La polyarthrite rhumatoïde (PR) est le rhumatisme inflammatoire le plus fréquent. Cette maladie s’accompagne d’une hyperplasie de la membrane synoviale qui entoure les articulations. La formation du pannus synovial est sous la dépendance de cytokines pro-inflammatoires et pro-angiogéniques. Les immunothérapies anti-TNF utilisées dans le traitement de la PR présentent des inconvénients (perte d’efficacité, risque infectieux), ce qui laisse la place pour le développement d’une stratégie vaccinale anti-TNF. Dans la première partie de mes travaux, nous avons développé des vaccins anti-VEGF afin d’étudier les liens entre angiogenèse et inflammation dans l’arthrite expérimentale au collagène (AEC). Dans la deuxième partie, nous avons développé un vaccin anti-TNF de souris afin d’évaluer les conséquences de la neutralisation du TNF-α par la vaccination dans des modèles infectieux. Le ciblage du VEGF avec un vaccin constitué de VEGF entier ou de peptides du VEGF couplés à la KLH, a permis une protection clinique et histologique dans l’AEC. Dans notre deuxième axe de recherche, nous avons développé un vaccin anti-TNF de souris (TNF-KLH). Ce vaccin est aussi efficace que l’etanercept dans l’AEC, mais n’augmente pas le risque infectieux dans un modèle d’infection à Mycobacterium tuberculosis. Dans le modèle d’infection à Listeria monocytogenes, TNF-KLH n’augmente pas la charge bactérienne et n’induit pas de mortalité, contrairement à l’etanercept. Mes travaux de thèse montrent que la stratégie vaccinale anti-cytokine est efficace dans l’arthrite, et que le ciblage du TNF par une telle stratégie ne semble pas altérer la réponse anti-infectieuse dans nos modèles. / Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatism. This disease is accompanied by hyperplasia of the synovial membrane surrounding the joint. Pannus formation is controlled by pro-inflammatory and pro-angiogenic cytokines. Anti-TNF immunotherapies used in the treatment of RA presents many drawbacks (loss of efficacy, infections), which leaves some place for the development of an anti-TNF immunization strategy. In the first part of my work, we developed an anti-VEGF vaccine to study the links between angiogenesis and inflammation in collagen-induced arthritis (CIA) model. In the second part, we developed a mouse anti-TNF vaccine to assess the consequences of the neutralization of TNF-α by vaccination in infectious models. Inhibition of VEGF with a vaccine consisting of whole VEGF or VEGF peptide coupled to KLH, showed a clinical and histological protection in the CIA model. In the second part of my work, we developed a mouse anti-TNF vaccine (TNF-KLH). This vaccine is as effective as etanercept in CIA, but does not increase the risk of infection in Mycobacterium tuberculosis model. In Listeria monocytogenes model, unlike etanercept, immunization with TNF-KLH does not increase the bacterial burden and mortality. My work contributed to the development of active anti-VEGF vaccine and our results show a partial protection with this strategy. Also, we demonstrate that targeting TNF by active immunotherapy does not alter the immune response in our models of infections.

