Primary Open-angle Glaucoma Patients Research Articles

Epidemiology and Treatment of Patients With Primary Open Angle Glaucoma in Germany: A Health Claims Data Analysis.

Based on a large administrative database of German claims data, our study provides current estimates of the prevalence and incidence of primary open-angle glaucoma (POAG) in Germany and describes selected outcomes for prevalent POAG patients. To estimate the prevalence and incidence of POAG in Germany, to describe the patient population in terms of comorbidity burden, routine care, and overall healthcare resource utilization (HCRU) and associated costs, and to describe treatment patterns over time in patients undergoing relevant laser procedures. Based on anonymized German claims data, we carried out a retrospective, non-interventional study covering calendar years 2016 to 2021. For the adult German population (≥18y), we estimated a POAG one-year prevalence of 1.70% and a one-year incidence of 0.17% in 2018; both increased with age, peaking in 80-89 year-olds. Prevalence and incidence were lower in 2020 (1.65% and 0.16%, respectively), the first year of the SARS-CoV-2 pandemic. Most patients solely received topical treatment. Most surgically-treated patients underwent laser trabeculoplasty, followed by laser iridotomy, trabeculectomy, and filtration operations with implant. In patients undergoing laser trabeculoplasty, the treatment regimen was nearly unchanged in the second year after, compared to two years before the procedure. Multimorbidity was commonly observed; 75.5% of patients had arterial hypertension and 50.0% had disorders of lipoprotein metabolism and other lipidemias, compared to 60.1% and 39.2%, respectively, in an age- and sex-matched control sample. Our study provides insights into epidemiology and routine care of POAG in Germany and HCRU in prevalent patients. There was little change in treatment regimens in patients who underwent laser trabeculoplasty, two years after the procedure. Most patients were multimorbid highlighting the need for comprehensive care.

A meta-analysis of the association between high-sensitivity c-reactive protein level and glaucoma.

Glaucoma is the second-leading cause of blindness in the US for people over the age of 40; the most common form is primary open-angle glaucoma (POAG). It has been suggested that inflammatory markers have a role in the development and the progression of glaucoma (GL). High-sensitivity C reactive protein (HsCRP) is an inflammatory marker that has been linked to cardiovascular disease and a possible link to GL. Although a number of studies have found a link between CRP and GL; POAG, normal tension glaucoma (NTG), exfoliation glaucoma (XFG), Exfoliation syndrome (XFS), other research has shown the opposite. This systematic review is to determine the association between HsCRP and GL. A literature search was conducted using the MEDLINE database. We identified thirty-six peer-reviewed studies. Five retrospective studies were included and summed up to 164305 study participants, 161759 POAG patients, and 2546 controls. The pooled result of all studies revealed that HsCRP (SMD: 0.44 mg/dl; [95% confidence interval -0.10 to 0.99]; P = 0.11, I2 89%) concentration was not significantly higher in POAG patients compared to the healthy controls. The SMD for NTG, XFG and XFS; 0.64 mg/dl; 0.03 mg/dl, 0.03 mg/dl respectively. The pooled result revealed that HsCRP concentration was not significantly higher in POAG, NTG, XFG, and XFS. No publication bias was found using the funnel plot. The meta-analysis concluded that there is no correlation between the elevated plasma levels of HsCRP and GL. Future studies should be conducted.

Comparison of surgical outcomes between Kahook Dual Blade goniotomy and Trabectome surgery in patients with open-angle glaucoma

