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Made available in DSpace on 2014-06-12T16:25:26Z (GMT). No. of bitstreams: 2 arquivo3123_1.pdf: 1759622 bytes, checksum: 82c6fa24829119f3da4a0e312eebc64e (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Objetivos: Avaliar a espessura da camada de fibras nervosas da retina (CFNR) em portadores de esquistossomose mansônica na forma hepatoesplênica (EHE), utilizando a tomografia de coerência óptica (OCT). Métodos: Realizou-se estudo prospectivo, analítico, de corte transversal, tipo caso controle. O grupo de doentes foi composto por 24 indivíduos (13 femininos e 11 masculinos), com idades variando entre 27 e 73 anos (55,7 ±11,6 anos). No grupo controle foram incluídos 22 indivíduos (12 femininos e 10 masculinos) com idades entre 31 e 77 anos (55,4 ±16,5 anos). Dos 92 olhos avaliados, três foram excluídos por apresentarem opacidade de meios que impossibilitaram o exame. Todos os participantes foram submetidos a exame oftalmológico completo e OCT da camada de fibras nervosas da retina. Resultados: A média das espessuras da CFNR foi de 98,1 ±15,2&#956;m no grupo dos doentes e 114,2 ±10,0 &#956;m no grupo controle (p< 0,001). Conclusão: Observou-se diminuição significante da espessura da CFRN, em todos os quadrantes, nos pacientes com EHE. É possível que as alterações hemodinâmicas secundárias à hipertensão porta em portadores de EHE sejam responsáveis por disfunção na microcirculação da retina, gerando isquemia, justificando os achados do atual estudo

O objetivo deste estudo foi descrever a distribuição dos neurofilamentos (NFs) e da proteína associada ao microtúbulo do tipo 2 (MAP-2) em retinas humanas e murinas. Para isso, usamos camundongos C57BL/6, submetidos à cirurgia estereotáxica para realização de lesão eletrolítica no colículo superior direito provocando degeneração retrógrada de células ganglionares da retina. Utilizamos ensaios de imunohistoquímica e PCR em tempo real (qPCR) para a caracterização dessas proteínas nas duas espécies. Na retina humana, observou-se que NFs e MAP-2 estão presentes nas células ganglionares do tipo M. No modelo animal, houve diminuição dos NFs e aumento de MAP-2, na análise de imuno-histoquímica. Já o ensaio com qPCR mostrou um aumento e diminuição da expressão dos NFs e MAP-2, respectivamente. Assim, concluímos que houve alterações na expressão do RNAm e na marcação dos NFs e do MAP-2 nas retinas murinas, e esses resultados podem ser extrapolados para os seres humanos, uma vez que essas proteínas estão presentes nas células M que são inicialmente afetadas no glaucoma. / This study aimed to describe the distribution of NFs and type 2 protein associated with microtubule (MAP-2) in human retinas of these proteins and evaluate a model of retrograde retinal ganglion cell degeneration in murine retinas. To achieve this, we submitted C57bl/6 to a stereotaxic surgery for superior colliculus electrolytic lesion in the right side. The characterization of these proteins was obtained through immunohistochemical essays and real-time PCR (qPCR). The results revealed that both proteins are present in the ganglion cell M in the human retina. In the experimental animal model the immunohistochemical essays demonstrated decrease of NFs and increased MAP-2. However, the qPCR analysis demonstrated increased NFs and decreased MAP-2 expression. We can conclude that there was variation of mRNA expression and structural protein levels in the experimental retina. And, the results related to NFs and MAP-2 in this animal model can be extrapolated to humans, as these proteins are also present in the human ganglion cell that are affected early in glaucoma.

