UNASSIGNED: Glaucoma is the leading cause of permanent blindness. Primary angle closure glaucoma (PACG) is diagnosed only after the onset of symptoms and can result in irreversible blindness despite the standard intraocular pressure (IOP) reduction therapy. The identification of potential biomarkers associated with prognosis will help improve disease management. This study aimed to identify mechanisms associated with disease progression, potential biomarkers, and therapeutic targets of PACG.
UNASSIGNED: The clinical data assessment of IOP, cup/disc ratio (CDR), Retinal Nerve Fiber Layer (RNFL) thickness of control, and PACG group were collected and analyzed for significant differences. The ATP levels were estimated, and targeted metabolomic analysis was performed on aqueous humor and cytokines in plasma. The pathways obtained from the metabolomics data set were compared with those obtained for data sets from the literature. Clinical parameters were correlated with cytokine levels. Targeted metabolomic analysis of cell culture supernatant from TNFα-treated N9 microglia was carried out, and overlap analysis was performed with data obtained from PACG patients.
UNASSIGNED: Elevated IOP, CDR, ATP, cytokines, and reduced RNFL thickness were found in PACG compared to controls. Analysis of PACG and TNFα-treated N9 microglial cell culture supernatant shows activation of immuno-metabolites. The metabolic pathways of PACG, TNFα, and ATP-treated microglia from the literature show considerable overlap. Biomarker analysis identified clinical parameters, ATP, cytokines, and immuno-metabolites.
UNASSIGNED: This study shows an association between elevated levels of ATP, cytokines, immuno-metabolism, and potential microglial inflammation with disease progression, rendering these levels potential biomarkers. P2 receptors, cytokines, and IDO1/2 could be potential therapeutic targets.

To compare the surgical outcomes of twin-site phacotrabeculectomy with Mitomycin C (MMC) in primary open-angle glaucoma (POAG) versus primary angle-closure glaucoma (PACG).
Prospective, comparative, observational study. Patients with visually significant cataract and primary glaucoma were divided into two groups: POAG and PACG. They underwent twin-site phacotrabeculectomy with MMC and followed up on days 1, 15, 1 month, 6 months, and 12 months. Baseline and follow-up visits were compared to find the differences in intraocular pressure (IOP), antiglaucoma medications (AGM), success rates, anterior chamber depth (ACD), and axial length (AXL).
There were 50 eyes each in POAG and PACG groups. Mean IOP reduction from baseline to 12 months (21.22 ± 6.0 to 11.40 ± 2.8-POAG group vs 24.16 ± 7.6 to 12.42 ± 3.2-PACG group) was statistically significant in both groups (P < 0.001), but no significant difference between groups (P = 0.095). There was a statistically significant decline in the number of AGM in POAG [1.66 (0.7) to 0.38 (0.7), P < 0.001] and PACG [2.10 (0.7) to 0.70 (0.8), P < 0.001]; the decline was more in POAG (P = 0.012) at last visit. Probability of overall (complete and qualified) success at 12 months postop was 72.0% [95% confidence interval (CI): 57.4-82.4] in PACG and 84.0% (95% CI: 70.5-91.7) in POAG group. There was a significant increase in ACD and a decrease in AXL in both groups (P < 0.001). More interventions were required in the PACG group (38, P = 0.012).
Phacotrabeculectomy with MMC causes a significant reduction in IOP and improvement in biometric parameters in both POAG and PACG. Patients with PACG required more postoperative interventions, while a lesser number of antiglaucoma medications were needed in POAG patients.

Objective: The aim of this study was to investigate the potential association between glaucoma and fecal calprotectin. Methods: A total of 144 glaucomatous patients and 66 healthy controls were enlisted for this study. The fecal calprotectin was assessed using enzyme-linked immunosorbent assay. Results: The median fecal calprotectin levels were significantly elevated in glaucoma (73.67 vs 41.97 μg/g; p < 0.001), primary angle-closure glaucoma (76.85 μg/g; p < 0.001) and primary open-angle glaucoma (69.29 μg/g; p = 0.016) groups compared with controls. A notable proportion of the glaucoma (24%; p < 0.001), primary angle-closure glaucoma (21%; p < 0.001) and primary open-angle glaucoma (24%; p < 0.001) subgroups exhibited highly abnormal fecal calprotectin levels (≥250 μg/g). Conclusion: Elevated fecal calprotectin might indicate potential intestinal inflammation in glaucoma.

