| 1. |
- Rydberg Sterner, Therese, et al.
(författare)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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| 2. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Genetic Variation of Superoxide Dismutases in Patients with Primary Open-angle Glaucoma
- 2014
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 35:2, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: Oxidative stress has been described as an underlying pathogenetic mechanism in retinal ganglion cell apoptosis, which is a hallmark of primary open-angle glaucoma (POAG). Superoxide dismutases (SODs) are enzymes involved in the protection against oxidative stress by detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in the copper-zinc-containing SOD1 and SOD3, and in the manganese superoxide dismutase SOD2, in POAG patients. Methods: The study included 239 patients with POAG and 185 controls, all of Estonian origin, recruited at two ophthalmic clinics in Tartu, Estonia. Eleven SNPs, either functional, disease-associated or tag SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. Results: Using binary logistic regression in an additive model, the rs2842980 SNP in SOD2 was significantly associated with POAG diagnosis (p=0.03) at a univariate level. None of the studied SNPs showed an association with risk of POAG in a multivariate analysis, including age and current smoking as covariates. Analysis of SOD2 haplotypes did not show any association with risk of POAG. Conclusions: If oxidative stress is an important mechanism in POAG-related retinal ganglion cell death, genetic variations in SOD1, SOD2 and SOD3 are not major contributors in the pathogenesis.
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| 3. |
- Rudolph, Thiemo, et al.
(författare)
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Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts.
- 2011
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 32:2, s. 75-9
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Tidskriftsartikel (refereegranskat)abstract
- Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. A protective role of the p.S18Y polymorphism of the UCHL1 gene has been shown in Parkinson`s disease. The current study aimed to examine possible effects on cataract formation.
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| 4. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease.
- 2010
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Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE epsilon4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD.
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| 5. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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No Association of LOXL1 Gene Polymorphisms with Alzheimer's Disease
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer's disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that have shown association with AD. The polymorphisms were genotyped by Taqman allelic discrimination in a study sample including AD patients (n = 318) and controls (n = 575). In a subgroup of the population, the polymorphisms were analyzed in relation to APOE epsilon 4 genotype and to CSF (T-tau, P-tau, and A beta(1-42)). No evidence for associations of these polymorphisms with risk for AD or any of the studied CSF biomarkers measured was found. These results do not support LOXL1 as being a major risk gene for AD.
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| 6. |
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| 7. |
- Celojevic, Dragana, 1985, et al.
(författare)
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EPHA2 polymorphisms in Estonian patients with age-related cataract.
- 2016
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 37:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Ephrin receptors (Ephs) are tyrosine kinases that together with their ligands, ephrins, are considered important in cell-cell communication, especially during embryogenesis but also for epithelium homeostasis. Studies have demonstrated the involvement of mutations or common variants of the gene encoding Eph receptor A2 (EPHA2), in congenital cataract and in age-related cataract. This study investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in EPHA2 in patients with age-related cataract. Materials and methods: The study included 491 Estonian patients who had surgery for age-related cataract, classified as nuclear, cortical, posterior subcapsular and mixed lens opacities, and 185 controls of the same ethnical origin. Seven SNPs in EPHA2 (rs7543472, rs11260867, rs7548209, rs3768293, rs6603867, rs6678616, rs477558) were genotyped using TaqMan Allelic Discrimination. Statistical analyses for single factor associations used χ(2)-test and logistic regression was performed including relevant covariates (age, sex and smoking). Results: In single-SNP allele analysis, only the rs7543472 showed a borderline significant association with risk of cataract (p=0.048). Regression analysis with known risk factors for cataract showed no significant associations of the studied SNPs with cataract. Stratification by cataract subtype did not alter the results. Adjusted odds ratios were between 0.82 and 1.16 (95% confidence interval 0.61-1.60). Conclusions: The present study does not support a major role of EphA2 in cataractogenesis in an Estonian population.
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| 8. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Superoxide dismutase gene polymorphisms in patients with age-related cataract
- 2013
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 34:3, s. 140-145
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract. MATERIALS AND METHODS: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. RESULTS: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract. CONCLUSIONS: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.
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| 9. |
- Daborg, Jonny, et al.
(författare)
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Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 35:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.
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| 10. |
- Jakobsson, Gunnar, et al.
(författare)
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Increased Levels of Inflammatory Immune Mediators in Vitreous From Pseudophakic Eyes
- 2015
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 56:5, s. 3407-3414
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine if pseudophakic eyes have an increased and sustained level of inflammatory immune mediators in the vitreous compared to phakic eyes. METHODS. Vitreous fluid samples were obtained from 73 patients undergoing elective pars plana vitrectomy (PPV) as a result of a macular hole, epiretinal membrane, vitreous macular traction, or vitreous floaters. Forty eyes were pseudophakic and had previously undergone uncomplicated cataract surgery, ranging from a few months to several years prior to PPV. The vitreous samples were analyzed for 29 different inflammatory immune mediators using multiplex bead immunoassays. RESULTS. A total of 14 cytokines (eotaxin, interferon-c-induced protein-10 [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage derived chemokine [MDC], macrophage inflammatory protein [MIP]-1 alpha, MIP-1 beta, thymus activation regulated chemokine [TARC], IL-12p40, IL-15, IL-16, IL-7, VEGF, IL-6, and IL-8) were detected in the vitreous of both study groups. Using multiple linear regression analysis, pseudophakiawas significantly correlated with higher levels of vitreous immune mediators compared to phakia. Elevated vitreous levels were estimated to decrease over time for IL-6, IL-8, IL-15, IL-16, and VEGF, though they remained elevated for many months and even years compared to the levels detected in phakic eyes. CONCLUSIONS. This is the first study to demonstrate that cataract surgery and pseudophakia can induce increased vitreous levels of a substantial range of inflammatory immune mediators. The elevated levels seem to be maintained for a long period of time. These increased levels of cytokines may be involved in inflammatory processes leading to several complications to cataract surgery, both early and late.
