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Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP)., Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG., Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 - -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 - -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 - -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 - -0.0008) in patients with POAG., Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk., (© 2024. The Author(s).)

Objective: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG)., Methods: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables., Results: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001)., Conclusion: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG., (© 2024. The Author(s).)

Purpose: It has been hypothesised that uric acid (UA) has a protective effect against oxidative damage in the central nervous system. Therefore, we investigated serum UA concentrations in patients with primary open-angle glaucoma (POAG) and explored the relationship between serum UA concentration and glaucoma severity., Methods: This prospective, cross-sectional, case-control study was conducted in 163 POAG patients and 103 normal controls. Clinical and demographic information was obtained from the medical data platform of the Eye & ENT Hospital of Fudan University, Shanghai, China. The POAG patients were categorised into mild [median deviation (MD) ≤ 6.00 dB], moderate (MD > 6 Db-≥12 dB) and severe (MD > 12 dB) subgroups, based on their visual field MD results., Results: The level of serum UA in the POAG group (0.321 ± 0.084 mmol/l) was approximately 12.77% lower (p < 0.001) than that of the control group (0.362 ± 0.053 mmol/l). The UA/creatinine (Cr) ratio was approximately 14.99% lower (p < 0.001) in patients with POAG (4.47 ± 1.15), compared with the control group (5.14 ± 1.05). The mean level of UA was lowest in the severe POAG group, followed by the moderate POAG group, and the mild POAG group (p < 0.001). A similar trend was observed when UA levels were compared between the POAG and control groups in males. Multivariate regression analyses showed a significant negative correlation between UA and vertical cup-disc ratio (B = -0.320, p = 0.034), and UA and MD (B = -0.441, p = 0.031) in males., Conclusion: Primary open-angle glaucoma patients have lower UA levels; however, a negative association between UA levels and disease severity was evident in male patients., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. We reported previously that the level of systemic antioxidative capacity is lower in patients with open-angle glaucoma than controls without glaucoma. Here, we assessed the correlation between IOP and systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in patients with glaucoma., Methods: Peripheral blood samples were collected from Japanese patients with primary open-angle glaucoma (n = 206), exfoliation syndrome (n = 199), and controls (n = 126). Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. To test the possible effect of oxidative stress on IOP levels, the patients were classified into one of four groups (Q1, Q2, Q3, and Q4, with Q1 having the lowest IOP) based on the quartile value of IOP. For this classification, the known highest IOP value in both the right and left eyes was regarded as each subject's IOP. For comparisons among the IOP groups, the differences were calculated using one-way analysis of variance followed by post-hoc unpaired t-tests. To adjust for differences in demographic characteristic distributions, the dROM, BAP, and SH test values were compared among the IOP groups using multiple logistic regression analysis; the odds ratio (OR) of each variable was calculated with the Q1 group as the reference., Results: The dROM and the SH levels did not differ significantly (p = 0.6704 and p = 0.6376, respectively) among the four IOP groups. The BAP levels differed significantly (p = 0.0115) among the four IOP groups; the value was significantly lower in the Q4 group (1,932 μmol/L) compared with the Q1 (2,023 μmol/L, p = 0.0042) and Q2 (2,003 μmol/L, p = 0.0302) groups and significantly lower in the Q3 group (1,948 μmol/L) than the Q1 (p = 0.0174) group. After adjustment for differences in various demographic characteristics, lower BAP values were significantly associated with the classification into higher IOP groups (Q3 group, p = 0.0261 and OR = 0.06/range; Q4 group, p = 0.0018 and OR = 0.04/range). The dROM and SH values did not reach significance in any comparisons., Conclusions: Lower systemic antioxidant capacity measured by ferric-reducing activity is involved in the pathogenesis of open-angle glaucoma via its roles in IOP elevation.