BACKGROUND: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).
METHODS: A retrospective analysis was performed on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM).
RESULTS: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance, longer whole eye movement, and longer whole eye movement time than patients with POAG. The highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL.
CONCLUSIONS: The biomechanical properties of the cornea differed between POAG and PACG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

Glaucoma is the largest cause of irreversible blindness with a multifactorial genetic etiology. This study explores novel genes and gene networks in familial forms of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) to identify rare mutations with high penetrance. Thirty-one samples from nine MYOC-negative families (five POAG and four PACG) underwent whole-exome sequencing and analysis. A set of prioritized genes and variations were screened in an independent validation cohort of 1536 samples and the whole-exome data from 20 sporadic patients. The expression profiles of the candidate genes were analyzed in 17 publicly available expression datasets from ocular tissues and single cells. Rare, deleterious SNVs in AQP5, SRFBP1, CDH6 and FOXM1 from POAG families and in ACACB, RGL3 and LAMA2 from PACG families were found exclusively in glaucoma cases. AQP5, SRFBP1 and CDH6 also revealed significant altered expression in glaucoma in expression datasets. Single-cell expression analysis revealed enrichment of identified candidate genes in retinal ganglion cells and corneal epithelial cells in POAG; whereas for PACG families, retinal ganglion cells and Schwalbe\'s Line showed enriched expression. Through an unbiased exome-wide search followed by validation, we identified novel candidate genes for familial cases of POAG and PACG. The SRFBP1 gene found in a POAG family is located within the GLC1M locus on Chr5q. Pathway analysis of candidate genes revealed enrichment of extracellular matrix organization in both POAG and PACG.

China faces increasing health risks from climate change. The structure and function of the eye and vision were affected by extreme heat and cold. The study aimed to evaluate the impacts of heatwaves and cold spells on glaucoma. A national cross-sectional study of the Rural Epidemiology for Glaucoma (REG-China) was conducted in ten provinces of China, and 36,081 adults aged 40 years or more were included. Glaucoma signs were assessed via a standard examination. A total of 15 heatwave definitions, based on intensity (95th to 99th percentiles of temperature distribution) and duration (≥2 days, 3 days, and 4 days), were used to quantify heatwave effects, and 6 cold spell definitions were defined based on threshold temperature percentile (5th and 10th) and duration (3 days, 5 days, and 9 days). Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the impacts of heatwaves and cold spells on glaucoma, and the dose-response relationships were assessed using a restricted cubic spline (RCS) model. Subgroup analysis was conducted stratified by gender, age, smoking status, occupation, and family history of glaucoma. The overall prevalence of glaucoma was 2.1% (95% CI 1.94-2.25%). Higher heatwaves were significantly correlated with higher OR of glaucoma, with the OR (95% CI) ranging from 1.014 (1.009, 1.018) to 1.090 (1.065, 1.115) by different definitions. Glaucoma was affected by heatwaves more strongly than by cold spells. The effects of both heatwaves and cold spells were higher in males than females and in smokers than nonsmokers. These results of the present study evoked the attention of prospective research to elucidate the relationship between extreme temperatures and eye diseases.

Genome-wide association studies (GWAS) have identified that single-nucleotide polymorphisms (SNPs) rs1258267 in CHAT and rs3753841 in COL11A1 are associated with primary angle-closure glaucoma (PACG). The purpose of the study was to evaluate the association of CHAT rs1258267 and COL11A1 rs3753841 with PACG. A comprehensive electronic database search was performed to include eligible studies, published from October 2010 to March 2022. By calculating summary odds ratios (ORs) and 95% confidence intervals (CI) under five genetic models, the risk of PACG related to these two SNPs could be estimated. Heterogeneity was measured with a Chi-square-based Q statistic test and the I2 statistic. By the Z test, we analyzed the overall effect of OR. We used funnel plots and Begg\'s funnel plots to evaluate the publication bias of included studies. The meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. There were eighteen studies associating CHAT rs1258267 with PACG indicating evidently decreased PACG risk in five genetic models. Thirty studies were included to demonstrate a notable increase in the risk of PACG-carrying COL11A1 rs3753841 genotypes. Subgroup analyses showed that the association of CHAT rs1258267 and COL11A1 rs3753841 with PACG was obvious in Asians, while no evidence was found to confirm this connection in Caucasians. This meta-analysis suggests that CHAT rs1258267 G/A polymorphisms could bring about a decreased risk of PACG susceptibility and COL11A1 rs3753841 G/A polymorphisms could cause an increased risk. These effects mainly manifest in Asians.

