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Tesis por compendio / [ES] Esta tesis presenta soluciones de vanguardia basadas en algoritmos de computer vision (CV) y machine learning (ML) para ayudar a los expertos en el diagnóstico clínico. Se centra en dos áreas relevantes en el campo de la imagen médica: la patología digital y la oftalmología. Este trabajo propone diferentes paradigmas de machine learning y deep learning para abordar diversos escenarios de supervisión en el estudio del cáncer de próstata, el cáncer de vejiga y el glaucoma. En particular, se consideran métodos supervisados convencionales para segmentar y clasificar estructuras específicas de la próstata en imágenes histológicas digitalizadas. Para el reconocimiento de patrones específicos de la vejiga, se llevan a cabo enfoques totalmente no supervisados basados en técnicas de deep-clustering. Con respecto a la detección del glaucoma, se aplican algoritmos de memoria a corto plazo (LSTMs) que permiten llevar a cabo un aprendizaje recurrente a partir de volúmenes de tomografía por coherencia óptica en el dominio espectral (SD-OCT). Finalmente, se propone el uso de redes neuronales prototípicas (PNN) en un marco de few-shot learning para determinar el nivel de gravedad del glaucoma a partir de imágenes OCT circumpapilares. Los métodos de inteligencia artificial (IA) que se detallan en esta tesis proporcionan una valiosa herramienta de ayuda al diagnóstico por imagen, ya sea para el diagnóstico histológico del cáncer de próstata y vejiga o para la evaluación del glaucoma a partir de datos de OCT. / [CA] Aquesta tesi presenta solucions d'avantguarda basades en algorismes de *computer *vision (CV) i *machine *learning (ML) per a ajudar als experts en el diagnòstic clínic. Se centra en dues àrees rellevants en el camp de la imatge mèdica: la patologia digital i l'oftalmologia. Aquest treball proposa diferents paradigmes de *machine *learning i *deep *learning per a abordar diversos escenaris de supervisió en l'estudi del càncer de pròstata, el càncer de bufeta i el glaucoma. En particular, es consideren mètodes supervisats convencionals per a segmentar i classificar estructures específiques de la pròstata en imatges histològiques digitalitzades. Per al reconeixement de patrons específics de la bufeta, es duen a terme enfocaments totalment no supervisats basats en tècniques de *deep-*clustering. Respecte a la detecció del glaucoma, s'apliquen algorismes de memòria a curt termini (*LSTMs) que permeten dur a terme un aprenentatge recurrent a partir de volums de tomografia per coherència òptica en el domini espectral (SD-*OCT). Finalment, es proposa l'ús de xarxes neuronals *prototípicas (*PNN) en un marc de *few-*shot *learning per a determinar el nivell de gravetat del glaucoma a partir d'imatges *OCT *circumpapilares. Els mètodes d'intel·ligència artificial (*IA) que es detallen en aquesta tesi proporcionen una valuosa eina d'ajuda al diagnòstic per imatge, ja siga per al diagnòstic histològic del càncer de pròstata i bufeta o per a l'avaluació del glaucoma a partir de dades d'OCT. / [EN] This thesis presents cutting-edge solutions based on computer vision (CV) and machine learning (ML) algorithms to assist experts in clinical diagnosis. It focuses on two relevant areas at the forefront of medical imaging: digital pathology and ophthalmology. This work proposes different machine learning and deep learning paradigms to address various supervisory scenarios in the study of prostate cancer, bladder cancer and glaucoma. In particular, conventional supervised methods are considered for segmenting and classifying prostate-specific structures in digitised histological images. For bladder-specific pattern recognition, fully unsupervised approaches based on deep-clustering techniques are carried out. Regarding glaucoma detection, long-short term memory algorithms (LSTMs) are applied to perform recurrent learning from spectral-domain optical coherence tomography (SD-OCT) volumes. Finally, the use of prototypical neural networks (PNNs) in a few-shot learning framework is proposed to determine the severity level of glaucoma from circumpapillary OCT images. The artificial intelligence (AI) methods detailed in this thesis provide a valuable tool to aid diagnostic imaging, whether for the histological diagnosis of prostate and bladder cancer or glaucoma assessment from OCT data. / García Pardo, JG. (2022). Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182400 / Compendio

No / To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS: Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS: A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 x 6-mm area with a resolution of 256 x 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES: Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS: Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 mum; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 mum; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS: Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.

