Clinical Significance of Albumin- and Bilirubin-Based Biomarkers in Glaucoma: A Retrospective Case-Control Study.

Glaucoma is the second leading cause of global blindness. The etiology of glaucoma is complicated. In addition to elevated intraocular pressure (IOP), several other mechanisms have been implicated in pathogenesis, such as oxidative stress and systemic inflammation. Serum albumin (ALB) and bilirubin (BIL) have been reported to have potent antioxidant properties and contribute to maintain redox homeostasis in various diseases. However, associations between these parameters and glaucoma remain mostly unknown. Here, we conducted a retrospective case-control study, revealing that serum ALB, total BIL (TBIL), and indirect BIL (IBIL) levels were markedly lower in glaucoma patients than those in healthy controls. Furthermore, the neutrophil-to-ALB (NAR), neutrophil-to-TBIL (NTBR), and neutrophil-to-IBIL (NIBR) ratios were greatly higher in glaucoma. Additionally, interestingly, lower ALB and BIL levels and higher NAR, NTBR, and NIBR were associated with severer glaucomatous visual impairment, and NAR, NTBR, and NIBR showed good accuracy as diagnostic tests for glaucoma severity, suggesting these indices might be useful as discriminative biomarkers for disease severity. Our current findings demonstrate associations between ALB, BIL, NAR, NTBR, NIBL, and glaucoma. It might be useful to use NAR, NTBR, and NIBR as predictive markers for disease severity and employ ALB/BIL as alternative therapy or adjuvant medicines in glaucoma patients.

Cholesterol and glaucoma: a systematic review and meta-analysis.

PURPOSE: Intraocular pressure is the main risk factor for glaucoma; however, additional risk factors may also matter. This systematic review and meta-analysis were conducted to summarize the evidence regarding the association of cholesterol parameters (total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels) and glaucoma. METHODS: Four electronic databases were searched for all publications containing 'glaucoma' and one of various forms of 'cholesterol' or 'lipoprotein'. Two independent reviewers screened abstracts and potentially full texts of identified articles for eligibility. Risk of bias was assessed with the Newcastle-Ottawa Scale. A random-effects meta-analysis was used to investigate the differences in total cholesterol, LDL and HDL levels between patients with and without glaucoma. RESULTS: Overall, 29 observational studies were included in the systematic review and 26 reported quantitative information to investigate differences in cholesterol parameters between patients with glaucoma (N = 7196) and patients without glaucoma (N = 350 441). Patients with glaucoma had significantly higher total cholesterol levels than patients without glaucoma (Mean Difference (MD) 7.9 mg/dl, 95% CI 3.3 to 12.5, p = 0.001) and lower mean HDL levels (MD -2.0 mg/dl, 95% CI: -3.1 to -0.9, p = 0.001). Patients with glaucoma had higher mean LDL levels than patients without glaucoma, albeit not statistically significant (MD 6.1 mg/dl, 95% CI: -4.3 to 16.4, p = 0.251). CONCLUSION: This systematic review and meta-analysis of observational studies found an association of glaucoma and high total cholesterol and low HDL levels, respectively. Although this supports the hypothesis that lipid levels pose an additional risk for glaucoma development, heterogeneity was substantial and causality cannot be presumed from identified observational studies.

Association Between the Asymmetric Dimethylarginine Levels and Glaucoma Severity: A Cross-Sectional Analysis of the LIGHT Study.

Purpose: Asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of nitric oxide synthase, may be involved in the pathophysiology of glaucoma by dysfunctioning nitric oxide and oxidative stress. The purpose of this study was to determine whether the serum ADMA level is associated with the severity of glaucoma. Methods: One hundred twenty-five patients with glaucoma (mean age 69.4 years) were analyzed in this cross-sectional study. The severity of glaucoma was determined by the visual field mean deviation in the worse eye; severe, a mean deviation ≤ -12 dB; and mild, a mean deviation > -12 dB. The serum ADMA levels were classified into three groups according to tertiles; low (T1), intermediate (T2), and high group (T3). Results: The mean serum ADMA levels in the severe glaucoma group was significantly higher than that in the mild glaucoma group (0.41 vs. 0.39 µmol/L; P = 0.031). A significantly higher prevalence of patients with severe glaucoma was found in the T3 group than that in the T1 group (T1, 44.7% and T3, 68.2%; P = 0.018). In the multivariable logistic regression analysis adjusted for the potential confounders, e.g., age, sex, obesity, smoking, hypertension, diabetes, and renal function, the odds ratio for severe glaucoma in the T3 group was significantly higher than that in the T1 group (odds ratio 3.02; 95% confidence interval 1.04 to 8.79; P = 0.043). Conclusions: A significant association between higher serum ADMA levels and severe glaucoma was found, and this association remained significant after adjusting for the potential confounders.