Normal tension glaucoma is a form of primary open angle glaucoma where the intraocular pressure remains within the normal range. In this case the main challenge is to establish the correct diagnosis. The clinical evaluation of a patient suspected of a normal tension glaucoma must answer two questions: 1) is the intraocular pressure normal and 2) is it a glaucomatous optic neuropathy or another type of optic neuropathy?

Purpose: To compare the plasma concentration of endothelin-1 (ET-1) among patients < 60 years of age with normal-tension glaucoma (NTG), primary open-angle glaucoma (POAG), and in age-matched normal participants., Methods: Plasma concentration of ET-1 was determined in 30 NTG 18 POAG patients, and 19 age-matched normal participants using an enzyme immunoassay., Results: The ET-1 level was 1.49 +/- 0.51 pg/ml in the NTG patients (49.4 +/- 8.8 years), 1.58 +/- 0.64 pg/ml in the POAG patients (44.7 +/- 10.7 years), and 1.33 +/- 0.50 pg/ml in the normal participants (49.9 +/- 5.6 years). The ET-1 levels were not significantly different among the three groups, and no significant correlation with the extent of visual field damage, intraocular pressure (IOP), refraction, or age was seen in the glaucoma patients., Conclusions: The plasma ET-1 level showed no difference among NTG patients, POAG patients, and normal participants < 60 years of age in the Japanese population.

Purpose: Vasospasm, resulting from a generalized dysfunction in the vascular endothelium, is implicated in the development of normal-pressure glaucoma (NPG). Impaired endothelium-derived nitric oxide activity and abnormalities of the endothelin system suggest systemic endothelial cell dysfunction in patients with NPG. Endothelin (ET)-1 vasoreactivity was assessed in the peripheral circulation of patients with NPG., Methods: Forearm blood flow was measured using venous occlusion plethysmography in eight patients with untreated NPG and eight age- and sex-matched healthy volunteers during intra-arterial infusion of ET-1 (5 pmol/min) and, on a separate occasion, to BQ123, a selective endothelin-A receptor antagonist, (100 nmol/min). Blood pressure and heart rate were measured in the noninfused arm, and plasma ET-1 concentrations were measured using a radioimmunoassay., Results: Forearm blood flow fell during infusion of ET-1 (P<0.001 for both) to a similar extent in both groups (P=0.7; patients versus control subjects). In contrast, BQ123 increased forearm blood flow in both groups (P<0.001 for both), although the vasodilatation was lower in patients than in control subjects (P<0.001; patients versus control subjects). There was no difference in basal plasma ET-1 concentrations between the two groups (P=0.81; patients versus control subjects)., Conclusions: Despite normal responses to ET-1, patients with NPG have reduced vasodilatation in response to ETA-receptor antagonism. This could be due to attenuated ETA-receptor-mediated tone, increased ETB-receptor-mediated contraction or impaired ETB-receptor-mediated release of endothelial nitric oxide. These results are consistent with the authors' previous demonstration of systemic vascular dysfunction in patients with NPG.

Background: The objective was to measure the plasma concentrations of thymulin and nerve growth factor (NGF) in a group of patients with primary open angle glaucoma (POAG) and compare them with age- and sex-matched normal controls., Methods: Twenty-eight patients newly diagnosed with POAG who were not undergoing treatment were compared with the same number of age- and sex-matched healthy controls. Blood samples were drawn into heparinized tubes and plasma samples were collected for the determination of the concentrations of thymulin and NGF, using specific enzyme-linked immunosorbent assay (ELISA). The Student's t test was used to perform the necessary statistical analysis of the results., Results: Seventeen women and 11 men were enrolled in each of the two groups (study and control), with a mean age of 63.7 (SD 10.3) years in the former and 63.3 (SD 9.6) years in the latter. There was a highly significant (p<0.001) elevation in the thymulin levels in POAG patients compared with the control group. However, no significant difference was observed when comparing the plasma NGF levels., Conclusion: This is the first report to measure plasma thymulin levels in glaucoma patients. The significant results point the possible role of this immunomodulator in the pathogenesis of primary open angle glaucoma. The potential role of NGF seems to be less likely. These findings warrant further investigation.

