Prolidase activity in aqueous and serum samples of cataract cases with Pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PEX) represents an age-related systemic disease that is characterized by the accumulation of extracellular matrix material in ocular tissues and visceral organs. Abnormal matrix remodeling is thought to be one of the important factors in the etiopathogenesis of the disease. Prolidase represents an enzyme, which takes a significant part in collagen biosynthesis and remodeling of the extracellular matrix. The purpose of the current research was to assess the prolidase enzyme activity in the aqueous and serum samples of subjects with PEX. The study population consisted of 66 subjects, involving 33 subjects with age-related cataract among patients with PEX and 33 subjects with age-related cataract without PEX. The prolidase activity measurement was performed using the modified Chinard's method. Significantly increased aqueous prolidase activity was detected in the group with PEX (p < 0.01). Despite about a three times higher increase in the serum prolidase activity of the group with PEX in comparison with the control group, the two groups did not differ statistically significantly (p > 0.05). The high prolidase enzyme activity in the aqueous samples of subjects with PEX suggests that the collagen cycle and the remodeling of the extracellular matrix are accelerated. These results can be a guide for understanding the formation mechanisms of PEX.

Serological Levels of Anti-clathrin Antibodies Are Decreased in Patients With Pseudoexfoliation Glaucoma.

Evidence for immunologic contribution to glaucoma pathophysiology is steadily increasing in ophthalmic research. Particularly, an altered abundance of circulating autoantibodies to ocular antigens is frequently observed. Here, we report an analysis of autoantibody abundancies to selected antigens in sera of open-angle glaucoma patients, subdivided into normal-tension glaucoma (N = 31), primary open-angle glaucoma (N = 43) and pseudoexfoliation glaucoma (N = 45), vs. a non-glaucomatous control group (N = 46). Serum samples were analyzed by protein microarray, including 38 antigens. Differences in antibody levels were assessed by ANOVA. Five serological antibodies showed significantly altered levels among the four groups (P < 0.05), which can be used to cluster the subjects in groups consisting mainly of PEXG or POAG/NTG samples. Among the altered autoantibodies, anti-Clathrin antibodies were identified as most important subgroup predictors, enhancing prospective glaucoma subtype prediction. As a second aim, we wanted to gain further insights into the characteristics of previously identified glaucoma-related antigens and their role in glaucoma pathogenesis. To this end, we used the bioinformatics toolset of Metascape to construct protein-protein interaction networks and GO enrichment analysis. Glaucoma-related antigens were significantly enriched in 13 biological processes, including mRNA metabolism, protein folding, blood coagulation and apoptosis, proposing a link of glaucoma-associated pathways to changes in the autoantibody repertoire. In conclusion, our study provides new aspects of the involvement of natural autoimmunity in glaucoma pathomechanisms and promotes advanced opportunities toward new diagnostic approaches.

Evaluation of thiol-disulfide homeostasis in pseudoexfoliation glaucoma and primary open-angle glaucoma.

AIMS: This study aimed to compare the serum thiol-disulfide homeostasis, total antioxidant status (TAS), and total oxidant status (TOS) in patients with pseudoexfoliation glaucoma (PEG) patients, primary open-angle glaucoma (POAG) patients, and healthy individuals (control). METHODS: Ninety subjects were included in this study. Three groups were separated as PEG, POAG, and control. All groups were chosen to be similar in terms of age and gender. Blood samples were obtained following an overnight fasting state and were collected on the ice at 4°C. The serum samples were separated from the cells by centrifugation at 3000 rpm for 15 min and were stored at -80°C. Serum samples analyzed for TAS and TOS, native thiol, total thiol, disulfide, and native thiol/disulfide ratio. RESULTS: TAS and TOS levels of PEG patients were 1.2892 ± 0.0905 mmol/L; 5.0191 ± 2.7722 µmol/L, respectively. TAS and TOS levels of POAG patients were 1.2741 ± 0.1252 mmol/L; 4.1674 ± 1.7723 µmol/L, respectively. TAS and TOS levels of the control group were 2.3414 ± 0.1409 mmol/L; 4.0931 ± 0.1107 µmol/L, respectively. The TAS level was significantly lower in PEG and POAG groups compared to control. TOS level showed no significant differ ¬ ence between PEG, POAG, and control groups (P > 0.05). The mean serum total thiol and native thiol levels were significantly lower in patients with PEG compared to POAG and control group; there was no significant difference between the POAG and control group (P > 0.05). The mean serum disulfide level was significantly lower in patients with PEG compared to POAG (P = 0.018). CONCLUSION: Low levels of TAS were observed in patients with glaucoma, which was likely a response to the increased oxidative stress observed in these patients. While total thiol and native thiol levels were higher in the PEG group, the disulfide level was higher in the POAG group. TAS and TOS levels showed no significant difference between POAG and PEG groups.

