of visual field lost was mapped on a sequential addition of medications used as a proxy for irreversible progression. Costs were derived from various publicly available sources and publications. Utility values were sourced from a published analysis that conducted a mapping exercise based on Health Utilities Index mark 3 using Canadian tariffs. We conducted deterministic and probabilistic sensitivity analyses to examine the uncertainty around alternative model input values. Scenario analyses explored structural uncertainty.

Total costs per patient, quality-adjusted life years (QALYs), and incremental cost-utility ratio.

Compared with CS alone, Hydrus + CS was a dominant strategy (greater benefits and lower costs). Although life years were equivalent between the 2 treatments (11.41 years), the Hydrus + CS arm was associated with higher benefits (9.351 vs. 9.040 in QALYs). This translated into an additional 0.311 QALYs for Hydrus + CS. Total costs were lower with Hydrus + CS (Can$ 26 770 vs. Can$ 27 145) resulting in a saving of Can$ 375. Results of scenario analyses showed robustness of the model. The cost-effectiveness acceptability curve shows a probability of 85.3% of Hydrus + CS being cost-effective compared with CS alone at a willingness-to-pay threshold of 50 000/QALY.

Hydrus Microstent combined with CS is a cost-effective long-term treatment for patients with POAG.

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

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.

Accumulating evidence has recognised central visual field defects (CVFDs) as a common feature of glaucoma. Current glaucoma screening guidelines include peripherally biased perimetry (24-2 protocols), but test grids exist to test the integrity of the central visual field (10-2 protocols). However, the added benefit of incorporating central visual field assessments alongside peripheral-biased testing grids remains unclear. This scoping review aimed to compare the diagnostic accuracy of central versus peripheral visual field tests. A systematic search of six databases yielded relevant studies among glaucoma subjects. These studies were synthesised narratively, focusing on diagnostic performance indicators such as the area under the curve, sensitivity, specificity, diagnostic agreement, and structure-function concordance. Of the 1875 studies screened, 16 were included in the review. The comparative analyses demonstrated a similar diagnostic performance when comparing the ability of the 24-2 and 10-2 test grids to detect glaucoma or CVFDs. When utilising the mean deviation, the 24-2 area under the curve ranged between 0.81-0.87 and 0.74-0.84 for the 10-2, whilst the area under the curve of the pattern standard deviation was 0.95 and 0.82, respectively. The pattern standard deviation showed sensitivities reaching 0.75 for the 24-2 and 0.60 for the 10-2, with specificities as high as 0.95 for both test grids. Across all disease stages, CVFDs detected on the 24-2 demonstrated up to 88% agreement with functional damage detected on the 10-2. The agreement between structure-function damage was greatest when combining test grids with optical coherence tomography (88.7%). This review indicates that the 24-2 and 10-2 testing protocols offer comparable diagnostic performance for glaucoma, including detecting CVFDs. While targeted macula screening could provide additional diagnostic value in certain contexts, the evidence remains inconclusive. Further longitudinal studies, incorporating optical coherence tomography, are necessary to confirm these findings and consider the routine inclusion of CVFD screening in clinical practice.

Visual impairment from normal-tension glaucoma (NTG) poses an increasing burden, yet the underlying mechanism remains unclear. Investigating protective mechanisms for NTG is critical. We aimed to investigate the role of ferroptosis in retinal ganglion cell (RGC) damage in glutamate-aspartate transporter (GLAST) knockout (GLAST-/-) mice, a model for NTG, and also to determine whether inhibiting ferroptosis can provide neuroprotection.

GLAST-/- mice and a glutamate-induced excitotoxicity model in primary RGCs were used to investigate retinal and RGC damage. RNA sequencing identified ferroptosis-related pathways in GLAST-/- retinas. Oxidative stress, lipid peroxidation, and ferroptosis activation were assessed using western blotting and immunofluorescence. Immunohistochemistry (IHC) assessed lipid peroxidation and ferroptosis activation in human retinal tissue. Ferrostatin-1 (Fer-1) was administered to evaluate its neuroprotective effects on RGC survival, retinal thickness, and visual function.

RNA sequencing revealed significant enrichment of ferroptosis-related pathways in GLAST-/- retinas. Both GLAST deletion and glutamate-induced excitotoxicity increased oxidative stress, lipid peroxidation, and ferroptosis activation in RGCs. IHC in human retinas confirmed elevated 4-hydroxynonenal (4-HNE) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Furthermore, Fer-1 treatment significantly reduced lipid peroxidation, thereby attenuating the ferroptosis pathways. This intervention ameliorated RGC loss associated with GLAST deletion, protected retinal structure and thickness, and improved amplitudes of the photopic negative response, a-wave, b-wave, and oscillatory potentials.

Ferroptosis significantly contributes to RGC and retinal damage in the GLAST-deletion NTG model. Inhibiting ferroptosis with Fer-1 presents a promising therapeutic strategy for protecting visual function in NTG.