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| 11. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Inhibition of Glycogen Synthase Kinase (GSK-3) Protects Against Oxidative Stress and Attenuates Apoptosis in Human Lens Epithelial Cells and the Mouse Lens in Organ Culure
- 2005
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3867-
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Konferensbidrag (refereegranskat)abstract
- Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment of HLEC with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by at least 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity.The whole mouse lens in organ culture showed essentially the same elevated mitochondrial potential. The GSH increase was even more evident in the whole lens preparation. Conclusions: Inhibition of GSK-3 may protect against oxidative stress (and cataract) via prevention of MPT induction and attenuate apoptosis in HLEC.
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| 12. |
- Landgren, Sara, 1980, et al.
(författare)
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No Association of VEGF Polymorphims with Alzheimer's Disease
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 224-228
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Tidskriftsartikel (refereegranskat)abstract
- The vascular hypothesis of Alzheimer's disease (AD) has brought the vascular endothelial growth factor (VEGF) into focus. The genomic region including the VEGF gene has been linked to AD and single nucleotide polymorphisms (SNPs) of the VEGF have in previous studies been associated with AD risk. To further evaluate these findings, we genotyped two SNPs in the VEGF gene (rs699947 [-2578]) and rs1570360 [-1154]) by TaqMan Allelic Discrimination in a study sample including AD patients (n = 801) and controls (n = 286). In a subgroup of the population these SNPs were analyzed in relation to APOE epsilon 4 genotype, to cerebrospinal fluid biomarkers (T-tau, P-tau, and beta(42)-Amyloid) as well as to neuropathological markers for AD (neurofibrillary tangles and senile plaques). No significant associations with risk for AD or any of the studied biomarkers could be found in this study, thus not supporting VEGF as being a major risk gene for AD.
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| 13. |
- Nordström, Moa, 1982, et al.
(författare)
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Pseudophakia and Lens Opacities in 70-Year-Olds in Gothenburg, Sweden; Gender Differences, Impact on Self-Reported Visual Function and Validation of Self-Reported Cataract and Pseudophakia
- 2022
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Ingår i: Clinical Ophthalmology. - 1177-5483. ; 16, s. 3269-3281
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The study aimed at determining the prevalence and sex differences in cataract, pseudophakia, lens opacities and self -reported cataract in 70-year-old people in Gothenburg, Sweden. The purpose was also to identify correlations between lens opacities, visual acuity and subjective visual function, and to validate self-reported cataract and cataract surgery.Patients and Methods: Population-based cross-sectional study where participants (n=1182) answered questions about self-reported diagnosis of cataract and cataract surgery. A total of 1139 subjects completed the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), 560 subjects underwent ophthalmic examination including visual acuity and lens photography. t-test, Pearson chi-square and Mann-Whitney U-test were used for obtaining p-values. ANOVA (analysis of variances, Kruskal- Wallis, one-way) was used to compare VFQ-25 between 3 groups; no cataract, cataract and pseudophakia. To clarify the differences between specific pairs of groups post-hoc test (Bonferroni) was used after ANOVA.Results: Self-reported cataract was more common in women than in men (27.2% vs 19.1%, p=0.001, chi-square). Cataract surgery was reported by 16.3% of women and 12.6% of men (p=0.072). Upon eye examination, the prevalence of pseudophakia was 16.9% in women compared to 10.2% in men (p=0.020). The prevalence of cataract, including pseudophakia, was 31.9% in women versus 23.8% in men (p=0.033). Significant correlations (Spearman's rho) were found between lens opacities and visual acuity. Self-reported cataract surgery showed a very high specificity and high sensitivity. The composite score from NEI VFQ-25 was lower in people with pseudophakia than in people with/without cataract (p=0.012, Kruskal-Wallis).Conclusion: The prevalence of cataract including pseudophakia in 70-year-olds in Gothenburg is higher compared to previous studies in similar geographical areas. Also, it is more common in women than in men. The lack of significant sex differences in lens opacities may be due to cataract surgery at an earlier stage. Validation showed very good agreement between pseudophakia and self-reported cataract surgery.
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| 14. |
- Petersen, Anne, 1962, et al.
(författare)
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The Mechanism of Antioxidant Actions by NSAIDs/ASA in Cultured Human Lens Epithelial Cells
- 2005
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3854-
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Konferensbidrag (refereegranskat)abstract
- Purpose: To study the possible mechanisms for protection against oxidative stress by indomethacin, diclofenac, celecoxib (NSAIDs) or acetylsalicylic acid (ASA) in cultured human lens epithelial cells (HLEC). Methods: Changes in peroxide levels in HLEC was measured after exposure to low concentrations (0, 0.005, 0.05 or 0,5 {micro}M) of indomethacin, diclofenac, celecoxib or acetylsalicylic acid for 24 hours. The cells were assayed at regular intervals during 24 h using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cultured HLEC were incubated with H2O2 (200 {micro}M) alone or in the presence of NSAIDs/ASA. The cells were then assayed for changes in GSH levels using monochlorobimane (MCB). Results: NSAIDs/ASA at concentrations previous described to be effective against oxidative stress in HLEC did not affect peroxide levels in cultured HLEC. The reducing capacity as measured as the GSH levels, were not significantly changed in oxidatively stressed HLEC. No toxic effects on GSH or peroxide levels were present. Conclusions: Indomethacin, diclofenac, celecoxib or acetylsalicylic acid does not exert their protective actions against oxidative stress via changed levels of endogenous peroxide or GSH.