Associating the biomarkers of ocular blood flow with lamina cribrosa parameters in normotensive glaucoma suspects. Comparison to glaucoma patients and healthy controls.

PURPOSE: To evaluate association between ocular blood flow biomarkers and lamina cribrosa parameters in normotensive glaucoma suspects compared to glaucoma patients and healthy controls. METHODS: A total of 211 subjects (72 normotensive glaucoma suspects, 70 with primary open-angle glaucoma and 69 controls) were included. Ocular blood flow biomarkers in ophthalmic artery, central retinal artery, as well as in nasal and temporal short posterior ciliary arteries were measured using colour Doppler imaging. Lamina cribrosa position was assessed by measuring its depth, deflection depth, lamina cribrosa shape index and its horizontal equivalent (LCSIH) on B-scan images obtained using optical coherence tomography. RESULTS: Ocular blood flow biomarkers in glaucoma patients were statistically significantly reduced when compared to healthy controls in peak systolic velocity (PSV) (P = 0.001 in ophthalmic artery and P<0.001 in central retinal artery) and mean flow velocity (Vm) (P = 0.008 in ophthalmic artery and P = 0.008 in central retinal artery), but not statistically significantly different to that of glaucoma suspects except for PSV in central retinal artery (P = 0.011). Statistically significant correlations corrected for age, central corneal thickness and intraocular pressure were found in glaucoma patients between LCSIH and end diastolic velocity of central retinal artery (P = 0.011), and of nasal short posterior ciliary artery (P = 0.028), and between LCSIH and Vm of central retinal artery (P = 0.011) and of nasal short posterior ciliary artery (P = 0.007). No significant correlations were observed between these parameters in glaucoma suspects and healthy controls. CONCLUSIONS: Impaired ocular blood flow associated with the deformation of lamina cribrosa was found in glaucoma patients, whereas glaucoma suspects had similar lamina cribrosa shape to glaucoma patients but that deformation was not associated with ocular blood flow biomarkers.

Circulating exosomes in ophthalmic disease: novel carriers of biological information circulating exosomes in ophthalmic disease.

Exosomes, small membrane vesicles with a diameter of 30-100 nm, transport lipids, proteins, DNA, and RNA. Exosomes originate from endocytic vessels and are processed and released through exocytosis. They can be taken up by target cells and mediate intercellular communication. Initially, exosomes were thought to be waste products excreted by cells. However, with more research, they have been found to play important roles in physiological and pathological processes. Therefore, they are promising biomarkers for the diagnosis and treatment of a variety of disease conditions, including fundus diseases, ocular surface diseases, retinal diseases, tumors, ocular trauma, and light damage. In this review, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as their future application prospects in ophthalmic diseases.

Evaluation of aqueous humor and serum clusterin levels in patients with glaucoma.

BACKGROUND: To compare the aqueous humor (AH) and the serum clusterin levels of patients with pseudoexfoliation syndrome (PEX), pseudoexfoliation glaucoma (PEXG), and primary open-angle glaucoma (POAG) with each other and with an age- and sex-matched control group. METHODS: This prospective, cross-sectionalstudy evaluated 92 eyes from 92 adult cases of uncomplicated phacoemulsification and posterior chamber intraocular lens (IOL) implantation. The cases were divided into PEX, PEXG, POAG, and control groups. Serum samples were taken from the antecubital vein just before the surgery, and the AH samples were aspirated at the beginning of the surgery. Kruskal-Wallis H, One-way ANOVA, Mann-Whitney U with Bonferroni correction and Chi-Square tests were used for statistical analysis. RESULTS: The serum clusterin levels were the highest in the PEXG group, but no statistically significant differences were observed between the groups (p=0.633). The mean AH clusterin levels were 286.79±29.64 µg/mL in the PEXG group, 263.92±31.70 µg/mL in the PEX group, 272.59±49.71 µg/mL in the POAG group, and 193.50±62.38 µg/mL in the control group (p< 0.001). This came out to be 1.48 times increase for the PEXG group, 1.36 for the PEX group, and 1.41 for the POAG group when compared with the control subjects. CONCLUSIONS: A higher level of clusterin in the anterior chamber was found to be associated with PEX and PEXG. In addition, a high level of anterior chamber clusterin in POAG, which is a new finding, showed that this molecule might be important not only in pseudoexfoliation, but also other types of glaucoma like POAG.

