Spectral-domain optical coherence tomography appearance of a retinal nematode.

A 65-year-old man presented with decreased visual acuity in his left eye of 10 days' duration. Ocular examination revealed visual acuity of 20/200 in the left eye caused by a visible retinal nematode (roundworm) located close to the fovea. Spectral-domain optical coherence tomography imaging showed the nematode in the retinal nerve fiber layer. The patient was followed up without treatment, and the nematode disappeared spontaneously after 5 weeks. Visual acuity in the affected eye improved to 20/25.

Histological and histomorphometric evaluation of the retina of mice infected with Schistosoma mansoni in its hepatosplenic form.

PURPOSE: To evaluate retinal manifestations of Schistosomiasis mansoni in its hepatosplenic form in mice. METHODS: It was performed a study with two groups of mice; one of them was infected with 40 cercariae of Schistosoma mansoni. After 120 days of the infection, the eyes underwent a retinal microscopy study. The histology findings were reported. Histomorphometric analysis was also performed, including: thickness measurement of the retinal layer and the number of the ganglion layer cells. RESULTS: In one case a retinal granuloma was found. The analysis of the other histological sections demonstrated normal architecture of the retina. The mean thickness of the retinal layer between the two groups were similar (41.81+/-6.09 microm versus 38.48+/-8.58 microm - p=0.279); as well as the mean number of the ganglion layer cells (20.93+/-4.88 versus 20.64+/-4.10 - p=0.864). Disorganization of the retinal layers was not identified and the histomorphometric analysis revealed no significant difference between the two groups. CONCLUSION: The absence of findings in this study does not exclude that hemodynamic and autoregulation changes associated with hepatosplenic schistosomiasis could be correlated to retinal manifestations. It is necessary that other methods with a high parasite infection should be performed.

Histological and histomorphometric evaluation of the retina of mice infected with Schistosoma mansoni in its hepatosplenic form / Avaliação histológica e histomorfométrica da retina de camundongos infectados pelo Schistosoma mansoni na forma hepatoesplênica

PURPOSE: To evaluate retinal manifestations of Schistosomiasis mansoni in its hepatosplenic form in mice. METHODS: It was performed a study with two groups of mice; one of them was infected with 40 cercariae of Schistosoma mansoni. After 120 days of the infection, the eyes underwent a retinal microscopy study. The histology findings were reported. Histomorphometric analysis was also performed, including: thickness measurement of the retinal layer and the number of the ganglion layer cells. RESULTS: In one case a retinal granuloma was found. The analysis of the other histological sections demonstrated normal architecture of the retina. The mean thickness of the retinal layer between the two groups were similar (41.81±6.09µm versus 38.48±8.58µm - p=0.279); as well as the mean number of the ganglion layer cells (20.93±4.88 versus 20.64±4.10 - p=0.864). Disorganization of the retinal layers was not identified and the histomorphometric analysis revealed no significant difference between the two groups. CONCLUSION: The absence of findings in this study does not exclude that hemodynamic and autoregulation changes associated with hepatosplenic schistosomiasis could be correlated to retinal manifestations. It is necessary that other methods with a high parasite infection should be performed.

OBJETIVO: Avaliar as repercussões da esquistossomose mansônica na forma hepatoesplênica na retina de camundongos. MÉTODOS: Foi realizado estudo com dois grupos de camundongos, sendo um infectado com 40 cercárias do Schistosoma mansoni. Decorridos 120 dias da infecção, os olhos foram submetidos à análise microscópica da retina com descrição dos achados histológicos e realizada análise histomorfométrica com mensuração da espessura de segmento retiniano e do número de células da camada ganglionar. RESULTADOS: Em um caso foi encontrado um granuloma retiniano. Já a análise dos demais cortes histológicos demonstrou uma arquitetura normal da retina. A média da espessura dos segmentos retinianos entre os grupos de camundongos, controle e infectado, foi similar (41,81±6,09µm versus 38,48±8,58µm - p=0,279) assim como a média do número de células da camada ganglionar (20,93±4,88 versus 20,64±4,10 - p=0,864). : A estrutura da retina encontrava-se íntegra e a análise histomorfométrica não revelava diferença significante entre os dois grupos. CONCLUSÃO: A ausência de alterações, neste estudo, não afasta a possibilidade de que desequilíbrios hemodinâmicos e no mecanismo de autoregulação, em portadores da forma hepatoesplênica da esquistossomose, possam acarretar dano retiniano. Demanda, entretanto, que outras metodologias com indução da infecção com uma maior carga parasitária sejam realizadas.

[Neuronal injury in multiple sclerosis]. / Compromiso neuronal en esclerosis múltiple.

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment.

Compromiso neuronal en esclerosis multiple / Neuronal injury in multiple sclerosis

La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment

Compromiso neuronal en esclerosis multiple / Neuronal injury in multiple sclerosis

La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral (AU)

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment (AU)

Compromiso neuronal en esclerosis multiple / Neuronal injury in multiple sclerosis

La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral (AU)

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment (AU)

Optical coherence tomography machine learning classifiers for glaucoma detection: a preliminary study.