La DMAE es la principal causa de ceguera en pacientes por encima de los 65 años. La investigación de esta enfermedad está adquiriendo gran importancia desde hace años por su alta prevalencia a nivel mundial. Desde la introducción de los fármacos anti-VEGF ha mejorado de manera sustancial el pronóstico de los pacientes afectos por la forma húmeda de esta enfermedad. El propósito de esta tesis es evaluar nuestra experiencia en un centro terciario de referencia con el uso de los anti- VEFG en la práctica clínica diaria para el tratamiento de esta enfermedad. En concreto nuestros objetivos son estudiar los resultados anatómico funcionales con nuestra pauta de tratamiento basada en 2+ PRN, comparar los principales fármacos utilizados ( Bevacizumab y Ranibizumab) y evaluar algunos factores de riesgo generales, locales y maculares para predecir si los mismos pueden influir en el resultado funcional final. Inicialmente se realiza una revisión de la literatura. Se profundiza en la etiopatogenia, epidemiología, factores de riesgo y clasificación de la enfermedad, para terminar revisando de manera amplia la evolución de los diferentes tratamientos utilizados para el tratamiento de la DMAE neovascular. El estudio diseñado es prospectivo, intervencional, comparativo y no randomizado y comprende una muestra de 94 ojos, homogénea a nivel de características demográficas y oculares basales, con valores medios en cuanto a las características poblacionales coincidentes con los de la típica población utilizada en la mayoría de los grandes estudios randomizados, todos los casos cuentan con un seguimiento mínimo de 6 meses. Se utiliza en todos los pacientes una pauta de 2+ PRN y como tratamiento se administra Bevacizumab, Ranibizumab o bien tratamiento combinado. Como conclusión los resultados obtenidos nos muestran que nuestra pauta utilizada de 2 inyecciones en la fase de carga presenta mayor número de recidivas y peores resultados visuales finales que las pautas de 3 inyecciones +mantenimiento usadas en la mayoría de series publicadas y que no hay diferencias entre los dos fármacos principales a estudio Ranibizumab y Bevacizumab a nivel de resultados anatómicos y funcionales finales, pero parece que el Ranibizumab es más efectivo a corto plazo. En cuanto al estudio de los factores de riesgo, se observa que la hipertensión arterial, el colesterol total y la edad son los factores que influyen de manera directa en el pronóstico funcional final. / AMD is the leading cause of blindness in patients over 65 years. The investigation of this disease has gained considerable importance over the years by its high prevalence worldwide. Since the introduction of anti-VEGF drugs have substantially improved the prognosis of patients affected by the wet form of the disease. The purpose of this thesis is to evaluate our experience in a tertiary referral center with the use of anti-VEGF in clinical practice for the treatment of this disease. Specifically our objectives are to study the functional anatomical results with our treatment regimen based on 2 + PRN, comparing the main drugs used (Bevacizumab and Ranibizumab) and evaluate some general risk factors, local and macular to predict whether they can influence the final functional outcome. Initially we review the literature. It delves into the pathogenesis, epidemiology, risk factors and disease classification, to finish reviewing comprehensively the evolution of the different treatments used to treat neovascular AMD. The study design is prospective, interventional, nonrandomized comparative and includes a sample of 94 eyes, homogeneous level of baseline demographic and ocular, with mean values, in terms of population characteristics, that match those of the typical population used in most of large randomized studies, all cases have a follow up 6 months or more. It is used in all patients a pattern of 2 + PRN and as treatment is administered Bevacizumab, Ranibizumab or combination therapy. In conclusion the results show that our regimen of 2 injections used in the loading phase shows more relapses and worse final visual results than patterns of 3 injections + manteinance used in most published series. They also indicate that there is no difference between the two main drugs Lucentis and Avastin in late anatomical and functional results, but it seems that Ranibizumab is more effective the short-term. As for the study of risk factors, we observe that high blood pressure, total cholesterol and age are factors that directly influence the functional prognosis.