Is Netrin-1 Deficiency Responsible for Inflammation and Systemic Diseases Related to Pseudoexfoliation?

PRECIS: Serum netrin-1 levels are significantly lower in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PEG) compared with the control group. PURPOSE: To investigate serum netrin-1 levels in PES and PEG patients and to determine the relevance of this molecule in the etiopathogenesis of PES-related and PEG-related diseases. MATERIALS AND METHODS: This prospective study included 29 PES and 17 PEG patients in the study groups and age-sex matched 47 cataract patients without pseudoexfoliative accumulation as a control group. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum netrin-1 level was significantly lower in the PES and PEG groups compared with the control group (P=0.007). Multinominal logistic regression analysis was performed in terms of netrin-1 levels ≤712.9 pg/mL, >712.9 pg/mL and sex which may affect PES and PEG. It were found that netrin-1 was a significant negative predictor for PES (odds ratio, 3.45; 95% confidence interval, 1.230-9.716; P=0.019) and PEG (odds ratio, 3.57; 95% confidence interval, 1.008-12.669; P=0.049), respectively. CONCLUSIONS: Decreased serum netrin-1 levels were detected in PES and PEG patients, similar to atherosclerosis and Alzheimer disease. Inflammation lays behind in the common pathogenesis of these diseases. Therefore, netrin-1 promises a potential anti-inflammatory role.

[Determination of cytokines in the blood serum and in the aqueous humor of the anterior camera during pseudoexfoliative syndrome and cataract.]

There have been studied changes of proinflammatory cytokines, IL-1ß and TNF-α, in anterior chamber aqueous humor and in blood serum before cataract surgery in 81 patients with cataract. Of these, 46 patients had verified diagnosis of pseudoexfoliative syndrome (PEÐ¥) of varying degree of manifestation of dystrophic changes and deposits of pseudoexfoliative material (main group). In 35 patients, PES (comparison group) has not been detected. 2-stage biomicroscopy (with a narrow pupil, after tonometry with mydriasis) and ultrasound biomicroscopy (UBM) have been conducted. According to the results of biomicroscopy and UBM structures of the eye, 3 stages of development of PEX have been identified: I - 11 (23,91%), II - 20 (43,48%), III - 15 (32,61%). Inflammatory complications after cataract surgery have been in 17,39% of eyes with PEÐ¥, of which PEX Stage II in 13,04% and PEÐ¥ Stage III in 4,35%. There have been no complications in the eyes with PEX Stage I and without PEX. In comparison with patients without PEX, significant differences in the indicators of IL-1ß and TNF-α both in the blood serum and in the aqueous humor of the anterior chamber of patients with PEX have been found. In particular, there have been confirmed significant differences of indicators depending on the stage of development of changes during PEX. At the same time, higher concentrations of IL-1ß and TNF-α during PEX, as well as somatic pathologies in patients with PES occurring 2 times more often, confirm the opinion that PEX should be considered as pathology of the organ of vision. Thus, decrease in the compensatory abilities of the body with age and a set of chronic age-related pathology form the pathogenetic mechanisms of PEX, including age-related changes in structures and surgery background in older patients, to a certain extent predetermining the nature and features of the postoperative period and possible complications.

