Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

Il est connu qu’on retrouve chez les femmes en post-ménopause un risque plus important de développer des maladies oculaires comparativement aux hommes du même groupe d’âge. Il semble que les changements hormonaux, et en particulier la baisse importante des niveaux d’estradiol, secondaires à la sénescence folliculaire constituent un facteur étiologique à long terme. Cela étant, il est légitime de se demander si les variations des niveaux d’hormones sexuelles endogènes peuvent également occasionner des effets à court terme sur les tissus de l’œil. Cette interrogation constitue d’ailleurs le motif principal de l’élaboration de la présente étude. Sachant qu’il se produit chez les femmes non ménopausées des variations continuelles des niveaux d’hormones sexuelles stéroïdiennes au cours de leur cycle menstruel, des femmes en âge de procréer ont été recrutées comme sujets d’étude. Dans un deuxième temps, afin de trouver le paramètre d’intérêt, on a effectué une revue de la documentation scientifique qui révèle un fait bien établi : les estrogènes favorisent la vasodilatation des vaisseaux sanguins par l’intermédiaire du monoxyde d’azote, et permettent, par le fait même, l’accroissement du débit sanguin tissulaire. Or, comment mesurer des variations de débit sanguin dans des tissus oculaires? Comme il est expliqué dans la discussion du présent mémoire, les variations d’oxygénation dans un organe dont le métabolisme est relativement stable sont le reflet de variations de débit sanguin. Grâce à une technique de mesure basée sur la spectroréflectométrie, il est possible de mesurer le taux d’oxyhémoglobine (HbO2) des lits capillaires du disque optique. En observant les variations du taux d’oxyhémoglobine au cours du cycle menstruel chez les sujets, on peut ainsi mesurer l’effet des variations hormonales cycliques sur l’irrigation des tissus oculaires. En somme, l’objectif de cette recherche est de mieux comprendre, en suivant le cycle menstruel des femmes, l’effet des hormones sexuelles endogènes sur l’oxygénation des lits capillaires du disque optique. Étant à la base du métabolisme de l’œil, l’apport en oxygène et en divers substrat véhiculés par la circulation sanguine est important au maintien de la santé oculaire. L’éclaircissement du lien entre les hormones et l’oxygénation de la rétine constituerait un avancement important, puisqu’il permettrait de comprendre pourquoi certaines atteintes oculaires, comme la cécité, touchent davantage les femmes. Les résultats de cette étude ont démontré que le taux d’oxyhémoglobine mesuré dans les lits capillaires du disque optique de l’œil ne subit pratiquement pas de variations significatives durant le cycle menstruel lorsqu’on considère les incertitudes des valeurs mesurées. Également, on observe une variabilité similaire des taux d’oxyhémoglobine mesurés chez les femmes en âge de procréation et chez les hommes du même groupe d’âge. Cela suggère que les changements hormonaux cycliques, qui ne se produisent que chez les femmes, n’occasionnent probablement pas de variation significative mesurable du taux d’oxyhémoglobine. Bref, malgré les effets possibles des estrogènes sur le diamètre artériolaire, il semble que les mécanismes locaux de régulation du débit sanguin tissulaire maintiennent un état d’équilibre propre au tissu irrigué et adapté aux besoins métaboliques locaux. / Postmenopausal women, when compared to men from the same age group, are more prone to develop ocular disease. It is thought that long term hormonal changes caused by ovarian senescence, and especially the drop in estradiol, are the etiological mechanism by which this phenomenon occurs. Whether variations in the levels of endogenous sexual hormones can produce short term effects in the tissues of the eye is less understood and, therefore, constitutes the main reason for carrying out the present study. Given that non menopausal women have repeated short term changes in the levels of sex steroid hormones during their menstrual cycle, we have recruited such women as study subjects. We also reviewed the scientific literature to establish what would be the parameter of interest and found a well characterised phenomenon: estrogens promote vasodilation by increasing nitrogen oxide production and thus promote a rise in blood flow. As to measuring variations in blood flow within the eye, it was explained in the discussion of the present memoir that changes in the oxygenation of an organ with a constant metabolism are induced by changes in the blood flow irrigating that organ. Using a method based on spectroreflectometry, it is possible to measure oxyhaemoglobin levels (HbO2) in the capillaries of the optic disc. By studying the variation of the HbO2 levels during the menstrual cycle, we can appreciate the effect of the cyclic hormonal changes on the ocular blood flow. The supply in oxygen and nutrients brought to an organ by its blood flow is essential for its metabolism. Therefore, the discovery of a correlation between sex hormone levels and the oxygenation of the retina would prove to be an important step towards understanding the higher frequency of certain ocular diseases in postmenopausal women, as compared to men of the same age group. The results of our study show that HbO2 levels in the capillary beds of the optic disc do not undergo statistically significant variations during the menstrual cycle. The same results were found, during a similar observational period, for male subjects used in the study as controls. These results suggest that cyclic variations in the levels of sex hormones, which occur only in nonmenaopausal women, do not induce significant changes in the oxygenation of the optic disc. In short, despite the possible effect of estrogens on the arteriolar diameter, it seems that local regulatory mechanisms of the blood flow maintain a tissue in a state of equilibrium that is adapted to its specific metabolic demand.