La compréhension des propriétés biomécaniques de la tête du nerf optique (TNO) est cruciale pour la gestion de conditions telles que le glaucome et le Syndrome Neuro-Oculaire Lié à l'Espace (SNOE). Cette thèse propose d’utiliser l'imagerie par tomographie de cohérence optique vidéo à haute fréquence (V-OCT) traitée avec des algorithmes de traitement d'image existants pour évaluer quantitativement la déformation pulsatile de la TNO due aux cycles cardiaques. Cette méthode est utilisée afin d’investiguer deux phénomènes: la réponse biomécanique de la TNO dans les conditions terrestres; et la réponse du TNO dans l'environnement de microgravité de l'espace. Le premier segment de cette thèse présente une nouvelle méthode non-invasive pour mesurer le déplacement pulsatile de la TNO via l'OCT vidéo (V-OCT), offrant des progrès significatifs dans la quantification des propriétés biomécaniques de l'œil in vivo. Une validation approfondie de cette technique, à la fois numérique et expérimentale, a confirmé la sensibilité de l'algorithme aux déformations induites, sa robustesse face à divers niveaux de bruit, et sa répétabilité. Deux groupes d’individus, sains et myopes, ont été évalués sous différentes conditions de contrainte physiologique. La déformation pulsatile des tissus de la TNO a été capturée quantitativement et représentée sous forme de cartes de déformation, montrant la sensibilité de la méthodologie aux déformations induites et la robustesse aux interférences de bruit élevé. Pour les sujets dont les yeux ont une longueur axiale de moins de 25mm, des différences notables de déformation pulsatile médiane ont émergé entre les positions primaires et en abduction de l'œil, avec une reproductibilité confirmée via des coefficients de corrélation intra-classe élevés. Ayant validé la méthode, elle a donc a été appliquée à une cohorte de glaucomateux pour examiner l'impact de la réduction de la pression intraoculaire (PIO) sur le déplacement pulsatile de la TNO. Chez les patients atteints de glaucome primaire à angle ouvert (GPAO), en particulier ceux sans myopie axiale, les interventions abaissant la PIO ont conduit à une réduction significative de la pulsation de la TNO. Cependant, les patients glaucomateux myopes n'ont affiché aucun changement substantiel, suggérant une relation nuancée entre la modulation de la PIO et la biomécanique de la TNO. Une étude de cohorte n’a révélé aucune différence marquée dans la pulsation de la TNO à travers divers degrés de gravité du glaucome. Pourtant, la déformation pulsatile a été corrélée à l'épaisseur de la couche de fibres nerveuses rétiniennes et à des mesures hémodynamiques spécifiques, soulignant les interconnexions complexes entre la biomécanique et l'hémodynamique oculaires. La dernière partie de cette thèse aborde les modifications de la rigidité oculaire chez les astronautes avant et après des vols spatiaux prolongés. En analysant les données de 26 yeux de 13 astronautes, la recherche a démontré des réductions significatives de la rigidité oculaire, de la pression intraoculaire et de l'amplitude du pouls oculaire après la mission. Ces découvertes explorent des effets précédemment inconnus de la microgravité sur les propriétés mécaniques de l'œil, améliorant notre compréhension du SNOE. Cette étude, tout en approfondissant notre compréhension des complexités biomécaniques et hémodynamiques de la TNO, démontre le potentiel du V-OCT comme outil pour le diagnostic et le suivi des conditions du nerf optique. Les techniques et les perspectives acquises ici posent également les bases pour de futures explorations prometteuses à la fois pour les patients atteints de glaucome et pour les astronautes. / The eye is a semi-rigid sphere with complex biomechanical properties. Chronic disease or stress like space flight can interfere with these properties, leading to vision loss. Noninvasive measurements of the biomechanical properties of the optic nerve head (ONH) could provide better tracking and management of conditions such as glaucoma and Space-Related Neuro-Ocular Syndrome (SANS). This thesis proposes to use high-frequency optical coherence tomography video imaging (V-OCT) with existing image processing algorithms to quantitatively evaluate the pulsatile displacement of the ONH due to cardiac cycles. This methodology is applied across two streams of research: examining the ocular biomechanical response of the ONH under terrestrial conditions; and the ONH