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Studies demonstrate neuro-retinal damage in patients with diabetes and no clinically visible diabetic retinopathy. It is unknown which retinal regions are most vulnerable to diabetes. We hypothesized that the standard and slow-flash (sf-) multifocal electroretinogram (mfERG) and adaptive optics (AO) imaging will localize retinal regions of vulnerability. Fifty-five adolescents with diabetes and 54 controls underwent mfERG testing to isolate predominately retinal bipolar cell activity and sf-mfERG testing to isolate three oscillatory potentials (OPs) from intraretinal amacrine and interplexiform cells. Greatest mfERG delays were in the superior temporal quadrant and at 5°-10° eccentricity. Greatest sf-mfERG delays were found at different eccentricities for each OP. Twenty adolescents with diabetes and 14 controls underwent AO imaging. No significant differences in cone photoreceptor density were found; however, patients showed a trend towards reduced density in the superior nasal region. Inner retinal structures may be more susceptible to damage by diabetes than outer retinal structures.

Studies demonstrate neuro-retinal damage in patients with diabetes and no clinically visible diabetic retinopathy. It is unknown which retinal regions are most vulnerable to diabetes. We hypothesized that the standard and slow-flash (sf-) multifocal electroretinogram (mfERG) and adaptive optics (AO) imaging will localize retinal regions of vulnerability. Fifty-five adolescents with diabetes and 54 controls underwent mfERG testing to isolate predominately retinal bipolar cell activity and sf-mfERG testing to isolate three oscillatory potentials (OPs) from intraretinal amacrine and interplexiform cells. Greatest mfERG delays were in the superior temporal quadrant and at 5°-10° eccentricity. Greatest sf-mfERG delays were found at different eccentricities for each OP. Twenty adolescents with diabetes and 14 controls underwent AO imaging. No significant differences in cone photoreceptor density were found; however, patients showed a trend towards reduced density in the superior nasal region. Inner retinal structures may be more susceptible to damage by diabetes than outer retinal structures.

Submitted by Cássio da Cruz Nogueira (cassionogueirakk@gmail.com) on 2017-09-11T18:18:08Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EletrorretinografiaMultifocalDesenvolvimento.pdf: 3263891 bytes, checksum: a89768008f3f46c900221a6944872516 (MD5) / Approved for entry into archive by Irvana Coutinho (irvana@ufpa.br) on 2017-09-19T12:27:38Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EletrorretinografiaMultifocalDesenvolvimento.pdf: 3263891 bytes, checksum: a89768008f3f46c900221a6944872516 (MD5) / Made available in DSpace on 2017-09-19T12:27:38Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EletrorretinografiaMultifocalDesenvolvimento.pdf: 3263891 bytes, checksum: a89768008f3f46c900221a6944872516 (MD5) Previous issue date: 2014-11-03 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / A presente tese foi composta por dois estudos desenvolvidos paralelamente. O primeiro objetivo foi o desenvolvimento de um método para classificar as respostas eletrorretinográficas e validar este método em toxoplasmose ocular. O segundo objetivo foi investigar o efeito do uso agudo de cloroquina na retina de paciente com malária (P. vivax) que receberam o tratamento estabelecido pelo Ministério da Saúde do Brasil. A ferramenta experimental de ambos os estudos foi o eletrorretinograma multifocal (mfERG). No primeiro estudo, o sistema Veris foi usado para testar 10 sujeitos saudáveis e calcular a razão sinal-ruído com o objetivo de achar os melhores valores para separar respostas normais de respostas retinianas diminuídas. O resultado final desta análise foi aplicado em três pacientes com perda visual devido toxoplasmose ocular. Os resultados mostraram uma razão sinal-ruído ótima de 0,47 para separar formas de onda com e sem sinal. As razões sinal ruído de 0,47, 0,44, 0,48, 0,57, 0,78 e 1,21 foram ótimas para separar respostas normais de respostas progressivamente atenuadas. A aplicação da análise sinal-ruído em pacientes com toxoplasmose ocular foi capaz de mapear a área retiniana sem atividade quando provocada pela luz. O segundo estudo foi desenvolvido usando o mfERG para avaliar 48 pacientes com malária, P. vivax, que receberam terapia medicamentosa de cloroquina. Estes dados foram comparados com os dados de 37 sujeitos saudáveis. Os resultados mostraram que o número de infecções variava de 1 a 18 vezes. Durante o tratamento, a dose média de cloroquina ingerida foi 5429 ± 782,3 mg. A estimativa da dose cumulativa normalizada pela massa corporal variou de 14,58 a 545,45 mg/kg. Nenhuma diferença foi observada na amplitude e tempo implícito do mfERG entre os pacientes e os controles em nenhum dos anéis concêntricos do campo visual. Não houve correlação significativa entre a atividade retiniana com a dose cumulativa de cloroquina. Concluiu-se que a análise da razão sinal-ruído desenvolvida nesta tese pode ser usada como um método confiável para estudar a função retiniana diminuída, incluindo o mapeamento das consequências da toxoplasmose ocular; e que o uso agudo da cloroquina para tratamento de malária não causou nenhuma piora da atividade retiniana registrada pelo mfERG. / The current thesis was composed by two studies performed in parallel. The first purpose was the development of a reliable method to classify the electroretinographic responses and to validate this method in ocular toxoplasmosis. The second purpose was to investigate the effect of the acute use of chloroquine in the retina of vivax malaria patients, which received the standard treatment of the Ministry of Health of Brazil. The experimental tool of both studies was the multifocal electroretinogram (mfERG). In the first study the Veris system was used to test 10 healthy subjects to calculate a signal to noise ratio analysis in order to find the best values to separate normal responses from impaired retinal responses. The final results of this analysis were applied in three patients with visual loss due ocular toxoplasmosis. The results showed an optimal signal to noise ratio of 0.47 to separate waveforms with and without signal. The signal to noise ratio of 0.47, 0.44, 0.48, 0.57, 0.78, 1.21 were optimal to separate normal responses from progressively attenuated responses. The application of the signal to noise ratio analysis into ocular toxoplasmosis patients was able to map the retinal area with no activity evoked by the light. The second study was performed using mfERG to evaluate 48 vivax malaria patients which received chloroquine-based treatment. Their data were compared to 37 healthy subjects. The results showed that number of infections ranged between from 01 to 18 times. During the treatment, the mean dosage of intaken chloroquine was 5429 ± 782.3 mg. The cumulative dosage normalized to the body mass ranged from 14.58 to 545.45 mg/kg. No difference was observed in the mfERG amplitude and implicit time obtained from malaria patients and control group at any concentric rings of the visual field. There was no significant correlation between the retinal activity with the chloroquine cumulative dosage. It was concluded that the signal to noise analysis developed in this thesis can be used as a reliable method to study impaired retinal function, including the mapping of ocular toxoplasmosis consequences; and the acute use of chloroquine for malaria treatment caused no impairments to retinal activity recorded by mfERG.

