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1.
Thorac Cardiovasc Surg ; 70(S 03): e15-e20, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36179762

RESUMO

BACKGROUND: The storage time of packed red blood cells (pRBC) is an indicator of change in the product's pH, potassium, and lactate levels. Blood-gas analysis is a readily available bedside tool on every intensive care ward to measure these factors prior to application, thus facilitating a calculated decision on a transfusion's quantity and duration.Our first goal is to assess the impact of storage time on pH, potassium, and lactate levels in pRBC. The influence of those parameters in the transfused children will then be evaluated. METHODS: In this retrospective study, we conducted blood-gas analyses of pRBC units before they were administered over 4 hours to neonates, infants, and children in our pediatric cardiac intensive care ward. All patients underwent regular blood-gas analyses themselves, before and after transfusion. RESULTS: We observed a highly significant correlation between the storage time of pRBC units and a drop in pH, as well as an increase in potassium and lactate of stored red cells (p< 0.0001). Median age of recipients with a complete blood-gas dataset was 0.1 (interquartile range [IQR] = 0.0-0.7) years; median pRBC storage duration was 6 (IQR = 5-8) days. Further analyses showed no statistically significant effect on children's blood gases within 4 hours after transfusion, even after stratifying for pRBC storage time ≤7 days and >7 days. CONCLUSION: Stored red blood cells show a rapid decrease in pH and increase in potassium and lactate. Slow transfusion of these units had no adverse effects on the recipients' pH, potassium, and lactate levels.


Assuntos
Cardiopatias Congênitas , Criança , Gases , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Humanos , Lactente , Recém-Nascido , Lactatos , Potássio , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
2.
Hum Mol Genet ; 26(2): 438-453, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28073927

RESUMO

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Glaucoma de Ângulo Aberto/genética , Proteínas de Homeodomínio/genética , Doenças do Nervo Óptico/genética , Proteínas de Peixe-Zebra/genética , Feminino , Genoma Humano , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular/genética , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Doenças do Nervo Óptico/patologia , Tonometria Ocular
3.
Heart Vessels ; 34(1): 134-140, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30043154

RESUMO

The study describes our experience with Amplatzer Vascular Plugs (AVP2 and 4) and highlights a more refindes telescopic technique for AVP2 delivery. AVPs are well-established occlusion devices for vascular anomalies in congenital heart disease (CHD). The AVP2 is sometimes preferred to the AVP4 due to its shorter length, flat-profiled retention disks, and the availability of larger diameters, but its profile requires a larger inner lumen for safe delivery. The latter may actually hamper access to target lesions. This is a retrospective analysis of all CHD patients treated with the AVP2 and AVP4 between 12/2012 and 12/2015. Target vessels were characterized, measured, and the device-to-vessel diameter ratio calculated. A modified pigtail technique for AVP2 delivery was frequently used: a floppy wire was simply reinforced by the curved tip of a pigtail catheter (instead of the long sheath's dilator) to guide the required delivery sheath towards the desired landing zone. 59 patients with a median age and bodyweight of 3.0 years (range 0.1-75) and 13.8 kg (range 2.5-80) underwent the implantation of 106 plug-devices (30 AVP2, 76 AVP4) in 91 target vessels. Indications for their use were ductus arteriosus (19%), aortopulmonary (43%) as well as venovenous collaterals (34%) and other miscellaneous lesions (4%). The pigtail-supported AVP2 delivery in six patients proved very convenient. No complications occurred. AVPs are excellent devices for embolizing shunt vessels in CHD patients. Here, we describe a simplified telescoping technique for AVP2 delivery to enter curvy target lesions gently and efficiently.


Assuntos
Cateterismo Cardíaco/métodos , Cateteres Cardíacos , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Dispositivo para Oclusão Septal , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Mol Vis ; 24: 127-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29422769

RESUMO

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.


Assuntos
Fosfatase Ácida/genética , Astigmatismo/genética , Claudinas/genética , Doenças da Córnea/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Povo Asiático , Astigmatismo/diagnóstico , Astigmatismo/etnologia , Astigmatismo/patologia , Estudos de Coortes , Córnea/metabolismo , Córnea/patologia , Doenças da Córnea/diagnóstico , Doenças da Córnea/etnologia , Doenças da Córnea/patologia , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Software , População Branca
5.
Ophthalmology ; 125(8): 1149-1159, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29548645

RESUMO

TOPIC: To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. CLINICAL RELEVANCE: Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. METHODS: Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 and 2010. RESULTS: The age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584 000 were blind in 2000, in comparison with 170 000 who were blind in 2010. CONCLUSIONS: Despite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.