deformation in the microgravity environment of space. The first section of this thesis introduces a non-invasive method to measure ONH pulsatile displacement via video-based OCT (V-OCT), quantifying biomechanical eye properties in vivo. A thorough validation of this technique, both numerically and experimentally, confirmed the algorithm’s sensitivity to induced deformation, robustness against various noise levels, and repeatability. Two groups, healthy and myopic individuals, underwent assessment under different physiological strain conditions. Pulsatile ONH tissue deformation was quantitatively captured and represented as deformation maps. For those subjects with eyes with an axial length of less than 25mm, notable median pulsatile displacement differences were found between primary and abducted eye positions. Reproducibility was confirmed via high intraclass correlation coefficients. Building on this foundation, the method was applied to a cohort of glaucoma patients to examine the impact of IOP reduction on ONH pulsatile displacement. In primary open-angle glaucoma (POAG) patients, particularly those without axial myopia, IOP-lowering interventions significantly reduced ONH pulsation. However, myopic glaucoma patients displayed no substantial changes, suggesting that myopic status moderates the relationship between IOP modulation and ONH biomechanics. This pilot study was expanded to a larger cross-sectional cohort study (N=176), revealing a decrease in ONH pulsatile displacement in people with early and moderate glaucoma compared to controls. . In addition, pulsatile displacement correlated with retinal nerve fiber layer thickness and specific hemodynamic measures, showing that ocular biomechanics and hemodynamics are closely linked. The last section of the thesis investigates ocular rigidity alterations in astronauts before and after extended space flights. Analyzing data from 26 eyes of 13 astronauts, significant reductions in ocular rigidity were observed; similarly, intraocular pressure and ocular pulse amplitude were reduced post-mission. These findings reveal previously undocumented microgravity effects on the eye's mechanical properties, improving our comprehension of SANS. This thesis demonstrates the potential of V-OCT as a tool for the diagnosis and assessment of the progression of optic nerve conditions. By gaining a deeper understanding of the biomechanical and hemodynamic intricacies of the ONH, we lay the groundwork for future explorations that hold promise for both glaucoma patients and astronauts.

Objetivo: Comparar o efeito da terapia da fotocoagulação panretiniana (PFC) associada à injeção intravítrea de Ranibizumabe (RBZ) versus terapia isolada com PFC em pacientes com retinopatia diabética proliferativa (RDP) precoce, virgens de tratamento, com ou sem edema macular diabético (DME) durante 6 meses de acompanhamento. Projeto: Estudo prospectivo intervencionista, randomizado e controlado. Métodos: Sessenta olhos de 30 pacientes com RDP bilateral precoce foram randomizados para o grupo de estudo (GE) que foram tratados com PFC associado a duas injeções de RBZ intravítreo (0.5mg/0.05ml) ou para o grupo controle (GC) tratados apenas com PFC. Mudanças na acuidade visual (AV) corrigida, na sensibilidade ao contraste (SC) e na espessura foveal (EF) foram comparados no início, e nos 1, 3 e 6 meses após o tratamento. Resultados: No GE, a diferença na média da AV do baseline para o mês 6 teve um aumento significativo de + 3,4 letras (p = 0,006) e uma diminuição significativa na EF de - 47.6um (p < 0,001). No GC, a diferença na média da AV teve uma diminuição de - 3,4 letras (p = 0,04) e uma mudança na EF de -3.8 um (p = 0,96). Com relação ao teste de SC dentre os 28 olhos do GE, houve uma melhora no mês 6 em relação ao baseline nos ciclos: 1,5 (p < 0.001) e 3,0 ciclo (p=0.023). Dentre os 30 olhos do GC, não houve uma diferença estatística nos momentos estudados. Conclusão: A injeção intravítrea de RBZ associado com PFC pode ser um tratamento eficaz em olhos de pacientes com RDP precoce e EMD / Purpose: To compare the efficacy of therapy with panretinal photocoagulation (PRP) and intravitreal ranibizumab (RBZ) injection versus PRP alone in patients with treatment-naive bilateral non-high risk proliferative diabetic retinopathy (PDR) with and without diabetic macular edema (DME) with a 6-month follow-up. Design: Prospective, interventional, randomized controlled trial. Methods: Sixty eyes of 30 patients with bilateral non-high risk PDR were randomized either to the study group (SG) receiving PRP plus two intravitreal ranibizumab injections (0.5mg/0.05ml), the first one week before and the second four weeks after the PRP or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS) and central macular thickness (CMT) were compared at baseline and 1, 3 and 6 months after treatment. Results: Changes from baseline to 6 months showed in the SG an increased in the BCVA by + 3.4 letters (p= 0.006) with a decrease in CMT by - 47.6um (p < 0.001). In the CG, a decrease by - 3.4 letters (p = 0.04) and an decrease by -3.8um (p= 0.96). Regarding the CS in the SG, there was an improvement compared to baseline for the sixth month in the 1.5 (p < 0.001) and 3.0 cycles (p = 0.023). The CG did not show significant results from baseline to month 6. Conclusion: Intravitreal RBZ associated with PRP can be an effective treatment in eyes with non-high risk PDR and DME

Objetivo: Estudar as medidas de espessura da camada de fibras nervosas da retina(CFNR) peripapilar obtidas com as tomografias de coerência óptia (oCT) time domain (TD) e spectral domain (SD) em pacientes com perda assimétrica glaucomatosa de hemicampo visual, compará-las entre si e com aquelas de controles normais. Métodos: Trinta e seis pacientes com glaucoma primário de ângulo aberto e perda de campo visual em um hemicampo (afetado) e ausência de perda no hemicampo oposto (não afetado), e 36 controles pareados por idade tiveram o olho de estudo examinado com Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, Califoprnia, USA) e o 3DOCT-1000 (Topcdon, Tokyo, Japan). As medidas de espessura da CFNR peripapilar e a classificação normativa fornecida pelos aparelhos foram registrados para análise. A média aritmética dos valores do mapa total deviation em cada hemicampo (mean deviation do hemicampo) foi calculada para cada indivíduo. \"Ìndices de assimetria\" para o campo visual e para a CFNR foram calculados como a razão entre o mean deviation dos hemicampos afetado e não-afetado, e como razão entre a espessura da CFNR das hemirretinas afetada e não-afetada, respectivamente. As variáveis contínuas foram comparadas usando os testes de Mann-Whitney, Kruskal-Wallis ou Wilcoxon, quando apropriados. As variáveis categóricas foram comparadas usando o teste qui-quadrado de Pearson. O coeficiente de correlação de Spearman foi usado para testar as correlações entre as medidas de espessura da CFNR fornecidas pelos OCTs. A presença de afinamento da CFNR foi estabelecida com base nos dados normativos fornecidos pelos softwares dos OCTs. As espessuras de CFNR fora do intervalo de previsão de 95% para a mesma faixa etária foram consideradas anormais. Resultados: As medidas de CFNR corespondentes a hemicampos não-afetados [média (DP) 87,0 (17,1) um e 84,3 (20,2) um, para TD e SD-OCT, respectivamente] foram menores do que as dos controles [média (DP) 119,0 (122,2)um e 117,0 (17,7) um, para TD e SD-OCT, respectivamente, P < 0,001, para ambos]. O banco de dados normativo classificou como alterado 42% e 67% das hemirretinas correspondentes a hemicampos não-acometidos com TD e SD-OCT, respectivamente (P = 0,01). As medidas da CFNR foram consistentemente mais espessas com TD comparadas com SD-OCT. Os índices de assimetria da CFNR em pacientes com glaucoma foram semelhantes entre TD [média (DP) 0,76 (0,17)] e SD-OCT [média (DP) 0,79 (0,12), P = 0,89] e significantemente maiores do que o índice de assimetria do campo visual [média (DP) 0,36 (0,20), P < 0,001]. Conclusões: Os hemicampos normais de pacientes com glaucoma apresentaram CFNR mais fina do que de olhos saudáveis. As medidas da CFNR foram mais espessas com TD do que com SD-OCT, o qual por sua vez detectou anormalidades na espessura da CFNR mais frequentemente do que o TD-OCT / Objective: To study the peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained with time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) in glaucomatous patients with asymmetric visual hemifield loss, to compare themselves and with those obtained from normal controls. Methods : Thirty -six patients with primary open-angle glaucoma with visual primary open-angle glaucoma with visual field loss in one hemifield (affected ) and absence of loss in other (non-affected), and 36 age-matched healthy controls had the eye study imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, Califoprnia, USA) and 3D