This study aimed to determine the microRNA (miRNA) profile extracted from exosomes in plasma samples in pseudoexfoliation (PEX) glaucoma patients compared to controls. A blood sample (10 mL) was obtained after acquiring written informed consent. Exosome was extracted from each plasma sample using an Exoquick-TC kit. RNA sequencing was performed for each exosome sample. A bioinformatics study was conducted for miRNA-related pathways and targets. A total of 14 Korean subjects (7 with PEX glaucoma; 7 age-matched controls) were involved in the final study. In exosomes of PEX glaucoma participants, 330 mature miRNAs were detected. Among these, three miRNAs were significantly upregulated, including hsa-miR-92b-5p (fold change: 24.68), hsa-miR-744-5p (fold change: 2.49), and hsa-miR-148b-3p (fold change: 3.96). Sixty-six miRNAs were significantly downregulated in PEX glaucoma patients compared to the controls (all p < 0.05). These significantly altered miRNAs (both upregulated and downregulated) were associated with the gene ontology (GO) category of neurogenesis (9.41%), which accounted for the largest proportion. The expression of exosomal microRNAs in plasma was significantly different between PEX glaucoma patients and the controls. This suggests their possible roles in the pathogenic mechanism and a good diagnostic marker for PEX glaucoma.

Based on two major risk factors of glaucoma, elevated intraocular pressure (IOP) and senescence, two new series of nitric oxide (NO) donating dasatinib derivatives 1a-f, 2a-f were designed, synthesized, and biologically evaluated. The results demonstrated that the most active compound 2e effectively released NO and increased the concentration of 3',5'-cyclic guanosine monophosphate in human trabecular meshwork cells, as well as maintained senolytic activity. Topical administration of 2e in chronic ocular hypertension (COHT) glaucoma mice not only significantly eliminated senescent cells in retina but also exhibited potent retinal ganglion cells (RGCs) surviving, IOP lowering, and visual function protection activities, which were superior to those of dasatinib. Compared with younger adult mice, aged COHT mice resulted in more severe RGCs loss, while 2e demonstrated a greater capacity to improve RGCs survival. Our findings show that dual IOP lowering and senolytic functions could be a promising therapeutic strategy for glaucoma, particularly in older patients.

This study aimed to evaluate the causal effect of sodium-glucose cotransporter protein 2 (SGLT2) inhibition on primary open-angle glaucoma (POAG) and explore potential mechanisms. A drug-targeted Mendelian randomization (MR) study was conducted using genetic variation related to SGLT2 inhibition, based on SGLT2 gene expression and glycated hemoglobin levels. Genetic summary statistics for POAG were obtained from the FinnGen consortium and a multi-ancestry genome-wide association study. Glaucomatous endophenotype data were also incorporated. A two-step MR analysis was performed to examine whether pathways related to obesity, blood pressure, lipid levels, oxidative stress, and inflammation mediated the association between SGLT2 inhibition and POAG. Genetically predicted SGLT2 inhibition was associated with a reduced risk of POAG (OR: 0.28; 95% CI: 0.12 to 0.63; P = 2.22 × 10- 3), confirmed in a multi-ancestry validation cohort. It was also associated with decreased optic cup area, reduced vertical cup-disc ratio, and increased optic disc area. Mediation analysis indicated that the effect of SGLT2 inhibition on POAG was partly mediated by diastolic blood pressure (4.8%). This study suggests that SGLT2 inhibition is a promising therapeutic target for POAG. However, further large-scale randomized controlled trials are required to confirm these findings.

To review current therapeutic strategies and innovations in the management of refractory glaucoma, with a focus on recent advancements in implantable surgical devices.

A comprehensive literature search across PubMed, Embase, and Cochrane Library, included terms such as "refractory glaucoma," "posterior drainage implants," "cyclodestruction," and "minimally invasive glaucoma surgery." Articles discussing surgical and medical interventions, as well as device innovations, were included.

Therapeutic options include creating new sites for filtering surgery, posterior drainage implants, minimally invasive devices, cyclodestruction, or continuing medical management without surgery.

Therapeutic decisions regarding refractory glaucoma should be made on a thoughtful, individualized basis, carefully weighing the expected benefits against the potential risks for the patient. Recent innovations in implantable devices expand the range of surgical possibilities.

Glaucoma is a leading cause of permanent blindness, currently affecting over 75 million individuals worldwide. Treatments primarily aim to lower intraocular pressure (IOP), with acetazolamide being a common pharmacotherapy. However, systemic side effects and poor bioavailability limit its clinical effectiveness. This study presents the development and physicochemical and safety evaluation of biodegradable intravitreal implants loaded with acetazolamide using polylactic-co-glycolic acid (PLGA), designed to enhance targeted drug delivery directly to the vitreous humor. The acetazolamide-loaded PLGA implants were successfully fabricated via hot molding, yielding cylindrical rods measuring 5.00 ± 0.02 mm in diameter. Incorporation efficiency reached approximately 92 %, with a uniform drug dose of 230 μg/g. Comprehensive physicochemical characterization confirmed compatibility between the drug and polymer, with stability demonstrated for at least 6 months. The implants exhibited a biphasic drug release profile, sustaining approximately 50 % of the drug over 42 days without an initial burst, indicating their potential for effective and prolonged glaucoma management. Safety assessments revealed that the implants did not induce retinal toxicity at doses up to 0.020 mmol/L. In vitro cytotoxicity assays with ARPE-19 cells and in vivo tests - electroretinography, Goldmann applanation tonometry, optical coherence tomography, and histological analysis - showed no adverse effects on retinal function or structure. Importantly, the implants significantly reduced IOP in normotensive rabbits, confirming their therapeutic potential. This innovative approach represents a promising alternative for glaucoma treatment, addressing the limitations of current modalities while providing sustained drug delivery and enhanced safety.

