The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

OBJECTIVE: To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. METHODS: This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. RESULTS: This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. CONCLUSIONS: Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

Association between plasma free fatty acid levels and primary angle-closure glaucoma based on a mass spectrometry metabolomics analysis.

PURPOSE: To determine the association between plasma free fatty acid (FFA) levels and primary angle-closure glaucoma (PACG). METHODS: Free fatty acid (FFA) levels in patients with PACG (n = 181) and people without glaucoma (n = 340) were compared. Twenty-two FFAs and six lipid classes were measured using metabolomics analysis. Odds ratio (OR) of these metabolites and their 95% confidence intervals (95%CI) for PACG were obtained by logistic regression. Stepwise forward selection was performed to identify FFAs that influenced PACG risk. Areas under the curve (AUC) were applied to assess the predictive performance. Spearman's rank correlation was used to assess the relationship between ocular parameters and FFAs. RESULTS: Most FFAs in the PACG group were lower than those in the non-glaucoma group. Docosahexaenoic acid (DHA; OR for fourth quartile (Q4) vs. first quartile (Q1): 0.32 (0.16-0.66); per standard deviation (SD) increase: 0.64 (0.49-0.83); p for trend: 0.0007) and total saturated fatty acids (SFAs; OR for Q4 versus Q1: 0.27 (0.13-0.56); per SD increase: 0.65 (0.50-0.87); p for trend: 0.0004) were associated with decreased PACG risk. The AUC of the model that included DHA, total SFAs, demographic and ophthalmic factors increased from 0.8230 (0.7811-0.8649) to 0.8512 (0.8133-0.8891) (increased AUC: 0.0282 (0.0112-0.0453); p for increased AUC: 0.0012). Additionally, the cup-disc ratio had a weak negative correlation with DHA and total SFAs (DHA: r = -0.12085, p = 0.0065; total SFAs: r = -0.13318, p = 0.0024). CONCLUSIONS: Decrease in FFA levels may be related to lipid peroxidation. Docosahexaenoic acid (DHA) and total SFAs may be screening indices for PACG patients.

Relationship between Oxidative Stress Biomarkers and Visual Field Progression in Patients with Primary Angle Closure Glaucoma.

PURPOSE: To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG). METHODS: A case-control and a prospective cohort study. A total of 94 patients with PACG and 89 normal controls were enrolled. Furthermore, 94 PACG subjects were followed up for at least two years (once every six months). All participants were evaluated for serum levels of superoxide dismutase (SOD), total antioxidant status (TAS), hydrogen peroxide (H2O2), malondialdehyde (MDA), glutathione peroxidase, glutathione reductase, and detailed eye and systematic examination. Binary logistic regression analysis and Cox regression analysis were performed. RESULTS: The serum levels of SOD and TAS in the PACG group were significantly lower than those in the control group (p < 0.001). Meanwhile, PACG subjects had significantly higher levels of MDA and H2O2 than the normal control subjects (p < 0.001). Serum levels of TAS (OR = 0.773, 95%CI = 0.349 - 0.714, p < 0.001), SOD (OR = 0.975, 95%CI = 0.955 - 0.995, p < 0.001), MDA (OR = 1.155, 95%CI = 1.080 - 1.235, p < 0.001), and H2O2 (OR = 1.216, 95%CI = 1.142 - 1.295, p < 0.001) were independent risk/protective factors for PACG. TAS levels (HR = 0.041, 95%CI = 0.008-0.218, p < 0.001), SOD levels (HR = 0.983, 95%CI = 0.971-0.994, p = 0.003), and MDA levels (HR = 1.010, 95%CI = 1.001-1.018, p = 0.015) at baseline were associated with visual field progression. Kaplan-Meier curves reveal that patients with TAS < 0.95/SOD < 143/MDA > 12 had a significantly higher percentage of PACG progression (p < 0.05). CONCLUSIONS: Decreased levels of TAS and SOD as well as increased levels of MDA at baseline were associated with VF progression in patients with PACG. These findings suggest that oxidative stress was involved in the onset and development of PACG.

Association Between 17-ß-Estradiol and Interleukin-8 and Visual Field Progression in Postmenopausal Women with Primary Angle Closure Glaucoma.

