PEX Patients Research Articles

Comparison of anterior segment parameters and corneal endothelial changes in patients with pseudoexfoliative glaucoma and pseudoexfoliation syndrome

Aim: The aim of this study is to evaluate the changes in anterior chamber morphology and corneal endothelium in patients with pseudoexfoliation syndrome (PEX) and pseudoexfoliative glaucoma (PEXG) and to determine the differences according to the control group. Material and Methods: 61 eyes of 61 PEX patients, 56 eyes of 56 PEXG patients and 46 eyes of 46 healthy subjects were included in the study. Measurement of intraocular pressure (IOP) was taken and axial length (AL), K1, K2, central corneal thickness (CCT), white-to-white distance (WTW), anterior chamber depth (ACD), pupil diameter (PD) by optical biometry and endothelial cell density (ECD), polimegatism (CV), pleomorphism (HEX) and average cell area (AVG) by specular microscope were taken of all the patients. Evaluation among the groups were made by ANOVA test, and p 0.05). There were no statistically significant differences among the groups in terms of IOP, AL, K1, K2, WTW, ACD (p> 0.05). Pupil diameter values were lower in the PEX group. CCT and endothelial cell counts were found to be higher in the control group compared to the other groups, while no significant difference was found between PEX and PEXG groups. AVG results were found to be significantly higher in the PEXG group than in the control group (p

Decorin, Tenascin C, Total Antioxidant, and Total Oxidant Level Changes in Patients with Pseudoexfoliation Syndrome.

Purpose Pseudoexfoliation syndrome (PEX) is an eye disease that develops under the influence of regional population differences, genetic factors, age, and environmental factors and is characterized by visualization of a gray-white fibrogranular substance in the lens anterior capsule and/or pupil margin during anterior segment examination. The underlying biochemical mechanisms of the disease have not yet been fully elucidated. Therefore, this study was designed to show the changes in aqueous humor and blood serum levels of matrix metalloproteinases (decorin and tenascin C), total antioxidants (TAS), and total oxidants (TOS) in both cataract patients who have unilateral PEX material and cataract patients who do not have unilateral PEX material. Methods Biological samples were simultaneously collected from 22 cataract patients who had unilateral pseudoexfoliation (PEX patients) and 22 cataract patients who did not have unilateral pseudoexfoliation (control patients). From the collected biological samples, decorin (DEC) and tenascin C (TN-C) were measured with the enzyme-linked immunosorbent assay (ELISA) method, and TAS and TOS were measured with an autoanalyzer. Results When decorin, tenascin C, and TOS values of PEX patients were compared with those of control patients, there was a statistically significant increase in all three parameters. Conversely, TAS values showed a statistically significant decrease in PEX patients compared to controls. DEC, TN-C, TAS values, and TOS values were significantly higher in aqueous fluid than in blood in both the PEX patient and control groups. Conclusions We suggest that parameters such as DEC, TN-C, TAS, and TOS play a role in the etiopathology of pseudoexfoliation syndrome. Thus, bringing these increased levels of extracellular proteins and TOS and decreased levels of TAS back to within physiological limits can mediate the reorganization of the blood-aqueous fluid barrier and slow the progression of pseudoexfoliation syndrome.

Evaluation of changes in retinal fiber layer thickness in pseudoexfoliation syndrome using spectral domain optical coherence tomography

