A Retrospective Study of 199 Xen45 Stent Implantations From 2014 to 2016.

PURPOSE: The aim of this study is to determine the postoperative course after Xen45 Gel Stent implantation at the Medical University of Graz from 2014-2016. METHODS: Single-center, retrospective study. All patients with Xen implantation between 2014 and 2016 were included. Clinical records and reports received from supervising ophthalmologists were used for evaluations. Investigated parameters were intraocular pressure (IOP), the number of medications, visual acuity, and the number of previous operations, IOP-follow-up, intraoperative and postoperative complications, the rate of interventions (needling), and additionally performed surgeries. RESULTS: Xen was implanted in 199 eyes of 160 patients. Mean preoperative IOP was 22.8±6.9 mm Hg on 2.9±1.0 IOP-lowering medication. After 12 months follow-up, mean IOP was 17.1±5.9 mm Hg (n=89, P<0.0001; mean reduction of 22.7%) on 1.8±1.4 (n=87; P<0.0001) IOP-lowering medications. There were no intraoperative complications and in two cases (1.0%) severe postoperative adverse events occurred (aqueous misdirection and late-onset endophthalmitis). Postoperative needling was indicated in 44 cases (22.1%), while in 28 cases (14.1%) an additional glaucoma surgery was performed. CONCLUSIONS: Our results indicate that Xen implantation is an effective surgical intervention leading to a significant reduction of IOP and number of medications with a low rate of complications. An attentive postoperative management seems to be mandatory.

Triglycerides and Open Angle Glaucoma - A Meta-analysis with meta-regression.

Although intraocular pressure is the main the risk factor for the development of glaucoma, other risk factors such as vascular dysfunction might play an additional pathogenic role. Hypertriglyceridemia, which may lead to vascular dysfunction, has been implicated in the development of glaucoma. The objective of this meta-analysis was to investigate the association of triglyceride levels with the risk of glaucoma in case-control studies. Seventeen case-control studies were included investigating the difference in triglyceride levels in patients with glaucoma (N = 1 391) compared to subjects without glaucoma (N = 25 575). In random effects meta-analysis, the pooled mean triglyceride level across all studies and patients with and without glaucoma was 132.9 mg/dL (95%CI: 124.0-141.7). Patients with glaucoma had significantly higher mean triglyceride levels than patients without glaucoma (absolute difference = 14.2 mg/dL, 95%CI: 5.8-22.5, p < 0.0001). A considerable amount of heterogeneity of included studies was observed (I2 = 66.2%, heterogeneity χ2 = 47.4 on 16 degrees of freedom, p < 0.0001). In conclusion, this meta-analysis of case-control studies found that patients with glaucoma had higher mean triglyceride levels than patients without glaucoma. This finding is consistent with the concept that hypertriglyceridemia represents an additional risk factor for glaucoma. Whether this association is causal and/or might be modified by glaucoma medications remains to be investigated.

Analysis of functional polymorphisms in apoptosis-related genes in primary open angle glaucoma.

PURPOSE: Glaucoma is a disease with high heritability in which the degradation of retinal ganglion cells occurs via apoptosis. Therefore, we investigated the role of four functional apoptosis-related gene variants (Akt1 rs1130233, Bax rs4645878, Fas rs223476, and FasL rs763110) in patients with primary open angle glaucoma. METHODS: 334 patients with primary open angle glaucoma and 334 controls were recruited for this case-control study. The main outcome measures were genotype distribution and allelic frequencies determined with PCR. RESULTS: After adjustment for multiple testing, no significant difference in either the genotype distribution or the allelic frequencies of any investigated gene variant was found. CONCLUSIONS: Our findings indicate that the investigated gene polymorphisms are unlikely to be major risk factors for primary open angle glaucoma in Caucasian patients.

Measurement of tumor necrosis factor-alpha, interleukin-6, Fas ligand, interleukin-1α, and interleukin-1ß in the aqueous humor of patients with open angle glaucoma using multiplex bead analysis.