Assuntos
Baixa Visão/epidemiologia , Acuidade Visual , Pessoas com Deficiência Visual/estatística & dados numéricos , Idoso , Europa (Continente)/epidemiologia , Humanos , Prevalência
6.
Graefes Arch Clin Exp Ophthalmol ; 256(9): 1695-1702, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29774418

RESUMO

PURPOSE: To determine the prevalence of glaucoma according to the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) classification in an adult German cohort. METHODS: The Gutenberg Health Study is a population-based, prospective cohort study in the Rhine-Main Region in mid-western Germany with a total of 15,010 participants. In this study, the first 5000 subjects with an age range between 35 and 74 years were included. Optic disk pictures were obtained by a non-mydriatic fundus camera (Visucam™) and analyzed using the Visupac™ software. Glaucoma prevalence was determined in two steps. First, the ISGEO classification was applied using "hypernormal subjects" (normal visual field) as reference. In the second analysis, we additionally considered the disk area (DA) in relation to the vertical cup-to-disk ratio by quantile regression. All results are given as weighted numbers for the population of Mainz/Bingen. RESULTS: The prevalence of definite glaucoma in our sample was 1.44% (n = 72). The prevalence adjusted for disk area was 1.34% (n = 67). The prevalence gradually increased in both models with each decade of age (from 0.9 to 2.4%, respectively). In both models, none of the glaucoma cases had a small optic disk (< 1.6 mm2). Glaucoma prevalence in medium optic disks was 1.0% (without DA adjustment) vs. 1.6% (with DA adjustment) and in large optic disks 5.6 vs. 2.5%. CONCLUSIONS: The prevalence of definite glaucoma was similar to other European population-based cohorts, with slightly higher prevalence in younger subjects. Our analysis highlighted the influence of optic disk size in determining the diagnosis of glaucoma based on cup-to-disk ratio in epidemiological studies.


Assuntos
Córnea/diagnóstico por imagem , Glaucoma/epidemiologia , Pressão Intraocular/fisiologia , Disco Óptico/diagnóstico por imagem , Vigilância da População/métodos , Acuidade Visual , Campos Visuais/fisiologia , Adulto , Idoso , Topografia da Córnea , Feminino , Alemanha/epidemiologia , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Humanos , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Prevalência
7.
Artif Organs ; 42(4): 394-400, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29423912

RESUMO

Extracorporeal life support (ECLS) weaning is a complex interdisciplinary process with no clear guidelines. To assess ventricular and pulmonary function as well as hemodynamics including end-organ recovery during ECLS weaning, we developed a standardized weaning protocol. We reviewed our experience 2 years later to assess its feasibility and efficacy. In 2015 we established an inter-professional, standardized, stepwise protocol for weaning from ECLS. If the patient did not require further surgery, weaning was conducted bedside in the intensive care unit (ICU). Most of the weaning procedures are guided via echocardiography. Data acquisition began at baseline level, followed by four-step course (each step lasting 10 min), entailing flow-reduction and ending 30 min after decannulation. Moreover, data from the preprotocol era are presented. Between May 2015 and 2017, 26 consecutive patients (18 male), median age 177 days (2 days-20 years) required ECLS with median support of 4 (2-11) days. Excluding eight not weanable patients, 21 standardized weaning procedures were protocolled in the remaining 18 children. Our generally successful protocol-guided weaning rate (with at least 24-h survival) was 89%, with a discharge home rate of 58%. Practical application of the novel standard protocol seems to facilitate ECLS weaning and to improve its success rate. The protocol can be administered as part of standard bedside ICU assessment.


Assuntos
Oxigenação por Membrana Extracorpórea/normas , Cuidados para Prolongar a Vida/normas , Choque Cardiogênico/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Protocolos Clínicos , Ecocardiografia , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/métodos , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Cuidados para Prolongar a Vida/instrumentação , Cuidados para Prolongar a Vida/métodos , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Choque Cardiogênico/diagnóstico por imagem , Choque Cardiogênico/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
8.
Hum Mutat ; 38(8): 1025-1032, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28493391

RESUMO

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61 ), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers.


Assuntos
Exoma/genética , Haplótipos/genética , Frequência do Gene/genética , Variação Genética/genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética
9.
Genet Epidemiol ; 40(8): 756-766, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27611182

RESUMO

Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; ß = 0.0016 per risk allele (P = 2 × 10-8 ) in <10 years, 0.0033 (P = 5 × 10-15 ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10-72 ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.