The corneal permeability of an eye drop is crucial in drug delivery into the eye, but our understanding of drug migration through the cornea and drug distribution within the anterior chamber still requires improvement. To this end, we developed an electrochemical method using boron-doped diamond (BDD) to monitor real-time changes in the drug concentration in the anterior chamber. A needle-shaped BDD microelectrode, with a respective length and tip diameter of ∼200 and ∼40 μm, was used in the in vivo detection of brimonidine tartrate (BRM), which is a widely used antiglaucoma drug. We inserted the tip of the electrode into the right cornea of an anesthetized mouse. BRM was then administered to the right eye, resulting in the successful real-time monitoring of the changes in current. The recorded current reflected the combined reduction of BRM and dissolved oxygen within the anterior chamber. Based on the subtraction of the contribution of the oxygen, the BRM-specific reduction current increased immediately after administration, corresponding to 4.1 μM. Validation via liquid chromatography-tandem mass spectrometry confirmed the accuracy of this approach. Notably, the pharmacological effect of BRM, i.e., a reduced intraocular pressure, was observed 30 min after administration, lagging behind drug migration. These findings may provide valuable insights into the ocular pharmacokinetics of novel drugs and facilitate the development of more effective therapeutic approaches.

The topic of neuroprotection in glaucoma and age-related macular degeneration (AMD) is well disseminated in the literature. However, the problem is providing ophthalmologists with clear, evidence-based messages to draw on. This review examines the landscape of neuroprotective therapies for glaucoma and AMD. While promising neuroprotective agents, such as citicoline and nicotinamide, have been explored for their potential to mitigate neurodegeneration in glaucoma, robust clinical evidence validating their efficacy remains limited and there is a need for further large-scale, long-term studies to substantiate the neuroprotective effects of these agents. Maintaining low intraocular pressure plays a vital role in preventing neuronal death in glaucoma. AMD has traditionally been considered a disease affecting the outer retinal layers; however, growing evidence suggests that the inner layers are also involved. Neuroprotection is an emerging area of research, with strategies focusing on alleviating oxidative stress, inflammation and apoptosis. A reassessment of clinical endpoints and methodologies in neuroprotection research is critical to better evaluate the efficacy of these therapies in glaucoma and AMD.

Background/Objectives: Primary open-angle glaucoma (POAG) is an anterior optic neuropathy that can lead to irreversible vision loss if untreated. Prostaglandin analogues are the first-line treatment, but new drug classes, such as rho kinase (ROCK) inhibitors, are being explored. This review evaluates the efficacy and safety of ROCK inhibitors in treating POAG based on completed trials, comparing results with available natural history data and identifying areas for further research. Methods: A systematic database search was conducted in Ovid MEDLINE and Ovid Embase on 5 April 2022 using the following keywords: 'glaucoma', 'rho kinase inhibitor', 'rho-kinase inhibitor', 'rock inhibitor', 'ripasudil', 'netarsudil', and 'fasudil'. Abstracts were screened for relevant studies and results summarized in tables. Results: The analysis of trials conducted for ROCK inhibitors reveals that they are a safe and efficacious drug to treat POAG, demonstrating non-inferiority to existing medical treatments. Comparison of data to natural history studies was inconclusive due to the lack of natural history studies and their limitations. The results showed ROCK inhibitors to be effective when combined with existing medical treatments. However, questions remain regarding the optimal dosage, patient selection, and cost-effectiveness. Outcome measures for future trials should be expanded to include additional methods of monitoring disease progression as well as patient quality-of-life. Conclusions: ROCK inhibitors have emerged with a favorable safety profile, efficaciously attenuating intraocular pressure. To elucidate their long-term therapeutic value and safety comprehensively, further independent, large-scale, prospective randomized controlled trials are warranted. Such studies are pivotal to augment our understanding of this emergent medication class.

Glaucoma is the leading cause of irreversible blindness, disproportionately affecting individuals of African ancestry. Limited research has examined the impact of neighbourhood quality and socioeconomic factors on primary open-angle glaucoma (POAG) risk in this population. This study aims to address these gaps by evaluating associations between ocular health and neighbourhood characteristics using geospatial data.

We conducted a case-control study with 5192 African ancestry individuals from the Philadelphia area using data from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Geocoded U.S. Census data were merged with individual-level demographics and neighbourhood-level measures, including air quality, food accessibility, and socioeconomic indicators, to assess their association with glaucoma risk and severity.

The study included 3039 controls (58.5%) and 2153 POAG cases (41.5%). Higher POAG risk was associated with older age (OR 1.72 per 10-year increase, p < 0.001), male gender (OR 2.04, p < 0.001), lower BMI (OR 0.87 per 10 kg/m2 increase, p = 0.003), and nonuse of alcohol (OR 0.56 for alcohol use, p < 0.001). Low food access was more common in controls (OR 0.86, p = 0.03), and severe POAG cases were associated with lower homeownership rates (OR 0.95 per 10% increase, p = 0.049). However, most socioeconomic and environmental factors (air quality, education, income, occupation, family structure) were not significantly linked to POAG risk or severity.

Socioeconomic status did not significantly protect against POAG in African ancestry individuals. Individual factors were more influential, suggesting neighbourhood and socioeconomic factors may have a lesser impact than previously hypothesised.