L’œdème maculaire est une complication majeure de nombreuses pathologies rétiniennes induisant la cécité. Les traitements actuels ne sont pas curatifs. Ce sont des injections intraoculaires de corticostéroïdes et d'anti-VEGF. Les mécanismes d'action de ces médicaments sont mal connus dans l'œil car ces thérapies ont été initialement développées pour des pathologies non-oculaires (tels que l'asthme et les maladies auto-immunes pour les corticostéroïdes et les cancers pour certains anti-VEGF). De plus, les effets bénéfiques de ces molécules sont contrebalancés par des effets secondaires graves (glaucomes et cataractes pour les corticostéroïdes) et la résistance au traitement. Le projet vise à élucider les mécanismes d'action oculaires des corticostéroïdes et anti-VEGF; dans le but d'identifier de nouvelles cibles thérapeutiques pour le traitement de l’œdème maculaire. Ce travail a porté sur : 1) La compréhension des mécanismes des corticostéroïdes et de leurs récepteurs (le récepteur aux glucocorticoïdes ou GR et le récepteur aux minéralocorticoïdes ou MR) suite à l’injection intravitréene de corticostéroïdes ou d’aldostérone chez le rat. Nous avons ainsi : -1.1. Identifier les protéines partenaires du GR et du MR avant et après traitements par une approche protéomique (immunoprécipitations endogènes suivies d’une analyse par spectrométrie de masse). -1.2. Identification les gènes cibles dont l'expression est modulée par les corticostéroïdes ou l’aldostérone par ARN-sequencing. 2) L'identification des mécanismes d’action des aux anti-VEGFs et leur comparaison avec des molécules de même nature physico-chimique. 3) L’identification des gènes différentiellement exprimés entre la rétine périphérique et la macula (zone d’acuité visuelle susceptible à la formation d’œdèmes) chez le singe (modèle qui possède, comme l’homme, une macula). Ceci afin de comprendre pourquoi la macula est particulièrement sensible. 4) L’analyse et la comparaison de ces différents traitements. Ces études ont permis d’identifier les cofacteurs des récepteurs aux corticostéroïdes, ainsi que la dynamique de leurs interactions avant et après traitement à la corticostérone et à l’aldostérone; ainsi que les gènes dont l’expression est régulée par les corticostéroïdes et les anti-VEGF. L’analyse croisée des données, des analyses bioinformatiques ainsi que l’étude bibliographique des protéines et gènes identifiés nous ont permis d’établir une liste restreinte de cibles potentielles des traitements anti-œdémateux, dans le but final de potentialiser l’effet de ces traitements, trop souvent associés à des effets secondaires qui limitent considérablement leur(s) action(s) bénéfique(s) sur la fonction visuelle dans le traitement de l’œdème maculaire. / Macular Edema is a major complication of numerous retinal pathologies that lead the blindness. The available treatments (intra-ocular injection of corticosteroids and anti-VEGF) do not cure this disease. The ocular mechanisms of action of these drugs are not very well understood. In fact, these molecules have been initially developed for non-ocular pathologies, such as asthma, auto-immune diseases (for corticosteroid) and cancers (for anti-VEGF). In addition, the beneficial effects of these drugs are counteracted by their side effects (cataracts and glaucoma for corticosteroids) as well as resistance to treatment. The project aims at unraveling the ocular mechanisms of action of corticosteroids and anti-VEGF; in order to identify new therapeutic targets for the treatment of macular edema. The project focused on: 1) The understanding of the mechanisms of the corticosteroids and their receptors after an intravitreal injection of Corticosterone or Aldosterone in the rat model. We therefore: 1.1. Identified the partner proteins of the glucocorticoid and mineralocorticoid receptors before and after treatment, using a proteomic approach. 1.2. Identified the target genes which expression is modulated by the corticosteroid using the RNA-Sequencing technique. 2) The identification of the mechanisms of action of anti-VEGF molecules and their comparison with molecules that have similar physico-chemical structure. 3) The identification of differentially expressed genes between the retina and the macula in the monkey model. This aimed at understanding why the macula is particularly sensitive to edemas. 4) The analysis and comparison of these treatments. We were able to identify co-factors for corticosteroids receptors as well as the dynamics of these interactions (before and after treatment), as well as the genes which expression is regulated by the corticosteroids or anti-VEGF. The analysis of the bio-informatic data as well as the bibliographic study of the identified proteins and genes allowed us to establish a list of partiMacularly interesting genes that are potentially therapeutic targets for the treatment of macular edema.