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| 15. |
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| 16. |
- Subramanian, M. L., et al.
(författare)
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Neurofilament light chain in the vitreous humor of the eye
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5-1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (A beta), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins,APOEgenotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of A beta(40)(p = 7.7 x 10(-5)), A beta(42)(p = 2.8 x 10(-4)), and t-tau (p = 5.5 x 10(-7)), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15,p = 5.3 x 10(-4)), IL-16 (p = 2.2 x 10(-4)), monocyte chemoattractant protein-1 (MCP1,p = 4.1 x 10(-4)), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1,p = 2.9 x 10(-6)), Vegf-C (p = 8.6 x 10(-6)), vascular cell adhesion molecule-1 (VCAM-1,p = 5.0 x 10(-4)), Tie-2 (p = 6.3 x 10(-4)), and intracellular adhesion molecular-1 (ICAM-1,p = 1.6 x 10(-4)). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients' clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.
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| 17. |
- von Otter, Malin, 1978, et al.
(författare)
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Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson's disease (PD), Alzheimer's disease (AD) and age-related cataract. This case-control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.
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| 18. |
- von Otter, Malin, 1978, et al.
(författare)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 19. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Evolution, exaptation, and stereopsis.
- 2005
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Ingår i: Archives of ophthalmology. - : American Medical Association (AMA). - 0003-9950. ; 123:9
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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The szilard hypothesis on the nature of aging revisited.
- 2009
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 182:1, s. 3-9
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Tidskriftsartikel (refereegranskat)abstract
- This year marks the 50th anniversary of a nearly forgotten hypothesis on aging by Leo Szilard, best known for his pioneering work in nuclear physics, his participation in the Manhattan Project during World War II, his opposition to the nuclear arms race in the postwar era, and his pioneering ideas in biology. Given a specific set of assumptions, Szilard hypothesized that the major reason for the phenomenon of aging was aging hits, e.g., by ionizing radiation, to the gene-bearing chromosomes and presented a mathematical target-hit model enabling the calculation of the average and maximum life span of a species, as well as the influence of increased exposure to DNA-damaging factors on life expectancy. While many new findings have cast doubt on the specific features of the model, this was the first serious effort to posit accumulated genetic damage as a cause of senescence. Here, we review Szilard's assumptions in the light of current knowledge on aging and reassess his mathematical model in an attempt to reach a conclusion on the relevance of Szilard's aging hypothesis today.
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| 22. |
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| 23. |
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| 24. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Association of complement factor HY402H gene polymorphism with Alzheimer's disease
- 2008
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 147B:6, s. 720-6
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD-associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n=800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non-demented controls (n 1265) were included in this multi-center case-control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini-Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phospho-tau(181), (P-tau(181)), and beta-amyloid(1-42) (A beta(1-42)). The AMD-associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02-1.50). When APOE 4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08-1.65, P=0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE epsilon 4 allele. Positive C carrier status was also associated with lower levels of CSF A beta(1-42) selectively in the control group in an APOE epsilon 4-independent manner (P=0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE epsilon 4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD. (c) 2007 Wiley-Liss, Inc.
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| 25. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Methylenetetrahydrofolate reductase genetic polymorphisms in patients with cataract.
- 2005
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Ingår i: American journal of ophthalmology. - : Elsevier BV. - 0002-9394. ; 140:5, s. 932-4
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Hyperhomocysteinemia is commonly associated with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. The level of homocysteine can be lowered by dietary intake of folate. A protective effect of folate supplementation has been reported against cataract. Here we investigate MTHFR polymorphisms in human cataract. DESIGN: Retrospective case-control association study. METHODS: Patients with nuclear (n = 77), cortical (n = 155), posterior subcapsular (n = 119), and mixed (n = 151) cataract, and 187 controls were analyzed for the MTHFR 677C-->T and 1298A-->C polymorphisms using minisequencing technique. RESULTS: The wild-type MTHFR 677CC/1298AA genotype was strongly overrepresented among cataract cases (P = .003). This effect was most pronounced in the mixed cataract group (P < .001). Hyperhomocysteinemia-associated genotypes had similar frequencies in cataract and control groups. CONCLUSIONS: The previously reported protective effect of folate against cataract is not due to overrepresentation of hyperhomocysteinemia-associated MTHFR genotypes. Instead, the strong predominance of wild-type MTHFR in cataract may suggest impaired DNA synthesis as a cataractogenic factor.
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| 26. |
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| 27. |
- Adelöf, Julia, 1990, et al.
(författare)
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Conclusions from a behavioral aging study on male and female F2 hybrid mice on age-related behavior, buoyancy in water-based tests, and an ethical method to assess lifespan.
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:17, s. 7150-7168
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Tidskriftsartikel (refereegranskat)abstract
- Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (nmales=48, nfemales=51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.
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| 28. |
- Adelöf, Julia, 1990, et al.
(författare)
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PA28α overexpressing female mice maintain exploratory behavior and capacity to prevent protein aggregation in hippocampus as they age.