Caveolae are small flask-shaped invaginations of the plasma membrane enriched in cholesterol and sphingolipids. They play a critical role in various cellular processes, including signal transduction, endocytosis, and mechanotransduction. Caveolin proteins, specifically Cav-1, Cav-2, and Cav-3, in addition to their role as structural components of caveolae, have been found to regulate the activity of signaling molecules. A growing body of research has highlighted the pivotal role of caveolae and caveolins in maintaining cellular metabolic homeostasis. Indeed, studies have demonstrated that caveolins interact with the key components of insulin signaling, glucose uptake, and lipid metabolism, thereby influencing energy production and storage. The dysfunction of caveolae or the altered expression of caveolins has been associated with metabolic disorders, including obesity, type 2 diabetes, and ocular diseases. Remarkably, mutations in caveolin genes can disrupt cellular energy balance, promote oxidative stress, and exacerbate metabolic dysregulation. This review examines current research on the molecular mechanisms through which caveolae and caveolins regulate cellular metabolism, explores their involvement in the pathogenesis of metabolic disorders, and discusses potential therapeutic strategies targeting caveolin function and the stabilization of caveolae to restore metabolic homeostasis.

The purpose of this study was to interrogate the potential role of N6-methyladenosine (m6A) regulators in the process of trabecular meshwork (TM) tissue damage in patients with primary open-angle glaucoma (POAG).

Firstly, the expression profile of m6A regulators in TM tissues of POAG patients was comprehensively analyzed by bioinformatics analysis; Plasmid transfection and siRNA gene interference were used to enhance or weaken the expression levels of YTHDC2 in human trabecular meshwork cells (HTMCs); Cell migration ability was detected by transwell chamber assay; Immunofluorescence staining assay was used to evaluate the expression of extracellular matrix (ECM) related proteins.

Through the analysis of GSE27276 database, 5 m6A regulators with different expression in POAG were screened out. The results of random forest model showed that these 5 m6A regulators exhibited diagnostic potential and were characteristic genes of POAG. All POAG samples could be effectively divided into two groups based on the expression levels of these 5 hub m6A regulators. Immune cell infiltration analysis indicated that the levels of activated CD8+ T cells and regulatory T cells were different in the two subtypes. HTMC oxidative stress cell model and TGF-β2 stimulation cell model were further constructed to verify the expression of the aforementioned hub m6A regulators, and it was found that YTHDC2 mRNA showed the same expression trend in both models. The silencing of YTHDC2 enhanced the migration ability of HTMCs and increased the synthesis ability of ECM. However, when YTHDC2ΔYTH, which lacks the YTH domain, is overexpressed in HTMCs, there is no significant change in the ECM synthesis ability.

The differentially expressed m6A regulators in TM tissues may serve as potential diagnostic biomarkers for POAG. And, in HTMCs, the expression level of YTHDC2 mRNA was changed under oxidative stress or TGF-β2 intervention, and then exerted its regulation on cell migration and ECM synthesis capability through m6A modification, which may be an important part of the disease process of POAG.

The aim of this study was to predict Bruch's membrane opening-minimum rim Width (BMO-MRW), a relatively new parameter using conventional optical coherence tomography (OCT) parameter, using retinal nerve fibre layer (RNFL) thickness and visual field (VF) global indexes (MD, PSD, and VFI). We developed an interpretable machine learning model that integrates structural and functional parameters to predict BMO-MRW. The model achieved the highest predictive accuracy in the inferotemporal sector (R2 = 0.68), followed by the global region (R2 = 0.67) and the superotemporal sector (R2 = 0.64). Through SHAP (SHapley Additive exPlanations) analysis, we demonstrated that RNFL parameters were significant contributing parameters to the prediction of various BMO-MRW parameters, with age and PSD also identified as critical factors. Our machine learning model could provide useful clinical information about the management of glaucoma when BMO-MRW is not available. Our machine learning model has the potential to be highly beneficial in clinical practice for glaucoma diagnosis and the monitoring of disease progression.

To evaluate the efficacy and safety of direct selective laser trabeculoplasty (DSLT) on eyes with primary open-angle glaucoma (POAG) and on primary angle closure glaucoma (PACG) eyes at 1 year follow-up.

In this study, 54 patients affected by POAG (76) or PACG (28) undergoing DSLT were enrolled, for a total of 104 eyes. Before each treatment and at each follow-up visit, all subjects underwent a complete eye visit, including the collection of data regarding the number and type of topical medications prescribed for glaucoma. The patients treated underwent 30-2 standardised automated perimetries prior to DSLT, at 6 months and 12 months post DSLT procedure. Each patient was checked at 1 week and subsequently at 1, 3, 6 and 12 months.

At 1 month follow-up, both the eyes affected by POAG and those affected by PACG showed significantly (p<0.01) lower mean intraocular pressure (IOP) (-3.67±2.95 mm Hg and -3.93±2.36 mm Hg, respectively) and lower mean number of IOP-lowering topical drugs taken (-0.62±0.57 and -0.78±0.64, respectively) after DSLT. These reductions remained significant until the 1 year follow-up, both for IOP (-3.76±2.84 mm Hg and 3.67±2.46 mm Hg, respectively) and for drugs assumed (-0.79±0.53 and 0.96±0.47, respectively). The mean deviation mean values showed perimetry stability both in POAG and in PACG eyes at 1 year follow-up. No major complications were observed in the eyes included in this study.