PURPOSE: Various cytokines, including tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), interleukin-1α (IL-1α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), contribute to the pathogenesis of primary open angle glaucoma (POAG). The present study was set to measure these cytokines in the aqueous humor of patients with POAG and in control subjects using multiplex bead analysis. METHODS: Twenty-five patients with POAG and 29 control subjects were enrolled in this case-control study. Aqueous humor concentrations of the cytokines (IL-1 α, IL-1 ß, IL-6, FasL, and TNF- α) were measured using multiplex bead analysis. RESULTS: Mean aqueous humor levels of IL-6 were significantly lower in patients with POAG compared to the control subjects (9.3±23.7 versus 55.3±94.4 pg/ml; p=0.002). No significant difference in the aqueous humor concentration of IL-1ß was found between patients with POAG and control subjects (0.5±0.8 versus 0.4±0.8 pg/ml; p=0.85.) Concentrations of IL-1α, TNF-α, and FasL were below limits of detection. No significant correlation was found between IL-6 concentration and age, duration of disease, cup/disc ratio, or mean deviation. CONCLUSIONS: In the present study, we found significantly lower concentrations of IL-6 in the aqueous humor of patients with POAG.

Role of rs1533428 and rs12994401 in patients with Primary Open Angle Glaucoma in an European population.

PURPOSE: Genetic factors have been shown to play a remarkable role in the pathophysiology of glaucoma. Recently, two polymorphisms (rs1533428 and rs12994401) on chromosome 2p were found to be strongly associated with POAG in an Afro-Caribbean population in Barbados, West Indies. As data with regard to the role of these polymorphisms in a Caucasian population are lacking, the present study was set to investigate a hypothetical association between these polymorphisms and POAG in a Caucasian population. METHODS: In total 723 participants were included in this study comprising 366 patients with POAG and 357 control subjects from the southern part of Austria. Genotyping of rs1533428 and rs12994401 was performed using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distributions of rs1533428 and rs12994401 did not show statistical significance between patients with POAG and control subjects (p < 0.05). Presence of the rs1533428 T-allele was associated with an odds ratio of 0.95 (95% CI: 0.76-1.19; p = 0.69) for POAG, while the rs12994401 T-allele was associated with an odds ratio of 0.94 (95% CI: 0.73-1.21; p = 0.65) for POAG. CONCLUSION: Our data suggest that rs1533428 and rs12994401 themselves are unlikely major risk factors for POAG in a Central European population.

Role of interleukin 6-174G>C polymorphism in primary open-angle glaucoma.

PURPOSE: In addition to its proinflammatory effects, interleukin (IL)-6 also possesses antiapoptotic properties. Recently, IL-6 has been reported to protect retinal ganglion cells from pressure-induced apoptosis, indicating a possible role in the pathogenesis of primary open-angle glaucoma (POAG). A common polymorphism in the promoter region of IL-6 gene at position -174 characterized by a substitution from G to C has been found to decrease transcription rate of IL-6. The aim of our study was to investigate a hypothesized association between IL-6-174G>C polymorphism and POAG in Caucasian patients. METHODS. The present case-control study comprised 191 unrelated patients with POAG and 191 control subjects, matched for age and sex. Genotyping of the IL-6-174G>C polymorphism was done using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distribution of IL-6-174G>C did not significantly differ between patients with POAG and control subjects (p>0.05). Presence of the IL-6-174C allele was associated with a nonsignificant odds ratio of 0.78 (95% confidence interval 0.46-1.32; p=0.78) for POAG. CONCLUSIONS: Our findings suggest that the functional IL-6-174G>C polymorphism itself is unlikely a major risk factor for POAG.

Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.

PURPOSE: The enzyme cholesterol 24S-hydroxylase (Cyp46A1) is responsible for the conversion of cholesterol to its more polar metabolite 24S-hydroxycholesterol, thereby enabling the intracerebral elimination of cholesterol. An intronic single nucleotide polymorphism in the gene CYP46A1 (IVS2 -150 T>C; rs754203) has recently been associated with primary open angle glaucoma (POAG). This association, however, lacks confirmation in other studies. The purpose of the present study was to investigate a hypothesized association between rs754203 and the presence of POAG in a Central European population of Caucasian descent. METHODS: The present institutional study comprised a total of 581 unrelated subjects: 330 patients with POAG, and 251 control subjects. Main outcome measures are genotype distributions and allelic frequencies determined by polymerase chain reaction. RESULTS: No significant differences in either genotype distribution or allelic frequencies were found between patients with POAG and control subjects (p>0.05). The presence of the rs754203 T-allele was associated with a nonsignificant odds ratio of 0.81 (95% CI: 0.63-1.04; p=0.11) for POAG. CONCLUSIONS: Our data suggest that the rs754203 polymorphism itself is unlikely a genetic risk factor for POAG in Caucasian individuals.

Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in open angle glaucomas.

PURPOSE: Matrix metalloproteinases (MMPs) play an essential role in the turnover of the extracellular matrix and cellular behavior. MMP1, MMP2, and MMP9 have previously been implicated in the pathogenesis of primary open angle glaucoma (POAG) and open angle glaucoma secondary to exfoliation syndrome (XFG), respectively. Functional gene polymorphisms of these MMPs such as MMP1 -1607 1G/2G (rs1799750), MMP2 -1306 C/T (rs243865), MMP2 -1575 G/A (rs243866), and MMP9 Q279R (rs17576) are thus plausible candidates as risk factors for open angle glaucomas. The purpose of the present study was to investigate hypothesized associations between these polymorphisms and the presence of POAG and XFG in a Caucasian population. METHODS: The present case-control study included 322 patients with POAG, 202 patients with XFG, and 248 control subjects. Genotyping of polymorphisms was done using polymerase chain reaction. RESULTS: No significant differences in either genotype distributions or allelic frequencies of MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R were found between patients with POAG and control subjects and patients with XFG and control subjects, respectively (p>0.05). The presence of POAG or XFG was not predicted by any of the investigated polymorphisms. CONCLUSIONS: Our data suggest that the MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R polymorphisms themselves are unlikely major risk factors among Caucasian patients with either POAG or XFG.

TNF-alpha -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.

PURPOSE: TNF-alpha has been suggested to participate in the pathogenesis of exfoliation glaucoma (XFG). The purpose of the present study was to investigate a hypothesized association between two common functional polymorphisms in the promoter region of the TNF-alpha gene (TNF-alpha -308 G>A, rs1800629, and TNF-alpha -238 G>A, rs361525) and the presence of XFG in a Caucasian population. METHODS: The present case-control study comprised 408 participants (204 patients with XFG and 204 control subjects). Control subjects were matched for age and sex. Genotypes of the TNF-alpha -308 G>A and TNF-alpha -238 G>A polymorphisms were determined by polymerase chain reaction (restriction fragment length polymorphism). RESULTS: No significant differences regarding genotype distribution or allelic frequencies were found between patients and control subjects (p>0.025). The presence of the TNF-alpha -308 G-allele was associated with an insignificant odds ratio of 0.98 (95% confidence interval [CI]: 0.66-1.46; p=0.99) while the presence of the TNF-alpha -238 G-allele was associated with an insignificant odds ratio of 0.64 (95% CI: 0.33-1.23; p=0.25). CONCLUSIONS: Our data suggest that both the TNF-alpha -308 G>A and the TNF-alpha -238 G>A polymorphisms are unlikely to be major risk factors for XFG in an European population of Caucasian descent.

Plasminogen activator inhibitor-1 4G/5G gene polymorphism and primary open-angle glaucoma.

PURPOSE: Alterations of the plasmin system have been suggested to participate in the multifactorial pathogenesis of primary open-angle glaucoma (POAG). The main physiological inhibitor of the plasmin system is plasminogen activator inhibitor-1 (PAI-1), which leads to decreased degradation of extracellular material. Interestingly, elevated PAI-1 levels in the aqueous humor of patients with POAG have been reported. A common polymorphism within the promoter region (PAI-1 4G/5G) has previously been shown to reduce the gene transcription rate of PAI-1. The purpose of the present study was to investigate a hypothesized association between PAI-1 4G/5G and the presence of POAG in a Caucasian population. METHODS: The present case-control study comprised 212 unrelated patients with POAG and 212 healthy control subjects, matched for age and sex. Genotyping of PAI-1 4G/5G polymorphisms was done using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distributions of PAI-1 4G/5G did not significantly differ between patients with POAG and control subjects (PAI-1 4G/5G: 29.7% versus 29.7%). Presence of the PAI-1 4G-allele was associated with a nonsignificant odds ratio of 0.98 (95% confidence interval: 0.74-1.30) for POAG. CONCLUSIONS: Our data suggest that PAI-1 4G/5G itself is unlikely to be a major risk factor among Caucasian patients with POAG.