PURPOSE: To investigate an association between sex hormones and inflammatory cytokines, and to determine whether baseline 17-ß-estradiol (E2) and interleukin-8 (IL-8) are associated with visual field (VF) progression in postmenopausal women with primary angle closure glaucoma (PACG). DESIGN: A prospective cross-sectional and cohort study. PARTICIPANTS: The cross-sectional study enrolled 200 postmenopausal women with PACG and 151 healthy postmenopausal women as normal control subjects. A total of 105 postmenopausal women with PACG were included and followed up for ≥2 years in the cohort study. METHODS: All participants were evaluated for levels of baseline sex hormones (follicle-stimulating hormone, prolactin, progesterone, testosterone, luteinizing hormone, and E2) and inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, and C-reactive protein) and underwent VF examinations. The cross-sectional study was conducted to establish risk factors for postmenopausal women with PACG using logistic regression analysis. The cohort study was designed to identify factors that could be used to predict VF progression in postmenopausal women with PACG using multivariate Cox regression analyses. The main outcome measures included factors associated with VF progression over time. RESULTS: Decreased E2 (odds ratio 0.88 [95% confidence interval {CI} 0.78-0.99], P = .007) and increased IL-8 (odds ratio 1.12 [95% CI 1.01-1.23], P < .001) levels were risk factors in postmenopausal women with PACG. A significant negative correlation was observed between IL-8 levels and E2 (r = -0.21, P = .02). Multivariable regression analyses revealed a significant correlation between E2 levels and visual field mean deviation (MD) (B = -0.16, P = .04 [95% CI -.09 to -.003) and between IL-8 levels and MD (B = 0.36, P < .001 [95% CI 0.01-0.02]). During follow-up, 48 (45.71%) patients showed VF progression. Lower baseline E2 (hazard ratio 0.85 [95% CI 0.82-0.88], P = .04) and higher baseline IL-8 levels (hazard ratio 1.01 [95% CI 1.00-1.02], P = .004) were associated with progression of glaucoma. Patients with lower E2 levels had a significantly higher rate of PACG progression (log-rank test P < .001), similar to those with higher IL-8 levels (log-rank test P = .04). CONCLUSIONS: Decreased E2 and increased IL-8 levels at baseline are significant predictors of VF progression in postmenopausal women with PACG.

Peroxynitrite is a novel risk factor and treatment target of glaucoma.

To investigate the association between systemic nitrotyrosine (NT) levels and primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and the mechanism involved. A case control study was conducted in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University from April 2017 to December 2017. A total of 400 participants were consecutively recruited into this study (100 PACG, 100 POAG and 200 controls). Multivariable logistic regression analysis was performed to identify the association between serum NT level and PACG or POAG. Clinical results were validated in cell and animal models. Among 200 glaucoma patients, 101 (50.5%) were women; the age was 57.07 ± 14.51 years. 106 (53%) control participants were women and age was 58.34 ± 14.04 years. Serum levels of NT in PACG and POAG patients are significantly higher than controls (1808.53 ± 417.76 nmol/L vs. 1270.62 ± 454.60 nmol/L, p < 0.001; 1718.63 ± 437.29 nmol/L vs. 1258.38 ± 460.72 nmol/L, p < 0.001). Further, elevated serum NT level increases the risk of developing PACG (OR = 1.003, 95% CI: 1.002 to 1.004, p < 0.001) and POAG (OR = 1.002, 95% CI: 1.002 to 1.003, p < 0.001). Consistent with the clinical data, serum and aqueous humour NT levels are significantly higher in caveolin 1 knockout (Cav1 KO) mice, an animal model of glaucoma. More importantly, peroxynitrite (PN) scavenger MnTMPyP and its transduction molecule PARP inhibitor significantly reduce intraocular pressure in Cav1 KO mice. Our data show for the first time that NT is a systemic risk factor and local treatment target of glaucoma.

Role of matrix metalloproteinase-9 gene polymorphisms in glaucoma: A hospital-based study in Chinese patients.