Although this study has some limitations such as the retrospective design, the lack of comparison with standard selective laser trabeculoplasty (SLT) and the relatively short follow-up, the results observed require confirmation through further studies, with extended follow-up and larger cohorts. This study suggests that DSLT would be a useful tool for the management of patients with glaucoma.

Baseline differences in sex hormone levels between males and females influence tissues including the brain and eye. To investigate the effects of estrogens and androgens on ocular physiology and glaucoma, we review the current literature on the influence of primary sex hormones on ocular function, glaucoma incidence and related parameters like intraocular pressure (IOP) at physiologic levels and related to hormone therapies in men and women. These articles reveal activity of estrogen, testosterone, and progesterone within ocular tissues including the retinal pigment epithelium and ciliary epithelium where they likely influence glaucoma pathophysiology through effects on ocular blood flow and aqueous outflow. A growing body of evidence demonstrates a protective role of estrogen in glaucoma. With fluctuations across a woman's lifetime through menstrual phases, pregnancy, and menopause, the general association seen is a lower risk of glaucoma and lower IOP with higher estrogen. Exogenous hormones in the form of oral contraceptive pills and hormone replacement therapy also appear to affect glaucoma risk, although published findings are inconsistent. Few studies have reported a positive association between IOP and serum testosterone, and men treated with androgen deprivation therapy have shown a reduced risk of glaucoma while masculinizing hormone therapies at supra-physiologic testosterone levels have significantly increased IOP. Sex hormone perturbations affect components of glaucoma pathogenesis including IOP and ocular blood flow and overlap with known risk factors like age and sex. Standardized studies are needed to further elucidate the roles of estrogen and testosterone in glaucoma risk and progression.

To assess the efficacy of adding Ahmed's sub-flap mattress suture to deep sclerectomy (DS).

Forty eyes with open angle glaucoma were assigned randomly into two groups: Group A: underwent DS with Ahmed's sub-flap mattress suture. Group B: underwent conventional DS. Patients were followed up closely for 6 months with serial IOP measurements and ultrasound biomicroscopy (UBM) was used to assess the surgical site functionally and anatomically at the first and sixth month.

Adding Ahmed's sub-flap mattress suture improved the IOP lowering effect of DS significantly from 43% in group B to 53% in group A at 6-month (p = 0.027). IOP in group A was at 1 week, 1 month and 6-month visits (7.9 ± 1.3, 11.7 ± 2.2 and 13.3 ± 1.9 mmHg respectively) compared to group B (10.1 ± 4.6, 14.1 ± 5.2 and 16.8 ± 4.1 mmHg respectively) (p = 0.025, 0.041 and 0.001 respectively). UBM parameters were significantly larger in group A at 1 and 6 months. Strong statistically significant negative correlations were established between IOP and all the UBM parameters apart from intrascleral lake height at the first and sixth month (p < 0.01 in all of them). Finally, significant correlations were found between IOP at 6 months and whole bleb anteroposterior length and height at 1 month (p = 0.001).

Adding Ahmed's sub-flap mattress suture to routine DS is an effective economical addition that will enhance the IOP lowering effect of DS. Also, assessment of the bleb by UBM is useful in predicting the success of deep sclerectomy surgery.

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.

To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD).

This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation.

A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1 mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively.

Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression.

What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Rho-associated protein kinase (ROCK) inhibitors are promising therapeutic agents for reducing elevated intraocular pressure in patients with glaucoma. We explored new ROCK inhibitors derived from bioactive metabolites produced by microbes, specifically cryptic metabolites from Nocardiopsis sp. MCY7, using a liquid chromatography-mass spectrometry-based chemical analysis approach integrated with metal stress-driven isolation. This strategy led to the identification of two previously undescribed linear peptides, nocarnickelamides A and B (1 and 2), and an unreported cittilin derivative, cittilin C (3). The planar structures of 1-3 were elucidated using UV spectroscopy, high-resolution mass spectrometry, and nuclear magnetic resonance. The absolute configurations of 1 and 2 were assigned using the advanced Marfey's method. Biological assays demonstrated that nocarnickelamides (1 and 2) exhibited dual inhibitory activity against ROCK1 (IC50 29.8 and 14.9 μM, respectively) and ROCK2 (IC50 27.0 and 21.9 μM, respectively), with molecular simulations suggesting binding to the ATP-binding site. In human trabecular meshwork cells, 2 significantly inhibited the activation of ROCK-regulated cytoskeletal contraction markers such as the myosin light chain. Nocarnickelamide B (2) is a novel dual ROCK1/2 inhibitor and a potential pharmacophore for designing new therapeutic agents to reduce intraocular pressure in glaucoma.

Glaucoma is characterised by progressive vision loss due to retinal ganglion cell deterioration, leading to gradual visual field (VF) impairment. The standard VF test may be impractical in some cases, where optical coherence tomography (OCT) can offer predictive insights into VF for multimodal diagnoses. However, predicting VF measures from OCT data remains challenging. To address this, five regression models were developed to predict VF measures from OCT, Shapley Additive exPlanations (SHAP) analysis was performed for interpretability, and a clinical software tool called OCT to VF Predictor was developed. To evaluate the models, a total of 268 glaucomatous eyes (86 early, 72 moderate, 110 advanced) and 226 normal eyes were included. The machine learning models outperformed recent OCT-based VF prediction deep learning studies, with correlation coefficients of 0.76, 0.80 and 0.76 for mean deviation, visual field index and pattern standard deviation, respectively. Introducing the pointwise normalisation and step-size concept, a mean absolute error of 2.51 dB was obtained in pointwise sensitivity prediction, and the grayscale prediction model yielded a mean structural similarity index of 77%. The SHAP-based analysis provided critical insights into the most relevant features for glaucoma diagnosis, showing promise in assisting eye care practitioners through an explainable AI tool.