Submitted by Viviane Lima da Cunha (viviane@biblioteca.ufpb.br) on 2017-06-16T12:44:17Z No. of bitstreams: 1 arquivototal.pdf: 1568113 bytes, checksum: 143c994d6a632a3c81bc4c4e5d8557f6 (MD5) / Made available in DSpace on 2017-06-16T12:44:17Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1568113 bytes, checksum: 143c994d6a632a3c81bc4c4e5d8557f6 (MD5) Previous issue date: 2017-02-24 / Diabetic macular edema (DME) is the main cause of visual impairment in patients with diabetes mellitus. The most widely used treatment today is intravitreal injection (IIV) of anti-VEGF (vascular endothelial growth factor). Optical coherence tomography (OCT) is the gold-standard diagnostic test, however it is expensive and inaccessible. Some risk factors are strongly associated with development of DME and its response to treatment. There is few surveys that analyzes the impact and risk percentages of these factors in the probability of developing EMD and, therefore, in the necessity of early therapeutic intervention, which motivated the accomplishment of this research. This study aimed to achieve a Predictive Model to guide the decision in the early treatment with intravitreal injection in patients with EMD, by quantifying and ranking the risk factors impact on the chance of a diabetic patient need this therapy. It is a cross-sectional, observational, descriptive and analytical study. The data were collected at the Ophthalmology Department of the Lauro Wanderley University Hospital - UFPB and at the Hospital Visão, both in João Pessoa, and at the Genival Barbosa de Lucena Vision Center, located in Guarabira-PB, from July 2015 to September 2016. Individuals with type 1 or 2 diabetes and older than 18 years were included, after signing the informed consent form. The logistic regression model was used to obtain and adapt the predictive model and all the data were analyzed in statistical software R®, version 3.2.0. Eighty diabetic patients were evaluated: 57.5% had no indication of IIV and 42.5% needed this treatment. Of those who had EMD and needed anti-VEGF injection, the mean age was 60.65 years, 47.05% male and 52.94% female. In the group without macular edema, the mean age was 58.02 years, 26.06% male and 73.91% female. Among the individuals who had no indication of intravitreal injection of anti-VEGF, most had no mild retinopathy or non-proliferative diabetic retinopathy (NPDR) (69.56%). Among the patients who needed the treatment, the majority had severe NPDR or proliferative retinopathy (79.41%). Were identified as risk factors to EMD and intravitreal anti-VEGF: be retired (OR = 5.22, p-value0.05), had a personal history of diabetic retinopathy (OR = 20.27; P-value 0.006) and positive history for previous treatment with anti-VEGF (OR = 23.23; p-value 0.002). From the results of this study, we conclude that a diabetic individual has low visual acuity and presents these three factors, should be referred as soon as possible to the specialist, since he has a risk of presenting DME with need for anti-VEGF IIV, with 91.17% of accuracy. In summary, an evaluative and predictive model was proposed to serve as a supporting tool in therapeutic decision, mainly to the non-retinal physician, to refer to the specialist the patients with diabetic retinopathy and its main cause of low visual acuity - diabetic macular edema - to early diagnosis and treatment, which may be decisive to preventing irreversible visual loss in these patients. / A injeção intravítrea (IIV) de anti-VEGF (fator de crescimento vascular endotelial) constitui a modalidade terapêutica mais utilizada nos dias de hoje para o tratamento do edema macular diabético (EMD), sendo esta a principal causa de baixa visual em pacientes portadores de diabetes mellitus. O exame padrão – ouro para o diagnóstico é a tomografia de coerência óptica (TCO) da mácula, no entanto possui alto custo e difícil acesso. O desenvolvimento de EMD e a resposta ao tratamento são fortemente associados a determinados fatores de risco. Na literatura especializada há uma escassez de estudos que estabeleçam uma quantificação dos percentuais de risco desses fatores, a fim de verificar aqueles que possuem maior impacto na probabilidade de desenvolver EMD e, portanto, na necessidade de intervenção terapêutica precoce, o que motivou a realização desta pesquisa. O estudo teve por objetivo a propositura de um Modelo Preditivo para auxiliar na decisão de realização de uma injeção intravítrea de anti-VEGF, a partir da quantificação e hierarquização dos fatores de risco que compõem o