Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY MESSAGES: 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.

Novel therapeutic targets for primary open-angle glaucoma identified through multicenter proteome-wide mendelian randomization.

Background: This study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG). Methods: The summary-data-based Mendelian randomization (SMR) method was used to evaluate the genetic association between plasma proteins and POAG. Two sets of plasma protein quantitative trait loci (pQTLs) data considered exposures were obtained from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. The summary-level genome-wide association studies data for POAG were extracted from the latest Round 10 release of the FinnGen consortium (8,530 cases and 391,275 controls) and the UK Biobank (4,737 cases and 458,196 controls). Colocalization analysis was used to screen out pQTLs that share the same variant with POAG as drug targets identified. The two-sample Mendelian randomization, reverse causality testing and phenotype scanning were performed to further validate the main findings. Protein-protein interaction, pathway enrichment analysis and druggability assessment were conducted to determine whether the identified plasma proteins have potential as drug targets. Results: After systematic analysis, this study identified eight circulating proteins as potential therapeutic targets for POAG. Three causal proteins with strong evidence of colocalization, ROBO1 (OR = 1.38, p = 1.48 × 10-4, PPH4 = 0.865), FOXO3 (OR = 0.35, p = 4.34 × 10-3, PPH4 = 0.796), ITIH3 (OR = 0.89, p = 2.76 × 10-4, PPH4 = 0.767), were considered tier one targets. Five proteins with medium support evidence of colocalization, NCR1 (OR = 1.25, p = 4.18 × 10-4, PPH4 = 0.682), NID1 (OR = 1.38, p = 1.54 × 10-3, PPH4 = 0.664), TIMP3 (OR = 0.91, p = 4.01 × 10-5, PPH4 = 0.659), SERPINF1 (OR = 0.81, p = 2.77 × 10-4, PPH4 = 0.59), OXT (OR = 1.17, p = 9.51 × 10-4, PPH4 = 0.526), were classified as tier two targets. Additional sensitivity analyses further validated the robustness and directionality of these findings. According to druggability assessment, Pimagedine, Resveratrol, Syringaresinol and Clozapine may potentially be important in the development of new anti-glaucoma agents. Conclusion: Our integrated study identified eight potential associated proteins for POAG. These proteins play important roles in neuroprotection, extracellular matrix regulation and oxidative stress. Therefore, they have promising potential as therapeutic targets to combat POAG.

[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process]. / Znachenie mitokhondrial'noi disfunktsii v stabilizatsii glaukomnogo protsessa.

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration. PURPOSE: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250. MATERIAL AND METHODS: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days. RESULTS: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests. CONCLUSION: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.

Evaluation of lamina cribrosa parameters, nerve fiber thickness, and macular thickness in primary open-angle glaucoma and pseudoexfoliation glaucoma using optical coherence tomography.

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Oxylipins in Aqueous Humor of Primary Open-Angle Glaucoma Patients.

PURPOSE: Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients. METHODS: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. RESULTS: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness. CONCLUSIONS: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG.

The Mirror Theory: Parallels between Open Angle and Angle Closure Glaucoma.

Glaucoma is a widespread ophthalmological disease, with a high impact and frequent visual morbidity. While the physiopathology of the two types of primary glaucoma (open angle and angle closure) has been studied, there seems to be little relationship between the two. In this study, we gather clinical and preclinical data to support the idea that the two primary glaucomas are "mirrored" in terms of morphological parameters and disease physiopathology. In short, primary angle closure glaucoma (PACG) is associated with hyperopia and low axial length, and primary open angle glaucoma (POAG) is associated with myopia and high axial length. Moreover, in PACG and in primary angle closure or primary angle closure suspect cases, while there is extensive iridotrabecular contact, the intraocular pressure (IOP) is still maintained in the lower half of the normal range throughout the evolution of the disease, which suggests a baseline trabecular hyperfiltration in PACG. In the opposite case, myopic eyes with open angles and a higher risk of developing POAG often have a baseline IOP in the upper half of the normal range, suggesting a baseline trabecular hypofiltration. As we explore clinical, genetic and animal model data regarding these opposing aspects, we hypothesize the existence of a mirroring relationship between PACG and POAG. Defining the relationship between the two potentially blinding diseases, with a high prevalence worldwide, may aid in understanding the mechanisms better and refining diagnosis and treatment. Thus, our theory has been named the Mirror Theory of Primary Glaucomas.