Serum Apelin and Asymmetric Dimethylarginine Levels in Patients With Exfoliation Syndrome or Exfoliative Glaucoma.

PRéCIS:: Apelin and asymmetric dimethylarginine (ADMA) concentrations, affecting the nitric oxide pathway, were different in the patient group compared with the control subjects. These 2 molecules may have potential effects in vascular pathologies and their possible role in predisposition to vascular comorbidities in exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). PURPOSE: To evaluate apelin and ADMA levels in serum samples from patients with XFS or XFG compared with healthy control subjects. METHODS: Serum ADMA and apelin concentrations were evaluated from 36 and 32 XFS patients; 27 and 24 XFG patients; and 34 and 30 healthy controls, respectively. Subjects without systemic disease (including diabetes mellitus, hypertension, coronary artery disease, obesity) were included in the study and body mass index was calculated in all participants. An enzyme-linked immunosorbent assay and high-performance liquid chromatography were used to determine serum apelin and ADMA concentrations. Independent sample t test, χ test, analysis of variance test, and Pearson test were used for statistical analysis. RESULTS: Mean serum apelin levels of XFG, XFS, and control group were 1063.3±373.4, 1196.7±433.7, and 1343.3±405.1 ng/mL, respectively. Patients with XFG demonstrated significantly lower level of apelin versus controls (P=0.034). Mean serum ADMA concentration was significantly greater in XFS subjects (2.05±0.98 µmol/L) compared with normal controls (1.57±0.58 µmol/L) (P=0.042). No association was detected between ADMA and apelin concentrations and age, sex, and body mass index for both XFS and XFG groups. CONCLUSIONS: Significant alterations in serum levels of apelin and ADMA may suggest potential effects in vascular pathologies and a possible role in predisposition to vascular comorbidities in XFS/XFG.

Monocyte/HDL Ratio and Lymphocyte/Monocyte Ratio in Patients with Pseudoexfoliation Syndrome.

Purpose: To evaluate the association between monocyte count/high-density lipoprotein (HDL) ratio (MHR) and lymphocyte count/monocyte count ratio (LMR) with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG).Materials and Methods: A total of 63 participants included in the study. Participants were divided into three groups. Twenty-one patients with PEXS regarded as group 1, 21 patients with PEXG regarded as group 2 and 21 participants without PEXS or PEXG regarded as the control group. Blood parameters were accessed from file records and database retrospectively.Results: The mean MHRs were significantly higher in group 1 and group 2 (p = 0.003, p = 0.036) than the control group, whereas there was no difference between group 1 and group 2 (p = 0.686). The mean LMRs were lower in group 1 and group 2 than the control group but the difference was insignificant (p = 0.232).Conclusion: We found that there is an association between higher MHR and lower LMR with PEXS.

Atherogenic indices in pseudoexfoliation syndrome.

OBJECTIVES: Evaluation of atherogenic indices in patients with pseudoexfoliation syndrome (PEXS) by traditional serum lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and non-HDL-c] and non-traditional serum lipid ratios [TC/HDL-c, TG/HDL-c, LDL-c/HDL-c and non-HDL-c/HDL-c]. METHODS: A total of 100 patients were included in the study. Fifty patients diagnosed with PEXS were regarded as group 1 and 50 patients without PEXS were regarded as group 2, respectively. RESULTS: The median TC, TG, LDL-c, HDL-c and non-HDL-c values were significantly higher in group 1 compared to group 2 (p = 0.007, p = 0.025, p = 0.016, p = 0.015 and p = 0.042, respectively). But there were no significant differences in the TC/HDL-c, TG/HDL-c, LDL-c/HDL-c and non-HDL-c/HDL-c ratios among the two groups (p = 0.581, p = 0.617, p = 0.292 and p = 0.583, respectively). CONCLUSIONS: Non-traditional serum lipid ratios are superior to traditional serum lipid profiles for identifying the risk of vascular disease and this study did not demonstrate a complete relationship between PEXS and increased risk of vascular disease.

