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1.
Cancer Treat Res Commun ; 31: 100519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35093682

RESUMO

PURPOSE: Gene expression tests can inform decisions on whether to recommend chemotherapy for patients with HR+, HER2- early breast cancer. The goal of this analysis was to compare treatment costs by an expanded budget impact model of reimbursed gene expression tests in Germany. METHODS: A cost comparison was constructed as an expanded budget impact model to calculate average total costs per patient covered by public health insurance. Based on the strong clinical evidence from the prospective randomized controlled trial TAILORx including more than 10,000 patients with HR+ and node negative breast cancer, the assumption was made that the Oncotype DX® test accurately predicts chemotherapy benefit and clinical outcomes. For the further reimbursed tests (EndoPredict®, MammaPrint®, Prosigna®), results from comparative studies - aligned with prognosis studies - as analyzed in IQWiG Rapid Report D19-01 were applied. RESULTS: The use of the Oncotype DX test led to estimated average savings per patient of 2,500 € vs. EndoPredict, 1,936 € vs. MammaPrint, and 649 € vs. Prosigna. Savings were achieved by reduction of unnecessary chemotherapy use, a consequence of false-positive test results (EndoPredict 73%, MammaPrint 42%, Prosigna 20%). False-negative test results (EndoPredict 5%, MammaPrint 22%, Prosigna 49%) reduced necessary chemotherapies, which initially results in cost savings, but may lead to increased long-term costs associated with management of progressive disease. CONCLUSION: The results from this model suggest that the use of the Oncotype DX test reduces the cost of health care in Germany making it the most cost effective test compared to the further tests.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Humanos , Prognóstico , Estudos Prospectivos
2.
Klin Monbl Augenheilkd ; 233(8): 951-7, 2016 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-27130973

RESUMO

OBJECTIVES: Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. METHODS: A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. RESULTS: For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years, which have to be compared to the costs of a single application of OT. CONCLUSIONS: The short-term economic analysis shows that anti-VEGF therapy combined with OT results in savings above the costs for OT itself over a 2 year time horizon. Overall, the approach gives potential cost reductions, if the appropriate indication is followed.


Assuntos
Quimiorradioterapia/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Modelos Econômicos , Radiocirurgia/economia , Degeneração Macular Exsudativa/economia , Degeneração Macular Exsudativa/radioterapia , Adulto , Inibidores da Angiogênese/economia , Inibidores da Angiogênese/uso terapêutico , Quimiorradioterapia/estatística & dados numéricos , Simulação por Computador , Relação Dose-Resposta à Radiação , Feminino , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Lesões por Radiação/economia , Lesões por Radiação/epidemiologia , Radiocirurgia/estatística & dados numéricos , Dosagem Radioterapêutica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/epidemiologia
4.
Ophthalmologe ; 111(8): 791-802, 2014 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-25092025

RESUMO

Screening is a strategy used in a systematic approach to identify an unrecognized disease or risk factors in individuals in a population without signs or symptoms. The test characteristics (specificity and sensitivity) and the prevalence of the disease are of vital importance for the achievable quality of prediction. Multidimensional decision-making must not only consider the benefits of screening but also its potential disadvantages, such as overtreatment, diagnostics of unclear findings and the psychological impact on healthy individuals. Besides medical, ethical and test theoretical considerations, economic considerations also have to be included in decision-making on a screening program. In Germany, a nationwide screening for diabetic retinopathy and regional programs for amblyopia screening exist. Screening for glaucoma or age-related macular degeneration is currently not funded by the statutory health insurance.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico , Oftalmopatias/prevenção & controle , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Oftalmologia/organização & administração , Diagnóstico Precoce , Alemanha , Humanos
5.
Ophthalmologe ; 111(5): 420-7, 2014 May.
Artigo em Alemão | MEDLINE | ID: mdl-24838862