Cigarette Smoking and its Association with Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically assess the association between cigarette smoking and development of Primary Open Angle Glaucoma (POAG) in the general adult population. Heterogeneity will be explored appropriately. METHODS: Outcomes of glaucoma, OAG and POAG were explored in adults who were current, former, and never cigarette smokers. An additional category of 'smokers with "any" smoking status' was used where former smokers were not clearly distinguished from current and never smokers and in smokers whose form of smoking was not defined. All studies were observational and there was no limit to time period. Databases used were MEDLINE, Embase, Global Health and Web of Science. Study quality was assessed using the JBI critical appraisal tool. The DerSimonian-Laird random-effects model and weighting method was applied for meta-analysis with subgroup and sensitivity analyses along with meta-regression. RESULTS: Four cohort, six cross-sectional and nine case-control studies were included. Only one cohort study attained a low risk of bias (RoB), two cohort studies were of medium RoB and the rest of the studies were of high RoB. There was no evidence for an association between smoking statuses: current smoking: OR 0.96, 95%CI (0.76,1.21), former smoking: OR 0.96, 95%CI (0.83,1.11), smoking (any): OR 1.48, 95%CI (0.96, 2.29) and glaucoma. Sensitivity analyses did not have a material impact on findings. Heterogeneity was not explained by smoking status, study quality, smoking exposure, and glaucoma outcome criteria. CONCLUSION: This review suggests no evidence for an association between cigarette smoking and the development of POAG. There was no evidence that current, former, and general smoking increased the risk of glaucoma.

Efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for primary open-angle glaucoma: A randomized controlled trial.

PURPOSE: To report the 2-year efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for the treatment of primary open-angle glaucoma (POAG). SETTING: A single surgical site in China. DESIGN: This was a prospective, randomized controlled trial. POAG patients were randomly assigned to the penetrating canaloplasty or ab externo canaloplasty group. METHODS: This study enrolled POAG patients who underwent penetrating canaloplasty or ab externo canaloplasty randomly. Surgical success, intraocular pressure (IOP), number of glaucoma medications, and surgical complications were evaluated until 24 months post-operatively. Surgical success was defined as 6 mmHg ≤ IOP ≤21 mmHg with an IOP reduction ≥20%, which included qualified success (with or without medications) and complete success (without medications). RESULTS: A total of 52 eyes (45 patients) were randomly assigned to one of two groups: the penetrating canaloplasty group (PCP, n = 26) or the ab externo canaloplasty group (CP, n = 26). The probabilities of qualified success and complete success were 92.3% and 76.9%, respectively, in the PCP group and 64.1% and 52.1%, respectively, in the CP group at 24 months (p = 0.013, p = 0.042, log-rank test). The mean IOP decreased from 30.8 ± 10.7 and 28.6 ± 11.8 mmHg to 14.1 ± 3.3 mmHg in the PCP group and 22.1 ± 13.6 mmHg in the CP group at year two (p = 0.007). The PCP group also received fewer medications (0.2 ± 0.5) than did the CP group (0.7 ± 1.2) at year two (p = 0.038). Post-operative complications were similar, and the most common complications were transient IOP elevation and hyphema in the PCP group (42.3%, 46.2%) and the CP group (38.5%, 23.1%) (p > 0.05). CONCLUSIONS: Compared to ab externo canaloplasty, penetrating canaloplasty had a greater surgical success rate and better IOP reduction with a comparable rate of complications.

Intraocular Pressure Response in the Untreated Contralateral Eye After Selective Laser Trabeculoplasty.