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.

This study evaluates the safety and visual outcomes of enhanced monofocal intraocular lenses compared to standard monofocal intraocular lenses in patients with varying severities of glaucoma. Utilizing data from surgeries performed in 2021, the study involved patients aged 40 and older with visually significant cataracts and diagnosed glaucoma or glaucoma suspects. The findings indicate that both enhanced and standard monofocal lenses lead to significant improvements in best-corrected visual acuity, visual field index, mean deviation, and retinal nerve fiber layer thickness postoperatively. No significant differences were observed between the two groups in the extent of these improvements, suggesting that enhanced monofocal lenses may offer a viable alternative for patients with glaucoma, providing significant visual benefits and potentially better intermediate vision while preserving overall visual function.

To use robotic visible-light optical coherence tomography (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration.

Anterior segment imaging using a robotic vis-OCT to maintain perpendicular laser illumination aimed at SC was performed. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. SC areas and volumes were measured circumferentially.

Circumferential vis-OCT provided high-resolution imaging of the AHO pathways. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; P = 0.018). After pilocarpine administration, the SC became larger (pilocarpine, 26.8 ± 5.0% vs. control, 8.9 ± 4.6% volume increase; P = 0.030). However, the pilocarpine alteration was also segmental, with a greater increase observed superior (pilocarpine, 31.6 ± 8.9% vs. control, 1.8 ± 5.7% volume increase; P = 0.023) and nasal (pilocarpine, 41.1 ± 15.3% vs. control, 13.9 ± 4.5% volume increase; P = 0.045).

Circumferential noninvasive imaging of the AHO pathways was done in vivo. Segmental SC anatomy was seen, consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was also observed. Segmental glaucoma drug response around the circumference of AHO pathways is an observation that may influence patient response to glaucoma treatments.

To determine the efficacy and safety of selective laser trabeculoplasty (SLT) in patients with uveitic glaucoma, we retrospectively evaluated 17 eyes from 13 consecutive uveitic glaucoma cases who were treated with SLT due to inadequate interocular pressure (IOP) control despite glaucoma medical therapy. The mean IOP was significantly decreased from 28.4 ± 6.50 mmHg to 17.3 ± 9.4 mmHg at baseline, and 6 months after SLT, respectively (P < 0.0001). There was no significant increase in inflammation or prednisolone dosage following SLT. We compared the success group, which demonstrated successful IOP reduction after 6 months of SLT, to the other failure group. The success group had shorter uveitis duration (1.37 ± 0.41 vs. 1.97 ± 0.80 years, P = 0.032) and lower baseline IOP (25.5 ± 5.09 vs. 33.7 ± 5.57 mmHg, P = 0.035). This study found that SLT had a positive IOP-lowering effect and was safe in patients with uveitic glaucoma who had not responded to medical treatment.

To investigate 5-year outcomes on intraocular pressure (IOP) and safety of micropulse transscleral cyclophotocoagulation (TSCPC) in patients with glaucoma.

Patients with mild to advanced glaucoma who underwent a standardized micropulse TSCPC procedure at the University Eye Clinic Maastricht from November 2016 to February 2019 were included.

A total of 165 eyes were included, with outcomes for 112 eyes available after 5-year follow-up. Mean age was 67.3 ± 13.9 years; 58.2% were male. Glaucoma subtypes were primary glaucoma (n = 108) and secondary glaucoma (n = 57). Prior glaucoma surgery was performed in 65 of 165 eyes (39.4%). In the primary glaucoma group, mean preoperative IOP was 20.7 ± 7.1 mmHg. Mean postoperative IOP at 1, 2, 3, 4, and 5 years significantly reduced to 15.2 ± 6.5, 14.3 ± 5.0, 14.0 ± 4.9, 13.5 ± 4.1, and 12.9 ± 4.3 mmHg, respectively. Preoperatively, the mean number of IOP-lowering medications was 3.3 ± 1.3, which changed to 2.8 ± 1.3, 2.8 ± 1.2, 2.8 ± 1.2, 2.9 ± 1.2, and 2.7 ± 1.3 at 1, 2, 3, 4, and 5 years, respectively. In the secondary glaucoma group, mean preoperative IOP was 28.7 ± 10.3 mmHg, dropping significantly to 19.3 ± 10.4, 18.6 ± 11.3, 17.8 ± 9.8, 18.1 ± 12.0, and 15.5 ± 7.6 mmHg at the same intervals. The number of IOP-lowering medication was significantly reduced from 3.5 ± 1.1 to 2.5 ± 1.5, 2.2 ± 1.5, 2.6 ± 1.4, 2.6 ± 1.5, and 2.5 ± 1.7. In the total group, mean IOP reduction was 32.5% after 5 years. Postoperative complications included cystic macular edema (n = 3), fibrinous/uveitic reaction (n = 1), and rejection of corneal graft (n = 2), all reversible after treatment. One patient developed late and persisting hypotony. Other adverse events were retinal venous occlusion (n = 1) and retinal vasculitis (n = 1), unrelated to the laser treatment. In patients with a preoperative Central Distance Visual Acuity (CDVA) > 0.05 on the Snellen chart, more than two lines of visual acuity (VA) loss were attributed to cataract (n = 10), retinal disease (n = 5), glaucoma progression (n = 3), corneal decompensation (n = 2), or other factors (n = 11).