RESUMO

BACKGROUND: Eye diseases that are relevant regarding their macroeconomic costs and their impact on society include cataract, diabetic retinopathy, age-related maculopathy, glaucoma and refractive errors. OBJECTIVES: The aim of this article is to provide a comprehensive overview of direct and indirect costs for major eye disease categories for Germany, based on existing literature and data sources. METHODS: A semi-structured literature search was performed in the databases Medline and Embase and in the search machine Google for relevant original papers and reviews on costs of eye diseases with relevance for or transferability to Germany (last research date October 2013). In addition, manual searching was performed in important national databases and information sources, such as the Federal Office of Statistics and scientific societies. RESULTS: The direct costs for these diseases add up to approximately 2.6 billion Euros yearly for the Federal Republic of Germany, including out of the pocket payments from patients but excluding optical aids (e.g. glasses). In addition to those direct costs there are also indirect costs which are caused e.g. by loss of employment or productivity or by a reduction in health-related quality of life. These indirect costs can only be roughly estimated. Including the indirect costs for the eye diseases investigated, a total yearly macroeconomic cost ranging between 4 and 12 billion Euros is estimated for Germany. CONCLUSION: The costs for the eye diseases cataract, diabetic retinopathy, age-related maculopathy, glaucoma and refractive errors have a macroeconomic relevant dimension. Based on the predicted demographic changes with an ageing society an increase of the prevalence and thus also an increase of costs for eye diseases is expected in the future.


Assuntos
Efeitos Psicossociais da Doença , Oftalmopatias/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Renda/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , Desemprego/estatística & dados numéricos , União Europeia , Oftalmopatias/epidemiologia , Alemanha/epidemiologia , Avaliação do Impacto na Saúde , Humanos , Modelos Econômicos , Prevalência , Perfil de Impacto da Doença
6.
Klin Monbl Augenheilkd ; 231(1): 54-60, 2014 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-24104961

RESUMO

BACKGROUND: The purpose of this study is to establish the correlation between functional and morphological aspects before and 12 months after macular hole surgery. METHODS: In this prospective, interventional, consecutive study 16 eyes of 16 patients were included. All eyes received a successful transconjunctival 23-gauge vitrectomy with ILM peeling after initial diagnosis and maximum duration of symptoms of two months. Preoperatively and 3, 6 and 12 months postoperatively determinations of best-corrected visual acuity (logMAR), a 10° microperimetry (MP-1) and a spectral-domain based optical coherence tomography (SD-OCT) examination were performed. The photoreceptor layer (inner and outer segment, IS/OS) was evaluated based on SD-OCT images and correlated with data assessed by microperimetry analysis in the foveal and parafoveal region. RESULTS: After three months a stabilisation of BCVA with regeneration of the IS/OS line, an improvement of the fixation behaviour and the macular sensitivity could be observed. A significant restitution of the IS/OS line was observed after 12 months. Best corrected visual acuity, mean overall macular sensitivity and fixation improved significantly within the twelve month observation period (p < 0.05). Comparison of patients with at least two lines of visual acuity gain with patients having less than two lines of visual acuity gain 12 months after surgery showed no statistically significant difference in regeneration of the IS/OS integrity in the fovea (p = 0.433), but a difference was seen in the parafoveal region. A postoperative visual acuity gain of at least two lines was significantly more often seen in eyes with postoperative continuous IS/OS line in the parafoveal sectors compared to eyes with persistent IS/OS defects (p < 0.02). CONCLUSION: Correlations of morphological and functional improvements can be observed after successful micro-invasive macular hole surgery. The extent of the preoperative IS/OS defect, particularly in the parafoveal region, is a good predictive parameter for the postoperatively obtained macular sensitivity. The prediction of the postoperative visual acuity should not be made on the basis of a single clinical, anatomic finding.