Assuntos
Conexinas/genética , Estudo de Associação Genômica Ampla , Laminina/genética , Miopia/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Alelos , Biometria , Criança , Feminino , Loci Gênicos , Genótipo , Humanos , Masculino , Fatores de Risco , Adulto Jovem , Proteína delta-2 de Junções Comunicantes
10.
Catheter Cardiovasc Interv ; 90(5): 824-829, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28296023

RESUMO

AIMS: The GORE® CARDIOFORM Septal Occluder (GSO) is a novel device designed for rapid and effective closure of patent foramen ovale (PFO) which has distinctive features making it suitable for a broad spectrum of anatomical variations. We report the procedural and 6 months follow-up results of the first prospective, multicenter study using GSO. METHODS AND RESULTS: This single-arm study included 150 subjects undergoing closure of PFO in 10 European centers. In 149 out of 150 patients implantation of a GSO device was successful. One patient had a different PFO-closure device implanted. Periprocedural complications were few including one patient with suspected transient ischemic attack, two access site bleedings, and one patient with AV-fistula. No device embolization occurred. During the 6-month follow-up period one patient had a transient asymptomatic thrombus on the device and four patients (2.6%) were diagnosed new onset paroxysmal atrial fibrillation, which were successfully treated. No thrombembolic events occurred. Closure was successful in 94.2% of subjects at discharge evaluation and 96.9% at 6 months follow-up. CONCLUSION: This prospective, multicenter study adds to previous published data and suggests that GSO is a versatile device for PFO closure with high procedural and closure success rates and low complication rates through mid-term follow-up. © 2017 Wiley Periodicals, Inc.


Assuntos
Cateterismo Cardíaco/instrumentação , Forame Oval Patente/terapia , Dispositivo para Oclusão Septal , Adulto , Cateterismo Cardíaco/efeitos adversos , Europa (Continente) , Feminino , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Fatores de Tempo , Resultado do Tratamento
11.
Pediatr Crit Care Med ; 18(2): 176-182, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27849657

RESUMO

OBJECTIVE: The objective of this study was to evaluate health-related quality of life in long-term survivors of mechanical circulatory support after acute cardiopulmonary failure. DESIGN: Prospective follow-up study. SETTING: Single-institutional in a center for congenital heart disease and pediatric cardiology. PATIENTS: Fifty patients who underwent 58 mechanical circulatory support therapies in our institution from 2001 to 2012. Median age was 2 (0-213) months, and median supporting time was 5 (1-234) days. Indication groups: 1) extracorporeal life support in low cardiac output: 30 cases (52%); 2) extracorporeal cardiopulmonary resuscitation: 13 cases (22%); 3) extracorporeal membrane oxygenation in acute respiratory distress syndrome: four cases (7%); and 4) ventricular assist devices: 11 cases (19%). INTERVENTIONS: Health-related quality of life was measured using standardized questionnaires according to the age group and completed by either parent proxies in children under 7 years old or the survivors themselves. MEASUREMENTS AND MAIN RESULTS: Fifty percentage of the patients were discharged home, and 22 long-term survivors (44%) were studied prospectively for health-related quality of life. Median follow-up period was 4.5 (0.3-11.3) years. Median age at follow-up was 5 (0.6-29) years old. Nineteen long-term survivors filled in the health-related quality of life questionnaires and were classified into three age groups: 0-4 years (n = 7): median health-related quality of life score, 69 (59-86) points; 4-12 years (n = 7): median health-related quality of life score, 50 (48-85) points; older than 12 years (n = 5): median health-related quality of life score, 90 (80-100) points. CONCLUSION: Long-term survivors' health-related quality of life as reported by their parents is lower than that of healthy children. However, the self-assessed health-related quality of life of the patients older than 12 years in our group is comparable to a healthy control population.


Assuntos
Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Indicadores Básicos de Saúde , Coração Auxiliar , Qualidade de Vida , Adolescente , Reanimação Cardiopulmonar/métodos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Sobreviventes
12.
Klin Monbl Augenheilkd ; 234(7): 931-948, 2017 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-28486733

RESUMO

Glaucoma is a heterogeneous group of diseases which all share retinal ganglion cell loss leading to a typical optic disc cupping and characteristic visual field defects. Glaucoma is the leading cause of irreversible blindness affecting 8.4 million people. In 2013, 65 million people suffered from glaucoma worldwide and the number will increase to about 112 million in 2040. This review provides an overview about the classification and genetic basics in glaucoma.