Micropulse TSCPC is a safe and effective treatment for reducing IOP and the number of IOP-lowering medications after a 5-year follow-up period. It is a viable alternative for patients after failed incisional glaucoma surgery or high-risk patients.

To characterize the presence of amyloid-beta (Aβ) in human glaucoma retina and to test the identification of retinal Aβ using a novel fluorescent Aβ-binding small molecule (AMDX-2011).

Postmortem human eyes with (n=4) and without (n=4) glaucoma were acquired from an eye bank. Retinas were dissected, flat-mounted, and fixed. Using the flat mounts, immunofluorescence was performed against Aβ, AMDX-2011 staining was conducted, and images were acquired using fluorescence microscopy.

Fluorescence microscopy demonstrated the presence of an Aβ signal that colocalized with AMDX-2011 staining in the glaucoma retina. Colabeled puncta appeared in all quadrants of the retina, including the retina temporal to the optic nerve. The puncta were mainly located within the inner layers of the retina. Glaucoma retinas had more colabeled puncta than control retinas in all locations ( P =0.002-0.02). Colabeled puncta were also larger in the superior quadrant of glaucoma compared with control retinas ( P =0.02).

Aβ was detected in human glaucomatous retina, and its distribution was mapped. AMDX-2011 identification of Aβ may lead to future diagnostic tests aimed at detecting Aβ in glaucoma patients.

This study aimed to serve as a reference for establishing glaucoma evaluation standards for the Korean by analyzing the results of visual field tests and optical coherence tomography (OCT). We also determined the correlation between these test results and patient demographics, such as age and sex, which is crucial for early glaucoma detection and management.

This study was conducted at a national hospital in Seoul and analyzed 1510 visual field tests and 1337 OCT tests. The patients underwent the Humphrey automated visual field test and OCT measurements. Glaucoma was classified into early, moderate, and advanced stages based on the mean deviation (MD) value. Statistical analyses were performed to assess the relationships between age, sex, and test results.

The visual field test results showed that the visual field index and MD values decreased as age increased for both males and females, with a more significant decrease observed in males. The OCT findings revealed gradual thinning of the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) with increasing age, although, compared to males, thicker GCIPLs and RNFLs were maintained in females until their 60s.

This study indicates that there may be an association between age and sex in glaucoma progression and provides valuable insights for establishing diagnostic and management modalities specifically for Korean patients. These findings support the use of both visual field testing and OCT in glaucoma diagnosis, emphasizing the importance of early detection and personalized treatment strategies for effective glaucoma management in Korea.

Glaucoma, a leading cause of irreversible blindness, is characterised by progressive optic nerve damage, with elevated intraocular pressure (IOP) and extracellular matrix (ECM) remodelling in the lamina cribrosa (LC) contributing to its pathophysiology. While current treatments focus on IOP reduction, they fail to address the underlying fibrotic changes that perpetuate neurodegeneration. The Src proto-oncogene, a non-receptor tyrosine kinase, has emerged as a key regulator of cellular processes, including fibroblast activation, ECM deposition, and metabolism, making it a promising target for glaucoma therapy. Beyond its well-established roles in cancer and fibrosis, Src influences pathways critical to trabecular meshwork function, aqueous humour outflow, and neurodegeneration. However, the complexity of Src signalling networks remains a challenge, necessitating further investigation into the role of Src in glaucoma pathogenesis. This paper explores the therapeutic potential of Src inhibition to mitigate fibrotic remodelling and elevated IOP in glaucoma, offering a novel approach to halting disease progression.

Glaucoma, a prevalent eye ailment causing irreversible vision loss, affects over 295 million individuals globally, necessitating the exploration of novel therapeutic avenues. Despite extensive research on targets like the phosphodiesterase enzyme and rho kinase, the potential of MAP4K4 in glaucoma remains untapped. This study aims to identify potent MAP4K4 inhibitors to counteract retinal cell apoptosis and oxidative stress associated with glaucoma. Using HTVS and XP docking, 911,059 compounds were screened. The MMGBSA calculation and pharmacokinetics analysis were used to shortlist the compounds. After performing 75 molecular dynamics simulations, further meta-dynamics were employed to calculate dissociation-free energy and find potential MAP4K4 inhibitors. Findings indicated that ZINC06717217 and ZINC38836256 exhibited remarkable promise, with docking scores of -9.57 and -11.12 and MMGBSA binding energies of -91.07 kcal/mol and -87.52 kcal/mol, respectively. Comparative analysis with the reference compound Q27453723 underscored their superior stability, requiring dissociation-free energies of -15.11 kcal/mol and -12.46 kcal/mol to disengage from the docked complex. This underscored their robust binding affinity. ZINC06717217 and ZINC38836256 show promising stability and strong binding to the MAP4K4 protein. Hence, these findings are promising in inhibiting MAP4K4 for glaucoma treatment, potentially leading to more effective treatment and curing blindness. KEY MESSAGES: First to incorporate the dissociation-free energy for identifying compounds for glaucoma treatment. In-silico analysis showed that ZINC06717217 and ZINC38836256 are promising compounds for targeting MAP4K4.