Orientadores: Rodrigo Pessoa Cavalcanti Lira, Carlos Eduardo Leite Arieta / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T06:50:41Z (GMT). No. of bitstreams: 1 Takasaka_Iuuki_M.pdf: 2254339 bytes, checksum: 4a21730e60893b2777df71653d5f38c2 (MD5) Previous issue date: 2012 / Resumo: Introdução: O descolamento de retina regmatogênico (DRR), uma das causas de cegueira, tem uma incidência anual de cerca de 6,3 - 17,9/100.000 habitantes na população mundial, e se não tratado pode levar a cegueira devido a degeneração das camadas retinianas. O uso de introflexão em conjunto com as adesões coriorretinianas em torno da rotura retiniana forma a base do tratamento para muitos DRR simples. A crioterapia realizada para retinopexia intra-operatoria tem sido implicada no desenvolvimento de pucker macular e vitreorretinopatia proliferativa. Eliminar a crioterapia da cirurgia convencional de introflexão poderia não afetar o resultado do sucesso anatômico e melhorar a recuperação visual. Objetivo: O objetivo primário deste ensaio clínico randomizado foi comparar a taxa de reaplicação retiniana e secundariamente os resultados da acuidade visual em pacientes com DRR que se submeteram a cirurgia de introflexão escleral e retinopexia com a crioterapia intra-operatória versus fotocoagulação a laser pós-operatório (um mês após a cirurgia). Método: É um ensaio clínico aleatorizado, mascarado, realizado em um único centro, composto por 86 pacientes submetidos à cirurgia de introflexão escleral. Os pacientes foram aleatorizados para serem submetidos à cirurgia de introflexão escleral e retinopexia com crioterapia intraoperatória (criopexia) ou retinopexia com fotocoagulação a laser pós operatória de 30 dias (laserpexia) após o procedimento. O desfecho primário foi avaliar a taxa de reaplicação retiniana no seguimento pós-operatório em 1 semana. Os desfechos secundários foram avaliar as taxas de reaplicação retiniana, as taxas de reoperação, as taxas de complicações pós-operatórias e recuperação da acuidade visual, em 1 mês e 6 meses de seguimento pós-operatório. Resultados: Foram incluídos 86 olhos de 86 pacientes a serem submetidos introflexão escleral. A amostra foi constituída de 43 pacientes pertencentes ao grupo laserpexia e 43 pacientes atribuídos ao grupo criopexia. Os dados demográficos foram semelhantes nos dois grupos. A taxa de sucesso anatômico em 1 semana, 1 mês e 6 meses foram semelhantes nos dois grupos, respectivamente, 93% (40 pacientes), 100% e 100% no grupo criopexia e 95,3% (41 pacientes), 100% e 100% no grupo da laserpexia (P, respectivamente, 0,5; 1,0 e 1,0). Três pacientes do grupo criopexia e 2 do laserpexia foram submetidos a uma cirurgia adicional (vitrectomia via pars plana) após a falha primária em 1 semana de seguimento. As complicações pós-operatórias foram semelhantes nos dois grupos, com exceção do edema de pálpebras. A recuperação visual foi mais lenta no grupo da crioterapia. A diferença na AV após 6 meses não foi significativa. Conclusão: Em pacientes com descolamento de retina regmatogênico sem complicações, ambas as técnicas de retinopexia mostraram resultados anatômico e funcional satisfatórios. A opção por laserpexia oferece recuperação visual mais rápida com menos complicações, porém requer uma segunda intervenção e maior custo em relação a criopexia / Abstract: Introduction: Rhegmatogenous retinal detachment (RRD), one of causes of blindness, has an annual incidence of about 6.3 to 17.9/100.000 people in the world population, and if untreated can lead to blindness due to degeneration of the retinal layers. The use of scleral buckles combined with chorioretinal adhesions around the retinal tear forms the basis of treatment for many simple RRD. Cryotherapy for retinopexy performed intraoperatively has been implicated in the development of macular pucker and proliferative vitreoretinopathy. Eliminating cryotherapy of conventional surgery might not affect the outcome of anatomic success and improve visual recovery. Objective: The aim of this randomized clinical trial was to compare the rate of retinal reapplication and secondly the results of visual acuity in patients with rhegmatogenuos retinal detachment who underwent surgery with scleral buckle retinopexy and intraoperative cryotherapy versus laser photocoagulation postoperatively (one month after surgery). Method: A randomized, masked, performed in a single center, comprising 86 patients undergoing scleral buckle surgery. Patients were randomized to undergo surgery, scleral buckle retinopexy with cryotherapy and intraoperative (criopexy) or postoperative retinopexy with photocoagulation 30 days (laserpexy) after the procedure. The primary endpoint was to evaluate the rate of replication in retinal postoperative follow-up within 1 week. Secondary endpoints were to evaluate retinal reapplication rates, reoperation rates, rates of postoperative complications and recovery of visual acuity at 1 month and 6 months postoperative follow-up. Results: We included 86 eyes of 86 patients undergoing scleral buckle. The sample consisted of 43 patients belonging to the group laserpexy and 43 patients assigned to the group criopexy. Demographic data were similar in both groups. The anatomic success rate in 1 week, 1 month and 6 months were similar in