- 2021
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Ingår i: Aging cell. - : Wiley. - 1474-9726 .- 1474-9718. ; 4:29
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Tidskriftsartikel (refereegranskat)abstract
- With age, protein damage accumulates and increases the risk of age-related diseases. The proteasome activator PA28αβ is involved in protein damage clearance during early embryogenesis and has demonstrated protective effects against proteinopathy. We have recently discovered that adult female mice overexpressing PA28α (PA28αOE) have enhanced learning and memory, and protein extracts from their hippocampi prevent aggregation more efficiently than wild type. In this study, we investigated the effect of overexpressing PA28α on aging using C57BL/6N×BALB/c F2 hybrid mice. We found that the hippocampal anti-aggregation effect was maintained in young adult (7months) to middle-aged (15months) and old (22months) PA28αOE females. While the PA28αOE influence on learning and memory gradually decreased with aging, old PA28αOE females did not display the typical drop in explorative behavior-a behavioral hallmark of aging-but were as explorative as young mice. PA28αOE lowered PA28-dependent proteasome capacity in both heart and hippocampus, and there was no indication of lower protein damage load in PA28αOE. The life span of PA28αOE was also similar to wild type. In both wild type and PA28αOE, PA28-dependent proteasome capacity increased with aging in the heart, while 26S and 20S proteasome capacities were unchanged in the timepoints analyzed. Thus, PA28αOE females exhibit improved hippocampal ability to prevent aggregation throughout life and enhanced cognitive capabilities with different behavioral outcomes dependent on age; improved memory at early age and a youth-like exploration at old age. The cognitive effects of PA28αβ combined with its anti-aggregation molecular effect highlight the therapeutical potential of PA28αβ in combating proteinopathies.
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| 29. |
- Adelöf, Julia, 1990, et al.
(författare)
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PA28αβ overexpression enhances learning and memory of female mice without inducing 20S proteasome activity
- 2018
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The proteasome system plays an important role in synaptic plasticity. Induction and maintenance of long term potentiation is directly dependent on selective targeting of proteins for proteasomal degradation. The 20S proteasome activator PA28αβ activates hydrolysis of small nonubiquitinated peptides and possesses protective functions upon oxidative stress and proteinopathy. The effect of PA28αβ activity on behavior and memory function is, however, not known. We generated a mouse model that overexpresses PA28α (PA28αOE) to understand PA28αβ function during healthy adult homeostasis via assessment of physiological and behavioral profiles, focusing on female mice. RESULTS: PA28α and PA28β protein levels were markedly increased in all PA28αOE tissues analyzed. PA28αOE displayed reduced depressive-like behavior in the forced swim test and improved memory/learning function assessed by intersession habituation in activity box and shuttle box passive avoidance test, with no significant differences in anxiety or general locomotor activity. Nor were there any differences found when compared to WT for body composition or immuno-profile. The cognitive effects of PA28αOE were female specific, but could not be explained by alterations in estrogen serum levels or hippocampal regulation of estrogen receptor β. Further, there were no differences in hippocampal protein expression of neuronal or synaptic markers between PA28αOE and WT. Biochemical analysis of hippocampal extracts demonstrated that PA28α overexpression did not increase PA28-20S peptidase activity or decrease K48-polyubiquitin levels. Instead, PA28αOE exhibited elevated efficiency in preventing aggregation in the hippocampus. CONCLUSIONS: This study reveals, for the first time, a connection between PA28αβ and neuronal function. We found that PA28α overexpressing female mice displayed reduced depressive-like behavior and enhanced learning and memory. Since the positive effects of PA28α overexpression arose without an activation of 20S proteasome capacity, they are likely independent of PA28αβ's role as a 20S proteasome activator and instead depend on a recognized chaperone-like function. These findings suggest that proteostasis in synaptic plasticity is more diverse than previously reported, and demonstrates a novel function of PA28αβ in the brain.
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| 30. |
- Adelöf, Julia, 1990, et al.
(författare)
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Survival-Span Method: How to Qualitatively Estimate Lifespan to Improve the Study of Aging, and not Disease, in Aging Studies
- 2021
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Ingår i: Frontiers in Aging. - : Frontiers Media SA. - 1663-4365 .- 2673-6217. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Lifespan analyses are important for advancing our understanding of the aging process. There are two major issues in performing lifespan studies: 1) late-stage animal lifespan analysis may include animals with non-terminal, yet advanced illnesses, which can pronounce indirect processes of aging rather than the aging process per se and 2) they often involves challenging welfare considerations. Herein, we present an option to the traditional way of performing lifespan studies by using a novel method that generates high-quality data and allows for the inclusion of excluded animals, even animals removed at early signs of disease. This Survival-span method is designed to be feasibly done with simple means by any researcher and strives to improve the quality of aging studies and increase animal welfare.
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| 31. |
- Allard, K., et al.