To evaluate the 6-year physiological rates-of-change in ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thickness measured with optical coherence tomography.

We included 2202 out of 2661 subjects from the population-based Singapore Chinese Eye Study who returned for follow-up 6 years after baseline examination (follow-up rate 87.7%). OCT scans with signal strength (SS) <6, imaging errors, and ocular pathologies were excluded. A linear mixed model was used to measure the rates-of-change in GCIPL and RNFL thickness. Time and difference between baseline and follow-up scan SS were modelled as fixed effect. Baseline age, baseline measurement, gender, hypertensive medication, diabetes status, cardiovascular disease, smoking status, body mass index, spherical equivalent (SE), intraocular pressure and optic disc area were each analysed in an interaction term with time.

The adjusted mean rate-of-change in average GCIPL was -0.312 μm/year in males and -0.235 μm/year in females. Older age and thicker GCIPL thickness at baseline were associated with higher rates-of-change while females and more hyperopic SE were associated with lower rates-of-change. The adjusted mean rate-of-change in average RNFL was -0.374 μm, with higher rates-of-change in the vertical quadrants and no differences between genders. Older age and thicker RNFL thickness at baseline were associated with higher rates-of-change in average RNFL and RNFL thickness in the vertical quadrants, and vice versa for each unit increase in scan SS and SE.

Our population cohort provides data on physiological thinning of GCIPL and RNFL with age. Differentiating physiological changes in GCIPL and RNFL is important for more accurate clinical assessment.

This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography.

In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders. Visual field tests were performed with the imo perimeter (CREWT Medical Systems, Inc., Tokyo, Japan) at central gaze, 6° abduction, and 6° adduction positions as fixation points. A mixed-effects model was used to compare MS under all conditions.

The analysis included a total of 82 eyes, with 41 POAG and 41 healthy after matching. The mean (standard deviation) age was 68.0 (11.0) years, with a mean deviation of -9.9 (6.6) dB for POAG and -1.0 (1.9) dB for healthy eyes using Humphrey field analysis 24-2. MS did not significantly differ among central gaze (27.0 [1.8] dB), abduction (27.1 [1.9] dB), and adduction (26.9 [2.2] dB) in healthy eyes (P = 0.650). However, MS was significantly lower for adduction (17.2 [5.9] dB) compared to central gaze (18.1 [5.9] dB) and abduction (17.9 [5.9] dB) in glaucoma eyes (P = 0.001 and P = 0.022, respectively).

Horizontal gaze, especially in adduction, significantly reduces visual sensitivity in glaucoma, suggesting a specific vulnerability associated with eye movement. This finding highlights the importance of eye positioning in glaucoma, warranting further investigation of its clinical significance.

To investigate patients with primary aldosteronism (PA) and the prevalence of normal-tension glaucoma (NTG).

Cross-sectional study.

Newly diagnosed PA patients were evaluated in this cross-sectional study, with ophthalmic examinations such as intraocular pressure measurements by a Goldmann applanation tonometer, central corneal thickness, slit-lamp biomicroscopic examination, gonioscopy, ophthalmoscopy, fundus photography, visual field test with a Humphrey Field Analyzer 24-2 SITA Standard program, and optical coherence tomography of the peripapillary retinal nerve fiber layer, performed in each of the subjects. Optic disc appearance, perimetric results, optical coherence tomography results, and other ocular findings were all used for determining the glaucoma diagnosis. The primary outcome was shown the prevalence of NTG in patients with PA.

NTG prevalence in the 212 PA patients was 11.8% (95% confidence interval [CI], 4.7%-20.7%). As compared to the hypertensive patients without PA, the hypertensive patients with PA exhibited a significantly increased NTG prevalence (odds ratio; 4.019, 95% CI, 1.223-13.205; P = .022). Increased NTG prevalence was associated with age, ranging from 8.8% (95% CI, 2.1%-15.6%) for those aged 40 to 49 years, to 37.5% (95% CI, 13.8%-61.2%) for those aged 70 years and older. In 72 hypertensive patients without PA, who were used as the controls, NTG prevalence was 5.2%, with a 95% CI ranging from 0.5% to 14.4%.

There was an 11.8% prevalence of NTG in PA patients, with these patients at an elevated risk of NTG, which was not mediated by blood pressure.

Glaucoma, a leading cause of global blindness, is marked by irreversible retinal ganglion cells (RGCs) loss, elevated intraocular pressure (IOP), and extracellular matrix (ECM) deposition in the trabecular meshwork (TM). Transmembrane and coiled-coil domain protein 1 (TMCO1), implicated in calcium regulation, has potential links to primary open-angle glaucoma (POAG). Ferroptosis, an iron-dependent cell death mechanism driven by lipid peroxidation, is also observed in glaucoma. This study investigates the role of TMCO1 in POAG, focusing on its involvement in TM ECM deposition via ferroptosis induction and ERK1/2 phosphorylation inhibition. In both in vivo and in vitro models, we demonstrated that dexamethasone (DEX) stimulation upregulates TMCO1, leading to increased ECM deposition and ferroptosis in human trabecular meshwork cells (HTMCs). Furthermore, treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly reduced ECM deposition and ferroptosis in HTMCs. These findings establish TMCO1 as a critical regulator of ferroptosis and ECM deposition through the ERK/MAPK pathway, positioning it as a promising therapeutic target for glaucoma.