Submitted by Cássio da Cruz Nogueira (cassionogueirakk@gmail.com) on 2017-10-16T16:55:39Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_AvaliacaoRazaoSinal.pdf: 12982053 bytes, checksum: 4d887a2c67f744e27eae380be94f9c33 (MD5) / Approved for entry into archive by Irvana Coutinho (irvana@ufpa.br) on 2017-10-19T16:59:13Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_AvaliacaoRazaoSinal.pdf: 12982053 bytes, checksum: 4d887a2c67f744e27eae380be94f9c33 (MD5) / Made available in DSpace on 2017-10-19T16:59:13Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_AvaliacaoRazaoSinal.pdf: 12982053 bytes, checksum: 4d887a2c67f744e27eae380be94f9c33 (MD5) Previous issue date: 2009 / Este trabalho objetivou desenvolver uma análise quantitativa que permita, em sujeitos saudáveis e pacientes com perda visual, separar registros com sinal correlacionado com a estimulação visual, dos registros que contenham ruído. Foi usado o sistema VERIS Science v6.0.5d para extrair o kernel de primeira ordem dos registros, e posterior exportação dos dados para análise no MATLAB. Neste ambiente de programação foi realizada a análise dos componentes principais (PCA), que é usada para reduzir a dimensionalidade dos dados conservando sua variação e minimizando a influência do ruído; e a avaliação da razão sinal ruído (SNR) das respostas multifocais (mfERG) usando a distribuição cumulativa SNR realizadas em dois intervalos de tempo, um compreendendo apenas o sinal e outro apenas o ruído, para classificação das respostas em válidas, diminuídas ou ausentes. No grupo dos sujeitos saudáveis, não houve sobreposição de curvas na distribuição cumulativa da SNR do sinal e do ruído, que ocuparam diferentes valores em todos os sujeitos. Com o critério de 1% para falsos positivos e falsos negativos foi possível definir as bordas da SNR do sinal, das respostas diminuídas e do ruído. Este mesmo protocolo foi aplicado a três (3) pacientes com perda visual decorrente da toxoplasmose ocular. Nestes casos, houve sobreposição das curvas da distribuição cumulativa da SNR do sinal e ruído. O limite de confiança da distancia entre os limites da SNR do sinal e do ruído obtidos do grupo de sujeitos saudáveis, foi usado para separar respostas válidas, respostas diminuídas e ausência de resposta. Os resultados da avaliação da SNR foram usadas para mostrar os registros do mfERG em gráficos topográficos que discriminam as respostas válidas (sinal), respostas diminuídas e ausência de resposta (ruído). O uso desta ferramenta nos permitiu identificar danos na topografia retiniana, com também a localização da cabeça do nervo óptico, e mais facilmente discriminado, artefatos como o pico central errôneo que podem ser rejeitados, além de áreas retinianas com diminuição funcional no caso dos pacientes. Conclui-se então que a combinação da PCA para reconstruir registros mfERG com a avaliação da SNR são ferramentas úteis para analisar a topografia retiniana de sujeitos saudáveis e acometido por doenças, como por exemplo, a toxoplasmose com complicações oculares. / The purpose of this work was to develop a quantitative analysis that allows, in healthful and patient with visual loss, to separate registers with signal correlated with the visual stimulation, of the registers that contain noise. System VERIS Science v6.0.5d was used to extract kernel first-class of the registers, and posterior exportation of the data for analysis in the MATLAB. In this environment of programming was carried the analysis of the main components (PCA), that is used to reduce the dimensionalidad of the data conserving its variation and minimizing the influence of the noise; the signal-to-noise analysis (SNR) of the multifocal responses (mfERG) using cumulative distribution SNR carried through in two intervals of time, one understanding only the signal and another one only the noise, for classification of the valid, diminished or absent responses. We have found that in a group healthy subjects, the noise and signal SNR cumulative distributions have not overlapped and occupy distinct ranges of SNR values in all subjects. By using a 1% criterion for false positives and false negatives, it was possible to define the borders of noise, low response, and signal SNR ranges. We have also applied this protocol to a three subject with visual loss due to ocular toxoplasmosis scares. In this case, there was a degree of overlapping between the noise and signal SNR distributions. It was still possible to separate the noise, low response, and signal SNR range by using the confidence limits for the distance between noise and signal boundaries obtained from the group of healthy subjects. The results of SNR evaluation were then used to display the mfERG waveforms in topographical plots that discriminate between reliable responses (signal), low responses, and no responses (noise). Using this approach, features of retinal topography, such as the optic nerve head, are more easily discriminate, whilst artifacts such as an erroneous central peak, are more easily rejected. The combinations of PCA to reconstruct mfERG waveforms with SNR evaluation are useful tools to analyze retinal topography both in healthy and impaired conditions.

