El documento digital no refiere asesor / Publicación a texto completo no autorizada por el autor / Determina las características clínicas de los pacientes infectados con el virus de la inmunodeficiencia humana que presentan retinitis por Citomegalovirus en tratamiento TARGA del Hospital Nacional Luis N Saenz. El estudio es descriptivo, observacional, transversal, retrospectivo. Se incluyeron a 31 pacientes con VIH+ diagnosticados con retinitis por CMV en el Hospital Nacional LNS- PNP durante el periodo de estudio 2009 - 2011. La recolección de los datos incluyó las características sociodemográficas, historia clínica y oftalmológica. Las características sociodemográficas frecuentes fueron ser mayores de 30 años (67.7%), varones (83.9%) y tener un tiempo de enfermedad mayor de 24 meses (61.3%). Las infecciones oportunistas fue la característica más frecuente (93.5%), siendo la tuberculosis (67.7%) y candidiasis (45.2%) los agentes de mayor proporción. El contacto sexual múltiple fue el comportamiento sexual de mayor proporción (80.6%). Los flotantes y los flashes fueron los síntomas más frecuentes (19.4%) junto con una rápida y progresiva disminución de la agudeza visual menor de 20/50 (87%); al igual que un recuento de linfocitos T CD 4 menor de 40 cl/ul (58.1%). Se concluye que las principales características fueron pacientes mayores de 30 años, varones y con un tiempo de enfermedad mayor de 24 meses, con Infecciones oportunistas y el antecedente de CMV previo, contacto sexual múltiple. Síntomas clínicos frecuentes fueron flotantes y los flashes, y pobre agudeza visual y recuento de linfocitos T CD 4 menor de 40 cl/ul. / Trabajo académico

Orientador: Renée Laufer Amorim / Resumo: O glaucoma é a principal causa global de cegueira irreversível e o número de pessoas com glaucoma em todo o mundo aumentará para 111,8 milhões em 2040, mesmo com os tratamentos vigentes. Deste modo, enseja uma necessidade de desenvolver terapias neuroprotetoras que possam ser usadas para reduzir os efeitos perniciosos do glaucoma, como a morte de células ganglionares da retina (CGR). Avanços na compreensão da fisiopatologia do glaucoma é um fator chave na compreensão da patogênese da neuropatia glaucomatosa. Neste contexto a isquemia retiniana desempenha um papel central em várias doenças da retina. A patogênese da isquemia retiniana envolve alterações temporais da morfologia e morfometria da retina assim como mudanças na expressão gênica e protéica. O Citrato de Sildenafila (SC) mostrou efeito protetor nos modelos de isquemia/reperfusão (I/R) com efeitos neuroprotetores. Contudo, a administração oral de CS, em humanos, encontra inúmeros efeitos colaterais, tais como redução da pressão arterial, dores de cabeça, rubor e congestão nasal são concomitantes, assim como pacientes com moderada a grave doença cardiovascular ou aqueles submetidos a terapia a base de nitrato apresentam riscos secundários aumentados para efeitos cardiovasculares adversos. Deste modo, propomos que a administração tópica de CS pode ser uma alternativa à via oral e também ser igualmente neuroprotetor no glaucoma e podem minimizar os riscos indesejados no uso sistêmico desse fármaco, além de oferecer uma n... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Glaucoma is the leading global cause of irreversible blindness and the number of people with glaucoma worldwide will increase to 111.8 million by 2040, even with current treatments. Thus, there is a need to develop neuroprotective therapies that can be used to reduce the deleterious effects of glaucoma, such as retinal ganglion cell death (RBC). Advances in understanding the pathophysiology of glaucoma are a key factor in understanding the pathogenesis of glaucomatous neuropathy. In this context, retinal ischemia plays a central role in various diseases of the retina. The pathogenesis of retinal ischemia involves temporal changes in retinal morphology and morphometry as well as changes in gene and protein expression. Sildenafil Citrate (SC) showed protective effect in the ischemia / reperfusion (I / R) models with neuroprotective effects. However, oral administration of CS in humans finds numerous side effects such as reduced blood pressure, headaches, flushing and nasal congestion are concomitant, as well as patients with moderate to severe cardiovascular disease or those undergoing nitrate therapy have increased secondary risks for adverse cardiovascular effects. Thus, we propose that the eye drops administration of CS may be an alternative to the oral route and also be equally neuroprotective in glaucoma and may minimize the undesirable risks in the systemic use of this drug, as well as offer a new approach for the therapeutic intervention in the pathogenesis of neuropathy... (Complete abstract click electronic access below) / Doutor