AIM: To examine the impact of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) in the untreated contralateral eye within 12 months after the procedure. METHODS: A retrospective chart review was conducted on patients with primary open-angle, normal-tension, pigmentary, or pseudoexfoliation glaucoma who received 360-degree SLT at George Washington University. Exclusion criteria included prior or subsequent laser or glaucoma surgery within 12 months of SLT, other glaucoma types, or corticosteroid use during follow-up. Primary outcomes were IOP and medication reduction, and SLT success, defined as reducing IOP by ≥20% without additional IOP-lowering procedures or medications. Follow-up occurred at six weeks, six months, and 12 months. Demographic and clinical data were analyzed using ANOVA, paired t-tests, and chi-squared tests. RESULTS: A total of 125 patients were included, representing a range of backgrounds: African American (57.6%), Caucasian (31.2%), Asian (5.6%), and Hispanic/Latino (4%), and 1.6% did not report their background. Significant reductions in mean IOP and medication numbers were observed in the contralateral eye at six weeks and six months (p<0.05) but not at 12 months. The contralateral eye success rates were 24% at six weeks and six months and 20.8% at 12 months. The contralateral eye was more likely to achieve success if the ipsilateral eye was successful at six weeks (odds ratio (95% confidence interval): 5.05 (1.89-13.48)), six months (16.1 (4.56-57.17)), and 12 months (5.94 (2.07-17.04)) (p<0.001 for all). CONCLUSION: First-time SLT results in statistically significant IOP and medication reductions in the contralateral eye at six weeks and six months. The contralateral eye was 5.05-16.1 times more likely to achieve success if the ipsilateral eye was successful within 12 months.

Integrated Bioinformatics-Based Identification and Validation of Neuroinflammation-Related Hub Genes in Primary Open-Angle Glaucoma.

Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene-miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation-related genes were found to overlap between the differentially expressed genes and neuroinflammation-related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene-miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, Müller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG.

Evaluating the impact of caloric restriction, body mass index and exercise on primary open-angle glaucoma: A review.

This literature review evaluates any possible links between primary open-angle glaucoma (POAG) and caloric restriction (CR), body mass index (BMI), and exercise, aiming to map the extent of the literature. Its primary objective is to recognise the nature and breadth of research evidence, identify possible gaps in these topics and develop future studies. The databases searched were MEDLINE (PudMed), Scopus and ScienceDirect, in April 2023 for articles published in English, with no date restriction. A total of 447 search results were retrieved. Of these, 73 were related to CR, 249 to BMI, and 125 to exercise. Records identified included systematic reviews, meta-analyses, randomised controlled trials, cohort studies and animal studies. CR has been shown to halt the degeneration of retinal ganglion cells and protect against various glaucomatous processes in animal models. Low BMI has been shown to be associated with an increased risk of POAG and a faster rate of visual field deterioration in POAG. However, the association between high BMI and POAG is not consistent. Exercise has been shown to cause mechanical, vascular, and neurobiological changes affecting the pathophysiology of POAG. The present review helps identify key characteristics and factors relating to the impacts of CR, BMI, or exercise on POAG.

Evaluation of Depression Levels in Patients With Primary Open-Angle Glaucoma Using the Geriatric Depression Scale.

Introduction Glaucoma is a chronic disease that can lead to severe visual impairment and blindness. Methods The study included 91 primary open-angle glaucoma patients aged 60 years and older (group 1) and 83 healthy controls (group 2) with similar age and gender distribution. The duration of the disease, the number of anti-glaucomatous drops used daily, and visual field parameters were recorded. All participants then underwent a comprehensive mental status examination by a psychiatrist and were administered the Geriatric Depression Scale (GDS). Results In Group 1, the mean duration of glaucoma was 10.2±6.0 years, and the mean number of drops used per day was 2.91±1.47 drops/day. According to visual field (24-2) data, the mean mean deviation (MD) was -7.76±4.78 dB and the mean pattern standard deviation (PSD) was 5.14±2.60 dB. According to the classification based on MD, 33 (36.3%) patients were in the early stage, 36 (39.5%) in the intermediate stage, and 22 (24.2%) in the advanced stage. The mean best-corrected visual acuity (BCVA) was 0.85±0.38 logMAR in group 1 and 0.34±0.19 logMAR in group 2. The mean GDS scores were 13.7±7.23 points in group 1 and 3.61±1.71 points in group 2. There were statistically significant differences between the groups in terms of BCVA and GDS scores (p=0.039 and p<0.001, respectively). Conclusion In conclusion, it is important that ophthalmologists provide adequate information about glaucoma to prevent the development of depression in patients with glaucoma. This information may protect patients from uncertainty. A multidisciplinary approach in the management of glaucoma, a chronic and vision-threatening disease, can positively affect patients' compliance with follow-up and treatment, increase the quality of healthcare, and improve treatment responses.

