Grażyna Malukiewicz

Analysis of LOXL1 single nucleotide polymorphisms in Polish population with pseudoexfoliation syndrome

Acta Ophthalmol. 2011: 89: e64–e66

Current Trends in the Monitoring and Treatment of Diabetic Retinopathy in Young Adults

The diagnosis and treatment of diabetic retinopathy (DR) in young adults have significantly improved in recent years. Research methods have widened significantly, for example, by introducing spectral optical tomography of the eye. Invasive diagnostics, for example, fluorescein angiography, are done less frequently. The early introduction of an insulin pump to improve the administration of insulin is likely to delay the development of diabetic retinopathy, which is particularly important for young patients with type 1 diabetes mellitus (T1DM). The first years of diabetes occurring during childhood and youth are the most appropriate to introduce proper therapeutic intervention before any irreversible changes in the eyes appear. The treatment of DR includes increased metabolic control, laserotherapy, pharmacological treatment (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and intravitreal injections), and surgery. This paper summarizes the up-to-date developments in the diagnostics and treatment of DR. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual ophthalmology journals, books, and leading pharmaceutical company websites.

The Diagnostic Function of OCT in Diabetic Maculopathy

Diabetic maculopathy (DM) is one of the major causes of vision impairment in individuals with diabetes. The traditional approach to diagnosis of DM includes fundus ophthalmoscopy and fluorescein angiography. Although very useful clinically, these methods do not contribute much to the evaluation of retinal morphology and its thickness profile. That is why a new technique called optical coherence tomography (OCT) was utilized to perform cross-sectional imaging of the retina. It facilitates measuring the macular thickening, quantification of diabetic macular oedema, and detecting vitreoretinal traction. Thus, OCT may assist in patient selection with DM who can benefit from treatment, identify what treatment is indicated, guide its implementing, and allow precise monitoring of treatment response. It seems to be the technique of choice for the early detection of macular oedema and for the followup of DM.

OCT angiography by absolute intensity difference applied to normal and diseased human retinas

We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion.

Temperament profile in patients with central serous chorioretinopathy: a case-control study

Purpose To assess temperament in patients with central serous chorioretinopathy (CSCR) compared to healthy controls. Methods A total of 32 patients diagnosed with acute CSCR and 30 healthy controls matched by age and sex were assessed with the self-report Cloningers Temperament and Character Inventory. Central serous chorioretinopathy was diagnosed based on fluorescein angiography and spectral optical coherence tomography. Results Significantly higher mean scores of harm avoidance in patients with CSCR were found. Differences also were noted in subscales of novelty-seeking and reward dependence. Conclusions The patients with CSCR demonstrated less exploratory behaviors, higher risk avoidance, restraint, and low extravagance. They were more quick-tempered, disorganized, and easily frustrated, with a tendency to avoid negative and potentially harmful stimuli, less tolerance to frustration, higher level of insecurity, and higher level of anticipatory anxiety.

Analysis of SOD1 polymorphisms in Polish population with pseudoexfoliation syndrome

Editor, T he incidence of pseudoexfoliation (PEX) syndrome varies among ethnic groups – from 0% in Greenland Eskimos to 25% in the Scandinavian countries (Challa et al. 2008; Arnarsson 2009). Three single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 gene (LOXL1) have been confirmed to be associated with PEX in our previous study (Malukiewicz et al. 2011). In a recent investigation, an association between PEX and two SNPs, rs2107856 and rs2141388 of the contactin-associated protein-like 2 encoded by the CNTNAP2 gene located in intron 11 was found in Germans but not in Italians (Krumbiegel et al. 2011). We investigated the association between the SNPs rs2107856 and rs2141388 and PEX in Polish population. We studied 48 patients (16 men and 32 women), mean age 75 (SD = 7) with PEX and no other ocular diseases, for example, glaucoma. Control group comprised 30 healthy subjects (11 men and 19 women), mean age 76 (SD = 8). Pseudoexfoliation changes were identified as the presence of typical PEX material on the anterior lens surface, iris or corneal endothelium in either eye. Genomic DNA was extracted from blood as described previously (Malukiewicz et al. 2011). Genotypes of the SNPs rs2107856 and rs2141388 were determined using a commercially available TaqMan genotyping assays with the ABI Prism Sequence Detector 7000 (Applied Biosystems, Foster City, CA, USA). Correctness of genotyping was evaluated by direct sequencing for randomly selected samples. The Arlequin software version 3.1. was used to determine the Hardy– Weinberg equilibrium and estimate haplotype frequencies. The Fisher exact test was performed to compare patient and control groups for possible associations between allele frequency and disease state. Odds ratios were also calculated. The significance level for all statistical tests was 0.05. Statistical analysis was performed using Statistica software (version 8). The genotype distribution of rs2107856 and rs214138 was found in Hardy–Weinberg equilibrium in both groups. The allele frequencies in patients with PEX sample were not significantly different from those in the control group, for either rs2107856 (p = 0.38) or rs214138 (p = 0.38) (Table 1). Linkage disequilibrium analysis gave the value of r = 1 which proved that both SNPs are perfectly correlated to each other. There were no significant differences in haplotype frequencies between PEX and control samples. The haplotype (GC), present in 72% of cases and 65% of controls, confers a 1.38-fold of increased disease risk (95% CI, 0.685–2.765; p = 0.367). Krumbiegel et al. (2011) detected a significant association of both SNPs and their haplotype TT with PEX ⁄ PEXG in German but not the Italian cohort. They reported that the TT haplotype confers risk of the disease of 1.42 for German population. In our study, the minor T allele frequency is 0.28 in cases and 0.35 in controls. While the T frequency in our cases is the same as in Krumbiegel et al. (2011), the frequency in controls is higher (0.35 compared to 0.224), and this difference is statistically significant (p = 0.0094). The main cause of these conflicting observations can be either relatively small sizes of Polish samples or genetic heterogeneity of European populations. It was shown that the pronounced population differentiation at the level of haploid markers exists between the two geographically neighbouring countries, Poland and Germany (Kayser et al. 2005). In this respect, it should be emphasized that our study has only 18% power to detect the association, because of the small sample size. These findings strongly support the need for both replication of the CNTNAP2 SNPs association studies with PEX in Polish and other groups of larger sizes and further research into hidden population substructure which may affect the case–control data.

