Plasma GDF-15 concentration is not elevated in open-angle glaucoma.

AIM: Recently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease. METHODS: Plasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models. RESULTS: Before correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15. CONCLUSION: The present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.

Serum Brain-Derived Neurotrophic Factor in Glaucoma Patients in Japan: An Observational Study.

PURPOSE: The aim of this study was to measure serum levels of brain-derived neurotrophic factor (BDNF) in Japanese patients with primary open angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This was a prospective observational study of serum BDNF levels in 78 patients who underwent cataract surgery or trabeculectomy (27 glaucoma patients and 51 non-glaucoma cataract patients as controls). Patient age was 68.8 ± 11.1 years (mean ± standard deviation; range 35-86 years). The numbers of patients with POAG and NTG were 16 and 11, respectively. POAG was diagnosed by intraocular pressure measurement, gonioscopy, optic nerve head change, and presence of a visual field defect. RESULTS: Serum BDNF concentration was significantly lower in the glaucoma group (including both POAG and NTG) than in the control group (7.2 ± 3.6 ng/mL vs. 12.2 ± 9.3 ng/mL, p=0.004). Serum BDNF concentration was lower in early glaucoma than in moderate glaucoma. There was no correlation between serum BDNF concentration and age. When patients with NTG and POAG were compared, serum BDNF concentration was lower in the former. Serum BDNF concentration was not significantly correlated with glaucoma parameters, including optical coherence tomography and visual field defects. CONCLUSION: This is the first study to investigate serum BDNF concentration in glaucoma patients in Japan. Future studies should evaluate the role of BDNF as a potential biomarker of glaucoma.

Analysis of Plasma Hydrogen Sulfide, Homocysteine, and L-Cysteine in Open-Angle Glaucoma Patients.

Purpose: To compare the plasma levels of hydrogen sulfide (H2S), homocysteine (Hcy), and L-cysteine (Cys) among primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT), and normal individuals. To explore associated factors and evaluate their diagnostic abilities in glaucoma. Methods: POAG, NTG, OHT, and normal subjects were recruited from Ruijin Hospital between December 2016 and December 2018. All subjects underwent thorough ophthalmological examinations, and fasting venous blood was taken to determine the concentrations of H2S, Hcy, and Cys. Results: Forty-two POAG, 20 NTG, 52 OHT, and 78 controls were enrolled. The H2S levels in POAG group were significantly lower than those in OHT group (P = 0.036) and normal group (P < 0.001), while the Hcy and Cys levels in POAG and NTG groups were significantly higher (P = 0.007-0.043). The concentrations of H2S, Hcy, and Cys in glaucoma patients with different stages were not significantly different (all P > 0.05). POAG patients with longer duration of diagnosis had lower concentrations (P = 0.026, P = 0.001, P < 0.001), but no significant differences in NTG patients (all P > 0.05). The Hcy and Cys levels in NTG patients showed negative but weak correlations with mean deviation (r = -0.450, P = 0.047; r = -0.478, P = 0.033). All these concentrations showed significant but poor diagnostic values in POAG-Normal group [area under curve (AUC) = 0.642-0.721, P < 0.05]. The H2S level showed poor diagnostic power in POAG-OHT group (AUC = 0.657, P < 0.01). Conclusion: Decreased levels of H2S and increased levels of Hcy and Cys may be associated with glaucoma, especially in POAG. However, the H2S/Hcy metabolic pathway is not sufficiently sensitive to be used as a reliable biomarker in glaucoma.

Age dependence of plasma endothelin levels in glaucoma patients.

The aim of the study was to investigate the endothelin-1 (ET-1) plasma level and its age dependence in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. In blood samples from 35 NTG patients, 34 HTG patients, and 36 controls, ET-1 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). After adjustment for age and gender, the mean ET-1 levels were found to be similar in all three study groups. The age dependency however was highest in NTGs and significantly different from that of the controls. For the HTGs, this dependence was weaker and not significantly different from that of the controls. Our findings suggest that age had a significantly greater influence on ET plasma level in the NTG patients than in the HTG patients and controls. This supports previous reports indicating that ET plays a role in the pathogenesis of glaucoma, and in particular normal NTG.

Predictive role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in normal-tension glaucoma.