Assuntos
Macula Lutea/patologia , Macula Lutea/cirurgia , Recuperação de Função Fisiológica , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Transtornos da Visão/diagnóstico , Transtornos da Visão/prevenção & controle , Vitrectomia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfurações Retinianas/complicações , Estatística como Assunto , Resultado do Tratamento , Transtornos da Visão/etiologia , Acuidade Visual
8.
Ophthalmologe ; 110(8): 776-82, 2013 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-23760425

RESUMO

Navigated laser therapy introduces for the first time computerized assistance systems for retinal laser therapy. The Navilas system offers high precision and safety and provides additional benefits regarding standardization of planning, execution, documentation and quality assurance. The current focus of clinical application for navigated laser therapy besides laser treatment after retinal vein occlusion and panretinal laser photocoagulation in proliferative diabetic retinopathy (PDR) is diabetic macular edema. Recent data indicate that combined initial anti-vascular endothelial growth factor (anti-VEGF) and navigated macular laser therapy allows achievement and maintenance of treatment success with a minimum number of interventions. Despite very promising results the current assessment of navigated laser therapy is still limited by the evidence available worldwide.


Assuntos
Retinopatia Diabética/cirurgia , Fotocoagulação a Laser/instrumentação , Terapia a Laser/instrumentação , Edema Macular/cirurgia , Cirurgia Assistida por Computador/instrumentação , Desenho de Equipamento , Humanos
9.
Ophthalmologe ; 109(7): 692-8, 2012 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-22532038

RESUMO

PURPOSE: The aim of this study was to investigate the accuracy of a navigated laser photocoagulator in clinically significant macular edema (CSME). METHODS: Focal laser treatment for diabetic macular edema (DME) in 36 patients was digitally planned on fundus images and performed with navigation using NAVILAS® (OD-OS, Teltow, Germany). Treatment intensity was controlled visually during treatment so the laser spots applied were barely directly visible after treatment. Using color images (CI) and optical coherence tomography (OCT) 4,137 laser spots (mean 115 per eye) were analyzed at 1 month follow-up and accuracy of spot placement was determined. RESULTS: In total 79% of laser spots were visible on CI of which 96% were within 100 µm of the planned target position. On an intention-to-treat (ITT) basis, 76% of the laser spots were placed and visible within the 100 µm target and OCT confirmed that laser effects were limited to the outer retina. The mean time for focal treatment was < 7 min (±3 min). CONCLUSIONS: After NAVILAS treatment for DME a high percentage of laser effects could be visualized on post-treatment color images and the location showed high concordance with the preplanning target.


Assuntos
Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Fotocoagulação a Laser/instrumentação , Fotocoagulação a Laser/métodos , Edema Macular/diagnóstico , Edema Macular/cirurgia , Retinopatia Diabética/complicações , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Ophthalmologe ; 108(10): 939-46, 2011 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-21779960

RESUMO

INTRODUCTION: Glaucoma is one of the leading causes of irreversible blindness worldwide and can have a significant impact on patient quality of life and vision-related functioning. The Glaucoma Quality of Life 15 (GQL-15) questionnaire is a disease-specific instrument to evaluate and quantify functional impairment of patients with glaucoma. This study evaluated the German version of the GQL-15 including correlations with perimetric parameters. METHODS: A German version of the GQL-15 containing 15 items was developed and evaluated in 98 patients with glaucoma in different stages of the disease. The GQL-15 results were correlated with the perimetric parameters mean deviation (MD) and pattern standard deviation (PSD) of the better and worse eye. Classical and probabilistic test analyses (Rasch model) were performed. RESULTS: The mean GQL-15 value was 77.3 ± 21.7 (SD) and most items of the GQL-15 correlated significantly with the MD of the worse eye (r = -0.416; p = 0.0014) and the better eye (r = -0.304; p = 0.02). There was also a highly significant correlation between glaucoma-specific QoL and visual acuity. A short version containing nine items yielding a higher psychometric performance can also be used. CONCLUSIONS: The German version of the GQL-15 is a potent instrument to evaluate impairment in vision-specific functioning of patients with glaucoma. The GQL-15 values are better correlated with the sensitivity of the eye with the more severe glaucomatous damage. The data can help for a better understanding of individual patient impairment to improve medical advice and therapy of patients with glaucoma.


Assuntos
Glaucoma/complicações , Glaucoma/diagnóstico , Perfil de Impacto da Doença , Inquéritos e Questionários , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Idoso , Feminino , Alemanha , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Testes Visuais
11.
Klin Monbl Augenheilkd ; 228(10): 892-9, 2011 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-21432767

RESUMO

BACKGROUND: Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. METHODS: Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. CONCLUSIONS: This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.