Analysis of the relationship between VEGF, NLRP3 inflammatory complex, EPO levels, and ocular hemodynamics in patients with primary open-angle glaucoma.

OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG). METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables. RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001). CONCLUSION: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.

Comparison of 1-year effectiveness between phaco-microhook ab-interno trabeculotomy and phaco-iStent trabecular micro-bypass stent in primary open-angle glaucoma with low-teen intraocular pressure.

PURPOSE: To investigate the surgical effectiveness of combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) in eyes with primary open-angle glaucoma (POAG) and preoperative intraocular pressure (IOP) controlled below 15 mmHg (low-teen IOP). METHODS: This retrospective cohort study included consecutive patients with POAG and low-teen IOP who underwent phaco-µLOT or phaco-iStent as their initial glaucoma surgery and were followed up for 1 year postoperatively. Surgical failure was defined as the inability to achieve the following criteria twice in a row: (A) IOP of 6-15 mmHg with over 20% IOP reduction; (B) IOP of 6-12 mmHg with over 20% IOP reduction. RESULTS: A total of 75 eyes from 75 subjects were included, with 48 in the phaco-µLOT group and 27 in the phaco-iStent group. The mean preoperative IOP and number of antiglaucoma medications were 13.1 ± 2.1 mmHg and 3.4 ± 0.9 in the phaco-µLOT group, and 12.6 ± 2.0 mmHg and 2.5 ± 1.2 in the phaco-iStent group, respectively. The number of antiglaucoma medications was significantly reduced to 2.5 ± 0.9 (phaco-µLOT) and 2.0 ± 1.1 (phaco-iStent) at 1-year postoperatively (all p < 0.05). For criteria A and B, the survival rates were significantly higher in the phaco-µLOT group than in the phaco-iStent group (all p < 0.01). CONCLUSION: Both phaco-µLOT and phaco-iStent hold promise in reducing the need for antiglaucoma medications in POAG eyes with low-teen IOP. Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. KEY MESSAGES: What is known Minimally invasive glaucoma surgeries (MIGS) procedures target the pressure gradient pathways in patients with higher preoperative intraocular pressure (IOP) levels, however, evidence on their effectiveness in normotensive glaucoma patients remains limited. What is new Combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) significantly reduced the number of antiglaucoma medications in primary open-angle glaucoma (POAG) eyes with preoperative IOP controlled below 15 mmHg (low-teen IOP). Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. These procedures should be limited to reducing the number of antiglaucoma medications used, as they did not significantly reduce the postoperative IOP in POAG eyes with low-teen IOP.

Removable regulating sutures during trabeculectomy for a safer and more effective intraocular pressure control.

PURPOSE: Comparing the effect of standard trabeculectomy with direct sutures versus trabeculectomy with compression and everting sutures. METHODS: Mono-centric randomized prospective comparative study on 38 glaucomatous eyes undergoing trabeculectomy: 19 with standard fixed sutures (group A) and 19 withremovable regulating sutures (group B). Preoperatively and at day-7, 1-month, 2-months, 3-months and 6-months after surgery, we recorded best-corrected visual acuity (BCVA), intraocular pressure (IOP) and possible complications. Complete, partial success and failure rates were recorded at the end of the study. RESULTS: In group B, we pulled everting sutures with the "horse bridle" technique at the 14th day, and successively removed all sutures between the 14th-30th post-operative day. At month-1, we recorded a significant IOP reduction in both groups (mean reduction of 11.5 mmHg for group A and of 14.4 mmHg for Group B, p = 0.001 and p < 0.0001, respectively). Furthermore, group B showed a significantly lower IOP than group A (-4.2 mmHg, 95% confidence interval [CI] -7.0 to -0.5 mmHg for group B, p = 0.01). At 2, 3 and 6-months, no significant IOP differences were reported between the two groups (all p > 0.05), but failure rate was higher for group A (21%) than for group B (11%). No differences in visual outcomes at any timepoints were noted. CONCLUSIONS: Trabeculectomy with removable regulating sutures showed a good safety profile, comparable to standard trabeculectomy. Moreover, we reported a lower IOP one month postoperatively, suggesting this technique may optimize early management of trabeculectomy.