(författare)
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Implantation of toric intraocular lenses in patients with cataract and keratoconus: a case series
- 2018
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Ingår i: International Medical Case Reports Journal. - : Informa UK Limited. - 1179-142X. ; 11, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the results of phacoemulsification and implantation of tonic intraocular lenses (IOLs) in patients with cataract and keratoconus. Patients and methods: Prospective study of 4 patients (4 eyes) with cataract and keratoconus who underwent phacoemulsification with implantation of a toric IOL. Two different toric IOLs were used: AcrySof IQ SN6AT9 and AT Torbi 709M(P). Corneal tomography was performed preoperatively using Scheimpflug technique with Pentacam. Astigmatism was regular or slightly irregular in all patients. Postoperatively, best-corrected visual acuity (BCVA), astigmatism, spherical equivalent, and complications were recorded for all patients. Follow-up time was between 4 weeks and 7 months. Results: BCVA increased and astigmatism decreased in all patients. BCVA increased from 20/50 to 20/40 in patient 1, from 20/63 to 20/20 in patient 2, from 20/40 to 20/32 in patient 3, and from hand motion to 20/40 in patient 4. Astigmatism decreased from -6.12 to -3.75 D in patient 1, from -4.62 to -1.75 Din patient 2, from -9.0 to -3.0 Din patient 3, and from -8.0 to -2.75 D in patient 4. One patient developed pseudophakic cystoid macular edema, but at last follow-up after 6 months the edema had resolved. Another patient developed posterior capsular opacification after 2 months. No misalignment of the axis of the IOL was observed. Conclusion: Correction of both astigmatism and cataract with phacoemulsification and implantation of a tonic IOL can be an effective and safe choice for patients with cataract and keratoconus. However, predicting the refractive outcome in cataract surgery is difficult in patients with keratoconus, and the surgeon should be aware of different sources of biometric errors and the possible consequences.
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| 32. |
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| 33. |
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| 34. |
- Ayala, Marcelo, 1965, et al.
(författare)
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Association of Single Nucleotide Polymorphisms Located in LOXL1 with Exfoliation Glaucoma in Southwestern Sweden
- 2021
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Glaucoma is an optic neuropathy that leads to visual field defects. Genetic mechanisms seem to be involved in glaucoma development. Lysyl Oxidase Like 1 (LOXL1) has been described in previous studies as a predictor factor for exfoliation glaucoma. The present article studied the association between three single nucleotide polymorphisms (SNPs) in the LOXL1 gene and the presence of exfoliation glaucoma in Southwestern Sweden. Methods: Case-control study for genetic association. In total, 136 patients and 1011 controls were included in the study. Patients with exfoliation glaucoma were recruited at the Eye Department of Sahlgrenska University Hospital and Skaraborgs Hospital, Sweden. Controls were recruited from the Gothenburg H70 Birth Cohort Study. Three different SNPs were genotyped: LOXL1_rs3825942, LOXL1_rs2165241 and LOXL1_rs1048661. Results: The distribution of allele frequencies was significantly different between controls and glaucoma patients; for rs3825942 (p = 2 x 10(-12)), for rs2165241 (p = 3 x 10(-16)) and for rs1048661 (p = 2 x 10(-6)). Logistic regression analyses using an additive genetic model, adjusted for sex and age, also showed associations between the studied SNPs and glaucoma (p = 9 x 10(-6); p = 2 x 10(-14); p = 1 x 10(-4)). Conclusion: A strong association was found between allele frequencies of three different SNPs (LOXL1_rs3825942, LOXL1_rs2165241, and LOXL1_rs1048661) and the presence of exfoliation glaucoma in a Southwestern Swedish population.
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| 35. |
- Ayala, Marcelo, 1965, et al.
(författare)
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Single nucleotide polymorphisms in LOXL1 as biomarkers for progression of exfoliation glaucoma in Sweden
- 2023
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 101:5, s. 521-529
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Exfoliation glaucoma is a common and aggressive type of glaucoma with high prevalence in Scandinavia. The aim of this study was to elucidate whether the allele frequencies of two single nucleotide polymorphisms (SNPs) located in LOXL1 were associated with the progression of exfoliation glaucoma in Swedish patients. Methods: In this non-randomised cohort study, we enrolled patients with exfoliation glaucoma, and they performed at least five reliable visual field tests. Blood samples were collected, and genotyping was performed using competitive allele-specific PCR genotyping. Glaucoma progression was evaluated using the guided glaucoma progression analysis (GPA), mean deviation (MD) difference and rate of progression (ROP). In addition, associations between allele frequencies and glaucoma progression were tested using logistic regression for GPA and linear regression for MD and ROP. Results: We enrolled a total of 130 patients in the study. The general genetic model showed statistical significance for LOXL1_rs2165241 (p=8 × 10−7, Fisher's exact test) and LOXL1_rs1048661 (p=2 × 10−6, Fisher's exact test). Regression analyses using an additive genetic model showed significant values for LOXL1_rs2165241SNP in relation to GPA, MD and ROP as outcomes (p=1.8 × 10−4, 4 × 10−2, 6 × 10−4) and for LOXL1_rs1048661 SNP in relation to GPA, MD and ROP (p=7 × 10−5, 8 × 10−3, 2 × 10−4). Conclusions: This was the first study to show an association of the SNPs LOXL1_rs2165241 and LOXL1_rs1048661 with the progression of exfoliation glaucoma. Further large-scale studies are required to verify these findings.
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| 36. |
- Belitsky, Yuri, et al.
(författare)
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Evaluation of selective laser trabeculoplasty as an intraocular pressure lowering option.