Serum levels of thyroid hormone, vitamin D, vitamin B12, folic acid, C-reactive protein, and hemoglobin in Pseudoexfoliation and primary open angle Glaucoma.

PURPOSE: To examine levels of serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), vitamin D, vitamin B12 (B12), folic acid (FA), c-reactive protein (CRP), and hemoglobin in pseudoexfoliation glaucoma (XFG) and primary open angle glaucoma (POAG) patients. MATERIALS AND METHODS: A hospital-based, prospective, cross-sectional study was conducted from October 2016 through June 2017 and October 2017 through January 2018. The number of patients was 33 in the control group, 29 in the XFG group and 77 in the POAG group. RESULTS: The mean±SD levels of TSH, fT4, fT3, vitamin D, B12, FA, CRP, and hemoglobin were 2.52±2.07 mU/l, 1.15±0.24ng/dl, 3.16±3.37pg/ml, 20.83±14.06ng/ml, 318.29±115.48pg/ml, 7.7±4.01ng/ml, 3.78±3.83mg/l, 13.36±2.08g/dl in control group respectively. The levels for the XFG patients were as follows: TSH 2.02±1.16 mU/l, fT3 3.10±0.46pg/ml, fT4 1.18±0.19ng/dl, vitamin D 20.02±19.30ng/dl, B12 302.13±142.44pg/ml, FA 9.55±3.67ng/ml, CRP 3.69±3.22mg/l, and hemoglobin 13.58±1.38g/dl. In the POAG group, serum levels of TSH, fT4, fT3, vitamin D, B12, FA, CRP, and hemoglobin were 1.88±1.13 mU/l, 1.23±0.14ng/dl, 3.16±0.43pg/ml, 15.7±12.0ng/ml, 297.71±150.66pg/ml, 9.1±4.1ng/ml, 4.16±5.12mg/l, and 14.09±1.45 respectively. Only mean vitamin D levels show a significant difference between the control group and POAG (p=0.015). CONCLUSION: POAG patients show decreased Vitamin D levels. Our study shows no significant differences in other biochemical markers between XFG, POAG and control subjects.

Identification of Candidate miRNA Biomarkers for Glaucoma.

Purpose: Glaucoma, a leading cause of blindness worldwide, often remains undetected until irreversible vision loss has occurred. Treatments focus on lowering intraocular pressure (IOP), the only modifiable and readily measurable risk factor. However, IOP can vary and does not always predict disease progression. MicroRNAs (miRNAs) are promising biomarkers. They are abundant and stable in biological fluids, including plasma and aqueous humor (AqH). We aimed to identify differentially expressed miRNAs in AqH and plasma from glaucoma, exfoliation syndrome (XFS), and control subjects. Methods: Plasma and AqH from two ethnic cohorts were harvested from glaucoma or XFS (often associated with glaucoma, n = 33) and control (n = 31) patients undergoing elective surgery. A custom miRNA array measured 372 miRNAs. Molecular target prediction and pathway analysis were performed with Ingenuity Pathway Analysis (IPA) and DIANA bioinformatical tools. Results: Levels of miRNAs in plasma, a readily accessible biomarker source, correlated with miRNA levels in AqH. Twenty circulating miRNAs were at least 1.5-fold higher in glaucoma or XFS patients than in controls across two ethnic cohorts: miR-4667-5p (P = 4.1 × 10-5), miR-99b-3p (P = 4.8 × 10-5), miR-637 (P = 5.1 × 10-5), miR-4490 (P = 5.7 × 10-5), miR-1253 (P = 6.0 × 10-5), miR-3190-3p (P = 3.1 × 10-4), miR-3173-3p (P = 0.001), miR-608 (P = 0.001), miR-4725-3p (P = 0.002), miR-4448 (P = 0.002), and miR-323b-5p (P = 0.002), miR-4538 (P = 0.003), miR-3913-3p (P = 0.003), miR-3159 (P = 0.003), miR-4663 (P = 0.003), miR-4767 (P = 0.003), miR-4724-5p (P = 0.003), miR-1306-5p (P = 0.003), miR-181b-3p (P = 0.004), and miR-433-3p (P = 0.004). miR-637, miR-1306-5p, and miR-3159, in combination, allowed discrimination between glaucoma patients and control subjects (AUC = 0.91 ± 0.008, sensitivity 85.0%, specificity 87.5%). Conclusions: These results identify specific miRNAs as potential biomarkers and provide insight into the molecular processes underlying glaucoma.