both groups, respectively, 93% (40 patients), 100% and 100% in criopexy and 95.3% (41 patients), and 100% 100% in group laserpexy (P, respectively, 0.5, 1.0 and 1.0). Three patients of group criopexy and 2 of laserpexy underwent additional surgery (pars plana vitrectomy) after the primary failure at 1-week follow-up. The postoperative complications were similar in both groups, except for edema of the eyelids. The visual recovery was slower in the cryotherapy group. The difference in VA after 6 months was not significant. Conclusion: In patients with uncomplicated rhegmatogenuos retinal detachment, both techniques of retinopexy showed satisfactory anatomical and functional results. The choice of laserpexy offers faster visual recovery with fewer complications, but requires a second intervention and higher cost compared to criopexy / Mestrado / Oftalmologia / Mestre em Ciências Médicas

In the vertebrate retina, bipolar interneurons consist of at least 13 distinct subtypes, which are classified based on their morphology, behavior and gene expression. The mechanisms underlying the formation of these subtypes is poorly understood. Our previous unpublished work has implicated Sonic Hedgehog (Shh) in the formation of cone and rod bipolar cell subtypes. In this thesis, I characterized the relationship between Hh signaling and bipolar subtype cell development in greater detail. Using an in vivo plasmid-based reporter approach, I show that Hh signaling is active in both retinal progenitor cells (RPCs) and bipolar cells of the postnatal retina. Next, to address function, I used a conditional gene targeting approach to show that activation of Smoothened (Smo), a downstream Hh signaling component, is both necessary and sufficient in postnatal RPCs to promote the formation of cone but not rod bipolar cells. In contrast, activation of Smo in postmitotic bipolar cells that are greater than 24 hours old from cell birth, does not affect bipolar subtype formation. Together, these results suggest that Hh signaling functions in postnatal RPCs (and potentially in early bipolar cell precursors) to promote cone bipolar cell formation. / Graduate / 2018-06-12

L’œil et le système nerveux central (SNC) ont une origine embryologique commune et les structures rétiniennes, facilement observables, pourraient refléter les atteintes cérébrales. L’objectif général de cette thèse était d'analyser les relations entre atteintes rétiniennes et manifestations cliniques (déclin cognitif, démence) et paracliniques (imagerie cérébrale) du vieillissement cérébral. Deux "biomarqueurs" rétiniens ont été analysés : les fibres nerveuses de la rétine (RNFL) et les structures vasculaires. Les données utilisées proviennent de la cohorte populationnelle 3 Cités-Alienor. Nous avons montré que les sujets ayant une épaisseur réduite de la RNFL (mesurée par tomographie par cohérence optique spectral-domain, SD-OCT) présentaient des performances diminuées en mémoire épisodique (principale fonction cognitive affectée dans la maladie d’Alzheimer, MA) après 2 ans de suivi ; sur une période aussi courte, aucune association n'a été trouvée avec le risque de démence. Une épaisseur réduite de la RNFL était aussi associée à des paramètres altérés en IRM au niveau des voies visuelles et des régions du système limbique, régions particulièrement vulnérables dans la MA. Enfin nous avons montré qu'une épaisseur réduite de la couche vasculaire choroïde était associée à un volume d’hypersignaux de la substance blanche plus important. Des processus pathologiques vasculaires et neurodégénératifs sont associés dans le vieillissement cérébral. Ainsi, la rétine pourrait refléter les altérations du SNC dans la MA et le vieillissement cérébral. D'autres recherches doivent encore être menées avant de considérer la rétine comme un biomarqueur potentiel du vieillissement cérébral. / The eye and central nervous system (CNS) have a common embryological origin, and easily observable retinal structures may reflect brain damage. The primary objective of this thesis was to analyze the relationship between retinal disorders and clinical (cognitive decline, dementia) and para-clinical (brain imaging) brain aging manifestations. Two types of retinal "biomarkers" were analyzed: the retinal nerve fiber layer (RNFL) and vascular structures. The data used come from the population-based cohort 3-Cities Alienor. We have shown that subjects with reduced RNFL thickness (measured by spectral-domain optical coherence tomography, SD-OCT) showed a reduced episodic memory score (cognitive function that is principally affected in Alzheimer's disease, AD) after 2 years of follow-up; over this short period of time no association with dementia risk was found. A reduced RNFL thickness was also associated with altered MRI parameters in visual pathways and in limbic system regions, which are particularly vulnerable in AD. Finally we have shown that reduced vascular choroid layer thickness was associated with larger white matter hyperintensities volumes. Vascular and neurodegenerative disease processes are associated with brain aging. Thus, alterations in the CNS by AD and brain aging could be reflected in the retina. Other research is still needed before considering the retina as a potential biomarker of brain aging.

Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject’s gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naïve subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naïve subjects were allowed to gaze freely for all phases. Using the subject’s gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ~15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naïve subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased. No significant difference was observed based on age.

This thesis present research work conducted in the field of retina image analysis. More specifically, the work is directed at the application of texture analysis technique for the segmentation of common retinal landmark and for retina image classification. The main challenge in this research is in identifying the suitable texture measurement for retina images. In this research we proposed the used of texture measurement based on Binary Robust Independent Elementary Features (BRIEF). BRIEF measure texture by performing an intensity comparison in a local image patch, thus it is very fast to compute and tolerant to any monotonic increase or decrease of image intensities, which makes the descriptor invariant to illumination. The performance of BRIEF as texture measurement is first shown in an experiment involving texture classification and segmentation using common texture datasets. The result demonstrates good performance from BRIEF in this experiment. BRIEF is next used in two applications of retinal image analysis, namely optic disc segmentation and glaucoma classification. In the former, we proposed the used of pixel classification using BRIEF as textural features and circular template matching to segment the optic disc. In addition, an extension of BRIEF called Rotation Invariant BRIEF (OBRIEF) is later proposed to improve the segmentation result. For glaucoma classification, we described two approaches for glaucoma classification using BRIEF/OBRIEF features. The first is based on determination of cup to disc ratio (CDR) and the second is classification using image features i.e. BRIEF features. Overall, our preliminary results on using BRIEF as texture measurement for retinal image analysis are encouraging and demonstrate that it has the potential to be used in retina image analysis.

L’imagerie super-résolue délivrée par l’optique adaptative permet d’imager la rétine à l’échelle cellulaire et rentre au service du diagnostic et du suivi de pathologie de l’oeil mais aussi à une meilleure connaissance de l’anatomie, des fonctions et des mécanismes de la rétine.Dans un premier temps nous avons défini la méthode permettant de positionner le centre de la fovéa ainsi que de mesurer la densité des cônes avec la meilleure répétabilité. Le centre de l’ellipse de plus fortes densités permet de positionner le centre de la fovéa. La densité des cônes est mesurée dans une fenêtre de 80 par 80 pixels à une excentricité mesurée sur un montage établi à partir de clichés réalisés tous les 2°.Un des aspects fondamental de ce projet est la réalisation d’une base de données cliniques normatives liées à des bio-marqueurs (densité, espacement et morphologie des cônes). En effet il est nécessaire de fournir des mesures quantitatives des structures visualisées. Cette étude a permis de caractériser la structure rétinienne d’une population saine ne présentant aucune maladie rétinienne, de façon à établir un référentiel de normalité. Cette étude nous a aussi permis de répondre aux questions laissées sans réponse par la littérature. Nous avons constaté que la densité des cônes différait nettement entre les méridiens horizontaux et verticaux. Nous avons également observé que la longueur axiale influait sur la densité des cônes exprimée en unité de surface mais pas en terme d'angle visuel, supportant l'hypothèse que la rétine s'étirait avec l'allongement du globe oculaire. Enfin, l'âge ne semble pas avoir d'impact sur la densité des cônes excepté à 2°.Nous nous sommes ensuite intéressé au lien entre l’acuité visuelle périphérique et l’espacement des cônes. Il est connu que les cellules ganglionnaires midgets (mRGC) sont responsables de la résolution visuelle. Mais, au niveau de la fovéa, chaque cône se connecte, via des cellules bipolaires, à une mRGC ON et OFF. Cette particularité anatomique rend la mesure de l’espacement entre les cônes un substitut observable aux cellules ganglionnaires permettant ainsi le lien avec l'acuité visuelle. Nous avons donc déterminé jusqu'à quelle excentricité les cônes ne sont plus un substitut observable des cellules ganglionnaires. Nous avons constaté que l’acuité visuelle est régit par l’espacement des cônes jusqu’à 2° d’excentricité, à la fois en rétine nasale et inférieure, soutenant l'idée que seulement 50% des mRGC fovéale détermine l’acuité visuelle (mRGC ON ou OFF). Au delà, l’espacement des cônes surestime l’acuité visuelle. Watson a développé un modèle permettant de prédire l’acuité visuelle sur la base de l’espacement entre les mRGC lui-même dérivé de l’espacement entre les cônes. Le modèle 50% (mRGC ON ou OFF) prédit également l’acuité visuelle dans le méridien vertical (inférieur) à 4° et 6° d'excentricité. Le long du méridien