- 2019
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Ingår i: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 97:7, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Selective laser trabeculoplasty (SLT) is one of the many treatment options for lowering intraocular pressure (IOP) in patients with glaucoma. This study aimed to evaluate the effect of SLT.Data were collected from medical records of 289 patients who underwent SLT treatment (180° of trabecular meshwork) during 2014 and 2015 at the Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden. Baseline characteristics and information from a follow-up within 100days were also recorded. The study analysed different subtypes of glaucoma with regard to SLT, with a particular focus on exfoliative glaucoma, a common subtype in Sweden. Successful treatment was defined as an IOP lowering effect of >20% with no further changes in treatment. The impact of surgeon's experience on treatment outcome was also analysed.Both patients with exfoliative glaucoma and those with primary open-angle glaucoma showed a reduction in mean IOP; no significant difference was found between these two subtypes before treatment or at the first follow-up. The success rate at follow-up (within 100days) was 52%. There was a significant difference in outcome between surgeons with different levels of experience, but this difference could likely be explained by differences in treatment strategies and total energy used.For many patients with glaucoma, SLT was an effective treatment option for lowering IOP. It was also effective for several glaucoma subtypes. However, not all patients had a significant reduction in IOP after treatment with SLT, and some may require additional treatment.
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| 37. |
- Belitsky, Y., et al.
(författare)
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Late-onset glaucoma following congenital cataract surgery: Occurrence, visual acuity and risk factors: A 37-year longitudinal follow-up
- 2022
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to determine the prevalence of late-onset glaucoma after surgery for congenital cataract in a cohort with long-term follow-up and to evaluate visual development following the diagnosis of postoperative glaucoma in comparison with no glaucoma development. Methods All children born between 1980 and 1997 in the western counties of Sweden who had undergone congenital cataract surgery were included (patients n = 77, eyes n = 122). Cataract was considered congenital if there was no proof of clear lens at birth. Medical records were reviewed with regard to onset of glaucoma, age at surgery, surgical technique, coexisting eye anomalies and changes in visual acuity. Glaucoma was considered late onset if occurring after 1 year following surgery. Results Total glaucoma prevalence was 14.8%, including late (10.7%) and early onset (4.1%), with a mean follow-up of 23.2 +/- 6.6 years. Microphthalmos was a significant risk factor for developing glaucoma (RR 7.75, p < 0.001). Bilaterally treated eyes had a mean visual acuity of 0.43 +/- 0.33 (decimal value) at the last follow-up. With glaucoma, mean visual acuity was 0.19 +/- 0.17 (decimal value). Treated eyes of patients with unilateral cataract surgery had a lower visual acuity. Conclusions Life-long follow-up of all patients who have undergone surgery for congenital cataract in childhood is recommended. Annual check-ups of adults, including measurements of IOP and visual acuity, are recommended for patients with microphthalmos and/or who had surgery <3 months of age.
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| 38. |
- Bergman, O., et al.
(författare)
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Optic perineuritis: a retrospective case series
- 2017
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Ingår i: International Medical Case Reports Journal. - : Informa UK Limited. - 1179-142X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Optic perineuritis (OPN) is a rare inflammatory disorder involving the optic nerve sheath characterized by visual loss. OPN may be isolated and idiopathic or part of an underlying disorder. This case series aimed to help clinicians investigate and manage this disorder. Presentation, clinical findings, and treatment of OPN are discussed. After review of medical records at the ophthalmology clinic at Sahlgrenska University hospital in Gothenburg, Sweden, seven OPN patients (three men and four women) were identified and included in the present case series. These included idiopathic cases and patients with underlying disorders. Age at OPN diagnosis ranged from 26 to 64 years (mean age 55 years, median age 58 years). Five of the patients were treated with corticosteroids. This study suggests that a high-dose course of corticosteroids is important in the treatment of OPN in severely affected patients.
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| 39. |
- Bond-Taylor, M., et al.
(författare)
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Posterior vitreous detachment - prevalence of and risk factors for retinal tears
- 2017
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Ingår i: Clinical Ophthalmology. - : Informa UK Limited. - 1177-5483. ; 11, s. 1689-1695
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The present study aimed to describe clinical characteristics of patients with posterior vitreous detachment (PVD), to determine the prevalence of retinal tears in PVD patients, and to find predictors for retinal tears in this patient group. Methods: Retrospective analysis of medical records on patients diagnosed with PVD, retinal tears, or vitreous hemorrhage at the Department of Ophthalmology at Sahlgrenska University Hospital, a tertiary eye center. Results: Between February and July 2009, 365 patients consulted the Department of Ophthalmology for PVD-related symptoms. The incidence of retinal tears was 14.5% (n = 53) and that of vitreous and/or retinal hemorrhage was 22.7% (n= 83). For analysis of possible predictors for complications to PVD, patients diagnosed with retinal tears or vitreous hemorrhage between May and July 2009 were also included in the study, resulting in a total of 426 patients. Predictors of a retinal tear were symptoms of visual impairment (P = 0.024), the presence of vitreous or retinal hemorrhage at examination (P = 0.001), and a duration of symptoms for <24 hours (P = 0.004). Symptoms of flashes did not constitute an extra risk of retinal tears (P = 0.135). Subsequent retinal pathology (follow-up time 4.5 years), including vitreous detachment/hemorrhage or retinal tears/detachment, occurred more often in patients presenting with a retinal tear. For patients with a retinal tear, the relative risk of having a retinal detachment in the same eye during the follow-up time was 17.7 when compared to patients without a retinal tear (risk ratio 17.7, 95% confidence interval 2.2-145). Conclusion: Patients seeking care on the first day have a higher risk of retinal tears. Also, symptoms of visual loss or a history of previous PVD-related pathology and vitreous/retinal hemorrhage at examination indicate a substantially higher risk of retinal complications. These findings may lead to better management and order of priority among these patients.
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| 40. |
- Bro, Tomas, et al.