No description available.

Actuellement, la presbytie peut être corrigée chirurgicalement à l’aide d’implants intraoculaires réfractifs ou diffractifs multifocaux (chirurgie endoculaire invasive et irréversible) ou en intracornéen avec une correction multifocale réfractive (correction laser irréversible, ou insertion d’un implant dans le stroma). L’objectif de ce travail est de développer un nouvel implant permettant de corriger la presbytie, qui allie l’innocuité et la réversibilité d’une correction intracornéenne, à l’efficacité du diffractif. Le design des profils optiques bifocaux a été permis grâce au développement d’outils de simulation optique. Les efficacités de diffraction sont calculées à partir de la propagation du champ électrique par spectre angulaire. La qualité optique est déterminée d’après les simulations de Fonction de Transfert de Modulation obtenues sous Zemax. Des simulations de rendu d’images permettent de visualiser les effets de différents profils envisagés. Les paramètres critiques du design optique sont déterminés. Le choix du matériau dépend des contraintes de biocompatibilité de l’implant et des techniques de fabrication. La solution retenue est un hydrogel à forte teneur en eau, couplé à une nouvelle architecture de l’implant. L’hydrogel est obtenu par polymérisation radicalaire de macromonomères difonctionnels de poly(éthylène glycol) de masses molaires de l’ordre de 8000 g.mol‐1 qui conduisent à des propriétés mécaniques et une perméabilité aux nutriments compatibles avec l’application. La réalisation, la stérilisation et la caractérisation optique de prototypes ont abouti à la preuve du concept d’un implant bifocal diffractif intracornéen / Presbyopia can be corrected with surgery by means of refractive or diffractive multifocal intraocular lenses (which imply an irreversible and invasive endocular surgery) or by intracorneal multifocal refractive correction (irreversible laser correction, or insertion of an intrastromal implant). This work aims at developing a new implant to correct presbyopia, which takes advantage of both the harmlessness and the reversibility of an intracorneal correction, and the efficiency of diffractive optics. The design of the bifocal optical profiles was based on the development of optical simulation tools. The diffractive efficiencies are calculated from the distribution of the electric field with the method of angular spectrum. The optical quality is determined according to the simulations of Modulation Transfer Function obtained with Zemax. Images simulations show the effects of the different profiles studied. The critical parameters of the optical design are also determined. The choice of the material depends on several constraints such as biocompatibility and techniques of manufacturing. The adopted solution relies on the used of an hydrogel with high water content and the design of a new implant architecture. The hydrogel is obtained by radical polymerization of difunctional macromonomers of poly(ethylene glycol) with molar masses around 8000 g.mol‐1, allowing mechanical properties and permeability to nutriments compatible with the application. The realization, the sterilization and the characterization of prototypes showed the proof of the concept of a diffractive bifocal intracorneal implant

We report on a stem cell-transplanted patient with B cell chronic lymphatic leukemia who presented with a subacute onset of focal neurological deficits, gait abnormalities, emotional lability and dementia. Progressive multifocal leukoencephalopathy was diagnosed by magnetic resonance imaging (MRI) of the brain and detection of JC virus genome in the cerebrospinal fluid. Cidofovir and the 5HT2A receptor antagonist chlorpromazine were subsequently administered. A follow-up MRI of the brain 2 weeks after initiation of the antiviral therapy displayed progress of the demyelination, and the patient died 3 months after onset of the neurological symptoms. This report highlights the need for the development of novel and potent strategies for treatment of progressive multifocal leukoencephalopathy. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.