Association between metabolic risk factors and optic disc cupping identified by deep learning method.

PURPOSE: This study aims to investigate correlation between metabolic risk factors and optic disc cupping and the development of glaucoma. METHODS: This study is a retrospective, cross-sectional study with over 20-year-old patients that underwent health screening examinations. Intraocular pressure (IOP), fundus photographs, Body Mass Index (BMI), waist circumference (WC), serum triglycerides, serum HDL cholesterol (HDL-C), serum LDL cholesterol (LDL-C), systolic blood pressure (BP), diastolic BP, and serum HbA1c were obtained to analyse correlation between metabolic risk factors and glaucoma. Eye with glaucomatous optic neuropathy(GON) was defined as having an optic disc with either vertical cup-to-disc ratio(VCDR) ≥ 0.7 or a VCDR difference ≥ 0.2 between the right and left eyes by measuring VCDR with deep learning approach. RESULTS: The study comprised 15,585 subjects and 877 subjects were diagnosed as GON. In univariate analyses, age, BMI, systolic BP, diastolic BP, WC, triglyceride, LDL-C, HbA1c, and IOP were significantly and positively correlated with VCDR in the optic nerve head. In linear regression analysis as independent variables, stepwise multiple regression analyses revealed that age, BMI, systolic BP, HbA1c, and IOP showed positive correlation with VCDR. In multivariate logistic analyses of risk factors and GON, higher age (odds ratio [OR], 1.054; 95% confidence interval [CI], 1.046-1.063), male gender (OR, 0.730; 95% CI, 0.609-0.876), more obese (OR, 1.267; 95% CI, 1.065-1.507), and diabetes (OR, 1.575; 95% CI, 1.214-2.043) remained statistically significant correlation with GON. CONCLUSIONS: Among the metabolic risk factors, obesity and diabetes as well as older age and male gender are risk factors of developing GON. The glaucoma screening examinations should be considered in the populations with these indicated risk factors.

Gender-Specific Association Between Serum Uric Acid and Incident High Intraocular Pressure in Chinese Population: A Cross-Sectional Study.

Purpose: The purpose of this study was to investigate the relationship between high intraocular pressure (IOP) and uric acid. Methods: In a retrospective cross-sectional study, 19,147 participants were included in 2018. Serum uric acid (SUA) was cut to four groups as Q1 to Q4, according to the quartiles. The odds ratio (OR) and 95% confidence interval (CI) of different SUA levels were estimated by a binomial logistic regression model in men and women. A restrictive cubic spline method was used to estimate the dose-response relationship between uric acid and high IOP. Subgroup analysis was performed to find the gender-specific association between uric acid and high IOP. Results: In women, after adjusting for confounding factors, the Q3 and Q4 of SUA levels were significantly associated with the risk of high IOP. The OR with 95% CI for Q3 and Q4 were 1.77 (1.22, 2.57) and 1.51 (1.01, 2.26), respectively, Q1 as a reference. For men, SUA levels were not associated with the incidence of high IOP. Moreover, the spline analysis found an inverted U-shaped relationship between uric acid and high IOP in women (P = 0.0171). Conclusions: Elevated levels of SUAwere independently associated with an increased risk of high IOP in women, but not in men. In addition, uric acid had an inverse U-shaped nonlinear dose-response relationship with high IOP in women.

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.

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.

The relationship between glutathione levels in leukocytes and ocular clinical parameters in glaucoma.