BACKGROUND: Glaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase-9 (MMP-9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP-9 levels and various functional variants of MMP-9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP-9 common variants with different clinical categories of glaucoma in Chinese population. MATERIALS AND METHODS: We enrolled total of 396 glaucoma patients those reported to hospital comprising of 212 primary angle closure glaucoma (PACG) cases and 184 primary open-angle glaucoma POAG patients. In addition, 329 normal individuals from similar geographical areas were enrolled as healthy controls. Five common single nucleotide polymorphisms (rs3918242, rs3918254, rs2250889, rs3918249, and rs17576) were genotyped by PCR-RFLP. Plasma levels of MMP-9 were quantified by ELISA. RESULTS: Heterozygotes (GC) and allele "G" for rs2250889 polymorphism were more frequent in PACG cases compared with healthy controls (GC: P < .0001, OR = 2.26; G: P < .0001, OR = 1.19). Similarly, heterozygous mutant and minor allele for rs3918242 polymorphism were more prevalent in POAG in comparison with healthy controls. Interestingly, distribution of rs17576 variant was statistically higher in both PACG and POAG cases than healthy controls. Furthermore, analysis of plasma MMP-9 with MMP-9 polymorphisms revealed significant association of rs2250889, rs3918242, and rs17576 with plasma levels of the protein. CONCLUSIONS: MMP-9 mutants are associated with elevated plasma MMP-9 and predisposed to development of glaucoma.

Imbalance of Matrix Metalloproteinases and Their Inhibitors Is Correlated With Trabeculectomy Outcomes in Acute Primary Angle Closure.

PURPOSE: To analyze matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and their molar ratios in the aqueous humor in previous acute primary angle closure (APAC) patients and their correlations with trabeculectomy outcomes. DESIGN: Prospective cohort study. METHODS: Aqueous humor samples were collected from a total of 78 eyes, including 52 previous APAC eyes and 26 cataract eyes. TIMP-1, 2, 3, and 4 and MMP-1, 2, 3, 7, 8, 9, 12, and 13 analyte concentrations were measured using multiplexed immunoassay kits. Patient follow-up occurred at 1 week and 1, 3, 6, 12, and 18 months. RESULTS: In the previous APAC group, 11 MMP/TIMP molar ratios were significantly lower. APAC eyes were then followed for up to 18 months after trabeculectomy and divided into success (37 eyes) and failure (15 eyes) groups. Five out of the 11 molar ratios were significantly lower in the failure group than in the success group. In multiple logistic regression analysis, failed filtration surgery was more likely in APAC eyes with lower MMP-2/TIMP-2 (P = .040, odds ratio = 44.499) and MMP-13/TIMP-1 (P = .034, odds ratio = 37.947) ratios. Previous APAC eyes were divided according to MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios. Compared to eyes with high ratios, eyes with low MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios had significantly higher failure rates. CONCLUSIONS: In previous APAC eyes, changes in MMP and TIMP levels resulted in MMP and TIMP imbalance. Lower MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios in aqueous humor are risk factors for trabeculectomy failure. Modulating specific MMP/TIMP ratios may have potential clinical applications for filtration surgery.

Association between Pretreatment Serum Uric Acid Levels and Progression of Newly Diagnosed Primary Angle-Closure Glaucoma: A Prospective Cohort Study.

PURPOSE: Increased evidence reveals that uric acid (UA) may have an important neuroprotective effect through its antioxidant properties. The aim of the present study was to investigate the relationship between pretreatment serum UA levels and the progression of newly diagnosed primary angle-closure glaucoma (PACG). METHODS: This prospective observational cohort study included 64 patients with newly diagnosed PACG who were followed up for a mean period of 12.77 months (range: 3-28 months). All subjects underwent a complete ophthalmological examination during the baseline and final follow-up visits, together with the acquisition of blood samples for UA measurements. During the follow-up period, the progression of PACG was defined as a clinical diagnosis of medically uncontrolled intraocular pressure and a loss of visual field with a mean deviation of >1 dB/year. Univariable and multivariable Cox regression models were used to investigate the association between baseline serum UA levels and the progression of PACG. The cumulative probability of progression of glaucoma was analyzed using the Kaplan-Meier method. RESULTS: During follow-up, 32 subjects were defined as progressive PACG, among whom baseline UA values were significantly higher in nonprogressing subjects than in progressing subjects (0.314 ± 0.069 mmol/l versus [vs.] 0.258 ± 0.069 mmol/l, respectively; P = 0.002). Similar results were also observed in male and female subgroups (P < 0.05). In a multivariable model, a decreased baseline serum UA level was associated with an increased risk for progressing PACG: both in male (hazard ratio [HR] 6.088 [95% confidence interval (CI) 1.163-31.8638]; P = 0.032) and female subjects (HR 3.565 [95% CI 1.131-11.236]; P = 0.030). Subjects with high UA levels demonstrated higher cumulative probabilities of nonprogressing PACG than those with low UA levels (male [16.67% vs. 80.00%; P = 0.0084] and female [29.41% vs. 68.00%; P = 0.0182]). CONCLUSION: An association between high baseline serum UA levels and a decreased risk for progressing PACG was found. This primary finding suggests that high serum UA levels may have a protective role against PACG and could slow disease progression.