As a type of primary open-angle glaucoma, normal-tension glaucoma (NTG) is a health problem that manifests itself with low intraocular pressure (IOP) levels and preserves its importance for public health care. In population-based screenings, which take the IOP levels of 21mmHg as a cut-off for the diagnosis of glaucoma, the diagnosis is usually delayed, and the treatment is started in an advanced stage by the referred ophthalmologists. NTG is associated with some autoimmune conditions and systemic diseases, such as paraproteinemia, nocturnal hypotension, and migraine. Recently, a simple and cheap test (namely the hemogram) was defined as measure of systemic inflammation, measuring the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). A recent study displayed an altered platelet function in NTG patients. We hypothesize that an automated hemogram analysis for NLR together with IOP measurements may be used to screen NTG patients who are admitted to primary care clinics if any relationship between NTG and NLR could be demonstrated in future researches.

Analysis of the Interleukin-6 (-174) Locus Polymorphism and Serum IL-6 Levels with the Severity of Normal Tension Glaucoma.

PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. METHODS: A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. RESULTS: The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06). CONCLUSION: The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.

Plasma endothelin-1 and single nucleotide polymorphisms of endothelin-1 and endothelin type A receptor genes as risk factors for normal tension glaucoma.

PURPOSE: The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) of endothelin and endothelin receptor type A genes can constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG). METHODS: The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. Endothelin levels were compared with genotype and allele distributions, patients' clinical status, and various risk factors for NTG. RESULTS: There was a significant difference between the patients with NTG and HTG and the controls (p = 0.035, p = 0.008) regarding the genotype of the C1222T and C70G polymorphism. Plasma concentrations of ET did not differ between the NTG and HTG groups, and no significant correlation with intraocular pressure (IOP), best-corrected visual acuity (BCVA), and the cup to disc ratio (c/d ratio) was seen in patients with NTG. Plasma endothelin levels showed a noticeably positive correlation with age in the NTG group (R = 0.249, p = 0.042). Higher endothelin levels corresponded to more advanced visual field damage. No statistical difference was observed between variant genotypes of K198N and the ET-1 plasma concentration in patients with NTG, whereas a slightly higher ET level was observed in the patients with HTG with the GT genotype in comparison to those with the GG genotype (p = 0.001). The C1222T polymorphism significantly affected the plasma ET level in patients with NTG. The TT genotype carriers had the highest ET level, and the CC genotype carriers the lowest (p = 0.034). The AA variant genotype of the G231A polymorphism exhibited the highest ET level, while the GG variant genotype represented the lowest level (p = 0.033). No significant differences were observed regarding the endothelin levels and the frequency of notches, peripapillary atrophy, low blood pressure, cold extremities, or migraine in the two groups studied. Slightly lower endothelin plasma levels were observed in patients with optic disc hemorrhages in the NTG group (p = 0.05). CONCLUSIONS: Polymorphic variants of endothelin EDN (K198N) and endothelin receptor type A genes EDN RA (C1222T, C70G, G231A) affected ET plasma concentrations. There was no association between the plasma endothelin levels and the risk factors for NTG. According to these results, plasma endothelin concentrations do not appear to be a marker for NTG.

Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

BACKGROUND: This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). MATERIALS AND METHODS: A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. RESULTS: A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 µmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 µmol/L (95% CI, -1.98, 0.74), 5.81 µmol/L (95% CI, -3.53, 15.14), and -16.79 µmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). CONCLUSION: NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

Evaluation of the Effect of Hypercapnia on Vascular Function in Normal Tension Glaucoma.

INTRODUCTION: Altered ocular perfusion and vascular dysregulation have been reported in glaucoma. The aim of this paper was to evaluate the vascular response to a hypercapnic stimulus. METHODS: Twenty normal tension glaucoma (NTG) patients and eighteen age- and gender-matched controls had pulsatile ocular blood flow (POBF) measurements, systemic cardiovascular assessment, and laser Doppler digital blood flow (DBF) assessed. Measurements were taken at baseline, after 10-minutes rest, in the stable sitting and supine positions and following induction and stabilization of hypercapnia, which induced a 15% increase in end-tidal pCO2. The POBF response to hypercapnia was divided into high (>20%) and low responders (<20%). RESULTS: 65% of NTG patients had a greater than 41% increase in POBF following CO2 rebreathing (high responders). These high responders had a lower baseline POBF, lower baseline DBF, and a greater DBF response to thermal stimulus. CONCLUSION: NTG patients that have a greater than 20% increase in POBF after a hypercapnic stimulus have lower baseline POBF and DBF values. This suggests that there is impaired regulation of blood flow in a significant subgroup of NTG patients. This observation may reflect a generalised dysfunction of the vascular endothelium.