Amyloid β Peptides and Cognitive Functions in Patients with Pseudoexfoliation Syndrome

Abstract 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.

Blood Plasma Levels of Microelements in Patients with History of Optic Neuritis

Abstract Purpose: To determine the concentration of microelements in the blood of patients with a history of retrobulbar optic neuritis (ON). Materials and methods: We examined 36 patients (18–63 years of age) – 11 with demyelinating ON (Group 1) and 25 with isolated ON (Group 2) – all of whom had been treated for retrobulbar ON. The control group comprised 38 healthy volunteers. Using atomic absorption spectroscopy, blood levels of zinc (Zn), iron (Fe), copper (Cu) and cadmium (Cd) were evaluated. Results: Compared with the control group, concentrations of Cd were elevated in Groups 1 and 2 (p = 0.003 and p = 0.003, respectively); Group 1 had higher levels of Cu (p = 0.02). Patients from both groups had significantly lower levels of Fe (p = 0.0003) compared with controls. No difference in the concentration of any of the microelements was found between Groups 1 and 2. Conclusion: Disturbances in Cd, Cu and Fe homeostasis may be associated with the inflammatory process of ON.

Endothelial cell markers in patients with pseudoexfoliation syndrome.

The aim of the study was the assessment of the von Willebrand antigen (vWF Ag), E-selectin, and P-selectin concentration in blood plasma of patients with pseudoexfoliation syndrome (PEX). The group studied comprised 30 patients with PEX, aged from 50 to 86 years (mean 73, SD ± 8 years). Patients with cardiovascular and cerebrovascular diseases, diabetes mellitus, infectious disease, cancer, renal or liver insufficiency, connective tissue disease, current smoking, and hormone, antiplatelet, hypolipidemic, antioxidant, or antihypertensive drug therapy were excluded from the study. Each subject underwent a complete ophthalmological examination. Venous blood samples from the cubital vein were taken into sodium citrate solution. VWF Ag, sP-selectin, and sE-selectin concentration were determined by a commercially available enzyme-linked immunosorbent assay (MedSystems, Diagnostica Stago/Roche, R&D). Concentrations of vWF Ag, soluble E-selectin, and soluble P-selectin in blood plasma in the study group were compared with the levels in blood plasma in the control group. No significant differences were found between the groups. Our results indicate that there might be no correlation between PEX and such endothelial cell markers as vWF Ag, sP-selectin, and sE-selectin concentrations. Since the study size is limited, further investigations to confirm that there is no association between endothelial dysfunction in PEX and risk of future cardiovascular disease are necessary.

Immunohistochemical analysis of microsomal glutathione S‑transferase 1 and clusterin expression in lens epithelial cells of patients with pseudoexfoliation syndrome

Pseudoexfoliation syndrome (PEX) is an age-associated, sight disorder affecting elastic fibers in the eye and visceral organs but its exact etiology remains unknown. The purpose of the current study was to determine the morphology and ultrastructure of lens epithelial cells (LECs), and to use immunohistochemistry to examine localization of microsomal glutathione S-transferase 1 (MGST1) and clusterin. Anterior lens capsules were obtained from 24 patients (13 PEX and 11 controls) who underwent phacoemulsification. Immunohistochemistry was performed, using antibodies against MGST1 and clusterin, to determine their expression. The morphology and ultrastructure of LECs were evaluated by light and transmission electron microscopy, respectively. The PEX LECs were characterized by significantly lower MGST1 (P=0.0001) and clusterin expression (P=0.0005) compared with the control group patients. PEX LECs were also observed to have significantly increased thickness compared with the control group patients (P=0.0002). The current findings suggest that low MGST1 and clusterin expression levels may be an early clinical indicator of PEX, and that oxidative stress may serve an important role, but that the specific etiology of this disease has yet to be revealed.