Objective: To compare the medium-term therapeutic effects of Kahook Dual Blade (KDB) goniotomy and Trabectome surgery in the treatment of patients with primary open-angle glaucoma (POAG). Methods: This study was a non-randomized prospective interventional controlled clinical study. POAG patients who underwent KDB goniotomy or Trabectome surgery at Beijing Tongren Hospital from May 2017 to April 2022 were enrolled. The definition of successful surgery was postoperative average intraocular pressure (IOP)≤21 mmHg (1 mmHg=0.133 kPa) and IOP decrease≥20%. Follow-up visits were conducted on the 1st day, 1st week, 1st, 3rd and 6th month after surgery. The IOP value, the number of IOP-lowering medications, the proportion of surgical success (average IOP≤21 mmHg at 6 months), and complications were evaluated. Statistical methods included independent sample t-test, Mann-Whitney rank sum test, χ2 test, repeated measures two-factor analysis of variance, Bonferroni, Friedman M test, Wilcoxon, and Log-rank. The Kaplan-Meier method was used to calculate the cumulative success rate of each group. Results: Seventeen male patients (17 eyes) and 10 female patients (10 eyes) were included. The mean age was (39.9±17.7) years old. There were 11 patients in the KDB group and 16 patients in the Trabectome group. There was no significant difference in clinical baseline conditions between the two groups (P>0.05). The IOPs in the KDB and Trabectome groups at postoperative 1 week [(16.6±6.3) and (16.4±4.1) mmHg) and 6 months [(17.8±5.3) and (19.9±4.4) mmHg) were lower than those before surgery [(25.1±9.3) and (27.4±9.1) mmHg) (all P<0.05). There was no significant difference in the overall IOP between groups (P>0.05). The IOP reduction rates in the KDB and Trabectome groups were 23.4% and 19.0%, with no significant difference (P=0.674). The numbers of IOP-lowering medications used in the KDB and Trabectome groups at 3 months [2.0 (1.0, 4.0) and 2.0 (1.0, 2.3)] and 6 months [2.0 (0.0, 4.0) and 2.0 (1.0, 3.0)] after surgery were not significantly different from those before surgery [4.0 (2.0, 4.0) and 3.0 (2.0, 4.0)] (both P>0.05). There was no statistical significance in the overall number of IOP-lowering medications used between the two groups (P>0.05). There was also no statistically significant difference in the proportion of patients with an IOP decrease of≥20% and the proportion of patients whose mean postoperative IOP was≤21 mmHg (all P>0.05). The proportions of IOP≤21 mmHg in the KDB group and the Trabectome group at 6 months after surgery were 81.8% and 68.8% (P>0.05). Serious intraoperative or postoperative complications occurred in neither group. Conclusions: Both KDB trabeculotomy and Trabectome surgery can effectively reduce IOP and have a good safety profile in treating POAG, with the same number of IOP-lowering medications.

One Year Outcomes of Preserflo Microshunt for Primary Open Angle Glaucoma: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis concludes that the PreserFlo Microshunt glaucoma drainage device significantly reduces intraocular pressure in primary open-angle glaucoma patients at 12 months post insertion. A systematic review and meta-analysis on the effect of the PRESERFLO™ MicroShunt (PF-MS) on intraocular pressure (IOP) at 12 months has been conducted. The Pubmed/MEDLINE, Embase, CENTRAL, Google Scholar, Scopus and Web of Science databases were searched. Inclusion criteria required a diagnosis of open-angle glaucoma, PF-MS insertion, and examination of IOP over time. Meta-analyses were conducted on the primary outcome of IOP and the secondary outcome of glaucoma medication regime. Adverse events were also noted. Fourteen studies were identified for inclusion in the meta-analyses, of which none had a high risk of bias. The meta-analyses found a significant mean reduction in IOP of 9.07mmHg (95% CI 7.88 - 10.25; P<0.0001) and a significant mean reduction in mean glaucoma medication requirement of 2.37 medications (95% CI 2.15 - 2.60); P<0.0001). Hypotony and hyphaema are common early complications. The PF-MS device significantly reduced both IOP and glaucoma medication requirement at 12 months post insertion in individuals with open-angle glaucoma without a significant adverse event burden. Further research is required to determine the economic and environmental effects of widely implementing the PF-MS device into clinical practice.