(författare)
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Two point four million cataract surgeries: 30 years with the Swedish National Cataract Register, 1992-2021
- 2023
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Ingår i: Journal of cataract and refractive surgery. - : Wolters Kluwer. - 1873-4502 .- 0886-3350. ; 49:8, s. 879-884
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Tidskriftsartikel (refereegranskat)abstract
- The present review summarizes data collected by the Swedish National Cataract Register (NCR), which by the end of 2021 contained data for more than 2.4 million cataract surgeries between 1992 and 2021. During these 30 years, the cataract surgery rate rose from 3700 to 12800. The coverage of NCR is very high including 93% of all cataract procedures in Sweden between 2010 and 2021. Independently of demographic changes, the proportion of operations of patients age 60 to 79 has increased while the proportion of 80 to 90+ has decreased. The median visual acuity of the first eye planned for surgery was 0.1 decimal in 1992 and has increased to 0.5 decimal in 2021. Patient-reported outcome measures have been registered with the Catquest-9SF questionnaire since 2008, demonstrating intervention at an earlier stage, but consistently favorable outcomes. Surgical complications have decreased; endophthalmitis has decreased from 0.10% to below 0.02%, and posterior capsule rupture from 2.8% to 0.6%.
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| 41. |
- Busch, T., et al.
(författare)
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Four-Year Outcome of XEN 45 Gel Stent Implantation in a Swedish Population
- 2023
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Ingår i: Clinical Ophthalmology. - 1177-5483. ; 17, s. 1897-1910
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To report the long-time success rate of XEN 45 gel stent implantation in a Scandinavian population.Patients and Methods: This was a retrospective single-center analysis of all patients undergoing XEN 45 stent surgery between December 2015 and May 2017. The main outcome was success rate according to several definitions of success. Subgroup analysis was performed. Secondary outcomes were change in intraocular pressure (IOP) and number of IOP-lowering agents. Need for secondary glaucoma surgery, needling rate and complications were recorded.Results: A total of 103 eyes could be evaluated after four years. Mean age was 70.6 years. Primary open-angle glaucoma (POAG) accounted for 46.6% and exfoliative glaucoma (PEXG) for 39.8%. Mean IOP dropped from 24.0 to 15.9 mmHg (p<0.001) and IOP-lowering agents from 3.5 to 1.5 (p<0.001). The success rate with individual target pressures after four years was 43.7%. Secondary glaucoma surgery was performed in 45 (43.7%) of cases. Combined cases (n=12) were not statistically different to stand-alone procedures (p=0.28). No difference between PEXG and POAG could be detected (p=0.44). During the learning curve, stent misplacement was common and resulted in worse outcome for less experienced surgeons. Conclusion: The overall success rate of XEN 45 gel stent surgery in the present cohort is relatively low in a long-time follow-up under the given circumstances if all initial patients are included to follow-up. The influence of the surgeon's learning curve is obvious, and improvement in success can be expected when used by experienced and high-volume surgeons. No significant differences were found in PEXG compared to POAG or in XEN surgery combined with cataract surgery compared to stand-alone.
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| 42. |
- Busch, T., et al.
(författare)
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Learning Curve and One-Year Outcome of XEN 45 Gel Stent Implantation in a Swedish Population
- 2020
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Ingår i: Clinical Ophthalmology. - 1177-5483. ; 14, s. 3719-3733
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evaluation of 1-year-outcome of XEN 45 gel stent surgery in a Swedish cohort with regard to clinical success, complications, and learning curve. Patients and Methods: This was a retrospective study of glaucoma patients undergoing glaucoma XEN-stent surgery alone or combined with phacoemulsification between December 2015 and May 2017. Intraocular pressure (IOP), number of medical agents, and adverse events were assessed. Clinical success rate was defined as achieving individual target pressure with/without medication. Results: A total of 113 eyes were included in the final statistics. Mean age was 70.8 +/- 11.8 years. Primary open angle glaucoma (POAG) accounted for 46.9% and exfoliative glaucoma (PEXG) for 40.7%. Mean preoperative TOP was 23.8 +/- 6.2 mmHg and mean number of agents 3.4. After 1 year, mean IOP was reduced to 16.1 +/- 4.7 mmHg and medication to 1.34 substances on average. Failure rate at 1-year follow-up was 34% with no significant difference between POAG and PEXG. There was a trend of higher success rate for combined cases (P=0.116). Stents with malpositioned or curved appearance had significantly worse outcome. The failure rate of the most productive surgeon dropped from 33% to 10% from the first implantations. Temporary hypotony (19.5%) and choroidal detachment (9.7%) were the most common complications. Blockage of the inner stent lumen was common (8.8%), with a high proportion of failure. Conclusion: XEN-stent surgery is a surgical option in uncontrolled glaucoma in both POAG and PEXG. A XEN-stent can reduce both IOP and the number of antiglaucoma medications needed. The learning curve is significant and stent positioning is crucial for optimal results. Combined XEN-cataract surgery is not inferior to stand-alone procedures. The long-time effectiveness is still to be proven.
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| 43. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Effects of 17beta-estradiol in human lens epithelial cells
- 2010
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Ingår i: Acta Ophthalmologica. 2010;88:S246. Presented at European Vision and Eye Research (EVER) Annual Meeting 2010, 6-9 Oct, Crete, Greece.. - : Wiley.
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Konferensbidrag (refereegranskat)
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Dahlgren, Tobias, et al.
(författare)
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Optimal Performance of Selective Laser Trabeculoplasty - Results from the Swedish Optimal SLT Multicenter Randomized Controlled Trial.