Association Between Platelet Function and Disc Hemorrhage in Patients With Normal-Tension Glaucoma: A Prospective Cross-Sectional Study.

PURPOSE: To evaluate the association between platelet function and disc hemorrhage in patients with normal-tension glaucoma. DESIGN: Prospective, cross-sectional study. METHODS: Study involved a total of 315 subjects, including patients with normal-tension glaucoma and disc hemorrhage (n = 120), patients with normal-tension glaucoma without disc hemorrhage (n = 75), and healthy individuals (control group, n = 120). A detailed eye examination including visual field testing, color disc photography, optical coherence tomography scanning, and measurement of collagen/epinephrine closure time using a platelet function analyzer were performed for all subjects. RESULTS: The collagen/epinephrine closure time (s) as measured by the platelet function analyzer was approximately 14%-24% longer in the normal-tension glaucoma and disc hemorrhage group compared with the other groups (141.92 ± 53.44 [with normal-tension glaucoma and disc hemorrhage] vs 124.60 ± 46.72 [with normal-tension glaucoma without disc hemorrhage] vs 114.84 ± 34.84 [healthy individuals], 1-way analysis of variance test, P < .001). The activated partial thromboplastin time (s) value of the normal-tension glaucoma with disc hemorrhage group was also higher than the control group. Stepwise multiple logistic regression analysis revealed that only a longer collagen/epinephrine closure time (OR adjusted for age, sex, prothrombin time, activated partial thromboplastin time, diabetes mellitus, hypertension, hypotension, heart disease, hypothyroidism, migraine, stroke, hypercholesterolemia: 2.94; 95% CI: 1.40-6.17) was independently associated with disc hemorrhage. A similar trend was observed when platelet function was compared among the 3 groups with respect to age. CONCLUSIONS: Our results suggest that platelet function is significantly associated with disc hemorrhage in patients with normal-tension glaucoma. Delayed absorption resulted from prolonged bleeding due to delayed platelet aggregation may have an effect on the detectability of disc hemorrhage in patients with normal-tension glaucoma.

Selected autoantibodies and normal-tension glaucoma.

BACKGROUND: Although intraocular pressure is an important risk factor in glaucoma, there is growing body evidence indicating an immunological component in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to determine if NTG coexists with elevated levels of autoantibodies detected in rheumatic diseases. MATERIAL AND METHODS: We enrolled 105 patients into the study: 35 with NTG, 34 with primary open-angle glaucoma (POAG), and 36 controls. All patients underwent ophthalmic examination and blood tests. Blood was examined for the level of: antibodies against antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), immunoglobulins (IgG, IgA, IgM), rheumatoid factor, anti-citrullinated protein antibodies (ACPA), and antiphospholipid antibodies (anticardiolipin antibodies, beta2-glycoprotein I antibodies, antiprothrombin antibodies). RESULTS: The level of ANA was increased among 6 patients in the NTG group (17.1%), 8 in the POAG group (23.5%), and 6 in the control group (16.5%). The difference was not statistically significant (p=0.97). None of the patients in the NTG, POAG, or control group had positive antibodies to ENA. The level of immunoglobulins IgG, IgM, and IgA in the 3 groups was similar and within normal values. The median level of rheumatoid factor and ACPA was the highest in the NTG group, but it was within normal laboratory values. There was a statistically significant difference between antiprothrombin antibodies IgG between the NTG and POAG group (p=0.01), but not between the NTG and control group (p=0.24). CONCLUSIONS: The results of our study do not confirm the hypothesis that NTG coexists with elevated blood levels of antibodies, which are a characteristic feature of rheumatic diseases.

Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma.

PURPOSE: To investigate in parallel the systemic glutathione levels of patients suffering from primary open angle glaucoma (POAG) or normal tension glaucoma (NTG) with comparable functional loss. METHODS: Thirty-four POAG patients, 30 NTG patients, and 53 controls were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. Systemic blood pressure (BP) and ocular perfusion pressure (OPP) parameters were also determined. RESULTS: Independent of age, POAG and NTG patients demonstrated significantly lower GSH and t-GSH levels than age-matched controls (P < 0.001). Additionally, a lower redox index was found, but in POAG patients only, in comparison to both NTG and control groups (P = 0.020). GSSG levels were, however, similar between all study groups (P > 0.05). CONCLUSIONS: This study demonstrates, for the first time, that both POAG and NTG patients exhibit lower GSH and t-GSH levels than age-matched controls, indicating a similar general compromise of the antioxidant defense systems may exist in both conditions.