SDPR expression in human trabecular meshwork and its potential role in racial disparities of glaucoma

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM from Black vs White POAG patients’ surgical specimens, with no significant expression differences in other caveolae-associated genes, confirmed by qPCR analysis. No racial differences in SDPR gene expression were noted in healthy donor tissue by PCR analysis, but there was greater expression as compared to specimens from patients with glaucoma. Analysis of SDPR protein expression confirmed specific expression in the TM regions, but not in adjacent tissues. TEM studies of TM specimens from healthy donors did not demonstrate any racial differences in caveolar morphology, but a significant reduction of caveolae with normal morphology and immuno-gold staining of SDPR were noted in glaucomatous TM as compared to TM from healthy donors. Linkage of SDPR expression levels in TM, POAG development, and caveolar ultrastructural morphology may provide the basis for a novel pathway of exploration of the pathologic mechanisms of glaucoma. Differential gene expression of SDPR in TM from Black vs White subjects with glaucoma may further our understanding of the important public health implications of the racial disparities of this blinding disease.

Reduction of Optic Disc Microvasculature and Retinal Nerve Fiber Layer Thinning in Patients with Glaucoma

PurposeTo assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DesignRetrospective case series. MethodsFor 105 POAG patients, ≥ 5 consecutive optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained during ≥ 2 years of follow-up.Based on enface OCTA imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < 0.05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by multivariable longitudinal linear mixed-effects model vs. time. ResultsDuring 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of 5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval (CI), 0.120 to 0.646; P = 0.006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = 0.002) and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = 0.001). ConclusionsReduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep ONH circulation in the glaucoma pathogenesis.

No Changes in Keratometry Readings and Anterior Chamber Depth after XEN Gel Implantation in Patients with Glaucoma.

Background: This study aimed to compare keratometry and anterior chamber depth (ACD) changes after XEN implantation in primary open-angle glaucoma (POAG) cases over a 3-month follow-up period. Methods: Twenty patients with POAG who underwent XEN63 implantation, either standalone or combined with cataract surgery, were included. Preoperative data, including best-corrected visual acuity (BCVA), refraction, gonioscopy, ophthalmoscopy, intraocular pressure (IOP) evaluation, and axial length, were collected. Corneal topography and ACD measurements were assessed preoperatively and at postoperative days 1, 7, 15, 30, 60, and 90. Each patient's eye that underwent XEN surgery was included in the study group, with the fellow eye serving as a control. Results: In the study group, there was a significant decrease in IOP after XEN stent implantation at all investigated time intervals (p < 0.05). However, changes in mean ACD did not show statistically significant differences at any follow-up examination in both the study and control groups. Additionally, keratometry readings revealed no significant changes in total astigmatism or steep keratometry values in either group. Conclusions: XEN implantation in POAG cases resulted in a significant decrease in IOP over the 3-month follow-up period. However, there were no significant changes observed in mean ACD or keratometry readings, indicating stability in these parameters post-XEN implantation. These findings suggest that XEN implantation may be an effective option for IOP reduction without affecting corneal curvature or ACD in POAG patients.

Preservative-Free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% for Treatment-Naive Patients with Open-Angle Glaucoma.

To assess efficacy, safety, and tolerability of the preservative-free fixed-dose combination of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in treatments-naïve patients with primary open-angle glaucoma (POAG). This was a retrospective, real-world clinical practice setting study that included 107 eyes of 107 subjects with POAG who had never been treated for glaucoma. All subjects were received PF tafluprost/timolol FC once daily. Intraocular pressure (IOP) levels were documented for each eye at the untreated baseline and up to six months after the initiation of medical treatment. All adverse events, including ocular and systemic adverse reactions, were recorded. Additionally, the reasons for medication discontinuations were thoroughly documented. A total of 32 POAG patients with high-baseline IOP (> 21 mmHg) and 75 with normal-baseline IOP were included in the study. The subjects' baseline mean age was 62.4 ± 8.7 (range: 26 - 85 years); among them, 42 were women (39.3%). Mean IOP at baseline for all patients was 18.6 ± 4.3 mmHg. The mean IOP at six months was 12.6 ± 4.7 mmHg, representing a significant decrease compared to the baseline (-32%; P< 0.001). In POAG patients with high-baseline IOP, mean IOP was significantly lowered from 28.0 ± 5.7 mmHg at baseline to 18.0 ± 5.5 mmHg (-35%; P< 0.001); in patients with normal-baseline IOP, from 14.6 ± 3.4 mmHg to 10.3 ± 4.1 mmHg (-29%; P< 0.001). PF tafluprost/timolol FC was well tolerated and safe. After 6 months, 97.2% of all patients remained on therapy. In this real-world observational study, once-daily treatment with PF tafluprost/timolol FC demonstrated clinically relevant and statistically significant efficacy, as well as safety and good tolerability, in treatment-naive patients diagnosed with POAG.

Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma.

Parkinson's disease (PD) patients experience visual symptoms and retinal degeneration. Studies using optical coherence tomography (OCT) have shown reduced thickness of the retina in PD, also a key characteristic of glaucoma. To identify the presence and pattern of retinal changes in de novo, treatment-naive PD patients compared to healthy controls (HC) and early primary open angle glaucoma (POAG) patients. Macular OCT data (10×10 mm) were collected from HC, PD, and early POAG patients, at the University Medical Center Groningen. Bayesian informative hypotheses statistical analyses were carried out comparing HC, PD-, and POAG patients, within each retinal cell layer. In total 100 HC, 121 PD, and 78 POAG patients were included. We showed significant reduced thickness of the inner plexiform layer and retinal pigment epithelium in PD compared to HC. POAG patients presented with a significantly thinner retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, outer plexiform layer, and outer photoreceptor and subretinal virtual space compared to PD. Only the outer segment layer and retinal pigment epithelium were significantly thinner in PD compared to POAG. De novo PD patients show reduced thickness of the retina compared to HC, especially of the inner plexiform layer, which differs significantly from POAG, showing a more extensive and widespread pattern of reduced thickness across layers. OCT is a useful tool to detect retinal changes in de novo PD, but its specificity versus other neurodegenerative disorders has to be established.

Optic Nerve Head Pulsatile Displacement in Open-Angle Glaucoma after Intraocular Pressure Reduction Measured by Optical Coherence Tomography: A Pilot Study

This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention (p = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease’s pathophysiology and warranting further investigation into underlying mechanisms and clinical implications.

Smoking Intensity is Associated with Progressive Optic Nerve Head Vessel Density loss in Glaucoma.

To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. In this longitudinal study, POAG patients who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. 164 eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss (-0.11 (-0.23 to 0.00)) %/year per 10 pack-year higher; P=0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked < 22.2 pack-years during their lifetime. A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients.

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710-0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

Clinical applications of aqueous angiography in glaucoma.

Aqueous humor outflow (AHO) pathways are the main site of resistance causing elevated intraocular pressure in glaucoma, especially primary open-angle glaucoma patients. With the recently introduced technique of aqueous angiography (AA); functional, real time assessment of AHO from proximal (trabecuar meshwork) to distal pathways under physiological conditions has been made possible. AHO pathways are segmental, and AA can identify high-flow region (increased angiographic signals) and low flow region (decreased angiographic signals) in an individual. With the introduction of canal-based minimally invasive glaucoma surgeries (MIGS), the assessment of AHO can help guide the placement of stents/incisions during MIGS procedures. This can allow individualized and targeted MIGS procedures in glaucoma patients for better results. Based on the density of AHO pathways visualized on AA, surgeons can decide whether to perform MIGS or conventional glaucoma surgery for improved outcomes for the patient. Immediate intraoperative assessment for functionality of the MIGS procedure performed is possible with AA, allowing for surgical adjustments of MIGS procedure in the same sitting, if needed. This review provides a summary of the studies performed with AA to date, with a special focus on Indian patients. It covers the basics and clinical applications of AA for improving surgical outcomes in glaucoma patients.