Blood Levels of Tumor Necrosis Factor Alpha and Its Type 2 Receptor Are Elevated in Patients with Boston Type I Keratoprosthesis.

Purpose: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-α) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-α, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. Methods: Venous blood samples were collected from KPro patients with glaucoma (KPro G, n = 19), KPro patients without glaucoma (KPro NoG, n = 12), primary angle closure glaucoma without KPro (PACG, n = 13), and narrow angles without glaucoma or KPro (NA, n = 21). TNF-α, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. Results: All groups had similar age, body mass index (BMI), IOP, and ESR (p ≥ 0.11). The mean time from KPro surgery to blood draw was 5.3 ± 3.7 years. Compared to NA patients (0.72 ± 0.3 pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF-α (1.18 ± 0.58 pg/ml, p = 0.006; 1.16 ± 0.50 pg/ml, p = 0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 ± 1368 pg/ml) than NA patients (2020 ± 435 pg/ml, p = 0.048). In multivariate analysis, KPro status remained positively associated with TNF-α levels (ß = 0.36; 95% confidence intervals [CI]: 0.14-0.58; p = 0.002) and TNFR2 levels (ß = 458.3; 95% CI: 32.8-883.7; p = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. Conclusions: We detected elevated serum levels of TNF-α and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF-α and TNFR2 as serum biomarkers related to KPro surgery. Abbreviations: BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2.

Microarray-based analysis of gene expression profiles in peripheral blood of patients with acute primary angle closure.

BACKGROUND: We investigated the expression of molecules in peripheral blood mononuclear cells (PBMCs) and plasma of patients with acute primary angle closure (APAC). MATERIALS AND METHODS: Peripheral blood was collected from patients with APAC (n = 10) and age-matched controls (n = 5). The gene transcription profile was analyzed in PBMCs using microarrays and validated by real-time reverse transcription polymerase chain reaction (RT-PCR). The levels of secreted proteins were evaluated in plasma by ELISA. RESULTS: 347 gene transcripts were up-regulated by 2-fold or more, and 696 transcripts down-regulated 2-fold or more in PBMCs from patients compared to controls. The most highly up-regulated gene was thrombospondin-1 (TSP-1, 8.66-fold increase), and the most down-regulated gene was prostaglandin-endoperoxide synthase 2 (PTGS2, 9.09-fold decrease). Real-time RT-PCR assay confirmed the increase of TSP-1 and the decrease of PTGS2 in PBMCs of patients. ELISA revealed that the levels of TSP-1 and active transforming growth factor (TGF)-ß1 that is activated by TSP-1 were elevated in plasma of patients, while the level of prostaglandin E2 (PGE2) that is converted by PTGS2 was reduced. The plasma level of TSP-1 was positively correlated with that of active TGF-ß1. CONCLUSIONS: Our data suggest that the molecular network including TSP-1, TGF-ß1, and PGE2 might be involved in the pathogenesis of APAC and PACG.

Association of Plasma Complement C3 Levels With Primary Angle-Closure Glaucoma in Older Women.