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.

Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage chemoattractant protein-1, and high-sensitivity C-reactive protein in normal-tension glaucoma.

PURPOSE: To investigate the roles of vascular dysregulation and inflammation in normal-tension glaucoma (NTG), we determined the plasma levels of endothelin-1 (ET-1), matrix metalloproteinase-9 (MMP-9), macrophage chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP). MATERIALS AND METHODS: Forty-five patients with NTG and age-matched 35 healthy controls were enrolled in this study. Blood samples from all subjects were assayed for ET-1, MMP-9, MCP-1, and hs-CRP concentrations and other systemic factors. RESULTS: There were no significant differences in hemoglobin, hematocrit, RBC count, WBC count, platelet count, fasting glucose, HbA1c, total cholesterol, triglyceride, LDL, and HDL between the NTG and control groups. The systemic levels of ET-1 and MCP-1 were significantly higher in the NTG group than in the control group (p = 0.05 and 0.02, respectively). The MMP-9 and hs-CRP levels were not significantly different between the NTG and control groups. CONCLUSIONS: After excluding patients with cardiovascular and other systemic diseases, plasma ET-1 and MCP-1 levels were elevated in patients with NTG. The MMP-9 and hs-CRP levels were not significantly different in NTG. Increased ET-1 and MCP-1 levels suggest that ischemia/inflammation may play a role in the pathogenesis of NTG.

Retinal ganglion cell loss in superoxide dismutase 1 deficiency.

PURPOSE: To investigate the influence of deficiency in superoxide dismutase (SOD) 1, a major antioxidative enzyme, on retinal ganglion cells (RGCs). METHODS: In the SOD1 total knockout (SOD1-deficient) mice, the level of superoxide anion was measured using dihydroethidium. The number of RGCs was counted in both the retinal sections and the flat-mount retinas after retrograde labeling. Thickness of nerve fiber layer (NFL) was measured in the sections, and the amount of neurofilament protein was measured by immunoblot analysis. Pattern electroretinogram (ERG), which reflects the function of retinal ganglion cells, dark-adapted ERG, and cone ERG were performed. The intraocular pressure (IOP) was measured with an induction-impact tonometer. The levels of SOD-1 and -2 were measured by ELISA, in the serum of 47 newly diagnosed consecutive normal tension glaucoma (NTG) patients and 44 consecutive control subjects. RESULTS: The level of superoxide anion in the RGC layer was significantly higher in 24-week-old SOD1-deficient mice than in wild-type mice. The RGC number was significantly reduced in 24-week-old SOD1-deficient mice, although they were not in 8-week-old mice. The NFL thickness and neurofilament protein were reduced in 24-week-old SOD1-deficient mice. The amplitude of pattern ERG was significantly reduced, although dark-adapted and cone ERGs showed no impairment, in 24-week-old SOD1-deficient mice. The IOP level was not changed in the SOD1-deficient mice. The serum level of SOD1, but not SOD2, was significantly lower in the NTG patients than in the healthy controls. CONCLUSIONS: SOD1 deficiency causes RGC vulnerability, which may be involved in the underlying condition of NTG.

Increased serum total antioxidant status and decreased urinary 8-hydroxy-2'-deoxyguanosine levels in patients with normal-tension glaucoma.