Background: Pseudoexfoliation syndrome (PEX) is a disorder characterized by the progressive accumulation of fibrillary extracellular deposits in several ocular tissues including the iris, anterior chamber angle, lens capsule, and zonules. It is an independent risk factor for glaucomatous optic nerve damage. Retinal nerve fiber layer thickness analysis using optical coherence tomography (RNFL-OCT) is a documented investigative tool to detect preperimetric glaucoma and helps to detect glaucoma early. Objective: The objective of this study was to evaluate the retinal nerve fiber thickness in eyes with PEX using OCT and to compare them with healthy controls. Materials and Methods: This prospective cross-sectional control study was conducted at GMC, Srinagar, in which retinal nerve fiber thickness 50 patients of PEX and 50 healthy control subjects were compared using Cirrus spectral domain OCT (Carl Zeiss). Complete ocular and physical examination was also done in all subjects. Results: Mean age of Group A (PEX group) was 59.06 ± 6.5 years and of Group B (control) was 57.04 ± 7.1 years (P = 0.51). Both groups were gender matched with male preponderance (P = 0.41). Mean average peripapillary RNFL thickness was 76.13 μm ± 13.65 in Group A (PEX group) and 82.61 ± 12.78 μm in Group B (control group) (P = 0.10). Mean superior RNFL thickness was 94.17 ± 16.25 in PEX group and 100.23 μm ± 13.21 in control group (P = 0.09). Mean inferior RNFL thickness was 89.67 μm ± 18.25 in PEX group and 102.45 μm ± 12.50 in control group (P = 0.03). Mean nasal RNFL thickness was 62.36 μm ± 15.36 in PEX group and 64.66 μm ± 13.71 (P = 0.56) in control group. Mean temporal RNFL thickness was 58.34 μm ± 14.32 in PEX group and 63.11 μm ± 15.25 (P = 0.08) in control group. Mean RNFL thickness was seen decreased in all PEX patients in all quadrants; however, statistically significant differences were detected only in inferior quadrant groups. Conclusion: RNFL thickness is decreased in PEX patients. SD-OCT is a very reliable investigative tool to measure RNFL thickness, which helps in detecting preperimetric glaucoma.

Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular disease: a systematic review and meta-analysis

ObjectivePseudoexfoliation syndrome (PEX) is a systemic disease, but evidence of its association with cardiovascular disease (CVD) and cerebrovascular disease (CVA) is controversial. A quantitative systematic review will provide an accurate summary of the current body of the literature. DesignMeta-analysis. ParticipantsNot applicable. MethodsA comprehensive literature search of published and unpublished English-language studies was performed. Summary statistics were calculated using inverse variance weighting and are presented in forest plots. Sources of variance were evaluated statistically. ResultsAfter screening 4547 studies, 47 articles were reviewed, and 25 eligible studies were selected that reported patients from around the world. Twenty studies enrolling 9583 individuals with PEX evaluated CVD, providing a summary odds ratio (OR) of 1.61 (95% CI 1.37–1.90). Eleven studies, enrolling 1308 PEX patients, evaluated CVA and generated a summary OR of 1.76 (1.40–2.22). For any vascular event (AVE) using all 25 studies, there were 9716 PEX patients and 363,312 control patients, yielding a summary OR of 1.64 (95% CI 1.39–1.92). Analysis for publication bias with the Egger’s test was not significant for studies reporting CVD and AVE (p = 0.92 and 0.64, respectively) but was significant for CVA (p = 0.03). Asymmetry of Begg’s funnel plot was noted for the CVA and AVE analyses. Multiple sensitivity analyses were performed, including assessment of study quality; the OR for all 3 outcomes varied minimally and remained significant in all analyses. ConclusionThere is strong evidence that PEX is significantly associated with both CVD and CVA.

The Association of Cataract and Lens Epithelial Cell Apoptosis in Patients with Pseudoexfoliation Syndrome

ABSTRACTPurpose: The aim of this study was to measure the density of apoptotic lens epithelial cells (LECs) and to determine its association with cataract formation in eyes with pseudoexfoliation syndrome (PEX).Materials and Methods: Twenty-one eyes of 21 patients diagnosed with PEX without glaucoma (Group 1) and 22 eyes of 22 subjects without PEX (Group 2) were enrolled in this study. During cataract surgery, anterior capsule samples were obtained by the 5.5 mm continuous curvilinear capsulorhexis method. Apoptosis was determined with a TUNEL kit (Boster, Wuhan, China) according to the manufacturer’s protocol. Four fields in each pathology preparation were chosen randomly under a microscope, and 100 cells were counted in each field to calculate the apoptosis rates.Results: Forty-three eyes of 43 subjects were enrolled in this study. There were no significant differences in age or sex between the two studied groups (p > 0.05). Under a microscope, the LECs were stained light blue and their nuclei were oval shaped. Positive stained cells were found occasionally in Group 2, while a significant amount of black-brown positively stained LECs with condensed nuclei was found in Group 1. The apoptosis rates were 35.2 ± 2.1% and 14.1 ± 1% in Groups 1 and 2, respectively. The proportion of positively stained LECs was higher in Group 1 (p < 0.001).Conclusion: Our study suggests that apoptosis in LECs is the pathophysiological mechanism for the higher rate of cataracts in PEX patients, in addition to the ocular ischemia hypothesis.