A ingestão de dieta deficiente em ferro pode causar alterações estruturais no Sistema Nervoso Central (SNC) bem como no nervo óptico por prejuízo no processo de mielinização. Essas alterações geradas pela anemia ferropriva pós-natal não são satisfatoriamente revertidas após a reposição de ferro. A estimulação tátil e o enriquecimento ambiental podem reduzir e/ou evitar os efeitos prejudiciais desta desnutrição sobre o SNC. O objetivo deste estudo foi avaliar estrutural e quantitativamente, o nervo óptico de ratos Wistar com anemia ferropriva submetidos à estimulação tátil e recuperação nutricional. Foram utilizados 4 grupos: Controle (C), Anêmico (A), Recuperado Não Estimulado (RN) e Recuperado Estimulado (E), compostos aleatoriamente por 1 rata mãe e 6 filhotes machos. Os grupos foram divididos de acordo com a variável dieta oferecida, pela quantidade de ferro/kg de dieta (com nível adequado em ferro (C), deficiente em ferro (A) e com recuperação do nível adequado de ferro (R)). O grupo C foi alimentado com dieta contendo 35 mg de ferro/kg de dieta, e o grupo A, com 4 mg de ferro/kg de dieta, e os grupos Recuperados (RN e RE), com 4 mg de ferro/kg de dieta do dia 0 ao 21º dia e, 35 mg de ferro/kg de dieta a partir do 22º dia. Os grupos Recuperados foram classificados de acordo com a variável estimulação: Estimulado (E), grupo submetido à estimulação tátil do dia 0 ao 32º dia, e Não Estimulado (N). Durante o período de amamentação, as ratas mães se alimentaram da dieta determinada para cada grupo, e no período pós lactação os filhotes receberam as mesmas dietas de suas respectivas mães. No 21º dia as ratas mães foram eutanasiadas e no 32º dia, todos os filhotes foram anestesiados e perfundidos via transcardíaca com uma solução de salina tamponada (PBS) 0,05M, pH 7,3, tendo seus nervos ópticos dissecados e os fragmentos selecionados refixados em tetróxido de ósmio a 1% em tampão fosfato 0,1 M, pH 7,3 e então processados para inclusão em araldite. Da área total da secção transversal do nervo óptico foram selecionadas 2 áreas que corresponderam aproximadamente 30% do nervo para a realização de análises morfológica e morfométrica. Na análise morfológica os animais do grupo RE mostraram um aspecto muito semelhante às características dos animais do grupo C, e com melhor aspecto em relação aos grupos A e RN, apresentando grande quantidade de fibras nervosas mielínicas, uniformemente distribuídas, bem agrupadas e compactadas, com espaço intersticial reduzido. Na análise morfométrica, em relação ao número de vasos sanguíneos, os fatores dieta, recuperação e estimulação não apresentaram interferência. Em relação ao número de astrócitos, a estimulação não interferiu, e em relação a dieta, o grupo A apresentou maior número que os grupos C e RN. Na avaliação do número de oligodendrócitos, em relação ao fator dieta, o grupo RN apresentou maior número que os grupos C e A, os quais não apresentaram diferença estatisticamente significante entre si. Já para o fator estimulação, o grupo RE apresentou menor número de oligodendrócitos quando comparado ao RN. Podemos concluir que: 1 - a dieta utilizada foi eficaz no desenvolvimento de anemia ferropriva leve nas ratas mães e severa nos filhotes; 2 - a associação das técnicas de estimulação tátil e recuperação nutricional resultou em uma reorganização estrutural do nervo óptico, semelhante ao grupo C e 3 - tal associação não interferiu no número de vasos sanguíneos, entretanto, resultou em uma normalização do número de astrócitos e de oligodendrócitos / Inadequate intake of dietary iron can cause structural changes in the Central Nervous System (CNS) and, thus, in the optic nerve with impaired myelination process. These changes generated by postnatal iron deficiency anemia are not satisfactorily reversed after replacement iron. The tactile stimulation and environmental enrichment can reduce and/or prevent the damaging effects of malnutrition on the CNS. The objective of this study was to evaluate structural and quantitatively the optic nerve of Wistar rats with iron deficiency anaemia submitted to tactile stimulation and nutritional recovery. We used 4 groups: Control (C), Anemic (A), Recovered Not Stimulated (RN) and Recovered Stimulated (R), randomly composed of 1 adult female rat and 6 male newborns. These groups were divided according to the variable diet provided, the amount of iron/kg in the diet (with appropriate levels of iron (C), deficient in iron (A) and with recovery of the appropriate level of iron (R)). The Control (C) group was fed with ration containing 35 mg iron/kg diet and the Anemic (A) group, with 4 mg iron/kg diet, and the Recovered groups (RN and RE) with 4 mg iron/kg diet from day 0 to day 21, and 35 mg iron/kg from day 22. The Recovered groups were classified according variable stimulation: Stimulated (E), group submitted to tactile stimulation from day 0 to day 32, and Not Stimulated (N). During the breastfeeding period, the mother rats fed the diet given to each group, and after lactation period the puppies received the same diets of their mothers. At day 21, the female rats were euthanized and at day 32 all juveniles were anesthetized and perfused transcardially with a buffered saline solution (PBS) 0,05M, pH 7,3, having