PURPOSE: To investigate the amount of systemic oxidative stress-related DNA damage and serum total antioxidant status of patients with normal-tension glaucoma compared with healthy controls. METHODS: Forty-three patients with normal-tension glaucoma selected from 60 consecutive newly diagnosed patients with primary open-angle glaucoma were enrolled. Each patient's intraocular pressure (IOP) was measured seven times over a 24-hour period. Those whose highest IOP was over 21 mmHg were excluded. Forty control subjects were recruited. The serum total antioxidant status was assessed colorimetrically by its ability to reduce the generation of the radical cation ABTS (2,2-azinobis-3-ethylbenzthiazoline sulphonate). The urinary 8-hydroxy-2'-deoxyguanosine was measured as a marker of oxidative DNA damage and normalized to creatinine. The results were compared between healthy subjects and patients with normal-tension glaucoma. RESULTS: The control and normal-tension glaucoma groups did now show significant differences for age, gender, serum fructosamine, cholesterol and triglyceride levels; systolic and diastolic blood pressure, body mass index; and prevalence of hypertension. The serum total antioxidant status was significantly higher (p = 0.01) and the urinary 8-hydroxy-2'-deoxyguanosine/creatinine level significantly lower (p = 0.03) in the patients with normal-tension glaucoma compared with the controls. Even after we adjusted the data for independent variables, the incidence of normal-tension glaucoma was significantly correlated with high serum total antioxidant levels (p = 0.03; odds ratio, 1.007; 95% confidence interval, 1.001-1.013) and low urinary 8-hydroxy-2'-deoxyguanosine/creatinine (p = 0.02; odds ratio 0.76; 95% confidence interval, 0.61-0.96). CONCLUSIONS: Increased serum total antioxidant and decreased 8-hydroxy-2'-deoxyguanosine may reflect compensatory alterations in response to increased systemic oxidative stress in patients with normal-tension glaucoma.

Plasma homocysteine levels in patients with normal tension glaucoma.

PURPOSE: To investigate whether there is an association of elevated plasma levels of homocysteine (Hcy) and normal tension glaucoma (NTG). PATIENTS AND METHODS: Plasma levels of Hcy (fluorescence polarization immunoassay), vitamin B6 (high-performance liquid chromatography), vitamin B12, and folate levels (immunoassay) were determined in 42 patients with NTG and in 42 age-matched and sex-matched controls. RESULTS: No significant difference regarding Hcy (NTG: 10.95 µmol/L±2.65; controls: 11.29 µmol/L±2.76) (P=0.639), vitamin B6 (NTG: 14.45 ng/mL±12.89; controls: 13.57 ng/mL±10.41) (P=0.629), vitamin B12 (NTG: 387.73 pg/mL±282.04; controls: 423.27 pg/mL±188.85) (P=0.052) and folate (NTG: 9.45ng/mL±3.42; controls: 10.82 ng/mL±4.48) (P=0.181) levels were found between both groups. CONCLUSIONS: An association of elevated Hcy levels and NTG was not found and therefore a role of Hcy as a modifiable risk factor in the pathogenesis of NTG seems unlikely.

Evaluation of plasma glutamate levels in normal tension glaucoma.

AIM/BACKGROUND: Abnormal metabolism of the neurotransmitter glutamate is implicated in a number of neurodegenerative conditions. Patients with migraine have been shown to have elevated plasma glutamate levels. Migraine is a risk factor both in terms of prevalence and progression in normal-tension glaucoma (NTG). The aim of this study was to determine whether or not plasma glutamate levels are also elevated in NTG. METHODS: Patients were recruited into 2 groups, NTG and control, according to inclusion and exclusion criteria. Patients with migraine were excluded from both groups. Fasting blood samples were collected in lithium heparin tubes, transported on ice, and centrifuged for storage at -21 degrees C. Plasma glutamate levels were measured by an amino acid analyser. Data for each group were compared by applying the Mann-Whitney test. Ethical approval and independent statistical advice for the study was obtained. RESULTS: A total of 27 subjects were recruited: 14 to the NTG group and 13 to the control group. No significant difference was found between the plasma glutamate levels in the 2 groups (p = 0.67). CONCLUSION: Although an association between normal tension and migraine is recognized, unlike studies in migraine sufferers, this study finds no evidence that patients with NTG have elevated plasma glutamate.

Reduced-serum vitamin C and increased uric acid levels in normal-tension glaucoma.

BACKGROUND: Vitamin A, B(9), C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B(9), C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls. METHODS: All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age +/- standard deviation: 59.9 +/- 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age +/- standard deviation: 59.5 +/- 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 +/- 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B(9), C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test. RESULTS: Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 +/- 4.0 microg/ml control; 6.3 +/- 3.9 microg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 +/- 1.5 mg/dl control; 4.9 +/- 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 +/- 26.7 microg/dl control; 77.1 +/- 30.1 microg/dl), B(9) (P = 0.37; normal-tension glaucoma; 8.7 +/- 4.3 ng/ml control; 8.0 +/- 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 +/- 0.6 control; 1.5 +/- 0.6) levels between normal-tension glaucoma and control groups. CONCLUSION: Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma.