Primary Open-angle Glaucoma Patients Research Articles

NEDD9 Mediates the FAK/Src Signaling Pathway to Promote the Adhesion of Human Trabecular Meshwork Cells after Dexamethasone Treatment

Purpose The differential gene expression of neural precursor cell expressed developmentally downregulated 9 (NEDD9) in human trabecular meshwork (HTM) cells after dexamethasone (Dex) treatment was confirmed through gene expression profiling. However, the regulatory mechanism of NEDD9 expression in HTM cells remains unknown. In this study, we investigated NEDD9 expression in HTM cells and gained a better understanding of glucocorticoid-induced glaucoma (GIG) pathophysiology. Methods The Gene Expression Omnibus database and GEO2R tool were used to identify differentially expressed genes in the GSE37474 and GSE124114 datasets, and NEDD9 gene expression was found to be upregulated. Human corneoscleral segments and HTM cells were treated with 100 nM Dex or an equal volume of ethanol (0.01%) for 7 days. NEDD9 expression in TM tissues was evaluated by immunohistochemistry, and NEED9 expression in HTM cells was confirmed by RT-qPCR and western blotting. HTM cell adhesive behaviors were assessed with a cell adhesion detection kit. NEDD9 expression was knocked down with short hairpin RNA in HTM cells, and FAK/Src signaling pathway activation was found to be regulated by NEDD9. Results After 7 days of HTM cell Dex treatment, NEDD9 expression was upregulated to be approximately twice that of control. FAK, Src, phospho-FAK, and phospho-Src expression in Dex-treated HTM cells was markedly increased. Downregulation of NEDD9 expression reduced HTM cell adhesion to the surface of culture wells and simultaneously led to a reduction in FAK, Src, phospho-FAK and phospho-Src expression. Conclusions NEDD9 expression is upregulated in HTM cells after Dex treatment and promotes HTM cell adhesion. These findings underscore the contribution of NEDD9 overexpression to altered HTM cell adhesion during glucocorticoid therapy and may play a key role in GIG pathological progression. Considering the similarity between GIG and primary open-angle glaucoma (POAG), our findings suggest that targeting NEDD9 may be a new therapeutic strategy for POAG patients.

Pulsatile Trabecular Meshwork Motion: An Indicator of Intraocular Pressure Control in Primary Open-Angle Glaucoma.

(1) Background: To investigate the value of pulsatile trabecular meshwork (TM) motion in predicting the diurnal intraocular pressure (IOP) fluctuation of primary open-angle glaucoma (POAG). (2) Methods: This cross-sectional study recruited 20 normal patients and 30 patients with POAG. Of the POAG group, 20 had stable diurnal IOP and 10 had high IOP fluctuation. A clinical prototype phase-sensitive optical coherence tomography (PhS-OCT) model was used to measure TM pulsatile motion with maximum velocity (MV) and cumulative displacement (CDisp). (3) Results: MV and CDisp were higher in the external region in both normal and POAG patients. All MV and CDisp reduced significantly in the POAG group (p < 0.001). In the POAG group, except MV in the external region (p = 0.085), MV and CDisp in the nasal area were significantly higher than those in the temporal area (p < 0.05). The MV and CDisp in the external region in the nasal area of POAG patients with high IOP fluctuation were much lower than those with stable IOP (pEMV3 = 0.031, pECDisp3 < 0.001); (4) Conclusions: Pulsatile TM motion reduced in POAG patients relevant to the level of diurnal IOP fluctuation. This study presents the segmental variance of TM stiffness in human living eyes and suggests the clinical potential of the measurement of pulsatile TM motion with PhS-OCT for the evaluation of diurnal IOP fluctuation.

Ex-PRESS® surgery versus trabeculectomy for primary open-angle glaucoma with low preoperative intraocular pressure.

To compare surgical outcomes between Ex-PRESS® surgery (EXP) and trabeculectomy (Trab) for primary open-angle glaucoma (POAG) with low preoperative intraocular pressure (IOP). This was a retrospective non-randomized study. We included POAG patients with preoperative IOP ≤ 16mmHg who were taking tolerance glaucoma medications. We compared the surgical outcomes, postoperative IOP, number of glaucoma medications, reduction rate of corneal endothelial cell density (ECD), visual acuity, and postoperative complications between POAG patients who underwent EXP (34 eyes) or Trab (38 eyes) and could be followed up for > 2years. Both surgeries significantly decreased the IOP (p < 0.001): At 2years, EXP provided decreases from 13.4 ± 2.3 to 10.2 ± 3.1mmHg, and Trab provided decreases from 13.5 ± 2.0 to 8.9 ± 3.2mmHg. No significant differences were observed in the postoperative IOP (p = 0.076), number of postoperative medications (p = 0.263), success rate (p = 0.900), reduction rate of ECD (p = 0.410), or difference in visual acuity (p = 0.174). The reduction rate of IOP was significantly high in the Trab group (p = 0.047). Both surgeries significantly decreased IOP and were useful surgical methods for low-IOP glaucoma. Our results suggest that trabeculectomy can decrease IOP more than Ex-PRESS surgery but might have more complications.

Rates of Choroidal Microvasculature Dropout and Retinal Nerve Fiber Layer Changes in Glaucoma

To evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes. Cohort study from clinical trial data. A total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning. MvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P=.008 and P=.009, respectively). Rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

Modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma: a prospective study with 12-month follow-up

BackgroundTo evaluate the efficacy and safety of modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma (POAG).MethodsA prospective, consecutive cases study, evaluating a modified canaloplasty by twisted 6/0 suture was performed on Asian POAG patients. Three modifications of this canaloplasty included opening the Schlemm’s canal by viscocanalostomy, circumferential probing by a twisted 6/0 suture and loose suture of the superficial scleral flap. The twisted 6/0 suture was selected as a prober based on characteristical analysis of size and contact measurement as well as chemical composition conducted among 5/0, twisted 6/0 polypropylene sutures and the microcatheter. Success criteria were defined as intraocular pressure (IOP) ≤ 21 mmHg, 18 mmHg, 15 mmHg, and ≥ 20% reduction without (complete success) or with medications (qualified success). Efficacy was assessed by the success rate of circumferential catheterization, IOP values, the success rate of the surgery, the number of IOP-lowering medications, best-corrected vision acuity (BCVA), cup-to-disc ratio (C/D), and mean deviation (MD). Safety was evaluated by adverse events.ResultsForty eyes from 40 consecutive patients were included with a mean follow-up of 14.8 ± 3.0 months. Circumferential catheterization was successfully conducted in 36 eyes (90%). Mean IOP decreased from 26.2 ± 6.9 mmHg to 14.5 ± 2.7 mmHg at 12 months postoperatively. While medication numbers were reduced from 3.2 ± 0.6 to 0.5 ± 0.8 at month 12 (both p < 0.001). Qualified success rate was 97.2% [95% confidence interval (CI) 0.92–1.03], 86.1% (95% CI 0.74–0.98) and 66.7% (95% CI 0.51–0.83) at 12 months with three criteria. BCVA, C/D and MD did not show progression at 1-year follow-up (p > 0.05). Age, baseline IOP, and spherical equivalent negatively influenced the success rate significantly (all p < 0.05). Adverse events included hyphema (30.6%), IOP spike > 25 mmHg (8.3%), and peripheral synechia to the trabecular-Descemet’s membrane (2.7%).ConclusionTwisted 6/0 suture can be an ideal material for cannulation. Modified suture-assisted canaloplasty is an effective, safe alternative with a cost-efficient feature for patients with POAG, especially in developing countries.Trial registrationThis trial was registered in the Chinese Clinical Trial Registry (ChiCTR1900028618, 29/12/2019).

The Effect of Autonomic Nervous System Dysfunction on the Progression of Primary Open-Angle Glaucoma.