Purpose: The plasma complement component (C)3 concentration and clinical characteristics of primary angle-closure glaucoma (PACG) subjects were analyzed to evaluate whether C3 levels were correlated with PACG severity. Methods: Peripheral blood samples from subjects with PACG (n = 237) and normal controls (n = 158) were collected. The plasma levels of C3 were measured by immunoturbidimetry. The assessments of intraocular pressure; vertical cup/disc ratio (VCDR); central corneal thickness; axial length; anterior chamber depth; visual field-derived mean deviation; and mean sensitivity were performed by glaucoma specialists. Based on their sex and age, the PACG subjects were categorized into female (0-49 years, 50-59 years, 60-70 years, and 70+ years) and male (0-49 years, 50-59 years, 60-70 years, and 70+ years) subgroups. Results: The mean plasma levels of C3 (101.71 ± 21.17 mg/dL) were significantly lower (P < 0.001) in PACG subjects compared with controls (110.68 ± 17.63 mg/dL). Plasma C3 concentrations were significantly lower (P < 0.001) in female subjects with PACG (100.74 ± 19.83 mg/dL) compared with controls (113.58 ± 18.80 mg/dL). A similar result was observed when plasma levels of C3 were compared between the PACG and control groups with respect to age (≥50 years). The mean plasma levels of C3 were lowest in the severe PACG group followed by moderate PACG and mild PACG, and the differences were significant (P = 0.003). Multivariable regression analyses showed that there was a significant correlation between C3 levels and VCDR (B = -0.310, P = 0.047). Conclusions: Older women with PACG have lower plasma C3 levels, which were further demonstrated to be negatively associated with PACG severity. These findings suggest the involvement of C3 in the pathomechanisms of PACG in older women.

The association between serum uric acid and glaucoma severity in primary angle closure glaucoma: a retrospective case-control study.

Uric acid (UA) is a major antioxidant molecule and has been hypothesized to have a protective effect on the central nervous system against oxidative damage. We prospectively investigated the serum concentration of UA in primary angle closure glaucoma (PACG), and explored the association between serum concentration of UA and the severity of PACG. Using a retrospective case-control study design, 886 PACG subjects and 994 control subjects who attended the Eye & ENT Hospital of Fudan University, were eligible for this study. Glaucoma severity was classified as mild (MD ≤ 6.00 dB), moderate (12 dB ≥ MD > 6 dB) and severe (MD > 12 dB) based on the MD (mean deviation). The levels of UA were significantly lower (p = 0.025) in PACG (0.286 ± 0.082 mmol/l) compared with control (0.295 ± 0.085 mmol/l). The mean serum UA levels were lowest in the severe group (0.281 ± 0.074 mmol/l) followed by moderate (0.282 ± 0.080 mmol/l) and mild (0.297 ± 0.090 mmol/l) with significant differences among the three groups (p = 0.032). In multivariate regression analysis, there was a significant negative correlation between UA level and vertical cup-disc ratio (B = -0.165, p = 0.035). Significantly lower serum UA concentration in PACG and its negative association with disease severity presented it as an important candidate in reaction to oxidative stress in glaucoma pathogenesis.

Association of total antioxidants level with glaucoma type and severity.

OBJECTIVES: To compare the mean total antioxidant status (TAS) among 3 glaucoma types, namely: pseudoexfoliation glaucoma (PEG), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG), and study its potential association with various clinical glaucoma-parameters.   METHODS: In this case-control study, plasma samples were obtained between September 2013 and October 2014 from 340 glaucoma patients (PEG [n=54]; POAG [n=147]; PACG [n=139]), and 351 controls of matching age, gender, ethnicity, and 5 different systemic co-morbidities from King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The TAS in all samples was determined by a colorimetric-based assay.   RESULTS: The mean±standard deviation of TAS was significantly lower among cases: 0.77±0.32  than controls: 1.1±0.22, p less than 0.0001. Moreover, the TAS levels were significantly different across the 3 types of glaucoma: 0.86±0.24 in PEG, 0.47±0.32 in POAG, and 0.98±0.41 in PACG (all p less than 0.0001). In addition, there was a significant correlation between TAS and age at onset (Pearson correlation coefficient [R] 0.17, p less than 0.0001), cup/disc ratio (R: -0.13, p=0.004), and number of anti-glaucoma medications (R: -0.16, p=0.001).   CONCLUSION: Our findings provide evidence that plasma TAS levels are decreased in patients with glaucoma, more so in POAG and PEG than PACG, supporting the hypothesis that decreased antioxidative defense and/or increased oxidative stress may have a critical role in the pathogenesis of glaucoma.