nasal, le modèle 50% sous-estime l’acuité visuelle. Un chevauchement partiel des champs récepteurs des mRGC ON + OFF pourrait en être la cause. Nous avons ensuite mesuré la densité des cônes dans les 48° centraux le long du méridien horizontal dans deux groupes, l’un présentant une histoire d’évolution myopique (i.e. allongement de l'oeil) et l'autre non. À ce jour, il n'existe qu’une seule étude ayant des mesures in-vivo de la densité des cônes au delà des 15° centraux. Cette étude nous a également permis d'affirmer que lors de l'évolution myopique, la rétine s’étirerait de manière uniforme dans la zone mesurée, excepté proche de la tête du nerf optique, où il semblerait qu'il y ait une adhérence plus forte. / The high-resolved imagery delivered by the adaptive optic is used to form pictures of the retina at the cellular level and to diagnose and follow up on eyes pathologies, but also to improve knowledge of the anatomy, functions and mechanisms of the retina.First we defined the method that allows us to position the center of the fovea and to measure the density of the cones with the best repeatability. The center of the ellipse of higher densities makes it possible to position the center of the fovea. The cone density is measured in a region of interest of 80 x 80 pixels to an eccentricity measured on a montage established from pictures made every 2°.One of the fundamental aspects of this project is the creation of a normative clinical database linked to bio-markers (density, spacing and morphology of cones). Indeed it is necessary to provide quantitative measures of the structures visualized. This study made it possible to characterize the retinal structure of a healthy population with no retinal disease, so as to establish a reference of normality. This study also allowed us to answer questions left unanswered by the literature. The density of the cones differs sharply between the horizontal and vertical meridians. We have also observed that the axial length influences cone density expressed in metric unit but not in terms of visual angle, supporting the hypothesis that the retina is stretched with the lengthening of the eyeball. Finally, age does not seem to have an impact on cone density except at 2°.We then examined the relationship between peripheral visual acuity and cone spacing. It is known that midget ganglion cells are in charge of visual resolution. But, at the fovea, each cone connects, via bipolar cells, to a midget ganglion cell ON and OFF. This anatomical particularity makes the measurement of the cone spacing an observable substitute for ganglion cells thus allowing the link with visual acuity. We have therefore determined to what eccentricity the cones are no longer an observable substitute for ganglion cells. We found that visual acuity is governed by the arrangement of cones up to 2° of eccentricity, both in nasal and inferior retinas, supporting the idea that only 50% of foveal mRGCs determine VA (mRGC ON or OFF). Beyond this, cone spacing over-samples ganglion cells. Watson developed a model to predict visual acuity based on the mRGC spacing, itself derived from the cone spacing. The 50% model (mRGC ON or OFF) also predicts visual acuity in the inferior meridian at 4° and 6° of eccentricity. Along the nasal meridian, the 50% model underestimates visual acuity. Partial overlap of the mRGC ON + OFF receptive fields may be the cause.Finally, we measured the cone density in the central 48° along the horizontal meridian in two study groups, one with a history of myopic evolution (i.e. elongation of the eye) and the other without. To this date, there is only one study with in-vivo measurements of cone density beyond the central 15°. This study also allowed us to assert that during myopic evolution, the retina stretches uniformly in the measured area, excepted near the optic nerve head, where it appears that there is a stronger adhesion.

PURPOSE: Normobaric hyperoxia (NBH) has been shown in animal models of experimental retinal detachment (RD) to effectively prevent photoreceptor degeneration. Furthermore, choroidal hyperpermeability has been implicated in the disease pathophysiology. In this study, we studied the effects of 3-hours of 40% FIO2 NBH on photoreceptor morphology and visual acuity in patients with vision loss associated with active central serous chorioretinopathy (CSCR). MATERIALS and METHODS: A total of 8 patients with active unilateral CSCR received at least one 3-hour NBH (40% FIO2) session. Best corrected visual acuity (BCVA) as well as thickness of the central macula, subretinal fluid (SRF), photoreceptor layer (PL), and outer nuclear layer (ONL) were assessed. RESULTS: In patients with unilateral acute CSCR, 3 hours of 40% FIO2 NBH showed a trend towards improved vision, but no statistical differences were obtained for BCVA, CMT, SRF, PL, or ONL. CONCLUSIONS: Administration of 3-hours of NBH did not induce any measurable anatomic changes in the retina nor any significant changes in visual acuity. These results challenge the hypothesis of choroidal hyperpermeability in CSCR and suggest that additional or alternative pathologies contribute to this disease. / 2022-11-29T00:00:00Z