This document is a critical synopsis of prior work by Michael Dwyer submitted in support of a PhD by published work. The selected work is focused on the application of quantitative magnet resonance imaging (MRI) analysis techniques to the study of multiple sclerosis (MS). MS is a debilitating disease with a multi-factorial pathology, progression, and clinical presentation. Its most salient feature is focal inflammatory lesions, but it also includes significant parenchymal atrophy and microstructural damage. As a powerful tool for in vivo investigation of tissue properties, MRI can provide important clinical and scientific information regarding these various aspects of the disease, but precise, accurate quantitative analysis techniques are needed to detect subtle changes and to cope with the vast amount of data produced in an MRI session. To address this, eight new techniques were developed by Michael Dwyer and his co-workers to better elucidate focal, atrophic, and occult/"invisible" pathology. These included: a method to better evaluate errors in lesion identification; a method to quantify differences in lesion distribution between scanner strengths; a method to measure optic nerve atrophy; a more precise method to quantify tissue-specific atrophy; a method sensitive to dynamic myelin changes; and a method to quantify iron in specific brain structures. Taken together, these new techniques are complementary and improve the ability of clinicians and researchers to reliably assess various key elements of MS pathology in vivo.

Purpose: To investigate species differences in the distribution and localization of alpha B-crystallin (ABC) in the normal retina and optic nerve head region, and to describe changes during outer and inner retina degeneration. Material and methods: Animals studied included mice, rats, cats, pigs, cows, and monkeys. Sections of the optic nerve and central retina were labeled with antibodies against ABC and glial fibrillary acidic protein (GFAP). Results: ABC was located in astrocytes and Muller cells with different intensities. During outer retina degeneration (dystrophic rat and Abyssinian cat), only late stages showed an increase in ABC in the retina and optic nerve head. Inner retina degeneration in the glaucoma mouse model showed no increase of ABC. In the monkey glaucoma model, only the innermost layer of the optic nerve head showed increased labeling for ABC. Conclusions: The distribution of ABC is species dependent and is (excluding the mouse) present in the nerve fiber layer of the retina and in the optic nerve head (localization of astrocytes). Chronic retinal degeneration does not necessarily lead to an over-expression of ABC. While in outer retinal degeneration induction was predominantly present in late stages, pressure-induced glaucoma led to a specific increase in ABC already in early stages indicating a local stress-response in this region.

Purpose: The aim of this study was to investigate differences in the nerve fiber layer and glaucoma-induced structural optic nerve head (ONH) damage in patients with normal- (NTG) and high-tension (HTG) glaucoma. Methods: In this retrospective pair-matched comparative study, 22 NTG and 22 HTG eyes were matched according to the same glaucomatous damage based on rim volume, rim area and disk size, as measured by Heidelberg retinal tomography (HRT III). Visual fields (VF) were assessed by Humphrey perimetry, and nerve fiber layer thickness was determined both by scanning laser polarimetry (GDxVCC) and spectral-domain optical coherence tomography (SD-OCT). Comparisons of all measured parameters were made between NTG and HTG groups. Results: Based on HRT results, both NTG and HTG eyes displayed comparable structural damage to the ONH (NTG/HTG, mean: disk area, 2.30/2.31 mm 2 , p = 0.942; rim area, 1.02/0.86 mm 2 , p = 0.082; rim volume, 0.19/0.17 mm 3 , p = 0.398). NTG eyes had significantly less VF damage than HTG eyes (NTG/HTG, mean deviation: –4.23/–12.12 dB, p = 0.002; pattern standard deviation: 5.39/8.23 dB, p = 0.022). The inferior nerve fiber layer of NTG patients was significantly thicker than that of HTG patients (NTG/HTG, mean: GDx inferior: 53.5/46.3 μm, p = 0.046). SD-OCT revealed a significantly thicker nerve fiber in NTG compared with HTG patients in all quadrants (NTG/HTG, total mean: 72.72/58.45 μm, p = 0.002). Conclusion: At comparable glaucomatous stages, nerve fiber loss was more advanced in HTG patients compared with NTG patients.

No description available.