perfil dos indivíduos adultos diabéticos. Trata-se de um estudo transversal, observacional, descritivo e inferencial. Os dados foram coletados na Unidade da Visão do Hospital Universitário Lauro Wanderley – UFPB e no Hospital Visão, ambos em João Pessoa, e no Centro da Visão Genival Barbosa de Lucena, localizado na cidade de Guarabira-PB, no período de julho de 2015 a setembro de 2016. Foram incluídos indivíduos com diabetes tipo 1 ou 2 e idade acima de 18 anos, após assinatura do termo de consentimento livre e esclarecido. O modelo de regressão logística foi utilizado para obtenção e adequação do modelo preditivo e todos os dados foram analisados no software estatístico R®, versão 3.2.0. Foram avaliados 80 pacientes diabéticos, dos quais 57,5% não tiveram indicação de IIV e 42,5% receberam indicação do tratamento em questão. Dos que tiveram EMD e indicação do tratamento com injeção de anti-VEGF, a média de idade foi de 60,65 anos, sendo 47,05% do sexo masculino e 52,94% do sexo feminino. Em relação àqueles sem edema macular, a média de idade foi de 58,02 anos, sendo 26,06% do sexo masculino e 73,91% do sexo feminino. Dentre os indivíduos que não tiveram indicação de injeção intravítrea de anti-VEGF, a maioria apresentou ausência de retinopatia ou retinopatia diabética não- proliferativa (RDNP) leve (69,56%). Já dentre os pacientes que necessitaram do tratamento, a maioria apresentou RDNP severa ou retinopatia proliferativa (79,41%). Foram identificados como fatores de risco para o edema macular diabético e, portanto, necessidade de IIV, o indivíduo ser aposentado (OR=5,22; p-valor0,05), ter histórico pessoal de retinopatia diabética (OR=20,27; p-valor 0,006) e histórico positivo para tratamento prévio com anti-VEGF (OR=23,23; p-valor 0,002). Concluímos, a partir dos resultados desta pesquisa, que um indivíduo diabético tenha baixa visual e apresente esses três fatores, deve ser encaminhado o quanto antes ao especialista, pois possui risco de apresentar EMD com necessidade de IIV de anti-VEGF, com 91,17% de acerto. Em suma, foi proposto um modelo de avaliação e de predição para servir como ferramenta coadjuvante na tomada de decisão, sobretudo do médico não-retinólogo, a fim de encaminhar para o diagnóstico e tratamento precoces os pacientes com retinopatia diabética e sua principal causa de baixa acuidade visual – o edema macular diabético –, o que pode ser decisivo na prevenção da perda visual irreversível nesses pacientes.

No description available.

L'embolisation artérielle a récemment émergé sur le plan interventionnel comme un traitement sûr et efficace pour arrêter une hémorragie ou induire la dévascularisation d'un tissu cible. La visualisation directe des agents d'occlusions vasculaires n'est pas toujours possible. L'estimation de leur position dans la branche vasculaire en se basant sur la distribution de produit opaque aux rayons X est partiellement incorrecte. Un marquage des agents d'occlusion vasculaire est souhaitable pour leur suivi par IRM pendant l'intervention ou a posteriori, ce, notamment en raison de la diffusion de l'IRM comme modalité d'imagerie anatomique et interventionnelle. Dans ce travail, plusieurs protocoles ont été établis pour repérer des agents d'occlusion vasculaire marqués avec le SPIO, in situ, in vitro et dans des « conditions » in vivo, sous IRM 1,5T et 3T. Les agents d'occlusion étudiés sont des microsphères de trisacryl (Embosphère®), et des microparticules ou microcapsules utilisées éventuellement comme vecteurs de principes actifs : parmi celles-ci, des microsphères gonflables (Hépasphère™) non dégradables ont été marquées, et des microbilles d'alginate et des systèmes d'émulsions dégradables réalisés par nos soins. L'établissement de protocoles de détectabilité sous IRM a impliqué le choix de séquences et l'optimisation des paramètres de ces séquences, le choix de l'antenne, ainsi que la mise au point d'une quantité suffisante de marqueur dans les agents d'occlusion afin qu'ils soient visibles à l'IRM. Une méthodologie de mesure de faible variation de l'intensité du signal des images IRM a été développée. Un modèle expérimental in vitro a été conçu avec la présence des microparticules marquées dans un environnement simulant grossièrement une vascularisation tumorale et son drainage veineux. La fixation des immunoglobulines (IgG1), équivalentes aux anti-VEGF, sur des microsphères (Hépasphères™) a été étudiée. Enfin, les propriétés mécaniques et électriques des systèmes de microémulsions ont été explorées par ultrasons et par impédancemétrie.