Disorders in erythrocyte morphology and function (impairment of erythrocyte membranes and decreased erythrocyte deformability), leading to impairment of capillary endothelium with release of Willebrand factor into the blood, increase of blood viscosity, and disorders in microcirculation and transcapillary exchange in the optic disk, were detected in 87.5% of 49 patients (70 eyes) with nonstabilized course of primary open-angle glaucoma with normalized intraocular pressure. Biochemical analysis of plasma lipids showed atherogenic hyperlipidemia with decreased antioxidant activity, which favored the development of these changes and was one of the factors determining the clinical course of disease.

Purpose: To determine if there were significant differences between the number of red blood cell ouabain binding sites in normals and untreated ocular hypertensives plus one open-angle glaucoma patient., Methods: We measured the binding of (3)H ouabain to erythrocyte membranes of 23 normals, 25 ocular hypertensives and one open-angle glaucoma. We also measured the levels of plasma cortisol and digoxin in these subjects. Characteristics of cupping of the optic disc and thickness of the retinal nerve fiber layer, as well as area of optic disc pallor of these subjects were measured by stereophotogrammetry and by computerized image analysis from single and stereo photographs., Results: The number of (3)H ouabain binding sites was observed to be significantly less in the ocular hypertensives and one glaucoma compared to the normals (p = 0.0009). In multi-variate analyses, to determine what other factors affected this difference, there was a significant negative association with mean intraocular pressure (p = 0.003) (average of both eyes) and total cup volume (average of both eyes) (p = 0.005), diagnosis of ocular hypertension and glaucoma (p = 0.0005) and male gender (p = 0.019). There was a significant positive association with plasma cortisol levels (p = 0.048), and diastolic blood pressure (p = 0.037)., Conclusions: The number of (3)H ouabain binding sites in red blood cells decreases significantly with increasing ocular pressure and increasing cup volume indicating the possible presence of an increased systemic endogenous digoxin-like inhibitor and/or difference in the isozymes of Na(+), K(+)-ATPase which may be associated with increased levels of plasma cortisol in ocular hypertensives and glaucomas.

The relationship of systemic and local hemodynamics with neurohumoral factors has been evaluated in 104 patients with primary open-angle glaucoma with normalized intraocular pressure. Changes in the functional activity of the sympathoadrenal activity and hydrocortisone levels were in high correlation with the initial type of systemic hemodynamics: the hormonal activity of the sympathoadrenal system predominated in patients with eukinetic and hyperkinetic circulation with normal levels of hydrocortisone, while in patients with hypokinetic circulation the mediator (norepinephrine) component of the sympathoadrenal system combined with a high plasma level of hydrocortisone predominated. A principal characteristic of unstable primary open-angle glaucoma, discriminating it from the stable condition in all types of circulation, is the presence of deep autonomic disorders in the neurohumoral mechanisms of autoregulation of ocular blood flow, because of excessive accumulation of norepinephrine, epinephrine, and hydrocortisone in the lacrimal fluid at the expense of their decreased utilization by the receptor systems of ocular tissues and blood vessels.