PurposeTo study the effect of autonomic nervous system (ANS) dysfunction on glaucoma progression in patients with primary open angle glaucoma (POAG).Patients and MethodsA retrospective study of 40 cases of POAG patients who underwent regular reexamination for more than 3 years was performed. All participants were subjected to heart-rate variability (HRV) assessment. Patients were divided equally into the lowest and highest HRV groups according to the standard deviation value of the qualified normal to normal intervals (SDNN), a representative indicator of HRV. The lower the HRV, the more severe the ANS dysfunction with sympathetic predominance. Visual field (VF) parameters and retinal nerve fiber layer (RNFL) thickness were used to evaluate and compare the progression of glaucoma damage between the two groups.ResultsThere were 20 cases in the lowest HRV group and 20 cases in the highest HRV group. The thinning rate of RNFL in the lowest HRV group was significantly faster than that in the highest HRV group (1.44±1.58 vs 0.29±0.56 μm/year, P=0.00), accompanied by greater fluctuation of intraocular pressure (IOP) (P=0.04), lower diastolic blood pressure (P=0.01), mean blood pressure (P=0.04), and lower mean ocular perfusion pressure (P=0.04). Meanwhile, the incidence of central VF defects in the lowest HRV group was significantly higher than that in the highest HRV group (65.0% vs 30%, P=0.03). Linear regression analysis showed that there was a significant correlation between SDNN and the thickness loss rate of RNFL (P=0.01).ConclusionPOAG patients with lower HRV, which reflects ANS dysfunction with sympathetic predominance, presented faster glaucoma progression than patients with higher HRV. The more rapid progression of POAG with lower HRV may be explained by IOP and vascular risk factors.

Identification of the potential biological target molecules related to primary open-angle glaucoma

BackgroundTo identify the potential biological target molecules and the corresponding interaction networks in primary open-angle glaucoma (POAG) development.MethodsThe microarray datasets of GSE138125 and GSE27276 concerning lncRNA and mRNA expression profiles in trabecular meshwork of POAG were downloaded from the Gene Expression Omnibus database. The R software was applied to identify differentially expressed (DE) lncRNAs and mRNAs in POAG, and to perform GO and KEGG functional enrichment analysis. Protein–protein interaction (PPI) network and module analysis, and lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network were performed by Cytoscape software.ResultsA total of 567 DE-mRNAs were identified from GSE138125 and GSE27276, including 298 up-regulated and 269 down-regulated mRNAs, which were found enriching in biological processes of extracellular matrix organization and epidermis development, respectively. KEGG pathway enrichment analysis further revealed that module genes in PPI network were primarily involved in the AGE-PAGE, PI3K-Akt and TGF-β signaling pathways. Moreover, 897 up-regulated and 1036 down-regulated DE-lncRNAs were identified from GSE138125. Through literature review and databases searching, we obtained 712 lncRNA-miRNA and 337 miRNA-mRNA pairs based on the selected eight POAG-related miRNAs. After excluding 702 lncRNAs and 284 mRNAs that were not comprised in the DE-lncRNA and DE-mRNAs, a total of 53 lncRNA nodes, eight miRNA nodes, 10 mRNA nodes, and 78 edges were included in the final ceRNA network.ConclusionsThis study demonstrated the lncRNA and mRNA expression profiles of trabecular meshwork in POAG patients and the normal controls, and identified potentially ceRNAs and pathways which might improve the pathogenic understanding of this ocular disease.

Estimated intracranial pressure in glaucoma patients and its correlation with disease severity

Purpose To compare the intracranial pressure (ICP) and the translaminar pressure difference (TLPD) between primary open-angle glaucoma (POAG) patients and non-glaucoma subjects and to assess the correlation between the ICP (and TLPD) and glaucoma severity. Methods This was a cross-sectional study. Patients with POAG and age-matched controls were included. ICP was calculated using proxy algorithm to attain indirect surrogate parameter values. Differences were compared between groups. The correlation between ICP (and TLPD) and both structural and functional variables was evaluated using linear and non-linear regression analysis and estimated with Pearson’s correlation coefficient. Results Fifty patients with POAG and 25 normal controls were included. The mean estimated ICP was lower in POAG (10.9 ± 3.2 mmHg) as compared to controls (15.0 ± 3.7 mmHg, p < 0.001). The TLPD was higher in POAG (2.6 ± 4.1 mmHg) when compared to non-glaucoma (−0.3 ± 3.6 mmHg, p = 0.002). ICP displayed a negative correlation with cup-to-disk ratio (r = −0.566; 95% CI, −0.699 to −0.369, p’0.000) and a positive correlation with retinal nerve fiber layer thickness (r = 0.441; 95% CI, 0.230 to 0.612; p’0.000). There was a positive correlation between ICP and mean deviation (r = 0.280; 95% CI, 0.05 to 0.482, p = 0.017). Conclusion Glaucoma patients presented lower ICP values; lower ICP values were associated with more advanced disease. These observations strengthen the role of ICP as a potential player on the glaucoma pathogeny.

Effect of Mydriatic Administration on Retinal Hemodynamics in Glaucoma: An Optical Coherence Tomography Angiography Study.

Pupillary dilation with 0.5% tropicamide and 2.5% phenylephrine resulted in a statistically significant decrease in foveal avascular zone (FAZ) metrics in glaucoma eyes. This observation emphasizes the critical role of pupillary status in interpreting glaucomatous vascular alterations detected by optical coherence tomography angiography (OCTA). The purpose of this study was to evaluate the influence of mydriatic eye drops on OCTA parameters in patients with primary open angle glaucoma (POAG). A total of 20 POAG eyes and 20 control eyes were recruited in the study. The imaging area on the fundus was visualized by AngioPlex (Cirrus 5000 HD-OCT) using en face view of 3×3 mm and 6×6 mm preview scans. Images were generated before and after the instillation of topical 0.5% tropicamide and 2.5% phenylephrine. Optic nerve head (ONH) perfusion, ONH flux index, macular perfusion density, macular vessel density, and FAZ measurements were consecutively obtained for each session. Differences between the predilation and postdilation measurements were evaluated in POAG patients and controls. POAG eyes showed a statistically significant decrease in the FAZ area from a mean of 0.29-0.25 mm 2 ( P =0.037) and FAZ perimeter from a mean of 2.27-2.09 mm ( P =0.045) in the OCTA 6×6 mm scan area after tropicamide/phenylephrine instillation. Predilation and postdilation measurements of ONH perfusion and ONH flux index were significantly lower in the glaucoma group compared with controls ( P <0.05, for all). Topical pupillary dilation with 0.5% tropicamide and 2.5% phenylephrine results in a statistically significant reduction in the FAZ area and FAZ perimeter in POAG eyes. Further OCTA studies are needed for the diagnostic value of vascular changes due to pupil dilation in glaucoma.

Two-Year Follow-up of MicroPulse Transscleral Laser Therapy in Patients with Primary Open-Angle Glaucoma.

To determine the long-term efficacy and safety of MicroPulse transscleral laser therapy (TLT) over a 24-month period in patients with primary open angle glaucoma. This prospective interventional case series evaluated data from 44 medically treated eyes of primary open angle glaucoma (POAG) patients who received MicroPulse TLT to achieve further reduction in IOP. The reduction in 24-hr mean diurnal intraocular pressure (IOP), diurnal IOP fluctuations, and peak IOP were monitored after 3, 12, and 24 months. Postoperative complications, failure rates, and factors influencing IOP reduction were also evaluated. IOP decreased from 16.1 ± 3.4 mmHg preoperatively to 13.0 ± 2.9 mmHg (n = 31; p < 0.001), 12.3 ± 3.0 mmHg (n = 27; p < 0.001), and 13.1 ± 2.6 mmHg (n = 23; p < 0.001) at the 3-month, 12-month and 24-month follow-ups. At 24months, 23 eyes (52%) had a sufficient IOP reduction to reach the individual target pressure. No severe complications were observed. No parameters could be identified that correlated with successful IOP reduction after treatment. The highest failure rate was observed during the first 3 months and remained stable thereafter. For about 50% of POAG eyes receiving the maximum tolerated treatment, MicroPulse TLT proved an effective method of further lowering IOP so as to reach the individual target pressure.

Posture-induced intraocular pressure changes among patients with primary open angle glaucoma in a Nigerian Tertiary Hospital: Any implication for management.

To determine the effect of postural changes on intraocular pressure (IOP) among newly diagnosed patients with primary open-angle glaucoma (POAG). This was a cross-sectional observational study of 55 consecutive newly diagnosed patients with POAG attending Glaucoma clinics at a Federal Teaching Hospital in Abakaliki, Ebonyi state, from July to September 2017. Patients IOPs were measured in the sitting position, supine without a pillow, and supine with pillow positions using Perkin's handheld applanation tonometer. All data were analyzed with SPSS version 20.0. A total of 55 subjects were recruited comprising 30 (54.5%) males and 25 (45.5%) females, with a mean age of 50.13 ± 9.97 years and an age range of 30-79 years. The mean intraocular pressure was 27.54 ± 3.98 mmHg in the sitting position, 30.15 ± 4.41 mmHg in the supine with pillow position, and 35.22 ± 4.61 mmHg in the supine without pillow position. The mean difference of mean IOP of sitting compared to supine without the pillow was 7.68 ± 2.08 mmHg (P-value < 0.001, 95% CI: 7.12-8.24); sitting compared to supine with the pillow was 2.61 ± 1.49 mmHg (P-value < 0.001, 95% CI: 3.01-2.21), whereas supine without the pillow compared to supine with the pillow was 5.07 ± 2.24 mmHg (P-value 0.001, 95% CI: 4.47-5.68). IOP was lowest in the sitting position and highest in the supine without pillow position. There was a statistically significant reduction in IOP on the assumption of supine with pillow position compared to supine without pillow position. The use of thick pillows in supine positions (such as during sleep or relaxations) rather than lying supine without pillows may reduce IOP spikes in POAG patients. This may have a positive effect as regards treatment and progression of glaucoma.

A New and Easier Approach to Preserflo MicroShunt Implantation.

PRESERFLO™ MicroShunt is a new minimally invasive glaucoma surgical (MIGS) device, implanted with an ab externo approach, which drains the aqueous humor to the subconjunctival space. It has been designed as a safer and less invasive approach for treating medically uncontrolled primary open-angle glaucoma (POAG) patients. The classic way of MicroShunt implantation involves different key steps, which includes creating a small scleral pocket with a 1mm blade; passing a 25-gauge (25G) needle through the scleral pocket into the anterior chamber (AC); and subsequently flushing the stent with a 23-gauge (23G) thin-wall cannula. However, sliding the needle into the scleral pocket can create false passages, thus making the device’s threading more difficult. The purpose of the current paper is to propose a simplified implantation approach. Our method proposes to make the scleral tunnel by using directly the 25G needle and, at the limbus, this 25G needle is used to slightly depress the sclera and enter into the AC. The MicroShunt is subsequently assembled on a 23G cannula mounted on a 1mL syringe. The syringe can then be used to flush the device. Outflow can thus be confirmed immediately by seeing drops of aqueous humor leaking from the external opening of the stent. This new approach may have different potential advantages, such as better control of the site of entry, avoids wrong passages, reduces or eliminates the risk of aqueous humor sideway flow, facilitates a parallel path to the iris plane, and it is faster.

Comparison of early-stage SD-OCT findings in patients with primer open angle glaucoma and Parkinson’s disease

AIM: To provide an insight to the common pathophysiology of both most frequent and neurodegenerative diseases by comparing thickness parameters of macula and retinal nerve fiber layer (RNFL) by using spectral-domain optical coherence tomography (SD-OCT) in patients with early stage of Parkinson’s disease (PD), and early stage of primary open angle glaucoma (POAG). METHODS: A retrospective review was conducted of 48 patients with an early stage of POAG, 34 patients with an early stage of PD and 37 age- and gender-matched healthy eyes as a control group. The RNFL and macular thicknesses in the nine macular quadrants according to the ETDRS were measured with an SD-OCT and Mean Deviation (MD) values by a visual field analyzer. POAG patients were selected only MD smaller than -6 dB. Patients with MD values below -6 dB were considered as early-stage glaucoma. PD severity was assessed using Hoehn and Yahr (H&amp;Y) and Unified Parkinson’s Disease Rating Scale (UPDRS). The PD group selected only H&amp;Y Stage I-III patients. RESULTS: Statistically significant difference was determined between all groups RNFL measurements except temporal RNFL (P&lt;0.05). Statistically significant difference was determined between all groups including fovea, mean macula thickness and macula outer quadrant thickness evaluations (P&lt;0.05). There was not any significant difference between thickness evaluation of macula inner quadrant for POAG and PD groups (P&gt;0.05). A weak negative correlation was determined between duration of disease and UPDRS score together with macula and RNFL thickness parameters in PD group. CONCLUSION: Similar thinning was detected by using SD-OCT for thickness parameters of macula and RNFL in early stage of POAG and early stage of PD group. However this thinning was more significant in early stage of POAG group. It can be declared that neurodegeneration on the macula which is caused by glaucoma is more destructive than PD. Thinning on foveal region is remarkable for PD patients.