their optic nerves dissected, and selected fragments were fixed in osmium tetroxide 1% and phosphate buffer 0,1 M, pH 7,3, and then processed for embedding in Araldite. Were selected 2 areas of the total area of optic nerve cross-section which approximately corresponded to 30% of the nerve to perform morphological and morphometric analysis. In the morphological analysis the optic nerve of the animals in RE group showed a very similar structural aspect to the characteristics of the optic nerves in group C, and looking better than in groups A and RN, with lot of myelinated nerve fibers well grouped and compacted and this organization was present uniformly across the nerve, resulting in reduced interstitial space. In the morphometric analysis, the number of blood vessels, dietary factors, recovery and stimulation showed no interference, since all groups showed no statistically significant difference. Regarding to the number of astrocytes, the stimulation did not influence it and, regarding to diet, the group A presented a higher number of cells than groups C and RN. In assessing the number of oligodendrocytes, in relation to diet factor, RN group had a greater number of oligodendrocytes that C and A groups, which showed no significant statistically difference between them. As for the stimulation factor, the RE group had fewer oligodendrocytes than the RN. With the results can be concluded that: 1- the used diet was effective in the development of mild iron deficiency anaemia in mothers and severe in young rats; 2- the association of tactile stimulation and nutritional recovery techniques resulted in a structural reorganization of the optic nerve, similar to C group and 3- this association did not affect the number of blood vessels, however it resulted in a normalization of the number of astrocytes and oligodendrocytes

A ingestão de dieta deficiente em ferro pode causar alterações estruturais no Sistema Nervoso Central (SNC) bem como no nervo óptico por prejuízo no processo de mielinização. Essas alterações geradas pela anemia ferropriva pós-natal não são satisfatoriamente revertidas após a reposição de ferro. A estimulação tátil e o enriquecimento ambiental podem reduzir e/ou evitar os efeitos prejudiciais desta desnutrição sobre o SNC. O objetivo deste estudo foi avaliar estrutural e quantitativamente, o nervo óptico de ratos Wistar com anemia ferropriva submetidos à estimulação tátil e recuperação nutricional. Foram utilizados 4 grupos: Controle (C), Anêmico (A), Recuperado Não Estimulado (RN) e Recuperado Estimulado (E), compostos aleatoriamente por 1 rata mãe e 6 filhotes machos. Os grupos foram divididos de acordo com a variável dieta oferecida, pela quantidade de ferro/kg de dieta (com nível adequado em ferro (C), deficiente em ferro (A) e com recuperação do nível adequado de ferro (R)). O grupo C foi alimentado com dieta contendo 35 mg de ferro/kg de dieta, e o grupo A, com 4 mg de ferro/kg de dieta, e os grupos Recuperados (RN e RE), com 4 mg de ferro/kg de dieta do dia 0 ao 21º dia e, 35 mg de ferro/kg de dieta a partir do 22º dia. Os grupos Recuperados foram classificados de acordo com a variável estimulação: Estimulado (E), grupo submetido à estimulação tátil do dia 0 ao 32º dia, e Não Estimulado (N). Durante o período de amamentação, as ratas mães se alimentaram da dieta determinada para cada grupo, e no período pós lactação os filhotes receberam as mesmas dietas de suas respectivas mães. No 21º dia as ratas mães foram eutanasiadas e no 32º dia, todos os filhotes foram anestesiados e perfundidos via transcardíaca com uma solução de salina tamponada (PBS) 0,05M, pH 7,3, tendo seus nervos ópticos dissecados e os fragmentos selecionados refixados em tetróxido de ósmio a 1% em tampão fosfato 0,1 M, pH 7,3 e então processados para inclusão em araldite. Da área total da secção transversal do nervo óptico foram selecionadas 2 áreas que corresponderam aproximadamente 30% do nervo para a realização de análises morfológica e morfométrica. Na análise morfológica os animais do grupo RE mostraram um aspecto muito semelhante às características dos animais do grupo C, e com melhor aspecto em relação aos grupos A e RN, apresentando grande quantidade de fibras nervosas mielínicas, uniformemente distribuídas, bem agrupadas e compactadas, com espaço intersticial reduzido. Na análise morfométrica, em relação ao número de vasos sanguíneos, os fatores dieta, recuperação e estimulação não apresentaram interferência. Em relação ao número de astrócitos, a estimulação não interferiu, e em relação a dieta, o grupo A apresentou maior número que os grupos C e RN. Na avaliação do número de oligodendrócitos, em relação ao fator dieta, o grupo RN apresentou maior número que os grupos C e A, os quais não apresentaram diferença estatisticamente significante entre si. Já para o fator estimulação, o grupo RE apresentou menor número de oligodendrócitos quando comparado ao RN. Podemos concluir que: 1 - a dieta utilizada foi eficaz no desenvolvimento de anemia ferropriva leve nas ratas mães e severa nos filhotes; 2 - a associação das técnicas de estimulação tátil e recuperação nutricional resultou em uma reorganização estrutural do nervo óptico, semelhante ao grupo C e 3 - tal associação não interferiu