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.

YKL-40 is a local marker for inflammation in patients with pseudoexfoliation syndrome.

PURPOSE: To investigate the YKL-40, as a marker of inflammation, in aqueous humor and serum of cataract patients with and without pseudoexfoliation syndrome (PEX). METHODS: Aqueous humor and serum samples were obtained from 44 patients who underwent phacoemulsification surgery. All patients were divided into two groups: PEX (n = 24) and control (n = 20). YKL-40 levels were measured with enzyme-linked immunosorbent assay (ELISA). The differences between the groups were assessed by using Chi-square and independent sample t-tests. The Pearson correlation coefficient was used to evaluate the correlation between variables. RESULTS: There was a significant difference between the mean YKL-40 levels in the aqueous humor of PEX group (112.0 ± 35.8 ng/mL) and control subjects (88.2 ± 30.6 ng/mL) (P = 0.025). However, the difference between the mean YKL-40 levels in the serum of PEX group (53.5 ± 29.1 ng/mL) and control subjects (44.6 ± 30.2 ng/mL) was non-significant (P = 0.326). The correlation between aqueous humor and serum YKL-40 concentrations was significant in both the groups (r = 0.833, P < 0.001; r = 0.840, P < 0.001, respectively). CONCLUSIONS: Increased aqueous humor levels of YKL-40 demonstrate that it is local, but not a systemic marker for inflammation in patients with PEX.

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome / Avaliação dos níveis de renina e angiotensina II na síndrome de pseudo-exfoliação

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

RESUMO Objetivo: A síndrome de pseudo-exfoliação tem sido associada ao comprometimento da função do coração e dos vasos sanguíneos. Foi realizado um estudo para investigar o papel do sistema renina-angiotensina na etiopatogenia da síndrome de pseudo-exfoliação. Métodos: Os sujeitos foram 14 pacientes com síndrome de pseudo-exfoliação e 14 controles saudáveis submetidos à extração de catarata. Amostras pré-operatórias de 5 ml de sangue venoso periférico e humor aquoso perioperatório foram coletadas dos pacientes em ambos os grupos. Os níveis de renina no plasma e humor aquoso foram analisados pelo método imunorradiométrico e os níveis de angiotensina II foram analisados por radioimunoensaio. O SPSS versão 16.0 foi utilizado para análises estatísticas. Considerou-se o valor de p<0,05 para indicar uma diferença estatisticamente significativa. Resultados: A média de idade dos pacientes nos grupos pseudo-exfoliação e controle foi de 71,7 ± 7,1 e 67,4 ± 9,3 anos, respectivamente (p=0,140). O nível médio de renina no humor aquoso foi de 7,73 pg / ml (4,15-21) no grupo controle e 11,95 pg/ml (3,75-18,54) no grupo pseudo-exfoliação (p=0,022). Não houve diferenças entre os dois grupos de renina plasmática, angiotensina II plasmática ou nos níveis de angiotensina II em humor aquoso. As correlações entre os níveis de renina no plasma e no humor aquoso e entre os níveis de angiotensina II no plasma e humor foram examinadas separadamente para cada grupo; n]ao foram observadas correlações significativas no grupo pseudo-exfoliação (r=-0,440, p=0,115; r=-0,414, p=0,142) ou no grupo controle (r=-0,232, p=0,425; r=0,482, p=0,081). Conclusão: Os níveis de renina no humor aquoso são mais elevados na síndrome de pseudo-exfoliação. Os resultados indicam um provável papel do sistema renina-angiotensina na síndrome de pseudo-exfoliação. Novos estudos com maior número de casos são necessários para esclarecer a associação precisa do sistema renina-angiotensina com a etiopatogenia da síndrome de pseudo-exfoliação.