PURPOSE: To investigate the effect of mitochondrial dysfunction on the autoregulation of blood flow, by measuring levels of glutathione, an indicator of mitochondrial dysfunction, in glaucoma patients. METHODS: Fifty-six OAG patients and 21 age-matched controls underwent a blood assay. Mitochondrial function was measured according to the levels of total glutathione (t-GSH), reduced GSH (GSH), and oxidized GSH (GSSG, glutathione disulfide) in peripheral blood mononuclear cells. Ocular blood flow in the optic nerve head was assessed with laser speckle flowgraphy parameters, including acceleration time index (ATI). We determined correlations between these measurements and other clinical parameters. Furthermore, we investigated the association between glutathione levels and glaucoma with a logistic regression analysis. Finally, we calculated the area under the receiver operating characteristic (ROC) curve in order to determine the power of redox index (the log GSH/GSSG ratio) to distinguish the groups. RESULTS: OAG patients demonstrated significantly higher GSSG levels and a lower redox index than the controls (p = 0.01, p = 0.01, respectively), but total GSH and reduced GSH levels were similar in the OAG subjects and controls (p = 0.80, p = 0.94, respectively). Additionally, redox index was significantly correlated with mean deviation (MD) of the visual field (r = 0.29, p = 0.03) and ATI (r = -0.30, p = 0.03). Multiple linear regression analysis showed that redox index contributed to MD (p = 0.02) and ATI (p = 0.04). The receiver operating characteristic curve (AUC) analysis suggested that redox index could differentiate between control eyes and eyes with glaucoma (AUC; 0.70: 95% interval; 0.57-0.84). The cutoff point for redox index to maximize its sensitivity and specificity was 2.0 (sensitivity: 91.1%, specificity: 42.9%). CONCLUSIONS: These results suggest that redox index is lower in OAG patients than in controls. Thus, it is possible that mitochondrial dysfunction contributes to glaucoma pathogenesis by causing vascular alterations.

Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner.

Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.

Glucose Tolerance Levels and Circumpapillary Retinal Nerve Fiber Layer Thickness in a General Japanese Population: The Hisayama Study.

PURPOSE: To investigate the relationship between glucose tolerance levels and the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in a general Japanese population. DESIGN: Population-based, cross-sectional study. METHODS: In 2012 and 2013, a total of 2809 Japanese community dwellers aged 40-79 years in the Hisayama Study underwent eye examinations including cpRNFLT measurement with spectral domain optical coherence tomography. Of these, 1324 subjects (578 men and 746 women) were enrolled. Glucose tolerance levels were determined by a 75-g oral glucose tolerance test. We conducted an analysis of covariance to estimate the mean values of cpRNFLT according to the subjects' glucose intolerance status. RESULTS: The subjects with prediabetes or with diabetes mellitus had significantly lower age- and sex-adjusted mean cpRNFLT values than those with normal glucose tolerance (P = .04 and P = .0004, respectively). The age- and sex-adjusted mean values of cpRNFLT decreased significantly with elevating fasting plasma glucose and 2-hour postload glucose levels (all P for trend < .05). These associations were substantially unchanged after adjustment for potential confounding factors. The coexistence of poorer glucose tolerance and higher intraocular pressure levels was additively associated with thinner cpRNFLT. CONCLUSIONS: Our analyses revealed that poorer glucose tolerance was significantly associated with the reduction of cpRNFLT in a Japanese general population, suggesting that the loss of neural tissue in the eye begins at the prediabetic stage, and that hyperglycemia may play a role in the reduction of cpRNFLT.

Platelet-generated amyloid beta peptides in Alzheimer's disease and glaucoma.

Amyloid beta (Aß) peptides have been implicated in both Alzheimer's disease (AD) and glaucoma and have been shown to be the key etiological factor in these dangerous health complications. On the other hand, it is well known that Aß peptide can be generated from its precursor protein and massively released from the blood to nearby tissue upon the activation of platelets due to their involvement in innate immunity and inflammation processes. Here we review evidence about the development of AD and glaucoma neuronal damage showing their dependence on platelet count and activation. The correlation between the effect on platelet count and the effectiveness of anti-AD and anti-glaucoma therapies suggest that platelets may be an important player in these diseases.

Potential metabolic markers in glaucoma and their regulation in response to hypoxia.