- 2024
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Ingår i: Ophthalmology. Glaucoma. - 2589-4196. ; 7:2, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Selective laser trabeculoplasty (SLT) is a first-line treatment for glaucoma and ocular hypertension. However, due to insufficient comparative evidence in efficacy and safety, several SLT treatment protocols are currently used in practice. The objective of this trial was to compare the clinical outcomes of the four most significant SLT variants. Design Prospective, multicenter, masked, randomized controlled trial. Participants Four hundred patients with glaucoma or ocular hypertension. The cohort consisted of both treatment-naïve patients and patients undergoing glaucoma treatment, at different stages of disease. Methods SLT was performed with 50±5 laser spots in 180 degrees, or with 100±10 spots in 360 degrees. The laser power was titrated to either just below the cavitation bubble level (“standard energy”) or to a level producing cavitation bubbles at 50–75% of laser applications (“high energy”). Thus, four different treatment protocols were included – 180/standard, 180/high, 360/standard, and 360/high. The study adhered as close as possible to regular clinical management, but within a scientific framework. Main Outcome Measures Reduction of intraocular pressure (IOP) 1–6 months after SLT. The proportion of patients achieving a 20% IOP reduction without any further intervention. Time to glaucoma treatment escalation in a Kaplan–Meier survival analysis. Results SLT performed with the 360/high protocol was shown to be superior regarding all primary endpoints. The IOP reduction 1–6 months after SLT was 5.4 mmHg in the 360/high group, compared to 3.4, 3.2, and 4.2 mmHg with the 180/standard, 180/high, and 360/standard protocols, respectively (p<0.001). Further, the success rate after 6 months was significantly higher – 58.3%, compared with 30.2%, 29.3%, and 41.7% (p<0.001). The median time to glaucoma treatment escalation was more than twice as long with 360/high SLT – 1323 days, compared to 437 days, 549 days, and 620 days (p<0.001). Although postoperative discomfort was more frequent with the 360/high protocol, symptoms were generally mild and transient. Adverse events were rare in all groups. Conclusions The magnitude and longevity of SLT results increases substantially if SLT is performed according to the 360/high protocol, without compromising safety. Therefore, we recommend that 360/high SLT be considered as standard treatment.
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| 48. |
- Dahlgren, Tobias, et al.
(författare)
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The impact of topical NSAID treatment on selective laser trabeculoplasty efficacy
- 2023
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 101:3, s. 266-276
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Selective laser trabeculoplasty (SLT) is a first-line intervention for glaucoma, with the aim to reduce the intraocular pressure (IOP). Topical non-steroidal anti-inflammatory drugs (NSAIDs) are sometimes prescribed after SLT. However, it has been proposed that such treatment may either increase or reduce SLT efficacy. The purpose of this study was to investigate this further. Methods The study was a retrospective chart review, including 192 eyes of 192 patients, half of which received a course of NSAID eyedrops after SLT. Absolute and relative IOP reduction 3-12 weeks after SLT was compared. Furthermore, subgroup analyses, a multiple linear regression analysis, and a Kaplan-Meier survival analysis regarding time to treatment escalation were performed. Results The mean absolute IOP reduction was 4.3 +/- 3.4 mmHg in the NSAID group and 5.4 +/- 4.1 mmHg in the control group (p = 0.049). Relative IOP reduction was 17.5% +/- 13.0% and 21.8% +/- 14.8% in the NSAID and control groups, respectively (p = 0.033). The same tendency of superior results in control eyes compared with NSAID eyes was seen in an extensive subgroup analysis. A multiple linear regression analysis confirmed NSAID treatment as a negative predictor of IOP reduction after adjustment for covariates (p = 0.023). Survival analysis showed a longer median time to treatment escalation in the control group, though not statistically significant. Conclusion Topical NSAID treatment was not associated with an increased SLT efficacy. On the contrary, the present study is the first to demonstrate that SLT effectiveness may even be reduced by NSAIDs.
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- Hashas, A. S. K., et al.
(författare)
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A new diagnostic method for retinal breaks in patients with posterior vitreous detachment: Ultra-wide-field imaging with the Zeiss Clarus 700
- 2023
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 101:6, s. 627-635
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study was performed with the aim of finding a more convenient and less time-consuming method to diagnose retinal breaks in posterior vitreous detachment (PVD) patients. MethodsA prospective double-blind observational case study was performed with patients who were admitted to the Eye Emergency Department Sahlgrenska University Hospital with PVD symptoms and approved to participate in the study (n = 128). Standard slit lamp examination was compared with images from a Zeiss Clarus 700 ultra-wide-field camera (UWFC). Patients were examined and photographed by an independent operator. Data and image review was performed by three independent reviewers with varying experience. Retinal break detection with the two different methods (detailed eye examination by well-trained ophthalmologist and UWFC evaluations) was analysed statistically. ResultsAfter excluding diagnoses other than PVD as well as unclear images due to cataracts, vitreous bleeding, etc., a total of 103 eyes with PVD were evaluated. A total of 38 ruptures in 25 patients were detected by routine examination and were subjected to laser treatment. UWFC images were reviewed by three ophthalmology consultants and compared with routine examinations. Sensitivity values in detecting retinal ruptures in UWFC images of the three reviewers were 0.89, 0.87 and 0.79, and specificity values were 0.88, 0.86 and 0.93 (kappa values: 0.742, 0.689 and 0.728) respectively. ConclusionAlthough there have been rapid developments in imaging with UWFC in recent years and it is a very promising method for the future, routine clinical examination is still the only valid method for the detection of retinal tears today.
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