Some anatomical parameters of the eyes of patients with different stages of glaucoma

Purpose: to study the morphological structures of the eyes of patients with primary open-angle glaucoma (POAG) and to identify the changes characteristic of this disease.Material and methods. We examined 90 patients with various stages of POAG and compensated ophthalmic tonus and 50 patients without glaucoma with ophthalmic pathology not associated with eye hydrodynamic disorders (control group), aged 40 to 81 years and older. In addition to the standard ophthalmological examination, all patients were examined for the curvature of the anterior surface of the cornea and its thickness, the depth of the anterior chamber and the thickness of the lens, the length of the eye axis, the thickness of the retinal nerve fiber layer (RNFL) and the condition of the optic nerve head (ONH), using ophthalmometry, keratotopography, anterior segment analyzer (Pentacam, OCULUS, USA), ultrasound biometry (UD-6000 Tomey, Japan), and optical coherence tomography (OCT).Results. No significant differences in the parameters of ultrasound biometry and pachymetry were revealed between the control group and POAG patients. The only types of data characterizing the glaucoma process were altered parameters of the optic disc and the peripapillary zone of the retina, namely, the thickness of the RNFL. In 81.1 % of glaucoma eyes, temporal excavation was detected, the average RNFL thickness in the temporal segment of the ONH was 44.2 ± 3.0 μm.Conclusion. Ophthalmoscopy and OCT of the ONH and RNFL are the main diagnostic methods that allow obtaining indisputable data on the morphological changes characteristic of POAG. These studies should become mandatory in the diagnosis of glaucoma and monitoring of patients with POAG..

Effect of oral citicoline therapy on retinal nerve fiber layer and ganglion cell-inner plexiform layer in patients with primary open angle glaucoma

To evaluate the short-term effects of oral citicoline therapy on the retinal nerve fiber layer (RNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) in patients with primary open angle glaucoma (POAG). Fifty-four eyes of 54 patients with POAG glaucoma included in the study. In addition to a topical hypotensive, 250-mg oral citicoline was administered to 27 patients, while 27 patients were assigned as the control group. RNFL and mGCIPL values were measured using optical coherence tomography (OCT) at 1d before treatment and 3mo after the initiation of treatment. At the third month visit, citicoline treatment was discontinued and drug-free control (wash-out) measurements were obtained at the fourth month in citicoline group. The average RNFL thickness was significantly higher at month 3 than the baseline (P=0.038) in citicoline group. However, this improvement partially regressed after a 1-month wash-out period. No statistically significant changes in RNFL were observed in the superior, nasal, temporal and inferior quadrants at months 3 and 4 (P>0.05). The change in the average and inferior quadrant RNFL thickness in the citicoline group at 3mo was significantly greater than the control group (P=0.006 and P=0.014, respectively). There were no significant differences between the groups according to the change in mGCIPL thickness and the superior, nasal and temporal quadrant RNFL thickness (P>0.05). With oral citicoline treatment, the loss in the average RNFL is prevented in POAG patients in the short-term. Study data show that citicoline may have a significant impact on slowing glaucoma progression, which could have a potential neuroprotective effect.

Aqueous Humour Malondialdehyde Level as Oxidative Stress Marker In Types Of Glaucoma

Background: Angle-closure glaucoma is the most common type of glaucoma in Asia, leading worse damage due to its oxidative stress. Another type is open angle glaucoma in second line. The oxidative stress level can be known by malondialdehyde level examination. The study about MDA levels in aqueous humour in primary angle-closure and open angel glaucoma has not been done before.Objective: To determine the difference of malondialdehyde levels in aqueous humour between primary open-angle glaucoma and primary angle-closure glaucoma.Methods: This study was an analytical observational study. Nine subjects were primary open-angle glaucoma patients and ten subjects were primary angle-closure glaucoma patients. The aqueous humour was aspirated from the anterior chamber during trabeculectomy and measured the MDA levels using a spectrophotometer. Data were analyzed by Mann Whitney test.Results: There was no significant difference (p=0.095) of MDA levels in aqueous humour between primary open-angle glaucoma (62.913±17.259 ?mol/L) and primary angle-closure glaucoma (53.485±9.670 ?mol/L).Conclusion: The oxidative stress level in primary open-angle glaucoma and primary angle-closure glaucoma are the same, indicate that inflammation status of both condition have been similar.

Biomarkers for primary open-angle glaucoma progression

Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia.