PURPOSE: To assess novel differences in serum levels of glucose, lactate and amino acids in patients with normal-tension glaucoma (NTG) compared to age-matched controls, at baseline and in response to universal hypoxia. METHODS: Twelve patients diagnosed with NTG and eleven control subjects underwent normobaric hypoxia for 2 hr. Peripheral venous blood samples were taken at baseline, during hypoxia and in the recovery phase. Serum glucose and lactate levels were measured by a blood gas analyser. Amino acids were analysed by high-performance liquid chromatography. RESULTS: Baseline levels of lactate and total amino acids were significantly lower in patients with NTG compared to healthy controls. No differences were seen in blood glucose levels between the two groups. Lactate levels remained unchanged during hypoxia in the control group, but increased in patients with NTG. In the recovery phase, total amino acid levels were reduced in the control group, whereas no changes were found in patients with NTG. CONCLUSION: Reduced serum levels of lactate and total amino acids were identified as potential markers for NTG. Moreover, significant differential regulatory patterns of certain amino acids were found in patients with NTG compared to control subjects. Overall, our results suggest a link between systemic energy metabolites and NTG and support a novel understanding of glaucoma as an inner retinal manifestation of a systemic condition.

The Association of Serum Vitamin D Levels with Pseudoexfoliation Glaucoma/Syndrome

OBJECTIVE: To investigate whether serum vitamin D levels have an effect on pseudoexfoliation (PEX) glaucoma/syndrome development and on the control of glaucoma in these cases. METHOD: A total of 31 cases with PEX glaucoma, 34 cases with the PEX syndrome and 43 control subjects of similar age and sex were included in the study. Vitamin D levels were compared between the groups and also between the cases where glaucoma surgery was performed or not. RESULTS: PEX glaucoma group consisted of 17 males and 14 females, PEX syndrome group of 27 males and 7 females, and the control group of 27 males and 16 females. The mean age was 70.9±8.9 years, 72.1±7.3 years, and 67.9±9.1 years in PEX glaucoma, syndrome and control group, respectively. Mean vitamin D levels were 9.4±7.7 ng/mL, 7.9±6,1 ng/mL, 11.5±14.2 ng/mL in PEX glaucoma, syndrome and control group, respectively (p>0.05). The mean serum vitamin D level was 8.04±4.7 ng/mL in those who underwent glaucoma surgery and 10.1±8.7 ng/mL in those who didn't undergo glaucoma surgery in PEX glaucoma group (p>0.05). No difference was found between the PEX glaucoma sub- groups in terms of the mean deviation when classified according to vitamin D levels (<10 ng/mL, ≥10 ng/mL) (p>0.05). CONCLUSION: Although we found no statistically significant difference between the PEX syndrome/glaucoma, and control group in terms of serum vitamin D levels, serum vitamin D levels were lower in PEX syndrome and glaucoma group than control group. Our results indicate that serum vitamin D levels have no effect on the development of PEX glaucoma/syndrome or the control of the disorder in cases with PEX glaucoma. However, these results need to be supported with further studies on a larger number of patients and with longer follow-up.

Comparison of T Helper Cell Patterns in Primary Open-Angle Glaucoma and Normal-Pressure Glaucoma.

BACKGROUND HSP60-related immunological activities are found in normal-pressure glaucoma (NPG) patients, in whom an elevated intraocular pressure (IOP) found in primary open-angle glaucoma (POAG) is not observed. HSP60 was found in POAG and NPG patients, while anti-HSP60 level was mainly found to be higher in NPG patients. The purpose of this study was to compare the percentages of Th cells and levels of related cytokines, attempting to provide evidence to explain this discrepancy. MATERIAL AND METHODS Blood samples from POAG, NPG, and normal control (NC) groups were collected and peripheral blood monocytes were isolated and cultured with or without the stimulation of HSP60. Flow cytometry and enzyme-linked immunosorbent assay were used to assess the percentages of Th1, Th2, Th17, and Treg cells, as well as HSP60 antibody levels and related cytokine levels, before and after culture. RESULTS Significantly higher titers of anti-HSP60 were observed only in NPG patients. Comparable Th1 and Th2 cell frequencies, IL-4 level, and IFN-γ level were found in POAG and NPG patients, while higher Treg cell frequency was only found in POAG patients. After culturing with HSP60, increased Th2 frequencies and decreased Th1 frequencies were observed in the POAG, NPG, and NC groups, while increased Treg frequency was only identified in the POAG and NC groups. CONCLUSIONS Different Th cell patterns were observed among POAG, NPG, and NC groups. Lack of induction of Treg cells and imbalance of the pro-inflammatory and anti-inflammatory response patterns of Th cells exist in some NPG patients.