Comparative Effects of GLP-1 Receptor Agonists and Metformin on Glaucoma Risk in Type 2 Diabetes Patients.

PURPOSE: To compare effects of glucagon-like peptide-1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes. DESIGN: A retrospective cohort study was conducted using electronic medical records (EMR) data from the from an international electronic health record network, covering a period from May 2006 to May 2024. PARTICIPANTS: Patients diagnosed with type 2 diabetes mellitus (T2DM) who were treated with either GLP-1 receptor agonists or metformin. METHODS: Data from 120 healthcare organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication usage. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. MAIN OUTCOME MEASURES: Incidence of POAG, ocular hypertension, and the need for first-line treatments including beta-blockers, prostaglandin analogues, brimonidine, brinzolamide, dorzolamide, netarsudil, and laser trabeculoplasty. RESULTS: After PSM, both groups included 61,998 patients at the 1-year follow-up, 27,414 at the 2-year follow-up, and 14,100 at the 3-year follow-up. Patients treated with GLP-1 receptor agonists had a significantly decreased risk of developing POAG compared to those on metformin at 1 year (RR 0.59, 95% CI 0.39-0.88), 2 years (RR 0.50, 95% CI 0.32-0.78), and 3 years (RR 0.59, 95% CI 0.37-0.94). Similar protective effects were observed for ocular hypertension with risk reductions of 56% at 1 year (RR 0.44, 95% CI 0.31-0.62), 57% at 2 years (RR 0.43, 95% CI 0.30-0.62), and 49% at 3 years (RR 0.51, 95% CI 0.34-0.75). The risk of first-line therapy initiation was also lower in the GLP-1 receptor agonists group at 1 year (RR 0.63, 95% CI 0.53-0.74), 2 years (RR 0.71, 95% CI 0.59-0.85), and 3 years (RR 0.75, 95% CI 0.62-0.91). CONCLUSIONS: GLP-1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared to metformin in patients with type 2 diabetes. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of diabetic patients.

The association between airborne particulate matter (PM2.5) exposure level and primary open-angle glaucoma.

The eye is vulnerable to the adverse effects of air pollution. Previous experimental study found that fine particulate matter (PM2.5) had a direct toxic effect on intraocular tissues. However, clinical evidence for the impact of air pollutants exposure on functional and structural changes in glaucoma remains scarce. A total of 120 patients with primary open-angle glaucoma (POAG) who met the inclusion criteria were included in this retrospective study. The standardized ophthalmic examination, such as intraocular pressure (IOP), visual field, optical coherence tomography, and comprehensive physical examination, were performed. The air pollution data, including PM2.5 concentration and air quality index (AQI), were collected. PM2.5 and AQI for the day of the medical examination, as well as one month, and three months before the medical examination date, were investigated. In our results, higher average exposure levels for one-month and three-month, were associated with increased IOP (r=0.229, P=0.013; r=0.204, P=0.028, respectively) and decreased visual field mean sensitivity (MS) (r=-0.212, P=0.037; r=-0.305, P=0.002, respectively). PM2.5 concentrations for the day of the medical examination was not significantly associated with ocular parameters. In multiple linear regression analysis adjusted for demographic and clinical factors, higher PM2.5 exposure for one month was associated with elevated IOP (P=0.040, ß=0.173, 95 %CI=0.008-0.337). We also found an association between PM2.5 and MS (one-month exposure: ß=-0.160, P=0.029; three-month exposure: ß=-0.238, P=0.002). The logistic regression analysis found that three-month average PM2.5 exposure level was significantly associated with the disease severity (ß=0.043, P=0.025, 95 %CI=1.005-1.084). In conclusion, this study is the first to investigate the relationship between air pollution and detailed ocular parameters of POAG patients in Shanghai over a three-year period, and to explore the effects of different exposure times of PM2.5 on glaucoma. This study found that PM2.5 exposure was correlated with elevated IOP and decreased MS. The one-month PM2.5 exposure level had the most significant effects on IOP. The three-month PM2.5 exposure level was an independent risk factor for POAG severity. Current evidence suggests there may be an association between PM2.5 exposure and POAG.

Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

OCT angiographic evaluation of changes in macula and optic nerve head vessel density after a water drinking test in glaucomatous and healthy eyes.

PURPOSE: To evaluate the effects of a water drinking test (WDT) on the intraocular pressure (IOP) and vascular density of the optic nerve head and macula in healthy individuals and those with primary open glaucoma using optical coherence tomography angiography. METHODS: In this prospective comparative study, 30 healthy patients and 44 POAG subjects were divided into two groups. The study's outcome measures were the IOP and vessel density of the optic nerve and macular area. After ingesting 1000 ml of water in 5 min, the effect of the WDT on the IOP and the vascular density of the macular area and optic nerve head were measured at baseline and then 20, 40, and 60 min later at intervals of 20 min. RESULTS: The initial IOP in the healthy and glaucomatous eye groups was comparable (15.94 ± 2.6 and 16.87 ± 4.21 mmHg, respectively, P = 0.506). The IOP of both groups peaked at 40' measurements. POAG eyes had significantly higher IOP elevation (4.34 ± 0.30 vs. 2.24 ± 0.30 mmHg, P < 0.001). The glaucomatous eyes had lower radial peripapillary capillary (RPC) and whole macular superficial capillary plexus (SCP) densities at baseline (48.55 ± 5.99 vs. 51.33 ± 3.75) and (48.92 ± 3.41 vs. 45.29 ± 5.29), respectively (P < 0.001). After the WDT, the change in vessel density between groups in the RPC, whole superficial, and deep capillary plexuses was insignificant (SCP and DCP of 0.66 and 0.70, respectively, P = 0.16). CONCLUSION: The WDT caused a significant IOP jump in both glaucomatous and healthy eyes, but generally, the alterations in the glaucomatous eyes were more pronounced. The changes in vascular density in the macula and optic nerve head were similar between the groups.

Evaluation of Intrascleral Lakes after Phaco-Viscocanalostomy using Anterior Segment Optical Coherence Tomography.

Purpose: This study aimed to investigate the results of combined phacoemulsification and viscocanalostomy (phaco-VC) in a six-month follow-up and its relationship with intrascleral lake (IL) using anterior segment optical coherence tomography (AS-OCT) in patients with primary open-angle glaucoma (POAG). Methods: In total, 36 eyes with POAG eligible for phaco-VC were enrolled in this prospective observational study. All patients underwent AS-OCT evaluation and ophthalmologic examination including Goldman tonometry, cup-disc ratio assessment, best corrected visual acuity (BCVA) measurement, and antiglaucoma medication(s) prior to surgery and one, three, and six months after the surgery. The width, length, area, and circumference of the ILs were evaluated using AS-OCT at each follow-up. Results: A total of 36 eyes of 34 patients with POAG were investigated in this study. According to the results, the mean age of the patients was 70.09 ± 8.73 years, and the majority of the cases were male (n = 23; 63.9%). The mean preoperative intraocular pressure (IOP) was 20.11 ± 7.22 mmHg on 2.47 ± 1.1 medications, and the mean postoperative IOP reduced to 11.11 ± 2.58 mmHg on 0.11 medications, which was statistically significant (P < 0.001). ILs were detectable in all cases which resulted in a 100% qualified success rate. The reduction in the width, area, and circumference of the IL was significant during the six-month follow-up. The relationship between IOP changes and IL parameters on AS-OCT was not significant. Conclusion: This study evaluated the associations between IL changes and IOP reduction after phaco-VC. A six-month follow-up showed a notable reduction in the IL, but unexpectedly, IOP control did not decline. A reduction in IL diameter, when there is sufficient IOP control, indicates that there may be various IOP lowering mechanisms through VC other than the IL diameters. Further evaluation of VC focusing on long-term changes in IL and Schlemm's canal diameter is necessary to explain the precise mechanisms of lowering the IOP.