Orientador: Renée Laufer Amorim / Resumo: O glaucoma é a principal causa global de cegueira irreversível e o número de pessoas com glaucoma em todo o mundo aumentará para 111,8 milhões em 2040, mesmo com os tratamentos vigentes. Deste modo, enseja uma necessidade de desenvolver terapias neuroprotetoras que possam ser usadas para reduzir os efeitos perniciosos do glaucoma, como a morte de células ganglionares da retina (CGR). Avanços na compreensão da fisiopatologia do glaucoma é um fator chave na compreensão da patogênese da neuropatia glaucomatosa. Neste contexto a isquemia retiniana desempenha um papel central em várias doenças da retina. A patogênese da isquemia retiniana envolve alterações temporais da morfologia e morfometria da retina assim como mudanças na expressão gênica e protéica. O Citrato de Sildenafila (SC) mostrou efeito protetor nos modelos de isquemia/reperfusão (I/R) com efeitos neuroprotetores. Contudo, a administração oral de CS, em humanos, encontra inúmeros efeitos colaterais, tais como redução da pressão arterial, dores de cabeça, rubor e congestão nasal são concomitantes, / Abstract: Glaucoma is the leading global cause of irreversible blindness and the number of people with glaucoma worldwide will increase to 111.8 million by 2040, even with current treatments. Thus, there is a need to develop neuroprotective therapies that can be used to reduce the deleterious effects of glaucoma, such as retinal ganglion cell death (RBC). Advances in understanding the pathophysiology of glaucoma are a key factor in understanding the pathogenesis of glaucomatous neuropathy. In this context, retinal ischemia plays a central role in various diseases of the retina. The pathogenesis of retinal ischemia involves temporal changes in retinal morphology and morphometry as well as changes in gene and protein expression. Sildenafil Citrate (SC) showed protective effect in the ischemia / reperfusion (I / R) models with neuroprotective effects. However, oral administration of CS in humans finds numerous side effects such as reduced blood pressure, headaches, flushing and nasal congestion are concomitant, as well as patients with moderate to severe cardiovascular disease or those undergoing nitrate therapy have increased secondary risks for adverse cardiovascular effects. Thus, we propose that the eye drops administration of CS may be an alternative to the oral route and also be equally neuroprotective in glaucoma and may minimize the undesirable risks in the systemic use of this drug, as well as offer a new approach for the therapeutic intervention in the pathogenesis of neuropathy... (Complete abstract click electronic access below) / Doutor