Electroneuromyographic findings in pseudoexfoliation syndrome.

To examine peripheral electroneuromyographic findings in patients with ocular pseudoexfoliation syndrome (PEX) and to compare them controls without PEX. A case-control study design was used to examine 31 patients with PEX and compare the findings with those of 31 age- and sex-matched healthy controls. All patients underwent complete ophthalmologic examination that included peripheral electroneuromyography examination. Motor and sensorial nerve conduction of the median, ulnar, tibial, peroneal, and sural nerve and the sympathetic skin response were measured. The average sensorial nerve latency of the ulnar and sural nerve was significantly longer in the PEX group compared to the control group (p<0.05). The average sensorial nerve conduction amplitude and the velocity of the ulnar and sural nerve were significantly lower in the PEX group (p<0.05). Peripheral nerves, especially sensorial fibers, appear to be affected in PEX patients. These finding may indicate that PEX is a systemic disease.

Cataract Surgery and Possible Complications in Patients with Pseudoexfoliation Syndrome.

The aim of this study was to evaluate the demographic characteristics and intraoperative complications of cataract surgery in patients with pseudoexfoliation syndrome (PEX). Cases of 225 eyes (80 eyes with pseudoexfoliation and 145 eyes without pseudoexfoliation as the control group) that underwent phacoemulsification cataract surgery and IOL implantation at the Silifke State Hospital Ophthalmology Clinic between April 2011 and April 2013 were analysed retrospectively. Patients with a history of previous ocular surgeries, ocular trauma, uveitis, glaucoma or corneal pathology were not included in the study. All cataract procedures were performed by the same surgeon. Patients' age, gender, anterior segment and fundus findings in both eyes, presence of pseudoexfoliative material, pre- and postoperative day 1 intraocular pressure (IOP) and surgery notes were evaluated. There were 51 (34.7%) males and 29 (38.6%) females among the PEX cataract patients, and 98 (65.3%) male and 47 (61.8%) female controls. The incidence of pseudoexfoliation was similar in women (38.2%) and men (34.7%) (p=0.660). The mean age was 74.64±6.8 in the PEX group and 68.95±7.5 in the control group. Mean age was significantly higher in the PEX group compared to controls (p<0.001). Poor pupil dilation occurred intra-operatively in 60 (75%) of the patients with pseudoexfoliation and in 17 (11.7%) of the control patients. Frequency of poor intraoperative pupil dilation was significantly higher in the PEX group (p<0.001). Intraoperative vitreous loss occurred in 7 (8.8%) PEX patients and 5 (3.4%) controls, but this difference was statistically insignificant (p=0.090). Surgeons should be aware of the potential complications of cataract procedures in patients with PEX. Caution should be taken at every stage of the surgery to prevent these complications, and surgeons should be knowledgeable and skilful in complication management should they arise.

MTHFR and MTHFD1 gene polymorphisms are not associated with pseudoexfoliation syndrome in South Indian population.

Pseudoexfoliation syndrome (PEX) is a late onset disorder of extracellular matrix turnover, associated systemically with cardiovascular and cerebrovascular disease. To evaluate the suggested association of polymorphisms of homocysteine metabolism genes MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) with PEX. A case-control association study was undertaken, comprising a total of 1472 individuals including 860 unrelated PEX cases and 612 ethnic-matched cataract controls (CC). All the study subjects were genotyped for three SNPs using the TaqMan allelic discrimination assay. Association and statistical analysis were performed with PLINK 1.07 and STATA 11.1. Among the three SNPs genotyped, MTHFR polymorphisms did not exhibit significant association with PEX (rs1801131; p=0.549, rs1801133; p=0.408). The intronic SNP rs8006686 showed nearly significant association (p=0.069), and however did not remain significant after Bonferroni correction. Our study suggests no significant genetic association of MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) polymorphisms in South Indian PEX patients.