World blindness is primarily caused by glaucoma. It has been predicted that by 2040, 118 million individuals will have glaucoma. Among Asians and Africans, primary angle-closure glaucoma (PACG) is the most prevalent type of glaucoma, for which treatment options are currently very limited. At present, lowering intraocular pressure (IOP) is the primary approach for PACG treatment. However, some PACG patients with decreased IOP measurements still advance. Additionally, because of the complicated pathophysiology, there are no biomarkers for diagnosis. Metabolomics is the study of the metabolites produced by all cellular processes in a biological sample, providing a method for identifying biomarkers and early diagnosis. Nevertheless, metabolomics has infrequently been applied to PACG. Previous research conducted by our lab on plasma metabolite fatty acids in PACG patients revealed reduced free fatty acid (FFA) levels, which may be connected to lipid peroxidation. To ascertain the relationship between other metabolites and PACG. We compared levels of amino acids and carnitine in patients with PACG (n = 147) and non-glaucoma (n = 340). Using metabolomics analysis, twenty-one amino acids and twenty-six carnitines (a total of ninety-six indicators) were examined. Odds ratios (OR) and 95% confidence intervals (CI) for these metabolites in relation to PACG were calculated. The relationship between ocular measures and metabolites was assessed by Spearman\'s rank correlation. Predictive performance was evaluated using the receiver operating characteristic (ROC). The C8/C2 level was comparable across patients with PACG and individuals without glaucoma based on the Wilcoxon rank-sum test. The PACG group had lower levels of Arginine (Arg), Ornithine (Orn), Arg/Orn, Orn/Cit, and C26/C20 than the nonglaucoma group, whereas Cit/Arg and C4/C2 ratios were greater. Both univariate and multivariate models showed a negative correlation between Orn and Orn/Cit and PACG. In the univariate model, palmitoylcarnitine (C16) had a negative correlation with PACG. According to our findings, metabolic profiles of plasma amino acids and carnitine between PACG patients and controls are different. The combination of amino acids and carnitine increased the predictive value of PACG. The Orn and Arg were negatively correlated with the local ocular neurodegenerative pathology. We speculate lipid peroxidation may explain the reduction in C16, and the decrease in Orn may be associated with hyperammonia neurotoxicity.

UNASSIGNED: Primary angle-closure glaucoma (PACG) is a serious and irreversible blinding eye disease. Growing studies demonstrated that PACG patients were accompanied by vision and vision-related brain region changes. However, whether the whole-brain functional network hub changes occur in PACG patients remains unknown.
UNASSIGNED: The purpose of the study was to investigate the brain function network hub changes in PACG patients using the voxel-wise degree centrality (DC) method.
UNASSIGNED: Thirty-one PACG patients (21 male and 10 female) and 31 healthy controls (HCs) (21 male and 10 female) closely matched in age, sex, and education were enrolled in the study. The DC method was applied to investigate the brain function network hub changes in PACG patients. Moreover, the support vector machine (SVM) method was applied to distinguish PACG patients from HC patients.
UNASSIGNED: Compared with HC, PACG patients had significantly higher DC values in the right fusiform, left middle temporal gyrus, and left cerebelum_4_5. Meanwhile, PACG patients had significantly lower DC values in the right calcarine, right postcentral gyrus, left precuneus gyrus, and left postcentral gyrus. Furthermore, the SVM classification reaches a total accuracy of 72.58%, and the ROC curve of the SVM classifier has an AUC value of 0.85 (r = 0.25).
UNASSIGNED: Our results showed that PACG patients showed widespread brain functional network hub dysfunction relative to the visual network, auditory network, default mode network, and cerebellum network, which might shed new light on the neural mechanism of optic atrophy in PACG patients.

(1) Purpose: To measure the change in vessel density (VD) and the flow area (FA) on the retina of eyes with primary angle-closure diseases (PACD), including primary angle-closure suspect (PACS), primary angle-closure (PAC), acute primary angle-closure (APAC) and primary angle-closure glaucoma (PACG). (2) Methods: Patients with PACD were prospectively enrolled in this study. All participants underwent thorough ophthalmic examinations. The mean defect (MD), retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness, VD measurement, and blood FA were measured. (3) Results: A total of 147 eyes from 121 subjects were included in this study. The VD of the nerve head layer was significantly lower in PACG and APAC (all p < 0.001). APAC and PACG had lower FA of all layers, except for the choroid layer (p < 0.05). The macular VD of the whole image and blood FA in the superficial layer was significantly lower in PACG (all p < 0.001). The MD, RNFL, and GCC thickness demonstrated a strong correlation with whole image VD in the superficial layer (p < 0.001), while the inside disc VD did not show a significant correlation with MD, RNFL, and GCC thickness (p > 0.05). (4) Conclusions: There was a significant decrease in the VD and FA on the optic disc as well as the VD and FA of the superficial layer in the macular area in APAC and PACG. The changes in VD and FA are correlated with the severity of the glaucomatous structural damage and functional impairment.