Understanding the treatment paradigm and the sequencing of antiglaucoma fixed-dose combinations in a tertiary center in South India.

To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta-blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with b-blockers being the most consistent one. This study is a fairly large study with a minimum of a 5-year follow-up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time.

Optic Disc Microvasculature Dropout in Pre-perimetric Glaucoma.

To investigate factors associated with optic disc microvasculature dropout (MvD-D) in pre-perimetric primary open-angle glaucoma (PPG) patients. 139 eyes of PPG patients were categorized according to the presence of MvD-D with optical coherence tomography angiography (OCTA). Factors including visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, focal lamina cribrosa (LC) defect, optic disc hemorrhage (DH), and parapapillary deep-layer microvasculature dropout (MvD-P) were compared between eyes with and without MvD-D. MvD-D was observed in 69 PPG eyes (49.6%). Compared with eyes without MvD-D, the ones with MvD-D had a significantly thinner RNFL in all areas except the nasal sector, worse VF MD, and a focal LC defect and MvD-P (P<0.05): male gender also was more highly prevalent. A considerable number of eyes with MvD-D lacked focal LC defect (62.3% (43/69)) or MvD-P (71.0% (49/69)), while a few eyes without MvD-D had focal LC defect (10.0% (7/70)) or MvD-P (2.9% (2/70)). In a multivariable logistic regression analysis, male gender (odds ratio [OR], 3.96; P<0.001), worse VF MD (OR, 1.44; P=0.019), thinner global RNFL (OR, 1.13; P<0.001), higher prevalence of focal LC defect (OR, 3.71; P=0.014) and MvD-P (OR, 7.85; P<0.001) were significantly associated with MvD-D. MvD-D was related to worse disease severity in PPG patients, and often was not accompanied by focal LC defect or MvD-P. This suggests that impaired optic disc circulation can be an early sign of glaucoma without noticeable changes in functional or structural features (i.e., VF, focal LC defect, MvD-P).

Histopathological findings of failed blebs after microinvasive bleb surgery with the XEN Gel Stent and Preserflo MicroShunt.

The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31-1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (- 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (- 45%; p < 0.0001) after 6 and 12months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy.

Identification of a circulating three-miRNA panel for the diagnosis of primary open angle glaucoma.

Conventional diagnosis of primary open angle glaucoma (POAG) needs a combination of ophthalmic examinations. An efficient assay is urgently needed for a timely POAG diagnosis. We aim to explore differential expressions of circulating microRNAs (miRNA) and provide novel miRNA biomarkers for POAG diagnosis. A total of 180 POAG patients and 210 age-related cataract (ARC) patients were enrolled. We collected aqueous humor (AH) and plasma samples from the recruited patients. The expressions of candidate miRNAs were measured using quantitative real time polymerase chain reaction. The diagnostic ability of candidate miRNAs was analyzed by receiver operating characteristic curve. The expressions of miR-21-5p and miR-29b-3p were downregulated significantly in AH and plasma of POAG and miR-24-3p expression was significantly increased in AH and plasma of POAG, comparing with those of ARC. A three-miRNA panel was constructed by a binary logistic regression. And the panel could differentiate between POAG and ARC with an area under the curve of 0.8867 (sensitivity = 78.0%, specificity = 83.3%) in aqueous humor and 0.7547 (sensitivity = 73.8%, specificity = 81.2%) in plasma. Next, we verified the three-miRNA panel working as a potential diagnostic biomarker stable and reliable. At last, we identified related function and regulation pathways in vitro. In conclusion, we built and identified a circulating three-miRNA panel as a potential diagnostic biomarker for POAG. It may be developed into an efficient assay and help improve the POAG diagnosis in the future.