Multi-level analysis of the prevalence of pseudoexfoliative syndrome and pseudoexfoliative glaucoma

To study the prevalence of PEX and pseudoexfoliative glaucoma (PXFG) among healthy people, naïve patients, and patients under observation as well as to evaluate the hypotensive efficacy of bimatoprost/timolol fixed combination (FCBT) over 4 months in PXFG. Epidemiological analysis, ophthalmological examination, statistical analysis. The prevalence of PEX among healthy Novosibirsk and Novosibirsk region citizens is 19.9%. In ophthalmologically compromised population and first-time patients, the prevalence of PEX is 24%, of which PXFG constitutes 57.2%. Retrospectively, the prevalence of PXFG in PEX patients who were treated and followed up appeared to be as high as 60.8%. PXFG also accounts for 70% of all open-angle glaucoma cases in the Novosibirsk region, which is much higher than the corresponding rates in the European part of Russia. A 4-month FCBT therapy in 5 groups of PXFG patients (no treatment, monotherapy, another fixed combination, two drugs, three drugs) has yielded an evident hypotensive effect in most patients. The decrease in intraocular pressure was clinically significant in all groups. There has been found a high prevalence of PEX and PXFG in the Novosibirsk region. FCBT has demonstrated high hypotensive efficacy at all stages of PXFG and was beneficial even in patients treated with other medications or fixed combinations and in refractory cases.

Utility of multilevel lateral interbody fusion of the thoracolumbar coronal curve apex in adult deformity surgery in combination with open posterior instrumentation and L5-S1 interbody fusion: a case-matched evaluation of 32 patients.

OBJECTIVE The aim of this study was to evaluate the utility of supplementing long thoracolumbar posterior instrumented fusion (posterior spinal fusion, PSF) with lateral interbody fusion (LIF) of the lumbar/thoracolumbar coronal curve apex in adult spinal deformity (ASD). METHODS Two multicenter databases were evaluated. Adults who had undergone multilevel LIF of the coronal curve apex in addition to PSF with L5-S1 interbody fusion (LS+Apex group) were matched by number of posterior levels fused with patients who had undergone PSF with L5-S1 interbody fusion without LIF (LS-Only group). All patients had at least 2 years of follow-up. Percutaneous PSF and 3-column osteotomy (3CO) were excluded. Demographics, perioperative details, radiographic spinal deformity measurements, and HRQoL data were analyzed. RESULTS Thirty-two patients were matched (LS+Apex: 16; LS: 16) (6 men, 26 women; mean age 63 ± 10 years). Overall, the average values for measures of deformity were as follows: Cobb angle > 40°, sagittal vertical axis (SVA) > 6 cm, pelvic tilt (PT) > 25°, and mismatch between pelvic incidence (PI) and lumbar lordosis (LL) > 15°. There were no significant intergroup differences in preoperative radiographic parameters, although patients in the LS+Apex group had greater Cobb angles and less LL. Patients in the LS+Apex group had significantly more anterior levels fused (4.6 vs 1), longer operative times (859 vs 379 minutes), and longer length of stay (12 vs 7.5 days) (all p < 0.01). For patients in the LS+Apex group, Cobb angle, pelvic tilt (PT), lumbar lordosis (LL), PI-LL (lumbopelvic mismatch), Oswestry Disability Index (ODI) scores, and visual analog scale (VAS) scores for back and leg pain improved significantly (p < 0.05). For patients in the LS-Only group, there were significant improvements in Cobb angle, ODI score, and VAS scores for back and leg pain. The LS+Apex group had better correction of Cobb angles (56% vs 33%, p = 0.02), SVA (43% vs 5%, p = 0.46), LL (62% vs 13%, p = 0.35), and PI-LL (68% vs 33%, p = 0.32). Despite more LS+Apex patients having major complications (56% vs 13%; p = 0.02) and postoperative leg weakness (31% vs 6%, p = 0.07), there were no intergroup differences in 2-year outcomes. CONCLUSIONS Long open posterior instrumented fusion with or without multilevel LIF is used to treat a variety of coronal and sagittal adult thoracolumbar deformities. The addition of multilevel LIF to open PSF with L5-S1 interbody support in this small cohort was often used in more severe coronal and/or lumbopelvic sagittal deformities and offered better correction of major Cobb angles, lumbopelvic parameters, and SVA than posterior-only operations. As these advantages came at the expense of more major complications, more leg weakness, greater blood loss, and longer operative times and hospital stays without an improvement in 2-year outcomes, future investigations should aim to more clearly define deformities that warrant the addition of multilevel LIF to open PSF and L5-S1 interbody fusion.