As serpentes são um grupo altamente diversificado, encontradas em praticamente todas as regiões do planeta, ocupando diferentes ambientes. Sua diversidade adaptativa indica a grande variabilidade dos órgãos sensoriais, adaptados ao hábitat e hábitos de cada espécie. Estudos sobre o sistema visual das serpentes são escassos e tem grande importância na compreensão de caracteres ecológicos, comportamentais e filogenéticos. Nos vertebrados as informações visuais são projetadas na retina e inicialmente processadas nessa camada neural, antes do processamento que ocorre no sistema nervoso central. Os tipos de células encontradas na retina, bem como sua densidade e distribuição variam entre as espécies e determinam especializações do sistema visual. Neste trabalho foi feita uma quantificaçao comparativa de fotorreceptores e neurônios da camada de células ganglionares (CCG) de duas espécies de serpentes colubrídeas diurnas, Philodryas olfersii e P. patagoniensis. Para tanto foram utilizadas técnicas de imunohistoquímica de opsinas e de marcação de Nissl. Serpentes adultas obtidas no Instituto Butantan foram anestesiadas com tiopental (30mg/kg) e sacrificadas com CO2. Os olhos foram enucleados e as retinas dissecadas e fixadas em paraformaldeido 4%. Um olho de cada serpente foi utilizado para fazer cortes radiais e testar diferentes tipos e concentrações de anticorpos. Para a preparação das retinas planas foram utilizados o anticorpo JH455, produzido em coelhos contra opsinas sensíveis aos comprimentos de onda curto de humanos (cones S) e o anticorpo JH492, produzido em coelhos contra opsinas sensíveis aos comprimentos de onda médio e longo de humanos (cones L/M). Foi utilizado anticorpo secundário biotinilado (gt -rb biot) e a revelação feita com estreptavidina acoplada a molécula florescente CY3. Os cortes radiais e as retinas planas foram observadas em microscópio fluorescente equipado com câmara digital conectada a microcomputador dotado de programa para captura de imagens. A partir de imagens da retina obtidas com espaçamento mínimo de 0,5 mm foram feitas as contagens das células e os mapas de isodensidade celular. A densidade média dos fotorreceptores foi semelhante nas duas espécies (11.183,1 ± 1.107,4 células/mm2 em P. olfersii e 11.531,2 ± 1.054,9 células/mm2 em P. patagoniensis), assim como a proporção dos diferentes tipos de cones (3% cones S e 83% cones L/M em P. olfersii, e 5% cones S e 85% cones L/M em P. patagoniensis). As densidades de células da CCG também foram semelhantes (10.117,5 ± 1.026 células/mm2 em P. olfersii e 9.834,9 ± 2.772,2 células/mm2 em P. patagoniensis). Entretanto, os mapas de isodensidade mostraram diferentes regiões de especialização. P. olfersii apresentou uma faixa horizontal e duas areas centralis de maior densidade celular, uma na região central e uma na região caudal, indicando a melhor acuidade visual nos campos de visão frontal e lateral, o que possivelmente auxilia na locomoção e forrageamento no extrato arbóreo. P. patagoniensis apresentou maior densidade celular na região ventral e rostral, indicando a maior acuidade no campo visual superior e posterior, auxiliando na percepção da aproximação de predadores e animais maiores, importante para a sobrevivência de serpentes terrestres e possivelmente para a percepção de presas localizadas em estrato arbustivo. / Snakes are a diversified group found in almost all regions of the planet, occupying different habitats, with exception to Polar Regions, a few islands and the deeper ocean waters. Its diversity indicates the high variability of sensory organs, which are adapted to the habits and habitats of each species. Studies about snakes visual system are scarce and have a great importance for the understanding of their ecology, behavior and phylogeny. In vertebrates the visual information is projected in the retina and initially processed in this neural tissue, before its processing in the central nervous system. The different kinds of cells present, as well as its density and distribution in the retina, vary between species and determinate specializations of the visual system. In this study we compared the density and distribution of photoreceptors and neurons of the ganglion cells layer (GCL) of two diurnal colubridae snakes, the arboreal Philodryas olfersii and the terrestrial P. patagoniensis, with opsins immunohistochemistry and Nissl staining. Adult snakes obtained in Instituto Butantan were anesthetized with thiopental (30mg/Kg) and the euthanasia was done with CO2. The eyes were enucleated and the retinas dissected and fixed in paraformaldeid 4%. One eye of each species was sectioned to test different antibodies and the counting for the determination of topographic distribution of density was made in flattened wholemount retinas. In the wholemounts retinas it was utilized the antibodies JH455 produced in rabbit against human S cone opsins and JH492 produced in rabbit against human L/M cone opsins. The photoreceptors density were similar in the two species (11,1831 ± 1,107.4 cells/mm2 in P. olfersii and 11,531.2 ± 1,054.9 cells/mm2 in P. patagoniensis), as well as the proportion of the different types of cells (3% S cones and 83% L/M cones in P. olfersii, and 5% S cones and 85% L/M cones in P. patagoniensis). The GCL cells density were also similar (10,117.5 ± 1,026 cells/mm2 in P. olfersii and 9,834.9 ± 2,772.2 cells/mm2 in P. patagoniensis). However, the isodensity maps showed different specializations regions. P. olfersii showed a horizontal streak and two areae (area centralis) with higher density, in the central and in the caudal regions, indicating a better visual acuity in the lateral and in the frontal visual field, what is possibly very important for locomotion and searching for preys (foraging) in the arboreal layer. P. patagoniensis showed a higher cell density in the ventral and rostral regions of the retina, indicating a better visual acuity in the superior and posterior visual field, what is important to perceive the approaching of predators and terrestrial animals and preys located in underbushes above the snake.

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Tese de mestrado. Engenharia Biomédica. Faculdade de Engenharia. Universidade do Porto. 2008