Assuntos
Antibacterianos/uso terapêutico , Citoproteção/efeitos dos fármacos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Minociclina/uso terapêutico , Antibacterianos/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Proliferação de Células , Células Cultivadas/efeitos dos fármacos , Humanos , Luz/efeitos adversos , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Minociclina/efeitos adversos , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/genética
12.
Klin Monbl Augenheilkd ; 228(6): 544-9, 2011 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-21442571

RESUMO

BACKGROUND: The aim of this study was to examine the changes in static analysis of the retinal vasculature during an acute rise of blood pressure in young normal subjects. MATERIAL AND METHODS: An increase of blood pressure was induced in 30 young normal subjects (age 18 - 30 years) by physiological stress. Retinal fundus photographs were taken before and immediately after the stress. The central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE) and the arterio-venous ratio (AVR) were calculated by automated vessel analysis software (Talia Technology, Lod, Israel). The same vessel segments were measured before and after the rise of blood pressure. RESULTS: At rest, mean CRAE was 97.3 ± 9.6 micrometer, CRVE 114.5 ± 12.5 micrometer and AVR 0.85 ± 0.08. The mean systemic perfusion pressure was elevated by physiological stress from a mean of 90.7 ± 7 mmHg by 18.0 ± 7.8 mmHg. The static retinal vessel analysis showed a constriction of the arteries by a mean of -1.3 ± 3.9 microns and a venous dilatation of 0.6 ± 7.2 microns. The retinal AVR was diminished significantly (p = 0.02) by -0.015 ± 0.032. The degree of arterial constriction - but not the change of AVR - correlated significantly (r = -0.39; p = 0.048) with the degree of rise of blood pressure. CONCLUSION: Retinal autoregulation during acute increase of blood pressure in young normal subjects can be measured by static retinal vessel analysis.


Assuntos
Pressão Sanguínea/fisiologia , Vasos Retinianos/fisiologia , Adaptação Fisiológica/fisiologia , Adolescente , Feminino , Humanos , Masculino , Adulto Jovem
13.
Ophthalmologe ; 108(5): 445-51, 2011 May.
Artigo em Alemão | MEDLINE | ID: mdl-21253747

RESUMO

BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells. METHODS: The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays. RESULTS: Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.


Assuntos
Benzenossulfonatos/farmacologia , Piridinas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Inibidores da Angiogênese/farmacologia , Citoproteção/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/farmacologia , Sorafenibe , Resultado do Tratamento , Adulto Jovem
14.
Ophthalmologe ; 108(2): 117-23, 2011 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-20683601

RESUMO

OBJECTIVE: The aim of the study was to compare the diagnostic properties of a non-mydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) with mydriatic ETDRS 7-field fundus photography for diabetic retinopathy screening. METHODS: A consecutive series of 66 eyes from 34 patients with different levels of diabetic retinopathy (DR) were examined. Grading of DR and macular edema (ME) obtained from mydriatic ETDRS 7-field fundus photography were compared with grading obtained from Optomap Panoramic 200MA SLO images. All SLOs were performed with an undilated pupil and no additional clinical information was used for evaluation of images by two independent, masked experts. RESULTS: A total of 14 eyes from ETDRS 7-field fundus photography and 11 eyes from Optomap could not be graded by at least one grader due to poor image quality, yielding 48 eyes for comparison purposes. Of the 48 ETDRS 7-field fundus photographs, 9 (11 for grader 2) eyes had no or mild DR (ETDRS levels ≤20) and 17 (23 for grader 2) eyes had no ME. Agreement of Optomap retinopathy grading with ETDRS 7-field fundus photography was good, kappa 0.70 for grader 1 and kappa 0.66 for grader 2. There was good agreement between both techniques for ME, grader 1 kappa 0.68 and grader 2 kappa 0.74. CONCLUSIONS: Grading of DR levels from Optomap Panoramic 200MA non-mydriatic images showed a good correlation with mydriatic ETDRS 7-field fundus photography. Both techniques are of sufficient quality for a valid assessment of DR. Optomap Panoramic 200MA images cover a larger retinal area and might therefore offer additional diagnostic properties.


Assuntos
Retinopatia Diabética/patologia , Angiofluoresceinografia/instrumentação , Microscopia Confocal/instrumentação , Fotografação/instrumentação , Retinoscópios , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Br J Ophthalmol ; 94(11): 1533-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20962354

RESUMO

BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor is the main target of current antiangiogenic treatment strategies in AMD. However, other growth factors, such as platelet-derived growth factor (PDGF) and placenta growth factor (PlGF), have a substantial impact on development of AMD. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of growth factors in human retinal pigment epithelial (RPE) cells. METHODS: Primary human RPE cells were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reactions, immunohistochemistry and enzyme-linked immunosorbent assays. RESULTS: Light exposure decreased cell viability and increased expression and secretion of VEGF-A, PDGF-BB and PlGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.


Assuntos
Inibidores da Angiogênese/farmacologia , Benzenossulfonatos/farmacologia , Degeneração Macular/tratamento farmacológico , Proteínas de Membrana/metabolismo , Piridinas/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Inibidores da Angiogênese/administração & dosagem , Benzenossulfonatos/administração & dosagem , Sobrevivência Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Luz , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Piridinas/administração & dosagem , RNA Mensageiro/metabolismo , Sorafenibe
16.
Ophthalmologe ; 107(9): 799-805, 2010 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-20821332

RESUMO

The results of conservative treatment for central retinal artery occlusion (CRAO) vary considerably and although local intraarterial fibrinolysis (LIF) is a promising treatment, outcomes have not been compared in randomized trials. The prospective randomized multicenter study by the European Assessment Group for Lysis in the Eye (EAGLE) is the first clinical trial to compare treatment outcomes of conservative standard treatment (CST) and LIF for acute non-arteritic CRAO. Patients (age 18-75 years) with CRAO present for less than 20 h and best-corrected visual acuity (BCVA) <0.5 logMAR were randomized to either CST or LIF group. Primary endpoint was BCVA after 1 month and secondary endpoint was safety. Mean BCVA (logMAR) improved significantly in both groups and did not differ between the groups. Because of similar efficacy and the higher rate of adverse events in the LIF group the study was halted after the first interim analysis. Due to the similar outcomes of the two therapies and the higher rate of adverse reactions associated with LIF superselective lysis cannot be recommended for the management of acute CRAO.


Assuntos
Fibrinolíticos/administração & dosagem , Oclusão da Artéria Retiniana/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Arterite/complicações , Arterite/tratamento farmacológico , Feminino , Alemanha , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Oclusão da Artéria Retiniana/etiologia , Retinite/complicações , Retinite/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
17.
Ophthalmologe ; 107(9): 814-20, 2010 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-20596712

RESUMO

Several systemic cardiovascular (CV) risk assessment algorithms exist, of which the ESC HeartScore, Framingham and PROCAM are the most frequently applied in Germany. The risk estimates generated differ and take a number of different risk factors into consideration. Due to existing homology of retinal vessels and brain vessels, eye fundus examination is a promising approach to improving risk prediction. Large cohort studies investigated retinal vascular changes, including arteriovenous ratio, as well as signs of retinopathy such as cotton-wool spots, microaneurysms, or retinal hemorrhages for their ability to predict systemic cardiovascular events. While signs of retinopathy proved to have high predictive power (but are rarely diagnosed,) the retinal vascular changes investigated could contribute little to enhancing systemic CV risk prediction. A number of new and promising approaches based on static and dynamic retinal analysis exist, but still need to be validated prospectively.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Angiofluoresceinografia/estatística & dados numéricos , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/epidemiologia , Retinoscopia/estatística & dados numéricos , Comorbidade , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Reprodutibilidade dos Testes , Retinoscopia/métodos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade
18.
Br J Ophthalmol ; 94(7): 940-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20606027