Lamina cribrosa displacement after trabeculectomy in pseudoexfoliation and primary open angle glaucoma

PurposeTo compare the changes in lamina cribrosa depth between eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle glaucoma (POAG) following trabeculectomy.MethodsThe prospective study included 37 glaucomatous eyes (23 PEXG and 14 POAG). The lamina cribrosa depth was measured using enhanced depth imaging spectral domain optical coherence tomography before trabeculectomy and three months after the surgery. The postoperative displacement of the lamina cribrosa (LCD) was compared between the PEXG and POAG groups. The relationship between LCD and intraocular pressure (IOP) reduction was analysed.ResultsThere was a significant reduction in the mean (±SD) IOP in PEXG and POAG eyes following the trabeculectomy (14.2 ± 7.2 mmHg, p &lt; 0.001, 14.4 ± 7.5 mmHg, p &lt; 0.001; respectively). In total, the median (IQR) depth of the lamina cribrosa decreased from 469.4 (209.3) μm at baseline to 443.7 (145.5) μm three months after the surgery (p &lt; 0.001). No significant difference in median (IQR) postoperative lamina cribrosa displacement between the PEX and POAG patients was found (42.1 (50.8) μm and 22.8 (53.9) μm, respectively; p = 0.186). The anterior displacement of lamina cribrosa after trabeculectomy did correlate significantly neither with the baseline IOP nor with the IOP reduction in the examined groups.ConclusionsIn glaucomatous eyes the anterior displacement of the lamina cribrosa occurred after the IOP reduction following trabeculectomy. However, no differences in the decrease of the lamina cribrosa depth were found between the pseudoexfoliation glaucoma and primary open angle glaucoma patients. The association between the lamina cribrosa displacement and IOP reduction was not significant.

Ocular Pseudoexfoliation Syndrome Linkage to Cardiovascular Disease.

Pseudoexfoliation syndrome (PEX) is a common cause of open-angle glaucoma that is characterized by stress-induced elastic microfibrillopathy related to an accumulation of matrix metalloproteinases. The accumulation of matrix metalloproteinases increases deposition of protein substance within ocular structures and other organs including the heart. Many studies have associated the presence of cardiovascular disease with pseudoexfoliation syndrome, but much debate exists between studies in terms of significant relationships. The following meta-analysis aims to relate pseudoexfoliation syndrome with certain cardiovascular events and disorders. A thorough literature review was performed to acquire information concerning PEX patients with certain cardiovascular disorders. Diseases considered included myocardial infarction, ischemic heart disease, angina, congestive heart failure, cardiomyopathy, aortic aneurysm, hypertension, and homocystinuria. Patients without evidence of pseudoexfoliation disease were the controls of our study. Multiple forest plots were created to compile and analyze collected data for statistical comparison. From a literature review, 18 studies were selected for our analysis. Cardiovascular disorders that had a statistically significant association (within a 95% confidence interval) with PEX included ischemic heart disease, aortic aneurysms, and homocystinuria. The association between ischemic heart disease and PEX was statistically significant (p = 0.045). Myocardial infarction, chronic ischemic heart disease, angina, and hypertension did not show a correlation of relationship with the presence of pseudoexfoliation. Patients with PEX are prone to present with ischemic heart disease in addition to abdominal aortic aneurysms and homocystinuria. Patients that present with PEX should be screened for these detrimental cardiovascular disorders.