Age-related macular degeneration (AMD) is the leading cause for visual impairment in the elderly. The etiology of AMD remains unclear. Clinical and histopathological studies suggest that photoreceptors play a role in disease progression. Here, we found that photoreceptors of AMD patients show adaptive changes in gene expression, suggestive of a nutrient shortage. To study the effect of these changes, we mimicked the metabolic alteration in mouse photoreceptors, by disruption of the Tuberous Sclerosis Complex (TSC). This led to AMD hallmarks, including the advanced stages of geographic atrophy (GA) and choroidal neovascularization (CNV). Furthermore, we found that disease onset requires the activity of the mammalian target of rapamycin complex 1 (mTORC1). To study the contribution of photoreceptors to disease, we profiled retinal phospholipids as photoreceptors are rich in phospholipids. We found a reduction in two docosahexaenoic acid (DHA)-containing phospholipids. Feeding DHA to mutant mice, alleviated most AMD-associated hallmarks. To study the inflammatory complications seen with current anti-vascular endothelial growth factor (VEGF) treatments for CNV we used rAAV-mediated gene transfer to overexpress an anti-VEGF protein. We found that inhibition of VEGF can promote retinal inflammation. The data suggests that targeting photoreceptor metabolism may provide novel therapies to treat AMD.

Retinale Venenverschlüsse kann man in Astvenenverschlüsse und Zentralvenenverschlüsse unterteilen. Beide Erkrankungen werden primär mit intravitrealen Injektionen behandelt, wie den Anti-VEGF-Antikörpern oder dexametasonhaltigen Implantaten. Ziel dieser Arbeit ist die Evaluation der Therapiewirksamkeit von Anti-VEGF- Injektionen bei Patienten mit geringem Visus von ≤ 0,2 bei Behandlungsbeginn anhand von OCT und Visus von 150 Patienten im Behandlungsverlauf von bis zu zwölf Monaten. Die Gruppe der Patienten mit Baseline-Visus >0,2 stellt dabei die Vergleichsgruppe dar. In der Patientengruppe A mit Visus ≤ 0,2 bei ZVV stellte sich ein Visusanstieg von 0,10 auf 0,20 ± 0,18 nach zwölf Monaten ein. Im Patientenkollektiv B mit Visus >0,2 und ZVV stellte sich eine Visusbesserung von 0,43 auf 0,61 ± 0,27 ein. In der Patientengruppe A mit Visus ≤ 0,2 bei VAV stellte sich ein Visusanstieg von 0,11 auf 0,27 ± 0,07 nach zwölf Monaten ein. Im Patientenkollektiv mit Visus > 0,2 und VAV stellte sich eine Visusbesserung von 0,52 auf 0,68 ± 0,18 ein. Damit ist bei allen Gruppen eine signifikante Visusverbesserung nachweisbar, wobei es ersichtlich ist, dass der bessere initiale Visus auch einen besseren Endvisus determiniert. Bei der Patientengruppe mit Anfangsvisus ≤ 0,2 konnte signifikant eine größere absolute Netzhautdickenabnahme bei stets höherer Netzhautdicke als in der Referenzgruppe nachgewiesen werden.:Inhaltsverzeichnis 1 Einleitung..........................................................................................................................1 1.1 Netzhautanatomie.....................................................................................................1 1.1.1 Blutversorgung der Netzhaut...............................................................................2 1.1.2 Venenverschlüsse der Retina..............................................................................3 1.2 Makulaödem..............................................................................................................7 1.3 Der molekulare Signalweg beim Makulaödem......................................................8 1.4 Diagnostik................................................................................................................10 1.4.1 Symptome.........................................................................................................10 1.4.2 Sehschärfenprüfung..........................................................................................10 1.4.3 .Ophthalmoskopie..............................................................................................11 1.4.4 Bildgebende Diagnostik.....................................................................................12 1.4.4.1 Fluoreszeinangiographie............................................................................12 1.4.4.2 Optische Kohärenz-Tomografie.................................................................13 1.5 Therapie der Venenverschlüsse............................................................................15 1.5.1 Intravitreale Injektionen.....................................................................................15 1.5.1.1 VEGF-Antikörper........................................................................................16 Bevacizumab.....................................................................................................17 Ranibizumab......................................................................................................17 Aflibercept..........................................................................................................17 1.5.1.2 Therapieschemata von intravitrealen Anti-VEGF-Injektionen....................18 1.5.1.3 Kortikosteroide...........................................................................................19 1.5.2 Laserkoagulation...............................................................................................20 Fokale Laserkoagulation....................................................................................20 Periphere Laserkoagulation...............................................................................21 1.6 Prognose.................................................................................................................21 2 Arbeitshypothese und Fragestellung..........................................................................23 3 Materialien und Methoden.............................................................................................24 3.1 Behandlungsablauf................................................................................................24 3.2 Patientenkollektiv und Statistik............................................................................26 4 Ergebnisse......................................................................................................................27 4.1 Patientenkollektiv...................................................................................................27 Demografie des Patientenkollektivs...................................................................30 4.2 Art der Behandlung................................................................................................35 4.3 Laserkoagulation....................................................................................................40 4.4 Patientengruppe Lucentis und ZVV......................................................................41 4.5 Patientengruppe Lucentis und VAV......................................................................49 5 Diskussion......................................................................................................................54 6 Zusammenfassung der Arbeit......................................................................................59

No description available.