Abnormalities in the vascular pattern of a retina, such as morphologic changes in vessel shape, branching pattern, width, tortuosity, or the appearance of retinal lesions, may be associated with the occurrence of retinopathies or cardiovascular diseases. Thus, an automated quantitative analysis of changes in vessel morphology may help indicating the clinical signs of aforementioned retinopathies, describing their early occurrence or severity. The responses obtained from different types of retinal vessels, i.e., arteries and veins, may be variable to retinopathies and their measurement may lead to a more precise diagnosis compared to that by the average response accounted for the entire vessel network. I propose a set of automated methods in order to analyze the retinal vessel network and to quantify its morphologic properties with respect to arteries and veins, in two-dimensional color fundus images. The analytical methods include; 1) Forma- tion of a well connected vessel network, 2) Structural mapping of a vessel network, 3) Artery-venous classification, and 4) Blood vessel hemorrhage detection. The quan- tification methods include vessel morphology analysis based on the measurement of tortuosity, width, branching angle, branching coefficient, and fractal dimension. The aforementioned morphologic parameters are measured with respect to arteries and veins separately in a vessel network. The methods are validated with the manually annotated retinal fundus images as a ground truth. The major contribution of this thesis includes the development of automated methods for; 1) Identification and separation of retinal vessel trees for individual vessel analysis, 2) Automated quantification of morphologic characteristics of retinal vessels for quick and precise measurement, 3) Automated quantification of vessel morphology with respect to arteries and veins, and 4) Analysis of two datasets, a) malarial retinopathy subject dataset, b) longitudinal study dataset. The ability of the automated methods to quantify the retinal vessel specific properties may enable the individual vessel analysis as an alternative to a time- consuming and subjective clinical evaluation, or to a quantitative morphology char- acterization averaged over the entire vessel network. The objective evaluation may indicate the progression of retinopathies precisely and may help characterizing nor- mal and abnormal vascular patterns with respect to arteries and veins. This may enable a quick diagnosis, treatment availability, prognosis, and facilitation of clinical health-care procedures in remote areas.

An estimated 170.38 million elderly adults suffer from some stage of age-related macular degeneration (AMD) worldwide, a vision defect that damages the macula, the central region of the retina required for sharp vision, such as reading, driving, and recognizing faces. Genetic factors strongly modify one's risk for developing AMD, and most of these genetic changes are found in genes of the alternative complement cascade, a component of the immune system. The lack of effective AMD prevention calls for the identification of druggable molecules and pathways. In my research, I use microarrays and RNA sequencing to investigate the events occurring in early AMD, the reasons for macular susceptibility to AMD, and the events triggering aberrant blood vessel growth in late AMD. First, I found that genes associated with endothelial cells tend to be expressed at lower levels in human donors eyes affected by early AMD than in control eyes, concordant with previous studies indicating loss of choriocapillaris in early AMD. Second, I found that molecular signals across regions of the retina, retinal pigment epithelium, and choroid generally mirror the distribution of cell types in these regions. Third, I found that damage to cultured primate chorioretinal endothelial cells by the end product of complement activation, membrane attack complex, produces an environment conducive to choroidal neovascularization, a symptom of late-stage AMD. I propose a model that bridges genetic variants in the complement cascade genes with blood vessel loss in early AMD and the pathological growth of blood vessels in late AMD.

Optical coherence tomography (OCT) is becoming an increasingly important modality for the noninvasive assessment of a variety of ocular diseases such as glaucoma, diabetic macular edema, and age-related macular degeneration. Even though individual layers of the retina are visible on OCT images, current commercial quantitative assessment is limited to measuring the thickness of only one layer. Because each intraretinal layer may be affected differently by disease, an intraretinal layer segmentation approach is needed to enable quantification of individual layer properties, such as thickness or texture. Furthermore, with the latest generation of OCT scanner systems producing true volumetric image data, processing these images using 3-D methods is important for maximal extraction of image information. In this thesis, an optimal 3-D graph search approach for the intraretinal layer segmentation of OCT images is presented. It is built upon the optimal 3-D multiple surface graph-theoretic approach presented by Li et al. (K. Li, X. Wu, D. Z. Chen, and M. Sonka, "Optimal surface segmentation in volumetric images - a graph-theoretic approach," IEEE Transactions on Pattern Analysis and Machine Intelligence, vol. 28, no. 1, pp. 119-134, 2006). In this method, multiple surfaces can be found simultaneously by transforming the 3-D segmentation problem into finding a minimum-cost closed set in a corresponding vertex-weighted geometric graph. However, the original formulation of this approach did not incorporate varying feasibility constraints or true regional information, two extensions that would aid in the intraretinal layer segmentation of OCT images. Thus, the major contributions of this thesis include: 1) extending the optimal 3-D graph-theoretic segmentation approach to allow for the incorporation of varying feasibility constraints and regional information, 2) developing a method for learning varying constraints and cost functions from examples for use in the approach, 3) developing and validating a method for the 3-D segmentation of intraretinal layers in both time-domain and spectral-domain OCT images (achieving error rates comparable to that of multiple human experts), and 4) analyzing layer thickness properties in normal subjects and in patients with anterior ischemic optic neuropathy (AION).