no número de vasos sanguíneos, entretanto, resultou em uma normalização do número de astrócitos e de oligodendrócitos / Inadequate intake of dietary iron can cause structural changes in the Central Nervous System (CNS) and, thus, in the optic nerve with impaired myelination process. These changes generated by postnatal iron deficiency anemia are not satisfactorily reversed after replacement iron. The tactile stimulation and environmental enrichment can reduce and/or prevent the damaging effects of malnutrition on the CNS. The objective of this study was to evaluate structural and quantitatively the optic nerve of Wistar rats with iron deficiency anaemia submitted to tactile stimulation and nutritional recovery. We used 4 groups: Control (C), Anemic (A), Recovered Not Stimulated (RN) and Recovered Stimulated (R), randomly composed of 1 adult female rat and 6 male newborns. These groups were divided according to the variable diet provided, the amount of iron/kg in the diet (with appropriate levels of iron (C), deficient in iron (A) and with recovery of the appropriate level of iron (R)). The Control (C) group was fed with ration containing 35 mg iron/kg diet and the Anemic (A) group, with 4 mg iron/kg diet, and the Recovered groups (RN and RE) with 4 mg iron/kg diet from day 0 to day 21, and 35 mg iron/kg from day 22. The Recovered groups were classified according variable stimulation: Stimulated (E), group submitted to tactile stimulation from day 0 to day 32, and Not Stimulated (N). During the breastfeeding period, the mother rats fed the diet given to each group, and after lactation period the puppies received the same diets of their mothers. At day 21, the female rats were euthanized and at day 32 all juveniles were anesthetized and perfused transcardially with a buffered saline solution (PBS) 0,05M, pH 7,3, having their optic nerves dissected, and selected fragments were fixed in osmium tetroxide 1% and phosphate buffer 0,1 M, pH 7,3, and then processed for embedding in Araldite. Were selected 2 areas of the total area of optic nerve cross-section which approximately corresponded to 30% of the nerve to perform morphological and morphometric analysis. In the morphological analysis the optic nerve of the animals in RE group showed a very similar structural aspect to the characteristics of the optic nerves in group C, and looking better than in groups A and RN, with lot of myelinated nerve fibers well grouped and compacted and this organization was present uniformly across the nerve, resulting in reduced interstitial space. In the morphometric analysis, the number of blood vessels, dietary factors, recovery and stimulation showed no interference, since all groups showed no statistically significant difference. Regarding to the number of astrocytes, the stimulation did not influence it and, regarding to diet, the group A presented a higher number of cells than groups C and RN. In assessing the number of oligodendrocytes, in relation to diet factor, RN group had a greater number of oligodendrocytes that C and A groups, which showed no significant statistically difference between them. As for the stimulation factor, the RE group had fewer oligodendrocytes than the RN. With the results can be concluded that: 1- the used diet was effective in the development of mild iron deficiency anaemia in mothers and severe in young rats; 2- the association of tactile stimulation and nutritional recovery techniques resulted in a structural reorganization of the optic nerve, similar to C group and 3- this association did not affect the number of blood vessels, however it resulted in a normalization of the number of astrocytes and oligodendrocytes

Introdução: O seio esfenoidal apresenta relações anatômicas extremamente importantes com estruturas neurovasculares. Estas podem apresentar diversas variações, tornando as suas relações com seio esfenoidal bastante complexas e potencialmente associadas a graves lesões durante sua abordagem. Objetivo: O objetivo deste estudo prospectivo foi descrever, através da dissecção endoscópica em cadáveres, os detalhes das variações anatômicas do SE, avaliando a concordância entre os lados e as diferenças dessas variações entre o gênero e a cor da pele. Casuística e Métodos: Quarenta e cinco cadáveres (90 fossas nasais) de ambos os sexos com idade no óbito entre 30 e 83 anos foram submetidos à dissecção endoscópica meticulosa do seio esfenoidal. A distância da parede anterior do SE à espinha nasal anterior; a localização e o formato do óstio do SE, o grau de pneumatização do SE, a presença de células de Onodi, a dominância entre os lados, a inserção de septo interssinusal e de cristas, a presença de proeminências e/ou deiscências da artéria carótida interna, do nervo óptico, do nervo maxilar e do nervo vidiano, assim como a presença de recessos óptico-carotídeo, pterigóide e lateral foram descritos. As prevalências foram comparadas entre o gênero e diferentes cor da pele. Também foi analisada a simetria entre os lados direito e esquerdo. Resultados: O óstio estava localizado medialmente à inserção póstero-inferior da concha superior em 85,6% das fossas nasais estudadas e em 50% apresentava-se com formato arredondado. A distância média do óstio do seio