Longitudinal changes in intraocular pressure and association with systemic factors and refractive error: Lingtou Eye Cohort Study.

OBJECTIVES: To investigate the longitudinal changes in intraocular pressure (IOP) and its associations with refractive error and systemic determinants in a Chinese geriatric population. DESIGN: Prospective cohort study. SETTING: Guangzhou Government Servant Physical Check-up Center, Guangzhou, China. PARTICIPANTS: 4413 government employees aged no less than 40 years (41.9% female) attending annual physical and eye examinations were included in this study. The inclusion criterion was having attended the 2010 follow-up examination. The exclusion criteria include glaucoma or intraocular surgery history, IOP >21 mm Hg at any visit or without available IOP data at all visits from 2010 to 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was IOP at each follow-up visit from 2010 to 2014. Mixed-effect model was used to assess the relationship between longitudinal changes in IOP and potential risk factors. RESULTS: For the 2653 participants who had available IOP data at both the 2010 and 2014 follow-up visits, the average change in IOP was an increase of 0.43 (95% CI 0.36 to 0.50) mm Hg. For the whole study population and in the optimised mixed model, there was a non-linear increase of IOP with age (P<0.001), with greater changes in younger subjects and in women (P<0.001 and P=0.002, respectively). Elevations in systolic blood pressure, diastolic blood pressure, body mass index (BMI) and fasting plasma glucose (FPG), as well as a myopic shift (all with P<0.001), during the follow-up were associated with an increasing trend of IOP, while serum lipids were found to be not significantly associated. CONCLUSIONS: In this cohort of elderly Chinese adults, IOP increases non-linearly with ageing. People with increasing blood pressure, BMI, FPG and myopic progression are more likely to have IOP elevation over time.

Lack of Association between Serum Vitamin B6, Vitamin B12, and Vitamin D Levels with Different Types of Glaucoma: A Systematic Review and Meta-Analysis.

Although vitamins play a major role in health, and their deficiency may be linked to symptoms of optic-nerve dysfunction, the association between serum vitamin levels and glaucoma in humans remains controversial. In this study, articles in the PubMed, Web of Science, and EMBASE databases were searched up to 25March 2017. Nine studies on primary open-angle glaucoma (POAG), four studies on normal tension glaucoma (NTG), and six studies on exfoliative glaucoma (EXG) were retrieved. The combined results showed no differences in the levels of serum vitamin B6 between POAG (p = 0.406) and EXG (p = 0.139) patients and controls. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were 2.792 ng/mL (-3.793 to 9.377) and 1.342 ng/mL (-3.120 to 0.436), respectively. There was no difference between POAG (p = 0.952), NTG (p = 0.757), or EXG (p = 0.064) patients and controls in terms of serum vitamin B12. The WMDs with 95% CIs were 0.933 pg/mL (-31.116 to 29.249), 6.652 pg/mL (-35.473 to 48.777), and 49.946 pg/mL (-102.892 to 3.001), respectively. The serum vitamin D levels exhibited no differences (p = 0.064) between POAG patients and controls; the WMD with 95% CI was 2.488 ng/mL (-5.120 to 0.145). In conclusion, there was no association found between serum vitamin B6, vitamin B12, or vitamin D levels and the different types of glaucoma.

Anticentromere antibody positive Ackerman's Syndrome with Granulomatous Anterior Uveitis.

Ackerman's Syndrome or Intersticial Granulomatous Dermatitis with Arthritis has been an issue of increasing number of reports in the last decade which had focused its heterogeneous cutaneous and rheumatologic expression besides the initial manifestations reported by Ackerman and his group. Granulomatosis anterior uveitis has not been previously described. Some patients are reported to have positive autoantibodies but association with anticentromere antibodies has not been previously described as well, to our knowledge. We report a new case of Ackerman Syndrome with cutaneous, articular and ocular involvement with positive anticentromere antibodies successfully treated with systemic steroids, methotrexate, hydroxychloroquine and cyclosporine. The ocular involvement and the association of anticentromere antibodies lead us to hypothesize that constellation of symptoms and autoimmune mechanisms of this uncommon multisystemic syndrome are yet to be clarified.