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome.

PURPOSE: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. METHODS: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. RESULTS: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). CONCLUSION: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

A Plasma Metabolomic Signature of the Exfoliation Syndrome Involves Amino Acids, Acylcarnitines, and Polyamines.

Purpose: To determine the plasma metabolomic signature of the exfoliative syndrome (XFS), the most common cause worldwide of secondary open-angle glaucoma. Methods: We performed a targeted metabolomic study, using the standardized p180 Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer, to compare the metabolomic profiles of plasma from individuals with XFS (n = 16), and an age- and sex-matched control group with cataract (n = 18). Results: A total of 151 metabolites were detected correctly, 16 of which allowed for construction of an OPLS-DA model with a good predictive capability (Q2cum = 0.51) associated with a low risk of over-fitting (permQ2 = -0.48, CV-ANOVA P-value <0.001). The metabolites contributing the most to the signature were octanoyl-carnitine (C8) and decanoyl-carnitine (C10), the branched-chain amino acids (i.e., isoleucine, leucine, and valine), and tyrosine, all of which were at higher concentrations in the XFS group, whereas spermine and spermidine, together with their precursor acetyl-ornithine, were at lower concentrations than in the control group. Conclusions: We identified a significant metabolomic signature in the plasma of individuals with XFS. Paradoxically, this signature, characterized by lower concentrations of the neuroprotective spermine and spermidine polyamines than in controls, partially overlaps the plasma metabolomic profile associated with insulin resistance, despite the absence of evidence of insulin resistance in XFS.

Serum and Aqueous Humor Levels of Fetuin-A in Pseudoexfoliation Syndrome.

PURPOSE: To evaluate serum and aqueous humor levels of fetuin-A in patients with pseudoexfoliation syndrome (PEXS) in comparison with those of age- and sex-matched healthy subjects. MATERIALS AND METHODS: This prospective study included 25 patients with PEXS and 25 control subjects who were undergoing cataract surgery without any systemic or ocular disease. Aqueous humor and serum fetuin-A levels were measured with enzyme-linked immunosorbent assay method. RESULTS: The mean age of the PEXS group (14 males, 11 females, n = 25) was 57.7 ± 6.9 years, and the control group (13 males, 12 females, n = 25) was 58.1 ± 5.7 years. There was no difference between the groups in terms of age (p = 0.77) and sex (p = 0.83). The mean serum fetuin-A level of the PEXS group did not differ from that of the control group (p = 0.53). The mean aqueous humor level of the PEXS group was significantly higher than that of the control group (p = 0.032). There were no significant correlations between aqueous humor and serum fetuin-A levels among patients with PEXS and control group (p > 0.05). CONCLUSIONS: Increased levels of fetuin-A in aqueous humor of patients with PEXS may show the local effect of fetuin-A on the anterior segment. With considering the wide range of possible biological functions of fetuin-A in the pathogenesis of PEXS, further studies are needed to clarify the clinical relevance of these findings.

Thiol Disulfide Homeostasis in Pseudoexfoliation Syndrome.

PURPOSE: To determine the serum thiol disulfide homeostasis in patients with pseudoexfoliation (PEX) syndrome. METHOD: Thirty-five patients with PEX syndrome and forty healthy subjects were included in this observational case-control study. Serum native thiol, total thiol, disulfide, and native thiol/disulfide ratio were determined using a novel and automated assay. RESULTS: The mean serum total thiol and native thiol levels were significantly lower in patients with PEX syndrome compared to healthy controls (p = 0.001). The mean serum disulfide level was significantly higher in patients with PEX syndrome compared to healthy controls (p = 0.023). The serum native thiol/disulfide ratio was lower in patients with PEX syndrome compared to healthy subjects (16 ± 10.1 vs 22.3 ± 11.5, respectively, p = 0.014). CONCLUSION: Our findings provide evidence that the dynamic native thiol/disulfide ratio is lower in PEX syndrome, which shows a reduction in the natural cell reductive capacity reservoir.