esfenoidal à espinha nasal anterior foi de 68 mm (+- 4,6mm) para ambos os lados. Não havia dominância dos lados direito ou esquerdo em 21 (46,7%) dos cadáveres. Em 17 cadáveres (37,8%) o seio esquerdo se apresentou mais pneumatizado e em 7 (15,6%), o seio esfenoidal direito apresentou dominância em relação ao esquerdo. O tipo selar foi o mais prevalente (53%) seguido do pré-selar (38%). O recesso mais prevalente foi o pterigóide (47,8%). As cristas estivaram presentes em 22,7% dos lados. O septo intersinusal se inseriu no trajeto da artéria carótida interna e do nervo óptico, respectivamente, em 16,7% e 2,2%. A artéria carótida interna esteve proeminente em 48,9% e deiscente em 31,1% das fossas estudadas. O nervo óptico estava proeminente e deiscente em 35,6% e 8,9%, respectivamente. O nervo vidiano foi a estrutura com proeminência mais prevalente (50%). O nervo maxilar esteve deiscente em 5,6% dos lados estudados. Uma célula de Onodi esteve presente em 23 (25,6%) dos lados dissecados. A análise da simetria mostrou concordância perfeita com relação ao grau de pneumatização e se apresentou bastante variável de acordo com a estrutura estudada. Cadáveres do sexo feminino apresentaram de forma estatisticamente significante maior prevalência de deiscência de carótida interna (p=0,002) e do nervo maxilar (p=0,02), assim como proeminência do nervo óptico (p < 0,001). Conclusão: Os dados demonstram a complexa anatomia interna do seio esfenoidal, e o conhecimento desta anatomia é de grande importância para evitar as potenciais complicações cirúrgicas nesta região. / Introduction: There are extremely important anatomic relationships between the sphenoid sinus (SS) and neurovascular structures. These structures may have several anatomic variations, which makes their relationship with the sphenoid sinus complex and carries risks of severe injuries during surgery. Objective: This prospective study used endoscopic cadaver dissection to describe details of SS anatomic variations and to evaluate agreement between sides and differences between sexes and ethnic groups. Casuistic and Methods: Fourty-five cadavers (90 nasal fossae) of both sexes ageing between 30 and 83 years underwent careful dissection of the sphenoid sinus. Distance from the SS anterior wall to the anterior nasal spine, the position and shape of the SS, the degree of SS pneumatization, the presence of Onodi cells, the dominance between sides, the insertion of the intersinus septum and crests, the presence of dehiscence and protrusions of the internal carotid artery (ICA), optic nerve (ON), maxillary and vidian nerves, and the presence of optic-carotid, pterygoid and lateral recesses were described. Data were analyzed according to sex, skin color and symmetry between nasal fossae of each cadaver. Results: Ostia were located medially to the posteroinferior insertion of the superior turbinate in 85.6% of the nasal fossae, and were circular in 50% of the cases. The mean distance from the ostium to the anterior nasal spine was 68 mm (+- 4.6 mm) for both sides. No dominance of right or left side was found in 21 (46.7%) of the cadavers. In 17 cadavers (37.8%), the left sinus was more pneumatized, and in 7 (15.6%), the right sphenoid sinus showed dominance over the left sinus. The sellar type was the most prevalent (53%), followed by the presellar type (38%). Pterygoid recesses were the most prevalent (47.8%). Crests were found in 22.7% of the sides. The intersinus septum was inserted on the course of the internal carotid artery and optic nerve in 16.7% and 2.2 % of the cases. ICA protrusions were found in 48.9% of the cases, and dehiscence in 31.1% of the fossae under study. Dehiscence and protrusion of the ON were found in 35.6% and 8.9% of the cases. The vidian nerve was the structure with the most prevalent protrusion (50%). Dehiscence over the maxillary nerve was found in 5.6% of the sides. Onodi cells were found in 23 (25.6%) of the dissected sides. The analysis of symmetry revealed perfect agreement of the degree of pneumatization and was greatly variable depending on the structure analyzed. Female cadavers had a statistically greater prevalence of dehiscence over the internal carotid artery (p = 0.002) and over the maxillary nerve (p = 0.02), as well as greater prevalence of optic nerve protrusion (p < 0.001). Conclusion: Our data showed that the SS internal anatomy is complex, and its knowledge is essential during surgical approaches to the sphenoid sinus.