OCT-1000 (Topcon , Tokyo, Japan). Peripapillary RNFL thickness measurements and normative classification were recorded for analysis. Total deviation values were averaged for each hemifield (hemifield mean deviation) for ecch subject. Visual field and RNFL \"asymmetry indexes\" were calculated as the ratio between the mean deviation of affected versus non-affected hemifields and RNFL thickness between as affected versus non-affected hemiretinas, respectively. Continuous variables were compared using the Mann-Whitney, Kruskal-Wallis or Wilcoxon tests, when appropriate. Categorical variables were compared using the Pearson\'s chi-square test. The Spearman\'s rank correlation coefficient was used to test correlations between RNFL thickness measurements provided by both OCTs . The presence of RNFL thinning was establised based on normative data provided by the OCT\'s software. The RNFL thicknesses outside the prediction interval of 95% for the same age group were considered abnormal. Results: The RNFL measurements in non-affected hemifields [mean (SD 87.0 (17.1) e 84.3(20.2) um, for TD and SD-OCT, respectively] were thinner than those of normal controls [mean (SD) 119.0 (12.2) um and 117.0 (17.7) um, for TD and SD-OCT, respectively, P < 0.001 for both ] . The OCT normative database classified 42 % and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P =0.01). The RNFL measurements were consistently thicker with TD compared with SD -OCT. The RNFL thickness asymetry index in patients with glaucoma was similar with TD [ mean (SD) 0.76 ( 0.17 ) ] and SD-OCT [ mean (SD)0.79(0.12), P = 0,89] and significantly greater than the visual field asymmetry index [ mean (SD ) 0.36 (0.20 ), P < 0.001]. Conclusions: Normal hemifields of glaucoma patients had thinner RNFL measurements than healthy eyes, as measured by TD and SD-OCT. The RNFL measurements were thicker with TD than SD-OCT, SD-OCT detected abnormal RNFL more often than TD-OCT

Objetivos: Determinar o efeito da panfotocoagulação retiniana (PFC) nos parâmetros topográficos do disco óptico e na camada de fibras nervosas da retina (CFNR) peripapilar em pacientes com retinopatia diabética proliferativa (RDP). Métodos: Este é um estudo observacional prospectivo, de centro único. Trinta e oito olhos de 26 pacientes diabéticos foram submetidos a PFC para retinopatia diabética proliferativa. As estereofotografias (EFs) e os parâmetros do disco óptico foram avaliados usando o retinógrafo Visucam da Zeiss e a Tomografia de varredura a laser (TVL), respectivamente. A espessura da CFNR peripapilar foi medida por tomografia de coerência óptica (OCT) e polarimetria de varredura a laser (PVL). Todas as medições foram realizadas no início e 12 meses após a conclusão da PFC. Resultados: Trinta e oito olhos de 26 pacientes (15 mulheres) com média de idade de 53,7 anos (faixa etária de 26 a 74 anos) foram recrutados. Nenhuma diferença significativa foi encontrada entre a média horizontal e vertical para relação escavação/disco óptico (E/D) determinadas pelas EFs antes e após o tratamento com PFC (P = 0,461 e 0,839, respectivamente). Os valores globais dos parâmetros do disco óptico analisados com a TVL não mostraram nenhuma mudança significativa entre o baseline e 12 meses após o tratamento (área do disco, área da escavação, área da rima, volume da escavação, volume da rima, relação área da escavação/área do disco, relação linear do tamanho da escavação/disco, profundidade média da escavação, profundidade máxima da escavação, medida do formato da escavação, variação na altura do contorno, espessura média da CFNR e área transversal da CFNR). O OCT e o PVL não encontraram diferença significativa entre a CFNR peripapilar antes e após a PFC (P = 0,114 e P = 0,813, respectivamente). Conclusões: Nossos resultados sugerem que a PFC nos padrões realizados no presente estudo não causa significantes alterações morfológicas no disco óptico em pacientes diabéticos com RDP após um ano de acompanhamento / Purpose: To determine the effect of panretinal photocoagulation (PRP) on optic disc topographic parameters and peripapillary retinal nerve fiber layer (RNFL) in nonglaucomatous patients with proliferative diabetic retinopathy (PDR). Methods: This is a prospective, single center, observational study. Thirty-eight eyes of 26 diabetic patients underwent PRP for proliferative diabetic retinopathy. Stereoscopic disc photographs and optic nerve head (ONH) parameters were evaluated