Serum Lipid Levels in Pseudoexfoliation Syndrome.

PURPOSE: To investigate the serum lipid levels in pseudoexfoliation (PEX) syndrome and its association with systemic vascular disorders. MATERIALS AND METHODS: Patients were divided into three groups: 52 patients with PEX syndrome (group 1), 20 patients with PEX glaucoma (group 2), and 47 control subjects without PEX syndrome or glaucoma (group 3). The fasting serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels were evaluated by Beckman Coulter DXC 800/USA biochemical analyzer. RESULTS: The mean LDL values were 138 ± 33 mg/dl in group 1, 150 ± 37 mg/dl in group 2, and 127 ± 36 mg/dl in group 3. The mean LDL values in groups 1 and 2 were found to be significantly higher than that of group 3 (p = 0.04). The patients in groups 1 and 2 were more often diabetic and hypertensive than group 3 (p < 0.008, p < 0.005, respectively). CONCLUSION: Increased LDL values are significantly associated with PEX.

Serum insulin-like growth factor-1 levels in patients with pseudoexfoliation syndrome and glaucoma.

Insulin-like growth factor-1 (IGF-1) is altered in several neurodegenerative diseases, the association between serum IGF-1 levels and glaucoma has not been evaluated. This study was designed to evaluate whether serum IGF-1 levels are different in patients with Pseudoexfoliation (PEX) with or without glaucoma. The study was conducted with 110 participants aged 65 years or older who were divided into three groups: group 1, patients with PEX syndrome; group 2, patients with PEX glaucoma; and group 3, participants without PEX or glaucoma. All participants underwent full ophthalmological examination and a detailed medical history was recorded. Patients with known neurodegenerative diseases other than PEX glaucoma were excluded. Serum IGF-1 levels were measured by automated chemiluminescent assay. Groups 1, 2, and 3 included 35, 34, and 41 patients, respectively; there were no differences regarding age, gender, or systemic disease status. There were also no statistically significant differences between the groups in terms of IGF-1 levels, which were 91.7 ± 39.1, 101.1 ± 40.2, and 107.2 ± 43.8 ng/ml for groups 1, 2, and 3, respectively (p = 0.276). Serum IGF-1 levels were similar by gender, the presence of systemic disease, status of diabetes mellitus, and laterality of the PEX material. There was no correlation between the cup-to-disk ratios and IGF-1 levels (r = -0.214, p = 0.223). IGF-1 levels in the circulation did not differ in the presence of PEX syndrome with or without glaucoma. This may indicate that the neurodegenerative process is local rather than systemic.

Comparison of Rotational Thromboelastography Findings in Pseudoexfoliation Syndrome Patients and Healthy Controls.

PURPOSE: Rotational thromboelastography (ROTEM) is a useful test for studying the characteristics of fibrin clot formation. As patients with pseudoexfoliation (PEX) have an increased risk for thrombotic events, clot-forming dysfunction may play a role. The aim of this study is to compare ROTEM findings in PEX syndrome patients with age-matched and sex-matched healthy controls. PATIENTS AND METHODS: A total of 21 patients with PEX syndrome and 22 age-matched and sex-matched healthy controls were included. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer. RESULTS: The mean age of patients with PEX and controls was 66.5±8.3 and 65.9±9.5 years, respectively (P=0.7). The 2 groups did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, PEX patients showed a significantly decreased clotting time when compared with healthy controls (79.8 vs. 98.0 s; P=0.01), indicating faster clot formation. Other ROTEM parameters did now show any difference between the 2 groups. CONCLUSIONS: PEX patients showed faster clotting time when compared with healthy controls. This fibrin clot formation dysfunction may lead to vascular thrombotic events in these patients. Further studies are needed to elucidate the exact underlying mechanism of thrombosis seen in PEX patients.