Prevalence of Pseudoexfoliation Syndrome in Turkish Patients with Senile Cataract

Purpose: To investigate the prevalence of pseudoexfoliation syndrome (PEX) among Turkish patients with senile cataract. Materials and Methods: Records of 352 eyes of 352 patients who underwent cataract surgery were analyzed in this retrospective study. The presence of PEX, type of cataract, intraocular pressure (IOP), glaucoma, age-related macular degeneration, and systemic diseases (coronary artery disease, hypertension, diabetes mellitus) were recorded. Results: The overall prevalence of PEX syndrome was detected to be 11%. The mean age of PEX patients was significantly higher than without PEX (74.4 ± 7.2 years and 69.3 ± 11.4 years, respectively, p = 0.004). The most common cataract type in the PEX patients was mixed-type cataract determined in 51.2% of patients. IOP was significantly higher in eyes with PEX than in eyes without it (16.1 ± 4.5 mmHg and 14.7 ± 3.8 mmHg, respectively; p = 0.03). Moreover, the prevalence of age-related macular degeneration was found to be significantly higher, and prevalence of glaucoma slightly higher in PEX patients than without PEX. Conclusion: Pseudoexfoliation syndrome is a common condition in Turkish people. PEX is associated with mixed type of cataract, age-related macular degeneration, and elevated IOP. Therefore, PEX patients should be checked for concomitant diseases.

Prediction of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma by Using Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio

ABSTRACTPurpose: To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls.Methods: In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection.Results: There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024).Conclusions: Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.

LOXL1 Hypermethylation in Pseudoexfoliation Syndrome in the Uighur Population.

High prevalence of pseudoexfoliation syndrome (PEX) occurs in the Uighur population. This study investigated DNA methylation of the lysyloxidase-like 1 (LOXL1) gene in Uighur PEX patients with cataracts. The research involved 10 lens capsule specimens from Uighur PEX patients with cataracts and 10 lens capsule specimens from Uighur control patients with age-related cataract (ARC) alone. All specimens were freshly collected during cataract surgery. Methylation status of the CpG islands was analyzed using pyrosequencing. The mRNA levels of LOXL1 were evaluated by quantitative real-time PCR, and protein levels were evaluated by Western blot assay. For all the six chosen CpG islands of the LOXL1 gene promoter, hypermethylation was found in the PEX with cataracts compared to the age-matched ARC group. At the same time, the expression level of LOXL1 mRNA was significantly reduced in the PEX with cataracts group than that in the ARC group, and the expression level of the LOXL1 protein product demonstrated a similar tendency. The susceptible PEX gene LOXL1 undergoes DNA hypermethylation in its promoter region in Uighur PEX with cataracts patients. This indicates that epigenetic regulation might play roles in PEX pathogenesis.

Amyloid β Peptides and Cognitive Functions in Patients with Pseudoexfoliation Syndrome

Purpose: The aim of this study was to evaluate if there is any relation between the Alzheimer’s peptides (amyloid β-40 and β-42) concentration in plasma and aqueous humor as well as cognitive functions with pseudoexfoliation syndrome (PEX).Methods: One-hundred forty-two patients with PEX have been included for this study; median age: 75 years (Q1 = 71,5; Q3 = 80,0). Control group comprised 93 subjects aged 74 years (Q1 = 68,0; Q3 = 80,0). Amyloid β-40 and β-42 (Aβ-40, Aβ-42) concentrations were assessed in plasma in 73 PEX patients and 49 controls. Aβ-40 concentration in aqueous humor was measured in 31 patients from each group. Mini Mental State Examination (MMSE) and Clock Drawing Tests were performed in 83 PEX patients and 36 controls.Results: The differences between amyloid concentrations both in plasma and in aqueous humor in PEX and control groups were not statistically significant. There were no differences in MMSE and Clock Drawing Tests between groups.Conclusion: Our results do not indicate any relation between PEX and Alzheimer’s amyloids or cognitive functions in cataract patients.