RESUMO

INTRODUCTION: Loss of corneal endothelial cells (CECs) is one major factor limiting transplant clarity and survival after keratoplasty. Amongst other factors, apoptosis due to cellular stress is responsible for these problems. This study investigates the possible anti-apoptotic and cytoprotective effects of minocycline on a human corneal endothelial cell line (HCEC-SV40) cultured under oxidative stress and with transforming growth factor beta (TGF-beta). METHODS: CECs were treated with 1-150 microM minocycline. Cell viability and the median inhibitory concentration (IC(50)) were evaluated after 48 h and after H(2)O(2) treatment (tetrazolium dye reduction assay and live-dead assay). Expression of B-cell CLL/lymphoma 2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP) and their mRNA were assessed by reverse transcriptase (RT)-PCR and western blot analysis after treatment with minocycline alone and consecutive incubation with 200 microM H(2)O(2) and TGF-beta2. A quantitative detection of histone-associated DNA fragmentation by ELISA was performed. RESULTS: Minocycline concentrations from 1-50 microM showed no toxic effects on CECs. Pre-treatment with 10-40 microM minocycline led to an increase in viability after H(2)O(2) treatment. In addition, minocycline pre-treatment attenuated the increase of histone-associated DNA fragmentation after treatment with H(2)O(2) and TGF-beta2 significantly. When CECs were treated with minocycline and then consecutively with H(2)O(2) or TGF-beta2, RT-PCR and western blot analysis yielded an overexpression of Bcl-2 and XIAP. CONCLUSION: In this study minocycline prevented apoptotic cell death in cultured CECs in vitro. Our results suggest that minocycline might offer cytoprotective properties that might help to prevent loss of corneal endothelial cells in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Endotélio Corneano/efeitos dos fármacos , Minociclina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/biossíntese , Células Cultivadas , Citoproteção , Relação Dose-Resposta a Droga , Endotélio Corneano/citologia , Endotélio Corneano/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
19.
Ophthalmologe ; 107(3): 228-34, 2010 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-20195613

RESUMO

Modeling plays an important role in value-based medicine (VBM). It allows decision support by predicting potential clinical and economic consequences, frequently combining different sources of evidence. Based on relevant publications and examples focusing on ophthalmology the key economic modeling methods are explained and definitions are given. The most frequently applied model types are decision trees, Markov models, and discrete event simulation (DES) models. Model validation includes besides verifying internal validity comparison with other models (external validity) and ideally validation of its predictive properties. The existing uncertainty with any modeling should be clearly stated. This is true for economic modeling in VBM as well as when using disease risk models to support clinical decisions. In economic modeling uni- and multivariate sensitivity analyses are usually applied; the key concepts here are tornado plots and cost-effectiveness acceptability curves. Given the existing uncertainty, modeling helps to make better informed decisions than without this additional information.


Assuntos
Modelos Econométricos , Programas Nacionais de Saúde/economia , Oftalmologia/economia , Escalas de Valor Relativo , Análise Custo-Benefício/economia , Medicina Baseada em Evidências/economia , Alemanha , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes
20.
Growth Factors ; 28(3): 211-20, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20166888

RESUMO

OBJECTIVES: Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells. METHODS: Primary human optic nerve head astrocytes (ONHAs) were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml. CONCLUSION: Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.


Assuntos
Benzenossulfonatos/farmacologia , Disco Óptico/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Proteínas da Gravidez/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Retina/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Astrócitos/efeitos dos fármacos , Astrócitos/efeitos da radiação , Benzenossulfonatos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Luz/efeitos adversos , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Disco Óptico/imunologia , Disco Óptico/metabolismo , Disco Óptico/efeitos da radiação , Compostos de Fenilureia , Fator de Crescimento Placentário , Fator de Crescimento Derivado de Plaquetas/biossíntese , Proteínas da Gravidez/biossíntese , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Retina/metabolismo , Retina/efeitos da radiação , Neovascularização Retiniana/tratamento farmacológico , Sorafenibe , Fator A de Crescimento do Endotélio Vascular/biossíntese
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