using the Zeiss fundus camera and the confocal scanning laser ophthalmoscopy (CSLO), respectively. The peripapillary RNFL thickness was measured by optical coherence tomography (OCT) and scanning laser polarimetry (SLP). All measurements were performed at baseline and 12 months after completion of PRP. Results: Thirty-eight eyes of 26 patients (15 female) with a mean age of 53.7 years (range 26 to 74 years) were recruited. No significant difference was found between mean horizontal and vertical cup to disc (C/D) ratio determined by stereoscopic disc photographs before and after PRP treatment (P=0.461 and 0.839, respectively). The global values of ONH parameters analyzed with the CSLO showed no significant change from baseline to 12 months (disc area, cup area, rim area, cup volume, rim volume, C/D area ratio, linear C/D ratio, mean cup depth, maximum cup depth, cup shape measure, height variation contour, mean retinal nerve fiber layer thickness and cross-sectional area). The OCT and SLP did not find significant difference between peripapillary RNFL before and after PRP (P=0.114 and P=0.813, respectively). Conclusion: Our results suggest that PRP as performed in this study does not cause significant morphological optic disk changes in diabetic PDR patients after one year of follow-up

Objetivo: Estudar as medidas de espessura da camada de fibras nervosas da retina(CFNR) peripapilar obtidas com as tomografias de coerência óptia (oCT) time domain (TD) e spectral domain (SD) em pacientes com perda assimétrica glaucomatosa de hemicampo visual, compará-las entre si e com aquelas de controles normais. Métodos: Trinta e seis pacientes com glaucoma primário de ângulo aberto e perda de campo visual em um hemicampo (afetado) e ausência de perda no hemicampo oposto (não afetado), e 36 controles pareados por idade tiveram o olho de estudo examinado com Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, Califoprnia, USA) e o 3DOCT-1000 (Topcdon, Tokyo, Japan). As medidas de espessura da CFNR peripapilar e a classificação normativa fornecida pelos aparelhos foram registrados para análise. A média aritmética dos valores do mapa total deviation em cada hemicampo (mean deviation do hemicampo) foi calculada para cada indivíduo. \"Ìndices de assimetria\" para o campo visual e para a CFNR foram calculados como a razão entre o mean deviation dos hemicampos afetado e não-afetado, e como razão entre a espessura da CFNR das hemirretinas afetada e não-afetada, respectivamente. As variáveis contínuas foram comparadas usando os testes de Mann-Whitney, Kruskal-Wallis ou Wilcoxon, quando apropriados. As variáveis categóricas foram comparadas usando o teste qui-quadrado de Pearson. O coeficiente de correlação de Spearman foi usado para testar as correlações entre as medidas de espessura da CFNR fornecidas pelos OCTs. A presença de afinamento da CFNR foi estabelecida com base nos dados normativos fornecidos pelos softwares dos OCTs. As espessuras de CFNR fora do intervalo de previsão de 95% para a mesma faixa etária foram consideradas anormais. Resultados: As medidas de CFNR corespondentes a hemicampos não-afetados [média (DP) 87,0 (17,1) um e 84,3 (20,2) um, para TD e SD-OCT, respectivamente] foram menores do que as dos controles [média (DP) 119,0 (122,2)um e 117,0 (17,7) um, para TD e SD-OCT, respectivamente, P < 0,001, para ambos]. O banco de dados normativo classificou como alterado 42% e 67% das hemirretinas correspondentes a hemicampos não-acometidos com TD e SD-OCT, respectivamente (P = 0,01). As medidas da CFNR foram consistentemente mais espessas com TD comparadas com SD-OCT. Os índices de assimetria da CFNR em pacientes com glaucoma foram semelhantes entre TD [média (DP) 0,76 (0,17)] e SD-OCT [média (DP) 0,79 (0,12), P = 0,89] e significantemente maiores do que o índice de assimetria do campo visual [média (DP) 0,36 (0,20), P < 0,001]. Conclusões: Os hemicampos normais de pacientes com glaucoma apresentaram CFNR mais fina do que de olhos saudáveis. As medidas da CFNR foram mais espessas com TD do que com SD-OCT, o qual por sua vez detectou anormalidades na espessura da CFNR mais frequentemente do que o TD-OCT / Objective: To study the peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained with time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) in glaucomatous patients with asymmetric visual hemifield loss, to compare themselves and with those obtained from normal controls. Methods : Thirty -six patients with primary open-angle glaucoma with visual primary open-angle glaucoma with visual field loss in one hemifield (affected ) and absence of loss in other (non-affected), and 36 age-matched healthy controls had the eye study imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, Califoprnia, USA) and 3D OCT-1000 (Topcon , Tokyo, Japan). Peripapillary RNFL thickness measurements and normative classification were recorded for analysis. Total deviation values were averaged for each hemifield (hemifield mean deviation) for ecch subject. Visual field and RNFL \"asymmetry indexes\" were calculated as the ratio between the mean deviation of affected versus non-affected hemifields and RNFL thickness between as affected versus non-affected hemiretinas, respectively. Continuous variables were compared using the Mann-Whitney, Kruskal-Wallis or Wilcoxon tests, when appropriate. Categorical variables were compared using the Pearson\'s chi-square test. The Spearman\'s rank correlation coefficient was used to test correlations between RNFL thickness measurements provided by both OCTs . The presence of RNFL thinning was establised based on normative data provided by the OCT\'s software. The RNFL thicknesses outside the prediction interval of 95% for the same age group were considered abnormal. Results: The RNFL measurements in non-affected hemifields [mean (SD 87.0 (17.1) e 84.3(20.2) um, for TD and SD-OCT, respectively] were thinner than those of normal controls [mean (SD) 119.0 (12.2) um and 117.0 (17.7) um, for TD and SD-OCT, respectively, P < 0.001 for both ] . The OCT normative database classified 42 % and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P =0.01). The RNFL measurements were consistently thicker with TD compared with SD -OCT. The RNFL thickness asymetry index in patients with glaucoma was similar with TD [ mean (SD) 0.76 ( 0.17 ) ] and SD-OCT [ mean (SD)0.79(0.12), P = 0,89] and significantly greater than the visual field asymmetry index [ mean (SD ) 0.36 (0.20 ), P < 0.001]. Conclusions: Normal hemifields of glaucoma patients had thinner RNFL measurements than healthy eyes, as measured by TD and SD-OCT. The RNFL measurements were thicker with TD than SD-OCT, SD-OCT detected abnormal RNFL more often than TD-OCT

Ce manuscrit de thèse présente l’étude des techniques de super-résolution latérale en nanoscopie optique, qui est une des nouvelles techniques d'imagerie haute résolution, aujourd'hui largement utilisée en biophysique et en imagerie médicale, pour imager et caractériser des nanostructures, tout en conservant les avantages de l'imagerie optique en champ lointain comme un vaste champ, la visualisation et l’analyse en temps réel…Un des défis futurs de la microscopie 3D super-résolue est d’éviter l’utilisation des marqueurs fluorescents. La microscopie interférométrique fait partie des techniques d’imagerie 3D sans marquage permettant la détection de nanostructures. Pour améliorer le pouvoir de détection de ce système optique, un premier protocole de traitement d’images a été développé et implémenté, permettant ainsi de révéler des structures initialement non mesurables. Puis, pour améliorer la résolution latérale du système, une nouvelle technique combinant l’interférométrie et le principe du nano-jet photonique a été développée permettant l’observation d’objets de taille inférieure à la limite de diffraction de l’instrument optique. / This manuscript presents the study of the lateral super-resolution techniques in optical nanoscopy, which is a new high-resolution imaging method now widely used in biophysics and medical imaging, to observe and measure nanostructures, with the advantages of far field optical imaging, such as a large field of view, visualization and analysis in real time…One of the future challenges of 3D super resolution microscopy is to avoid the use of fluorescent markers. Interferometric microscopy is a 3D label-free imaging technique enabling the detection of nanostructures. To improve the detection capability of this optical system, a first version of a protocol composed of image processing methods was developed and implemented, revealing structures initially unmeasurable. Then, to improve the lateral resolution of the system, a new technique combining interferometry and the principle of the photonic nano-jet has been developed, thus allowing the observation of objects of a size smaller than the diffraction limit of the optical instrument.