Evaluation of Choroidal Thickness, Intraocular Pressure, and Serum Osmolality After the Water Drinking Test in Eyes With Primary Angle Closure.

PURPOSE: We evaluated changes in choroidal thickness (ChT), IOP, ocular biometry, and serum osmolality after the water drinking test (WDT) in subjects with previous acute primary angle closure (APAC) and primary angle closure glaucoma (PACG). METHODS: We evaluated 38 subjects, including 21 with APAC and 17 with PACG. Each subject underwent IOP measurement, A-scan biometry, spectral domain-optical coherence tomography (SDOCT), anterior segment-optical coherence tomography (ASOCT), and osmolality measurements at baseline, 30, and 60 minutes after consuming at least 10 mL/kg of water. The ChT at the macula was measured from SDOCT images using the 7-line scan protocol. The fellow-eyes of APAC (FE-APAC) were compared to eyes with PACG. RESULTS: The mean age ± SD of the study subjects was 62.8 ± 8.6 years and 21 (55.3%) were females. At baseline, serum osmolality was significantly lower (P < 0.001) in the FE-APAC group, whereas ChT was similar in both groups (P = 0.56). At 30 minutes after WDT, both groups demonstrated a significant increase in IOP (FE-APAC, 3.0 [95% confidence interval {CI}, 1.52, 4.48] mm Hg; PACG, 5.06 [95% CI, 3.68, 6.26] mm Hg; P < 0.001 for both) and decrease in serum osmolality (P < 0.001 for both), but no significant change in ChT. The magnitude of change in IOP was significantly greater in PACG eyes (P = 0.04). After multivariate analysis, a lower mean baseline serum osmolality (ß = -0.44, P = 0.003) was associated with a greater change in ChT at 30 minutes after WDT. CONCLUSIONS: The increase in IOP after WDT was higher in PACG eyes compared to FE-APAC; however, the latter had lower serum osmolality at baseline. Change in mean ChT following WDT was associated with a lower baseline serum osmolality.

Bilateral acute angle closure glaucoma associated with hydrochlorothiazide-induced hyponatraemia.

We report a case of a 67-year-old woman presenting with bilateral acute angle closure. On investigation, she was found to have bilateral ciliary effusions and profound hyponatraemia. Her effusions resolved with the cessation of hydrochlorothiazide and normalisation of her blood sodium levels by fluid restriction. This case displays a novel association of hyponatraemia as a possible mechanism for the development of bilateral acute angle closure.

Total antioxidant level is correlated with intra-ocular pressure in patients with primary angle closure glaucoma.

BACKGROUND: To evaluate total antioxidant status (TAS) in the plasma of primary angle closure glaucoma (PACG) patients and to compare it to that of the control group. Additionally, we aim to investigate the association of various PACG clinical indices with TAS level. METHODS: Plasma samples were obtained from 139 PACG patients and 149 glaucoma-free controls of matching age, sex, and ethnicity. TAS in all samples was determined by spectrophotometric and enzyme-linked immunosorbent assay methods. We studied the possible association of the TAS level with various clinical indices relevant to PACG. RESULTS: The mean (±SD) total antioxidant (TAS) value was almost similar in patients 1 (±0.22) compared to controls 0.97 (±0.43); p = 0.345. Among cases, mean TAS concentration showed a statistically significant lower pattern among subjects with glaucoma onset at the age of ≤ 50 years (p = 0.037) and female subjects (p = 0.014) as well as having a family history of glaucoma (p = 0.010). Interestingly, a statistically significant inverse correlation was detected between TAS concentration and intra ocular pressure (IOP), (R = -0.14, p = 0.037). CONCLUSIONS: The inverse correlation of TAS level with IOP, highlights TAS potential role as a predictive-marker for PACG-severity.

Association between plasma endothelin-1 and severity of different types of glaucoma.