PURPOSE: Machine-learning classifiers are trained computerized systems with the ability to detect the relationship between multiple input parameters and a diagnosis. The present study investigated whether the use of machine-learning classifiers improves optical coherence tomography (OCT) glaucoma detection. METHODS: Forty-seven patients with glaucoma (47 eyes) and 42 healthy subjects (42 eyes) were included in this cross-sectional study. Of the glaucoma patients, 27 had early disease (visual field mean deviation [MD] > or = -6 dB) and 20 had advanced glaucoma (MD < -6 dB). Machine-learning classifiers were trained to discriminate between glaucomatous and healthy eyes using parameters derived from OCT output. The classifiers were trained with all 38 parameters as well as with only 8 parameters that correlated best with the visual field MD. Five classifiers were tested: linear discriminant analysis, support vector machine, recursive partitioning and regression tree, generalized linear model, and generalized additive model. For the last two classifiers, a backward feature selection was used to find the minimal number of parameters that resulted in the best and most simple prediction. The cross-validated receiver operating characteristic (ROC) curve and accuracies were calculated. RESULTS: The largest area under the ROC curve (AROC) for glaucoma detection was achieved with the support vector machine using eight parameters (0.981). The sensitivity at 80% and 95% specificity was 97.9% and 92.5%, respectively. This classifier also performed best when judged by cross-validated accuracy (0.966). The best classification between early glaucoma and advanced glaucoma was obtained with the generalized additive model using only three parameters (AROC = 0.854). CONCLUSIONS: Automated machine classifiers of OCT data might be useful for enhancing the utility of this technology for detecting glaucomatous abnormality.

Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic nerves during fatal murine cerebral malaria.

We examined the optic nerve, as an analogous tissue to brain white matter, to assess possible relationships between changes in the blood-nerve barrier, axonal integrity, and astrocyte morphology in the central nervous system during fatal murine cerebral malaria (FMCM). In the FMCM model, namely, CBA mice infected with Plasmodium berghei ANKA, neurological symptoms begin around day 5 post-inoculation (p.i.) and mice become increasingly ill by day 7 p.i., at which time they lapse into coma and die. Using intravascular perfusion with horseradish peroxidase combined with light and electron microscopy, and GFAP immunohistochemistry, the optic nerves in malaria-infected mice were found to display i) breakdown of the blood-nerve barrier, detectable as early as day 3 p.i. (about 2 days before the onset of neurological symptoms) increasing to peak severity by day 7 p.i.; ii) monocytosis, vascular congestion, and monocyte adherence to the endothelium in the microvasculature during the later stages of the disease process; iii) an increased incidence of patchy axonal demyelination and degeneration, mostly associated with vascular changes and astrogliosis, beginning at day 5 p.i. and more evident by day 7 p.i.; and iv) an increased intensity of GFAP immunostaining, detectable from day 3 p.i. and peaking at day 7 p.i. These optic nerve changes were always seen in the infected individuals, though they varied in intensity. The temporal and anatomical coincidence between the compromised blood-nerve barrier, monocyte adherence to the vascular endothelium, astrocyte changes, neuronal degeneration, and demyelination in the optic nerve in FMCM suggests that these factors are mechanistically inter-related. These findings are consistent with the proposed immunopathological nature of FMCM and provide further evidence for the pivotal role of the CNS microvasculature in the disease process. This is the first investigation of involvement of the optic nerve in FMCM and the first demonstration, to our knowledge, of loss of axonal viability in this condition in any CNS tissue. The observed demyelination is consistent with reports by other workers on such changes in the brain in human cerebral malaria.

The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part I: The localization and morphology of Toxoplasma cysts in the retina.

This study describes the ultrastructural characteristics of retinal parasitization by Toxoplasma gondii in a congenital mouse model. Forty-two eyes from infected mice, 18-22-weeks-old, and 24 control eyes were initially studied by light microscopy of semithin sections. Twenty-six eyes from infected animals and six from the controls were further investigated by transmission electron microscopy. A total of 13 Toxoplasma cysts was found in samples of the retinas of six eyes from five infected animals. These were located in the inner retina, particularly the ganglion-cell layer, but in no other ocular tissue. The cyst wall interdigitated with the host cell which in most cases was probably glial in origin (Müller cell). Two cysts showed evidence of parasitization of neural cells. The individual Toxoplasma cystozoites demonstrated characteristic ultrastructural features. There was no evidence of morphological changes indicative of toxicity to surrounding retinal tissues, and the associated inflammatory cell reaction (described in Dutton, McMenamin, Hay and Cameron, 1986b) was remote from the parasite. There was no morphological evidence of rupture or degeneration of cysts. No free parasites (endozoites) or pseudocysts were observed.