Corneal Biomechanical Comparison of Pseudoexfoliation Syndrome, Pseudoexfoliative Glaucoma and Healthy Subjects

Purpose: To evaluate the differences in corneal biomechanical properties between healthy subjects and patients with pseudoexfoliation syndrome (PEX) and pseudoexfoliative glaucoma (PEXG) using the ocular response analyzer (ORA).Materials and methods: One hundred eighteen eyes of 45 healthy, 43 PEX and 30 PEXG eyes were included in to the study. Corneal biomechanical parameters measurements were obtained using ORA. The main parameters assessed were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated pressure measurement (IOPg) and corneal compensated intraocular pressure (IOPcc). Ultrasound pachymetry was used for measurement of central corneal thickness (CCT).Results: In healthy subjects, PEX and PEXG eyes’ mean CH values were 10.3 ± 1.4, 8.2 ± 1.4 and 6.8 ± 1.7 mmHg, respectively. The difference in mean CH between the PEXG and other two groups were statistically significant (p < 0.001). Mean CRF values were 10.3 ± 0.7, 7.9 ± 1.6 and 7.9 ± 1.9 mmHg, in healthy subjects PEX and PEXG, respectively. The difference in mean CRF between the PEX and PEXG was not statistically significant (p = 0.630), however the mean CRF was significantly higher in healthy subjects, compared to other two groups. Mean CCT were 546.3 ± 28, 525.5 ± 35 and 509 ± 36 μ, in healthy subjects, PEX and PEXG, respectively. The differences on CCT were also significant among the three groups (p < 0.001).Conclusion: In this study, the corneal biomechanical features of subjects with PEX were found to be changed as compared to healthy controls. In these patients; CH, CRF and CCT were decreased which was more obvious in patients with PEXG in comparison to PEX patients.

Lysosomal enzymes activity in patients with pseudoexfoliation syndrome

Pseudoexfoliation syndrome (PEX) is a complex systemic disorder of the extracellular matrix affecting the eye and visceral organs. Pseudoexfoliation material deposits on various structures of the anterior segment of the eye and around blood vessels of connective tissue. Animal studies have suggested that the lysosomal trafficking regulator (LYST) gene is potentially important in PEX (Liton et al. 2009). Lysosomes are the cellular recycling centres responsible for the physiologic turnover of cell constituents. Inadequate enzyme activity results in disruption of the degradation process and accumulation of substrates for that specific enzyme, leading to variety of pathological changes. Increasing evidence suggests that the oxidative–antioxidative balance is disturbed in patients with PEX (Uçakhan et al. 2006; Lesiewska-Junk et al. 2013). The lysosomal proteolytic activity is compromised under oxidative stress conditions (Wenger et al. 2013). We studied 52 consecutive patients with PEX (16 males and 36 females), who presented for senile cataract surgery, median 75 years, range 59–89. The reference group consisted of 30 individuals (10 males and 20 females), matched for age and gender, with senile cataract without PEX, median 72 years, range 61–90. Both groups did not differ in stage of cataract nor body mass index and smoking habits. PEX was recognized based on typical material in the anterior segment seen after pupil dilation. The exclusion criteria were systemic and local diseases except cataract and PEX (including diabetes, rheumatoid arthritis, lipid profile disorders, intraocular surgery in history). The activity of four lysosomal enzymes in plasma was assessed as follows: acid phosphatase (AcP) with the use of Bessey method, alpha-1-antitrypsin (AAT) using Eriksson method, cathepsin D (CAT D) using Anson method and arylsulphatase (AS) using Robinson method. Kolmogorov–Smirnov test was used to assess normality of the data. Mann-Whitney test was used for comparison of data from small size independent samples. P-value of <0.05 was considered statistically significant. The values of activities of assessed enzymes are shown in Table 1. Reduced activity of proteolytic enzymes and subtle inflammatory processes may trigger the PEX-specific fibrotic matrix process (Schlötzer-Schrehardt 2012). Although Mizuno et al. (1980) found acid phosphatase activity significantly higher in the aqueous humour of eyes with PEX than in that of cataractous eyes without PEX, in our group, these values in blood plasma appeared to be lower in PEX patients. According to Cumurcu et al. (2008) serum A-1-AT activity was increased in patients with PEX, which is in accordance with our results. It may indicate the role of inflammation in this group of patients. To our best knowledge, this is the first study on AS and CAT D activities in PEX patients. Our observations may shed light on the complex metabolic contribution and molecular pathway of the disease.