PURPOSE: Endothelin-1 (ET-1) has been suggested to play an important role in the pathogenesis of glaucoma. Herein, we studied whether increased levels of plasma ET-1 are associated with changes in the visual field and changes in optical coherence tomography (OCT)-measured retinal nerve fiber layer (RNFL) thickness in patients with different types of glaucoma. PATIENTS AND METHODS: : Plasma concentration of ET-1 was determined in 31 patients with primary open-angle glaucoma, 18 patients with normal tension glaucoma, 16 patients with primary angle-closure glaucoma, and in 37 normal controls. In all participants, visual field testing was performed and OCT was used to measure RNFL thickness. The correlation between mean ET-1 level and changes in the visual field (mean deviation, dB) and changes in OCT-measured RNFL thickness in 1 randomly selected eye from each patient in each group was then evaluated. RESULTS: The ET-1 level was 3.27±1.25 pg/mL in the primary open-angle glaucoma group (-14.09±8.76 dB), 3.12±1.46 pg/mL in the normal tension glaucoma group (-8.87±6.15 dB), 2.58±.22pg/mL in the primary angle-closure glaucoma group (-14.55±10.2 dB), and 1.53±1.49 pg/mL in the control group. Although mean ET-1 levels were significantly higher in all 3 of the glaucoma groups than in the control group, there was no significant difference in ET-1 level among the 3 glaucoma groups. In addition, no significant correlation was found between levels of plasma ET-1 and structural or functional changes in patients with different types of glaucoma. CONCLUSIONS: : There was no correlation between plasma levels of ET-1 and severity of glaucoma. The role ET-1 plays in the pathogenesis of glaucoma remains to be determined.

The evaluation of the oxidative stress parameters in patients with primary angle-closure glaucoma.

OBJECTIVE: To clarify the presence of oxidative stress in patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between oxidative stress and PACG. METHODS: Fifty patients with primary angle-closure glaucoma and fifty healthy controls of matched age and gender were included in the study prospectively. Serum samples were obtained to detect the oxidation degradation products malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), advanced oxidation protein products (AOPP), protein carbonyl (PC), ischemia-modified albumin (IMA) and 8-hydroxydeoxyguanosin (8-OHdG). RESULTS: The concentration of MDA and CD in PACG patients was significantly higher than those of the control subjects (P<0.05, P<0.01). The serum 4-HNE concentrations were increased in PACG patients, but the differences with those of the healthy controls were not statistically significant. Compared to normal subjects, there was significant higher in serum AOPP and PC in PACG patients (P<0.01). PACG patients had higher levels of 8-OHdG in serum with respect to the comparative group of normal subjects (P<0.01). When plasma IMA levels in the PACG group were compared with those in the control group, significant increases in IMA were observed in the former (P<0.05). CONCLUSIONS: Our study demonstrated that IMA is a new biomarker available for assessing oxidative stress in PCAG. Oxidative stress is an important risk factor in the development of primary angle-closure glaucoma. Increased levels of oxidative stress products may be associated with primary angle-closure glaucoma.

Endothelin-1 and nitric oxide levels in patients with glaucoma.

AIMS: To investigate the levels of endothelin-1 (ET-1) and nitric oxide (NO) in the aqueous humor and plasma of human eyes with different types of glaucoma: primary open-angle glaucoma (POAG) and chronic closed-angle glaucoma (CCAG). METHODS: Patients were classified into 3 groups: group I comprised 35 patients with POAG, group II comprised 25 patients with CCAG, and 30 patients with senile cataract (group III) were used as a control group. Aqueous humor and corresponding plasma were analyzed for ET-1 and NO concentrations by enzyme-linked immunosorbent assay. A Bonferroni correction for multiple comparisons was performed. RESULTS: There was no significant difference in plasma levels of either ET-1 or NO metabolites between the groups studied. ET-1 and NO were significantly elevated in the aqueous humor of patients with CCAG and POAG compared to the corresponding value in patients with cataract (p < 0.001). ET-1 and NO concentrations in the aqueous humor were more marked in CCAG than in POAG. NO levels were correlated with ET-1 in the aqueous humor of patients with glaucoma (p < 0.001). CONCLUSIONS: Increased concentrations of ET-1 and NO in aqueous humor may be useful with POAG and CCAG. In addition, ET-1 and NO may have useful metabolite levels in the aqueous humor of POAG and CCAG patients as a result of glaucoma damage and may not be a cause of it.