Purpose: To compare the effects of 0.5% timolol maleate, 2% carteolol, and 0.3% metipranolol on intraocular pressure (IOP) in 45 patients with primary open-angle glaucoma (POAG) and ocular hypertension. A secondary goal of this study was to evaluate the ocular and systemic side effects of these medications., Methods: Measurements of IOP were taken at baseline (pretreatment) and 2, 6, and 12 hours after instillation on treatment days 15, 30, 60, and 90. Mean sensitivity (MS) and mean defect (MD) values of perimetry before and after treatment and the effects of the three beta blockers on serum lipid profiles were determined. Ocular and systemic side effects were recorded., Results: The most prominent IOP lowering effect was noted with metipranolol at 2 and 6 hours on day 15, and with timolol maleate at 12 hours on day 15 and at all hours of the subsequent days on which measurements were taken. Timolol maleate produced a significant decrease in IOP at 12 hours on day 15 compared with carteolol. There was not a statistically significant difference between the MS and MD values on perimetry before and after treatment for any treatment. There was a statistically significant decrease in levels of total cholesterol and high-density lipoprotein (HDL) cholesterol and a significant increase in triglyceride levels; these changes were observed for all treatments., Conclusion: The effects of the three medications were not statistically different from each other in terms of IOP reduction and visual field changes. Careful monitoring of blood lipid levels is necessary with long-term treatment with beta blockers, because these agents reduced serum levels of HDL and total cholesterol while increasing triglycerides. Such changes in lipid levels could lead to increased incidence of complications, particularly in patients with atherosclerosis or coronary heart disease.

The authors studied the ocular haemodynamics by means of the Color Doppler Imaging (CDI) technique and the levels of cyclic guanosine monophosphate (cGMP), the intracellular mediator of NO action in plasma and the aqueous humour in a Normal Pressure Glaucoma group and in a normal group. They found significant alterations of both the velocities, systolic and diastolic, in the Ophthalmic Artery and lower cGMP levels in NPGs than in the controls. These data suggest that a disorder of NO regulation processes might be involved in blood supply to the optic nerve and in aqueous humour outflow.

Comparative study of blood rheology in 53 patients (76 eyes) without stabilization of primary glaucoma with normalized intraocular pressure (group 1) and in 43 patients (61 eyes) with stabilized course (group 2) showed significant differences between the two groups. In group 1 erythrocyte aggregation was increased in 79.3% and their deformability decreased in 88.7%; high content of Willebrandt's factor was detected in 83% patients. By contrast, in group 2 these shifts were detected in only 20.9 and 23.3% patients, respectively, while the content of Willebrandt's factor was normal. The detected rheological shifts were in high correlation with an unstable course of glaucoma, and their severity may serve as a prognostic sign for predicting the course of glaucoma in patients with normalized intraocular pressure.

The exact cause of primary open angle glaucoma is still unknown. Intraocular pressure is a major factor but it is impossible to explain the whole mechanism of glaucomatous optic nerve damage with only increased intraocular pressure. Other factors play important roles in the development of glaucoma. With this point of view, vascular factors have been implicated in the pathogenesis of glaucoma. We tried to determine the etiopathogenetic role of decreased erythrocyte deformability in normal tension glaucoma and high-tension glaucoma. The study group consisted of 16 patients with the diagnosis of normal tension glaucoma, 17 patients with the diagnosis of high-tension glaucoma, and 24 patients as controls. Independent t-tests were used to compare the three groups two by two for age, hematocrit, mean cell volume, plasma protein level, cardiovascular risk factors, and erythrocyte deformability. There was no statistically significant relationship (p>0.05) between the groups concerning the erythrocyte deformability. When we consider all of 57 patients, we found that both increasing age (>60 years) and greater mean cell volume (>84 fl) had a statistically significant relationship with decreased erythrocyte deformability (p<0.05). When we performed Pearson correlation analysis, we found that only mean cell volume and erythrocyte deformability had a statistically significant relationship (r = 0.31, p = 0.02). We conclude that decreased erythrocyte deformability is not a major factor in the ethiopathogenesis of normal tension glaucoma and high-tension glaucoma.

Purpose: To determine whether high-density lipoprotein and total cholesterol levels were risk factors for increased intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension., Methods: We measured total cholesterol, high-density lipoprotein, and total cholesterol/high-density lipoprotein ratio in 25 patients with open-angle glaucoma or ocular hypertension who had taken no glaucoma medications for four weeks. We individually matched these patients to 25 control subjects who had no history of open-angle glaucoma or ocular hypertension, on the basis of age, race, gender, and history of vascular disease or diabetes mellitus., Results: We found no statistical difference in the high-density lipoprotein (P = .702) or total cholesterol (P = .177) levels or total cholesterol/high-density lipoprotein ratio between groups (P = .178, paired t test)., Conclusion: This study indicates that increased high-density lipoprotein and total cholesterol levels are not risk factors for increased intraocular pressure.

Purpose: To explore further the potential role autoimmunity may play in the pathogenesis of normal-pressure glaucoma (NPG) in some patients, the authors examined the sera of patients with NPG for the presence of antibodies directed toward retinal antigens., Methods: Using patient sera, immunoblotting was performed on subcellular fractions of retina, purified bovine rhodopsin, and immunoaffinity-purified recombinant human rhodopsin. A chemiluminescence-enzyme-linked immunosorbent assay (ELISA) to detect anti-rhodopsin antibodies was developed and used., Results: A patient with NPG was found to have a high titer of immunoglobulin M-lambda antibody against a 40-kd retina-specific glycoprotein antigen subsequently identified as rhodopsin. ELISA analysis conducted on sera from 28 patients with NPG and 26 patients with primary open-angle glaucoma (POAG) revealed highly significant differences in anti-rhodopsin antibody activity between these groups (P < 0.0002, Mann-Whitney test). For example, the majority of patients with NPG (19/28; 68%) had anti-rhodopsin antibody activity higher than the highest value obtained from among 26 age-matched patients with POAG., Conclusions: An elevated anti-rhodopsin antibody count is related to NPG. This may indicate that there is an autoimmune component in the optic neuropathy in these patients. The specific role of these autoantibodies, if any, in the pathogenesis of the disease remains to be determined.

Impaired ocular blood flow is suspected to be one of the causes of normal tension glaucoma (NTG). We investigated whether endothelin (ET), a potent and continuous vasoacting peptide which was discovered recently, is associated with NTG. Plasma ET-1 levels of 52 patients with NTG but without systemic vascular or circulatory disorders were measured by radioimmunoassay, and were found to be significantly higher than those of 10 normal controls. The patients with NTG in the initial stage of visual field loss (Kosaki's classification) showed higher plasma ET-1 levels than those in the middle stage. These facts suggest that elevated plasma levels of ET-1 are correlated with NTG and its stages. We then studied the effects of ET-1 on rabbit eyes. Intravenous administration of ET-1 (10(-10) mol/kg) induced reductions in both intraocular pressure (IOP) and blood flow in the optic nerve head during three hours' observation, although it affected systemic blood pressure slightly and transiently. Blood flow in the choroid also decreased, but recovered at 90 minutes. Intravitreal injection of ET-1 (10(-5) M, 0.1 ml) also caused reductions in IOP (for 14 days) and in blood flow in the optic nerve head (during three hours' observation). Prolongation of VEP-N1 latency was observed for 14 days. These results indicate that ET-1 may be associated with NTG, especially with blood flow in the optic nerve head.

The effects of 3 mg orally administered dexamethasone on the intraocular pressure (IOP) were examined in four patients with primary open-angle glaucoma hospitalized for this study. Plasma-free glucocorticoid activity was measured by a radioreceptor assay. Diurnal rhythms of IOP and plasma-free glucocorticoid activity were detected prior to administration of dexamethasone. The plasma-free glucocorticoid activity rose two- to threefold in the 30-min period following steroid administration and then declined throughout the rest of the day. IOP was approximately 2 mmHg higher in the 0-4-hr period and approximately 5.5 mmHg higher in the 4-8-hr period following the pharmacologic doses of dexamethasone compared with similar periods on control days. The increase in the IOP was highly significant (P less than 0.006) in the latter time period. These findings suggest that the glucocorticoids may have a greater role in regulating IOP than generally has been appreciated.