Ocular Pseudoexfoliation Syndrome and Vascular Disease: A Systematic Review and Meta-Analysis

ObjectiveMany studies have assessed the association between ocular pseudoexfoliation syndrome (PEX) and vascular disease and produced controversial results. We performed a meta-analysis of epidemiologic studies to evaluate this relationship.MethodsEligible studies that reported the incidence of vascular disease among PEX and control groups were identified via computer searches and reviewing the reference lists of the key articles. The summary odds ratio (OR) and 95% confidence interval (CI) were pooled using a random-effects model. Meta-regression to assess heterogeneity by several covariates and a subgroup analysis on study design and population were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test.ResultsSixteen eligible studies involving 8,533 PEX patients and 135,720 control patients were included in the meta-analysis. All studies were performed primarily in whites with a mean age between 54.7 and 77.1 years. The overall combined ORs for patients with PEX compared with the reference group were 1.72 (95% CI: 1.31 to 2.26) for any vascular disease, 1.61 (95% CI: 1.22 to 2.14) for coronary heart disease, 1.59 (95% CI: 1.12 to 2.23) for cerebrovascular disease, and 2.48 (95% CI: 1.30 to 4.72) for aortic aneurysm. There was evidence of statistical heterogeneity; however, subgroup and sensitivity analyses showed this result to be robust. No evidence of publication bias was observed.ConclusionsThe overall current literature suggests that PEX was associated with increased risk of vascular disease. Because of the limitations of the included studies and meta-analysis, the findings need to be confirmed in future research via well-designed cohort studies.

Evaluation of Oxidative Stress and Paraoxonase Phenotypes in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Our purpose was to determine whether total oxidant and antioxidant status, total thiol levels and activities of serum paraoxonase 1, an HDL-associated antioxidant enzyme, are related with pseudoexfoliation syndrome (PEX) and pseudoexfoliation glaucoma (PG). Serum samples from 32 PEX, 30 PG, and 32 control subjects were collected at the Gülhane Military Medical Academy, Ankara. Basal paraoxonase (PON1), salt stimulated paraoxonase (stPON1), arylesterase (ARE), and total thiol levels were measured spectrophotometrically. Total antioxidant status (TAS) and total oxidant status (TOS) were determined on an autoanalyzer. Oxidative stress index (OSI) was calculated using the TAS and TOS values. PON1 phenotypes were calculated from the ratio of stPON1 to ARE. Continuous variables were compared by independent samples t-test and one-way ANOVA, except for age which was compared using Mann-Whitney U test. Categorical variables were compared using Fisher's exact test (PON1 phenotypes) or chi-square test (gender). TAS levels were significantly lower in PEX and PG patients compared to controls. TOS, OSI and total thiol levels did not differ significantly among the study groups, although there was a trend towards lower TOS and total thiol levels in patients compared to controls. PON1 activities were significantly higher in PEX patients (131.37 +/- 81.20 U/L) compared to controls (95.53 +/- 55.65 U/L; p = 0.046). The PON1 phenotype which is known to have high activity towards the substrate paraoxon, but low antioxidant activity (BB phenotype) was observed significantly more in PEX patients compared to controls. PON1 phenotypes and lack of antioxidants might play an important role in the development of PEX/ PG.