Aqueous humour protein dysregulation in Asian eyes with primary open angle glaucoma

The pathophysiology of Primary Open Angle Glaucoma (POAG) remains poorly understood. Through proteomic analysis of aqueous humour (AH) from POAG patients, we aim to identify changes in protein composition of these samples compared to control samples.High resolution mass spectrometry-based TMT6plex quantitative proteomics analysis is performed on AH samples collected from POAG patients, and compared against a control group of patients with cataracts. Data are available via ProteomeXchange with identifier PXD033153.1589 proteins were quantified from the aqueous samples using Proteome Discoverer version 2.2 software. Among these proteins, 210 were identified as unique master proteins. The proteins which were up or down-regulated by ±3 fold-change were considered significant. Human neuroblastoma full-length cDNA clone CS0DD006YL02 was significantly upregulated in patients with severe POAG on >2 medications, while actin, cytoplasmic 1, V2-7 protein (fragment), immunoglobulin-like polypeptide 1 and phosphatidylethanolamine-binding protein 4 were only present in these patients with severe POAG on >2 medications.Beta-crystallin B1 and B2, Gamma-crystallin C, D and S were significantly downregulated in the severe POAG ≤2 glaucoma medications group.Beta-crystallin B2, Gamma-crystallin D and GCT-A9 light chain variable region (fragment) were significantly downregulated in the non-severe POAG group.Actin, cytoplasmic 1 was significantly upregulated in subjects with severe POAG who required more than 2 glaucoma medications. Crystallins (Beta-crystallin B1 and B2, Gamma-crystallin C, D and S) were significantly downregulated in subjects with severe POAG who required less than 2 glaucoma medications.

Prevalence and &lt;em&gt;in silico&lt;/em&gt; analysis of p.D658G variant of WDR36 gene in patients affected with primary open angle glaucoma from Punjab Pakistan

The aim of the present study was to check the frequency of genetic variants in exons 8, 11, 13, and 17 of the WDR36 gene among primary open angle glaucoma (POAG) patients from Punjab, Pakistan, and to perform the in silico analysis of identified variants on protein function. Ninety-two individuals affected with primary open angle glaucoma were enrolled for this study. The clinical investigation involved the examination of the optic nerve head, visual field loss and elevated intraocular pressure (IOP). Selected exons (8, 11, 13, and 17) of the WDR36 gene was screened by Sanger sequencing. Sequencing results revealed a previously reported missense mutation p.D658G in exon 17 in two out of ninety-two POAG patients, while no mutation has been identified in the exons 8, 11, and 13. To predict the structural and functional effect of the p.D658G variant, SIFT, Polyphen-2, PROVEAN, mutation taster, I-mutant 3.0, and MuPRO were used. The MODELLER-CABS based hybrid approach was used for protein structure modelling. In silico analysis predicted the p.D658G variant to be deleterious, and it may affect the stability of protein and protein-protein interaction. The findings of this study suggested that the genetic variant p.D658G of the WDR36 gene is a rare genetic cause of POAG in Pakistani patients. The in silico tools predicted the variant p.D658G to be deleterious; however the modelled normal and mutant structure showed no effect on protein structure and function. To further confirm the pathogenic effect of this SNP, in vivo experiments, X-ray Crystallography of the WDR36 protein and population-based studies are needed.

Oxidized low-density lipoprotein changes the inflammatory status and metabolomics profiles in human and mouse macrophages and microglia

The conjunctiva of primary open angle glaucoma patients showed high level of oxidized low-density lipoprotein (ox-LDL), which is associated with the inflammatory response. Microglia and macrophages are the immune cells involved in retinal ganglion cell survival regulation; yet, their roles of the ox-LDL-induced inflammation in glaucoma remain elusive. Here we aimed to investigate the lipid uptake, inflammatory cytokine expression, and metabolomics profiles of human and murine-derived microglial and macrophage cell lines treated with ox-LDL. Under the same ox-LDL concentration, macrophages exhibited higher lipid uptake and expression of pro-inflammatory cytokines as compared to microglia. The ox-LDL increased the levels of fatty acid metabolites in macrophages and sphingomyelin metabolites in microglia. In summary, this study revealed the heterogeneity in the inflammatory capacity and metabolic profiles of macrophages and microglia under the stimulation of ox-LDL.