Before year 1895, the doctors could only make a probable diagnosis based on what the patient could tell and it was hurt and there was no discernable change to the outside of the body. With X-ray, it was possible to see inside the patient without first cutting it, you can say that the X-ray was the starting point for diagnostic imaging.The further development of X-ray gave CT (Computed Tomography), where X-ray tubes and detectors rotate around the patient while the patient table moves. Besides CT also developed MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) and Ultrasound. Common to these methods is that the produced 3D images.In 1990 a completely new approach for diagnostic imaging, OCT (optical coherence tomography), by measuring the phase shift and the intensity of reflected light, it provides real-time and non-destructive measurements (in vivo) a resolution of 1 to 15 microns, much higher than all other standard imaging techniques. You could say that OCT machine can be compared to ultrasound, which uses the reflection of sound waves to interpretation.The first OCT machines were of type TD (Time Domain), these had low resolution and low scanning speed. In 2005 came the SD-OCT, they had higher resolution and scanning speed, SD stands for spectral domain, SD-OCT is sometimes called FD-OCT as Fourier transformed signals and operating in the frequency domain.The development of OCT machines are only in their infancy, resolution, scanning speed and accuracy will increase all the time, this allows new uses and ways to diagnose developed. OCT can be used in such Oncology, MSD (Musculoskeletal disorders), cardiovascular medicine, teeth, nerves, but the largest field is the eye and then the back of the eye called the retina (retina).This thesis is limited to the eye, the purpose is to provide input to those who are likely to purchase an OCT-machine, but also show the measurement data OCT-machines are performing and how to use the OCT-machine more than to see age-related macular degeneration. Another aim is to increase understanding of the physics behind an OCT-machine for ease of understanding the output given.The manufacture/model that have selected for evaluation are Zeiss Cirrus 4000, Topcon 3D OCT-2000 and Heidelberg Spectralis, the reason is that there are only these three on the Swedish market and all are SD-OCT. The way to evaluate OCT-machines is to scan performance and what the various analysis programs can handle. Furthermore, each OCT-machine scans the macula and optic disk on a experimental person/ reference eye, in order to get the output of the precision, or if you want to call it repeatability, which is very important if one wants to follow a solitary disease course.The conclusion of this thesis is to OCT machines are quite similar. When it comes to ease of use when doing scans is the Cirrus is lightened by the use of the extra screen where you always look eye (iris camera), which makes it easy to adjust the sharpness and position of the mouse buttons. Topcon and Heidelberg is not difficult to use but requires more experience of the person making the OCT scans. Most measurement functions in the analysis program is Topcon and Heidelberg and best accuracy/repeatability is Heidelberg, both the macula and RFNL.OCT machine is a good tool to use on the anterior segment, but in the case the precision allows the precision used to monitor RNFL thickness changes in those with glaucoma. / <p>Validerat; 20131029 (global_studentproject_submitter)</p>