Introdução: O seio esfenoidal apresenta relações anatômicas extremamente importantes com estruturas neurovasculares. Estas podem apresentar diversas variações, tornando as suas relações com seio esfenoidal bastante complexas e potencialmente associadas a graves lesões durante sua abordagem. Objetivo: O objetivo deste estudo prospectivo foi descrever, através da dissecção endoscópica em cadáveres, os detalhes das variações anatômicas do SE, avaliando a concordância entre os lados e as diferenças dessas variações entre o gênero e a cor da pele. Casuística e Métodos: Quarenta e cinco cadáveres (90 fossas nasais) de ambos os sexos com idade no óbito entre 30 e 83 anos foram submetidos à dissecção endoscópica meticulosa do seio esfenoidal. A distância da parede anterior do SE à espinha nasal anterior; a localização e o formato do óstio do SE, o grau de pneumatização do SE, a presença de células de Onodi, a dominância entre os lados, a inserção de septo interssinusal e de cristas, a presença de proeminências e/ou deiscências da artéria carótida interna, do nervo óptico, do nervo maxilar e do nervo vidiano, assim como a presença de recessos óptico-carotídeo, pterigóide e lateral foram descritos. As prevalências foram comparadas entre o gênero e diferentes cor da pele. Também foi analisada a simetria entre os lados direito e esquerdo. Resultados: O óstio estava localizado medialmente à inserção póstero-inferior da concha superior em 85,6% das fossas nasais estudadas e em 50% apresentava-se com formato arredondado. A distância média do óstio do seio esfenoidal à espinha nasal anterior foi de 68 mm (+- 4,6mm) para ambos os lados. Não havia dominância dos lados direito ou esquerdo em 21 (46,7%) dos cadáveres. Em 17 cadáveres (37,8%) o seio esquerdo se apresentou mais pneumatizado e em 7 (15,6%), o seio esfenoidal direito apresentou dominância em relação ao esquerdo. O tipo selar foi o mais prevalente (53%) seguido do pré-selar (38%). O recesso mais prevalente foi o pterigóide (47,8%). As cristas estivaram presentes em 22,7% dos lados. O septo intersinusal se inseriu no trajeto da artéria carótida interna e do nervo óptico, respectivamente, em 16,7% e 2,2%. A artéria carótida interna esteve proeminente em 48,9% e deiscente em 31,1% das fossas estudadas. O nervo óptico estava proeminente e deiscente em 35,6% e 8,9%, respectivamente. O nervo vidiano foi a estrutura com proeminência mais prevalente (50%). O nervo maxilar esteve deiscente em 5,6% dos lados estudados. Uma célula de Onodi esteve presente em 23 (25,6%) dos lados dissecados. A análise da simetria mostrou concordância perfeita com relação ao grau de pneumatização e se apresentou bastante variável de acordo com a estrutura estudada. Cadáveres do sexo feminino apresentaram de forma estatisticamente significante maior prevalência de deiscência de carótida interna (p=0,002) e do nervo maxilar (p=0,02), assim como proeminência do nervo óptico (p < 0,001). Conclusão: Os dados demonstram a complexa anatomia interna do seio esfenoidal, e o conhecimento desta anatomia é de grande importância para evitar as potenciais complicações cirúrgicas nesta região. / Introduction: There are extremely important anatomic relationships between the sphenoid sinus (SS) and neurovascular structures. These structures may have several anatomic variations, which makes their relationship with the sphenoid sinus complex and carries risks of severe injuries during surgery. Objective: This prospective study used endoscopic cadaver dissection to describe details of SS anatomic variations and to evaluate agreement between sides and differences between sexes and ethnic groups. Casuistic and Methods: Fourty-five cadavers (90 nasal fossae) of both sexes ageing between 30 and 83 years underwent careful dissection of the sphenoid sinus. Distance from the SS anterior wall to the anterior nasal spine, the position and shape of the SS, the degree of SS pneumatization, the presence of Onodi cells, the dominance between sides, the insertion of the intersinus septum and crests, the presence of dehiscence and protrusions of the internal carotid artery (ICA), optic nerve (ON), maxillary and vidian nerves, and the presence of optic-carotid, pterygoid and lateral recesses were described. Data were analyzed according to sex, skin color and symmetry between nasal fossae of each cadaver. Results: Ostia were located medially to the posteroinferior insertion of the superior turbinate in 85.6% of the nasal fossae, and were circular in 50% of the cases. The mean distance from the ostium to the anterior nasal spine was 68 mm (+- 4.6 mm) for both sides. No dominance of right or left side was found in 21 (46.7%) of the cadavers. In 17 cadavers (37.8%), the left sinus was more pneumatized, and in 7 (15.6%), the right sphenoid sinus showed dominance over the left sinus. The sellar type was the most prevalent (53%), followed by the presellar type (38%). Pterygoid recesses were the most prevalent (47.8%). Crests were found in 22.7% of the sides. The intersinus septum was inserted on the course of the internal carotid artery and optic nerve in 16.7% and 2.2 % of the cases. ICA protrusions were found in 48.9% of the cases, and dehiscence in 31.1% of the fossae under study. Dehiscence and protrusion of the ON were found in 35.6% and 8.9% of the cases. The vidian nerve was the structure with the most prevalent protrusion (50%). Dehiscence over the maxillary nerve was found in 5.6% of the sides. Onodi cells were found in 23 (25.6%) of the dissected sides. The analysis of symmetry revealed perfect agreement of the degree of pneumatization and was greatly variable depending on the structure analyzed. Female cadavers had a statistically greater prevalence of dehiscence over the internal carotid artery (p = 0.002) and over the maxillary nerve (p = 0.02), as well as greater prevalence of optic nerve protrusion (p < 0.001). Conclusion: Our data showed that the SS internal anatomy is complex, and its knowledge is essential during surgical approaches to the sphenoid sinus.