Lysyl oxidase-like protein 1 (LOXL1) gene polymorphisms and exfoliation glaucoma in a Central European population.

PURPOSE: Exfoliation syndrome (XFS) is characterized by an accumulation of abnormal extracellular material in the anterior part of the eye that frequently leads to increased intraocular pressure and glaucomatous optic neuropathy. Recently, two non-synonymous polymorphisms (rs1048661 G>T and rs3825942 G>A) of lysyl oxidase-like protein 1 (LOXL1), a monoamine oxidase that catalyzes the polymerization of tropoelastin to elastin, were found to be associated with increased risk for XFS and exfoliation glaucoma (XFG). The aim of the present study was to investigate the role of these LOXL1 variants in a Central European cohort of Caucasian patients with XFG. METHODS: The present case-control study comprised of 167 unrelated patients with XFG and 170 control subjects. Genotyping of the LOXL1 rs1048661 and rs3825942 polymorphisms was done using polymerase chain reaction. RESULTS: The frequency of allele G of rs1048661 as well as rs3825942 was significantly higher in patients than in controls (rs1048661: 0.841 in patients versus 0.669; p<0.001; rs3825942: 0.994 in patients versus 0.817; p<0.001). Odds ratios of 52.1 (95% confidence interval [CI]: 13.85-195.6) and 14.67 (95% CI: 3.81-56.2), respectively, were calculated for the two high-risk haplotypes GG and TG compared to the haplotype GA. CONCLUSIONS: Our data confirm the previously reported association between LOXL1 polymorphisms and XFG and extend our knowledge to a Central European population.

Impact of dose rate on clinical course in uveal melanoma after brachytherapy with ruthenium-106.

BACKGROUND AND PURPOSE: It has been suggested that the actual dose rate of an irradiating source may be a distinct influencing factor for the biological effect after brachytherapy with ruthenium-106 for uveal melanoma. The purpose of this study was to investigate a hypothesized impact of the dose rate on the clinical and echographic course after brachytherapy. PATIENTS AND METHODS: In total, 45 patients were included in this retrospective study. According to the actual dose rate, two groups were defined: group 1 with a dose rate <4 Gy/h and group 2 with a dose rate >or=4 Gy/h. Regarding age, tumor height, basal diameter, scleral and apical dose, differences between the groups were not significant. Clinical parameters, including early and late side effects, and echographic courses were compared. RESULTS: A significantly lower metastatic rate was found in group 2. Using univariate Cox proportional hazards regression, only dose rate predicted metastatic spread significantly (p<0.05), while in a multivariate analysis, using age at the time of treatment, greatest tumor height and greatest basal diameter as covariates, the variable dose rate was of borderline significance (p=0.077). Patients in group 2 had more early side effects and more pronounced visual decline, but these differences were of borderline significance with p-values of 0.072 and 0.064, respectively. CONCLUSION: These data suggest that a higher dose rate may confer a lower risk for metastatic spread, but may be associated with more side effects and more pronounced visual decline.

[Myopia and glaucoma]. / Myopie und Glaukom.

The question is whether there is an increased risk to develop glaucoma in co-existing myopia. The different kinds of glaucoma dealing with this problem are described. The highly myopic eye with increased axial length shows many structural changes. Especially the changes of the optic nerve head in a highly myopic eye make it very difficult to differentiate between a beginning glaucoma and a normal structure or to define a progression of glaucomatous changes. The visual field defects are often close to fixation and may reduce visual acuity and therefore the quality of life of these usually younger patients. An increase of the thickness of the lens induced by senile cataract, drugs or diabetes mellitus, a forward shift of the lens or the iris-lens-diaphragm will lead to refractive myopia and may provoke an angle closure glaucoma. Pigmentary glaucoma occurs in younger patients in connection with low or medium myopia and more rapidly destroys the optic nerve head due to higher intraocular pressure values in comparison to the primary open-angle glaucoma. After refractive surgeries of myopic eyes one has to expect different kinds of glaucoma (steroid induced, pupillary block, angle closure). Due to the increased risk to develop glaucoma patients especially with high myopia are advised to consult their ophthalmologist on a regular basis.

Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration.

OBJECTIVE: Exudative age-related macular degeneration (AMD) is a common cause for a severe central visual loss. The complement system has been implicated in the pathogenesis of drusen. Recently, a complement factor H (CFH) polymorphism, which is characterized by a tyrosine (Y)-to-histidine (H) exchange at position 402 of the CFH gene, has been suggested as a major risk factor for AMD in a North American population. The aim of the present study was to investigate a hypothesized association between the CFH Y402H polymorphism and the presence of exudative AMD in a Central European population of Caucasoid descent as well as to determine the genotype distribution among different types of exudative AMD. DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort consisted of 179 patients with exudative AMD and 163 controls. METHODS: Determination of genotypes was carried out by allele-specific digestion of polymerase chain reaction products. MAIN OUTCOME MEASURES: Genotypes of CFH Y402H polymorphism. RESULTS: The prevalence of the CFH 402HH genotype was significantly higher in patients with exudative AMD than among controls (35.2% vs. 8.6%; P<0.001). Homozygosity for the CFH Y402H polymorphism was associated with an odds ratio of 5.78 (95% confidence interval, 3.09-10.83) for exudative AMD. Subgroup analysis revealed that the CFH 402HH genotype was significantly more prevalent in eyes with predominantly classic with no occult choroidal neovascularization (CNV) than in those with either retinal angiomatous proliferation, occult with no classic CNV, or predominantly classic with occult CNV. CONCLUSION: Our data suggest that the CFH Y402H polymorphism is a major risk factor for exudative AMD in a Central European population.

Methylenetetrahydrofolatereductase (MTHFR) 677C>T polymorphism and open angle glaucoma.

PURPOSE: Increased plasma homocysteine levels have been found in patients with primary open angle glaucoma (POAG) and glaucoma secondary to pseudoexfoliation syndrome (PEXG). A common polymorphism of the methylenetetrahydrofolatereductase (MTHFR 677C>T) leads to moderately elevated plasma homocysteine levels particularly under conditions of impaired folate status. It was the aim of this study to investigate a hypothesized association between this polymorphism and the presence of either POAG or PEXG. METHODS: The present retrospective case-control study included a total of 553 participants comprising 204 patients with POAG, 138 patients with PEXG, and 211 control subjects. Genotyping for the MTHFR 677C>T polymorphism was performed by polymerase chain reaction (PCR). RESULTS: No significant difference in the genotype distribution of the MTHFR 677C>T polymorphism was found between control subjects and patients with POAG or PEXG. The prevalence of the MTHFR 677TT genotype was 6.9% in patients with POAG, 11.6% in patients with PEXG, and 9.5% in control subjects. CONCLUSIONS: The present data suggest that the MTHFR 677C>T polymorphism itself is not a major genetic risk factor for POAG and PEXG in a central European population.

Rapid diagnosis of adenoviral keratoconjunctivitis by a fully automated molecular assay.

OBJECTIVE: To establish and evaluate a new test system for rapid detection and diagnosis of adenoviral keratoconjunctivitis. DESIGN: After establishment of the molecular assay, 52 conjunctival smears were studied. PARTICIPANTS: Samples were derived from patients with a clinical presentation compatible with keratoconjunctivitis. METHODS: A molecular assay for detection of human adenovirus (HAdV) based on automated nucleic acid extraction and real time polymerase chain reaction was established and evaluated. The new assay included a heterologous internal control. MAIN OUTCOME MEASURES: Statement about the presence or absence of adenoviral DNA in the specimen. RESULTS: The amplification efficiency was found to be 100%. The detection limit was calculated to be 116 copies per LightCycler capillary. When clinical specimens were tested, 15 of 52 conjunctival smears were found to be positive for HAdV DNA. The internal control was detected in all samples. CONCLUSIONS: The new molecular assay proved to be suitable for rapid diagnosis of adenoviral keratoconjunctivitis in the routine diagnostic laboratory.