The aim of this study was to investigate the role of functionally significant loci of the matrix metalloproteinases genes 1, 3, 9 (MMP1, MMP3, and MMP9) in the development of primary open-angle glaucoma (POAG) in Caucasians of the Central region of Russia. In total 604 participants were recruited for the study, including 208 patients with POAG and 396 healthy controls. They were genotyped at eight single nucleotide polymorphisms (SNPs) of the three MMP genes. The association was analyzed using logistic and log-linear regression. POAG-associated loci and their proxies were in silico assessed for their functional prediction. Variant allele G*rs2250889 of MMP9 was significantly associated with higher risk of POAG (ORcov = 1.57-1.71). Haplotype CCA [rs3918242-rs3918249-rs17576] of the MMP9 gene was associated with lower risk of POAG (ORcov = 0.33). Allele А*rs3787268 of MMP9 was associated with the low intraocular pressure in the POAG patients (βcov = -0.176 - -0.272), and so were haplotypes AA [rs17576-rs3787268] (βcov = -0.577) and AAC [rs17576-rs3787268- rs2250889] (βcov = -0.742) of the same gene, whereas allele 2G*rs1799750 of MMP1 was associated with the earlier onset of the disease (βcov = -0.112 - -0.218). In silico analysis of the polymorphisms suggested the functionality of POAG-associated SNPs and their proxies (epigenetic potential, expression and alternative splicing effects for several genes). The MMP9 gene polymorphisms are associated with POAG and intraocular pressure in POAG patients; rs1799750 of MMP1 was associated with the earlier age of manifestation of the disease symptoms.

Myocilin Mutations in a Zambian Population Attending Selected Referral Eye Health Facilities

Purpose: Research has shown that primary open-angle glaucoma (POAG) in Zambia has an earlier age of onset and is more clinically severe than in Europe and the United States of America. Mutations of Myocilin have been reported to be associated with POAG in multiple populations. We therefore, investigated the role of myocilin gene mutations in Primary Open Angle Glaucoma in a Zambian population. Methods: The unrelated POAG patients and unaffected controls seen at the University Teaching Hospitals Eye Hospital, Kitwe Teaching Eye Hospital and Lusaka Eye Hospital were recruited for this study. Glaucoma specialists from the participating institutions ascertained all POAG and control patients. Age, sex and ethnicity matched unaffected controls were obtained in patients with an IOP &lt; 22 mm Hg, clear ocular media and normal-appearing optic nerve heads. A complete eye examination, including visual field assessment, was performed in all cases. Genomic DNA was extracted from whole peripheral blood, then subjected to polymerase chain reaction to amplify exons, flanking introns and promoter regions of the myocilin gene. The amplified products were screened for base mutations by autosequence based on the Sanger method. The study used the chi square test and conditional logistic regression to compare the cases and controls. Identified mutations were compared to known myocilin mutations. Results: Unrelated 165 POAG patients and unaffected 173 controls enrolled for the study. The analysis revealed four variants of myocilin mutations in 49 participants which included one synonymous (silent) mutation (Thr474Thr; 45/338) and three missense mutations (Ala446Thr; 16/338), (Leu158Arg; 4/338) and (Arg342Lys; 1/338). The prevalence of myocilin (MYOC) gene mutations in this study was 14.5% (49/338). The study observed two previously reported mutations, Ala446Thr and Arg342Lys, as glaucoma causing mutations. The variant (Lys158Arg) observed in the study was a novel finding. These mutations were detected in age, sex and ethnically matched controls. The missense mutation, Ala446Thr, was found in eight cases and eight controls. Twenty (20) controls and 25 cases had the synonymous or silent (neutral) mutation, (Thr474Thr). Conclusions: The myocilin mutations represent a prevalence of 14.5 in a Zambian population. The Leu158Arg seems to represent novel glaucoma, causing missense mutation. Mutations in myocilin appear to play a big role in the pathogenesis of POAG in a Zambian population.

Role of vasorin, an anti-apoptotic, anti-TGF-β and hypoxia-induced glycoprotein in the trabecular meshwork cellsand glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open‐angle glaucoma patients compared to non‐glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti‐apoptotic and anti‐TGF‐β activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF‐β2‐induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride‐induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF‐α‐induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF‐β induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.