In recent years, probabilistic models have become fundamental techniques in machine learning. They are successfully applied in various engineering problems, such as robotics, biometrics, brain-computer interfaces or artificial vision, and will gain in importance in the near future. This work deals with the difficult, but common situation where the data is, either very noisy, or scarce compared to the complexity of the process to model. We focus on latent variable models, which can be formalized as probabilistic graphical models and learned by the expectation-maximization algorithm or its variants (e.g., variational Bayes).<br> After having carefully studied a non-exhaustive list of multivariate kernel density estimators, we established that in most applications locally adaptive estimators should be preferred. Unfortunately, these methods are usually sensitive to outliers and have often too many parameters to set. Therefore, we focus on finite mixture models, which do not suffer from these drawbacks provided some structural modifications.<br> Two questions are central in this dissertation: (i) how to make mixture models robust to noise, i.e. deal efficiently with outliers, and (ii) how to exploit side-channel information, i.e. additional information intrinsic to the data. In order to tackle the first question, we extent the training algorithms of the popular Gaussian mixture models to the Student-t mixture models. the Student-t distribution can be viewed as a heavy-tailed alternative to the Gaussian distribution, the robustness being tuned by an extra parameter, the degrees of freedom. Furthermore, we introduce a new variational Bayesian algorithm for learning Bayesian Student-t mixture models. This algorithm leads to very robust density estimators and clustering. To address the second question, we introduce manifold constrained mixture models. This new technique exploits the information that the data is living on a manifold of lower dimension than the dimension of the feature space. Taking the implicit geometrical data arrangement into account results in better generalization on unseen data.<br> Finally, we show that the latent variable framework used for learning mixture models can be extended to construct probabilistic regularization networks, such as the Relevance Vector Machines. Subsequently, we make use of these methods in the context of an optic nerve visual prosthesis to restore partial vision to blind people of whom the optic nerve is still functional. Although visual sensations can be induced electrically in the blind's visual field, the coding scheme of the visual information along the visual pathways is poorly known. Therefore, we use probabilistic models to link the stimulation parameters to the features of the visual perceptions. Both black-box and grey-box models are considered. The grey-box models take advantage of the known neurophysiological information and are more instructive to medical doctors and psychologists.<br>

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

Il est connu qu’on retrouve chez les femmes en post-ménopause un risque plus important de développer des maladies oculaires comparativement aux hommes du même groupe d’âge. Il semble que les changements hormonaux, et en particulier la baisse importante des niveaux d’estradiol, secondaires à la sénescence folliculaire constituent un facteur étiologique à long terme. Cela étant, il est légitime de se demander si les variations des niveaux d’hormones sexuelles endogènes peuvent également occasionner des effets à court terme sur les tissus de l’œil. Cette interrogation constitue d’ailleurs le motif principal de l’élaboration de la présente étude. Sachant qu’il se produit chez les femmes non ménopausées des variations continuelles des niveaux d’hormones sexuelles stéroïdiennes au cours de leur cycle menstruel, des femmes en âge de procréer ont été recrutées comme sujets d’étude. Dans un deuxième temps, afin de trouver le paramètre d’intérêt, on a effectué une revue de la documentation scientifique qui révèle un fait bien établi : les estrogènes favorisent la vasodilatation des vaisseaux sanguins par l’intermédiaire du monoxyde d’azote, et permettent, par le fait même, l’accroissement du débit sanguin tissulaire. Or, comment mesurer des variations de débit sanguin dans des tissus oculaires? Comme il est expliqué dans la discussion du présent mémoire, les variations d’oxygénation dans un organe dont le métabolisme est relativement stable sont le reflet de variations de débit sanguin. Grâce à une technique de mesure basée sur la spectroréflectométrie, il est possible de mesurer le taux d’oxyhémoglobine (HbO2) des lits capillaires du disque optique. En observant les variations du taux d’oxyhémoglobine au cours du cycle menstruel chez les sujets, on peut ainsi mesurer l’effet des variations hormonales cycliques sur l’irrigation des tissus oculaires. En somme, l’objectif de cette recherche est de mieux comprendre, en suivant le cycle menstruel des femmes, l’effet des hormones sexuelles endogènes sur l’oxygénation des lits capillaires du disque optique. Étant à la base du métabolisme de l’œil, l’apport en oxygène et en divers substrat véhiculés par la circulation sanguine est important au maintien de la santé oculaire. L’éclaircissement du lien entre les hormones et l’oxygénation de la rétine constituerait un avancement important, puisqu’il permettrait de comprendre pourquoi certaines atteintes oculaires, comme la cécité, touchent davantage les femmes. Les résultats de cette étude ont démontré que le taux d’oxyhémoglobine mesuré dans les lits capillaires du disque optique de l’œil ne subit pratiquement pas de variations significatives durant le cycle menstruel lorsqu’on considère les incertitudes des valeurs mesurées. Également, on observe une variabilité similaire des taux d’oxyhémoglobine mesurés chez les femmes en âge de procréation et chez les hommes du même groupe d’âge. Cela suggère que les changements hormonaux cycliques, qui ne se produisent que chez les femmes, n’occasionnent probablement pas de variation significative mesurable du taux d’oxyhémoglobine. Bref, malgré les effets possibles des estrogènes sur le diamètre artériolaire, il semble que les mécanismes locaux de régulation du débit sanguin tissulaire maintiennent un état d’équilibre propre au tissu irrigué et adapté aux besoins métaboliques locaux. / Postmenopausal women, when compared to men from the same age group, are more prone to develop ocular disease. It is thought that long term hormonal changes caused by ovarian senescence, and especially the drop in estradiol, are the etiological mechanism by which this phenomenon occurs. Whether variations in the levels of endogenous sexual hormones can produce short term effects in the tissues of the eye is less understood and, therefore, constitutes the main reason for carrying out the present study. Given that non menopausal women have repeated short term changes in the levels of sex steroid hormones during their menstrual cycle, we have recruited such women as study subjects. We also reviewed the scientific literature to establish what would be the parameter of interest and found a well characterised phenomenon: estrogens promote vasodilation by increasing nitrogen oxide production and thus promote a rise in blood flow. As to measuring variations in blood flow within the eye, it was explained in the discussion of the present memoir that changes in the oxygenation of an organ with a constant metabolism are induced by changes in the blood flow irrigating that organ. Using a method based on spectroreflectometry, it is possible to measure oxyhaemoglobin levels (HbO2) in the capillaries of the optic disc. By studying the variation of the HbO2 levels during the menstrual cycle, we can appreciate the effect of the cyclic hormonal changes on the ocular blood flow. The supply in oxygen and nutrients brought to an organ by its blood flow is essential for its metabolism. Therefore, the discovery of a correlation between sex hormone levels and the oxygenation of the retina would prove to be an important step towards understanding the higher frequency of certain ocular diseases in postmenopausal women, as compared to men of the same age group. The results of our study show that HbO2 levels in the capillary beds of the optic disc do not undergo statistically significant variations during the menstrual cycle. The same results were found, during a similar observational period, for male subjects used in the study as controls. These results suggest that cyclic variations in the levels of sex hormones, which occur only in nonmenaopausal women, do not induce significant changes in the oxygenation of the optic disc. In short, despite the possible effect of estrogens on the arteriolar diameter, it seems that local regulatory mechanisms of the blood flow maintain a tissue in a state of equilibrium that is adapted to its specific metabolic demand.

Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à la survenue de neuropathies optiques, en particulier la neuropathie optique ischémique antérieure aigue non artéritique (NOIAA-NA). Parmi les mécanismes d’apparition de cette neuropathie et potentiellement associés au SAOS, la dysrégulation et l’inflammation vasculaires pourraient jouer un rôle. Il n’existe aucune donnée dans la littérature sur l’effet de l’hypoxie intermittente (HI) chronique sur la fonction vasculaire de l’œil.Le but de ce travail était de développer des techniques d’évaluation de la fonction vasculaire oculaire chez le rat et de les appliquer à l’étude des conséquences vasculaires oculaires de l’HI. Ainsi, deux approches complémentaires ont été développées : 1) un prototype de fluxmètre laser Doppler (LDF) adapté au rongeur pour l’évaluation in vivo de la perfusion sanguine rétinienne et de la tête du nerf optique (TNO) et 2) le modèle d’étude de l’artère ophtalmique (AO) du rat par myographie vasculaire, in vitro.La mise au point du LDF chez le rat sain a permis de valider la pertinence du signal provenant des artères rétiniennes. A l’inverse, nos données invalident l’intérêt de la mesure au niveau de la TNO. En réponse à l’inhalation d’oxygène pur, nous observons une diminution de 17,0 ± 13,7 % de la vélocité artérielle rétinienne (VelART). Nous n’observons pas de variation significative de VelART lors d’injection intra-carotidienne d’endothéline 1 (ET-1) malgré une forte vasoconstriction des vaisseaux rétiniens. Les perspectives consistent à associer une caméra de haute résolution à un système bidirectionnel de LDF. L’étude de la réactivité de l’AO par myographie chez le rat soumis à 14 jours d’HI a mis en évidence une augmentation de la contraction à l’ET-1, associée à une augmentation de la réponse médiée par les récepteurs de type A (ETRA)et à une surexpression des ETRA au sein de l’AO. La relaxation NO-dépendante était diminuée chez le rat HI, et associée à un effet prédominant des produits vasoconstricteurs du cytochrome P450. Ces réponses étaient associées à une augmentation de la présence d’anions superoxyde dans la paroi de l’AO. Des études complémentaires sont nécessaires pour explorer les mécanismes à l’origine des ces altérations vasculaires, en particulier le rôle du stress oxydant. / Obstructive sleep apnea (OSA) has recently been associated with the occurrence of optic neuropathies, especially acute non-arteritic anterior ischemic optic neuropathy (NAION). Among the mechanisms of NAION onset potentially associated with OSA, vascular dysregulation and inflammation may play a role. There is still no data on the effect of chronic intermittent hypoxia (IH) on vascular function of the eye. The purpose of this work was to develop techniques for assessing rat ocular vascular function and apply them to the study of the ocular vascular consequences of IH. Thus, two complementary models have been developed: 1) a laser Doppler flowmeter (LDF) prototype adapted for rodents, to evaluate in vivo retinal and optic nerve head (ONH) blood perfusion and 2) in vitro model of rat ophthalmic artery (OA) study by myography. Preliminary work on healthy rat enabled us to validate the relevance of retinal arteries LDF signal, but not that of the ONH. Retinal blood velocity (VelART) dropped by 17.0 ± 13.7% in response to pure oxygen inhalation. We did not observe any significant change in VelART signal after intracarotidian endothelin 1 (ET -1) injection, despite strong vasoconstriction of retinal vessels. OA reactivity study by myography in rats exposed to a 14-day IH showed increased contraction to ET-1, associated with an increased endothelin receptor A-mediated (ETRA) response and ETRA overexpression within the AO. NO-dependent relaxation is reduced in IH rats, and associated with a shift towards vasoconstrictive effects of cytochrome P450 products. These responses were associated with an increase in superoxide anions in the OA wall. Further studies are needed to explore the underlying mechanisms of these vascular changes, particularly the role of oxidative stress. Understanding of the LDF signal is partial and should be further explored to permit application to the study of IH rat.