Assuntos
Glaucoma/classificação , Glaucoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Endofenótipos , Feminino , Predisposição Genética para Doença/genética , Glaucoma/epidemiologia , Glaucoma/terapia , Humanos , Lactente , Pressão Intraocular/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acuidade Visual
13.
Genet Epidemiol ; 39(3): 207-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25631615

RESUMO

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.


Assuntos
Estudo de Associação Genômica Ampla , Glaucoma/genética , Disco Óptico/patologia , Doenças do Nervo Óptico/genética , Locos de Características Quantitativas/genética , Povo Asiático/genética , Glaucoma/etnologia , Glaucoma/patologia , Humanos , Doenças do Nervo Óptico/etnologia , Doenças do Nervo Óptico/patologia , População Branca/genética
14.
Am J Hum Genet ; 93(2): 264-77, 2013 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-24144296

RESUMO

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.


Assuntos
Comprimento Axial do Olho/metabolismo , Proteínas do Olho/genética , Loci Gênicos , Predisposição Genética para Doença , Erros de Refração/genética , Adolescente , Adulto , Idoso , Povo Asiático , Comprimento Axial do Olho/patologia , Proteínas do Olho/metabolismo , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Erros de Refração/etnologia , Erros de Refração/patologia , Transdução de Sinais , População Branca
15.
Eur J Epidemiol ; 31(11): 1101-1111, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27613171

RESUMO

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.


Assuntos
Pressão Intraocular/fisiologia , Hipertensão Ocular/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Hum Genet ; 134(2): 131-46, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25367360

RESUMO

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.


Assuntos
Astigmatismo/genética , Moléculas de Adesão Celular Neuronais/genética , Estudo de Associação Genômica Ampla , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas do Tecido Nervoso/genética , Adulto , Fatores Etários , Povo Asiático , Astigmatismo/patologia , Proteínas de Ligação ao Cálcio , Estudos de Coortes , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Moléculas de Adesão de Célula Nervosa , População Branca
17.
Ophthalmology ; 122(7): 1489-97, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25983215

RESUMO

PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level. RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.


Assuntos
Escolaridade , União Europeia/estatística & dados numéricos , Miopia/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Etnicidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Distribuição por Sexo
18.
Eur J Epidemiol ; 30(4): 305-15, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25784363

RESUMO

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E(3)) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤-0.75 diopters (D), high myopia ≤-6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4-30.9], high myopia 2.7 % (95 % CI 2.69-2.73), hyperopia 25.2 % (95 % CI 25.0-25.4) and astigmatism 23.9 % (95 % CI 23.7-24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8-52.5) in 25-29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.


Assuntos
Erros de Refração/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Estudos Transversais , Etnicidade/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Erros de Refração/diagnóstico , Fatores de Risco , Distribuição por Sexo , População Urbana/estatística & dados numéricos , População Branca
20.
Ophthalmol Ther ; 13(6): 1513-1525, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581605

RESUMO

INTRODUCTION: The aim of this study was to investigate the 2-year postoperative efficacy of the XEN45 Gel Stent by evaluating the reduction of intraocular pressure (IOP) and the need for eye pressure-lowering medications in a multicenter setting in Switzerland. METHODS: Patients with various types of glaucoma who received a XEN45 Gel Stent with or without combined phacoemulsification cataract surgery at five hospitals in Switzerland were retrospectively enrolled. Pre- and postoperative IOP, the number of antiglaucoma medications, and the need of subsequent interventions to control IOP were assessed. The success rate was defined as a ≥ 20% reduction of IOP 2 years postoperatively without the need for subsequent glaucoma surgery. RESULTS: A total of 345 eyes were included: 44.3% with primary open-angle, 42.0% pseudoexfoliation, and 13.7% with other types of glaucoma. Of these, 206 patients were followed for 2 years. Preoperatively, the mean IOP was 26.3 ± 8.9 mmHg and the mean number of antiglaucoma medications administered was 3.0 ± 1.3. Two years postoperatively, the success rate was 66.0% (95% confidence interval 59.3-72.1%), the IOP had dropped by 43.8% to 14.8 ± 5.7 mmHg, and the number of medications was reduced by a mean of 2.0 ± 1.7 per day. Postoperative complications and the need for interventions remained low. CONCLUSION: The XEN45 Gel Stent successfully reduced IOP and the number of antiglaucoma drugs in most patients at 2 years postoperatively.

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