Il est généralement accepté que les lits vasculaires oculaires auraient la faculté d’autoréguler leur apport sanguin afin de contrebalancer les variations de pression de perfusion oculaire (PPO). Plusieurs études ont tenté d’évaluer ce mécanisme en mesurant les effets d’une variation de la PPO - induite par un exercice ou par une augmentation de la pression intra-oculaire (PIO) à l’aide d’une suction sclérale - sur le débit sanguin oculaire (DSO). Or, les méthodes de mesure du DSO utilisées jusqu'à maintenant présentent de nombreux désavantages et limites, ce qui rend difficile leur usage clinique. De récents développements dans le domaine des investigations non-invasives des paramètres sanguins oculaires proposent un modèle capable de mesurer en temps réel la concentration en oxygène, un autre paramètre important du métabolisme rétinien. Dans le cadre de la présente étude, ce nouveau modèle est utilisé afin de mesurer les effets d’un effort physique dynamique sur la concentration d’oxygène dans les capillaires de la tête du nerf optique (COTNO) de sujets jeunes et en santé. Six jeunes hommes non fumeurs ont participé à l’étude. L’effort physique dynamique consistait en une séance de bicyclette stationnaire de 15 minutes menant à une augmentation du pouls à 160 battements par minute. La COTNO était mesurée avant et immédiatement après la séance d’exercice. La pression artérielle (PA) et la PIO étaient mesurées ponctuellement alors que le pouls et la saturation sanguine en oxygène (SpO2) au niveau digital étaient mesurés tout au long de l’expérience. L’effort physique a entrainé une réduction de la PIO chez tous les sujets, une réduction de la COTNO chez tous les sujets sauf un tandis que la SpO2 demeura constante chez tous les sujets. Une corrélation quadratique entre les variations de la PIO et de la COTNO a pu être notée. Ces résultats suggèrent une corrélation directe entre les variations de la COTNO et celles de la PPO et de la PA. Les résultats de la présente étude suggèrent que les variations de la COTNO chez un sujet en santé suite à un effort physique dynamique pourraient représenter sa capacité à compenser un tel effort. De plus, les changements métaboliques sanguins induits par l’effort physique dynamique pourraient représenter une cause commune aux variations de la PIO et de la COTNO. / It is generally accepted that ocular vascular beds have the ability to autoregulate their blood flow to counter balance the variations in the ocular perfusion pressure (OPP). Many studies have tried to evaluate this mechanism by quantifying the effects of a variation in OPP on the ocular blood flow (OBF). This was induced by either exercise or scleral suction which increases intra-ocular pressure (IOP). However, the methods used for these measurements have many disadvantages and limitations, which deters their clinical use. Recent developments in the field of non-invasive investigation of ocular blood parameters propose a model for the measurement, in real-time, of oxygen concentration in the blood streams, another important parameter of the retinal metabolism. In the present study, this new model is used to evaluate the effects of dynamic physical efforts on the blood oxygenation in the optic nerve head capillary structures (BOONH) in young healthy subjects. Six non-smoking young men participated in the study. 15-minute sessions of stationary bicycle leading to a heart rate of 160bpm were performed as dynamic physical effort. The BOONH was measured before and immediately after the exercise. The blood pressure (BP) and the IOP were measured periodically while the heart rate and the oxygen saturation in blood (SpO2) were measured in a finger throughout the exercise. The physical effort led to a reduction of the IOP in all subjects, a decrease in the BOONH in all but one subjects and a constant SpO2 in all subjects. A quadratic correlation was observed between the variations in IOP and in BOONH. These results suggest a direct correlation between the variations in BOONH and those of the OPP and the BP. The results of the present study suggest that the variations in BOONH in a healthy subject following a physical dynamic effort could indicate his/her capacity to compensate for such an effort. Moreover, the metabolic changes in the blood due to physical dynamic efforts could be a common cause of the variations in IOP and BOONH.

Il est généralement accepté que les lits vasculaires oculaires auraient la faculté d’autoréguler leur apport sanguin afin de contrebalancer les variations de pression de perfusion oculaire (PPO). Plusieurs études ont tenté d’évaluer ce mécanisme en mesurant les effets d’une variation de la PPO - induite par un exercice ou par une augmentation de la pression intra-oculaire (PIO) à l’aide d’une suction sclérale - sur le débit sanguin oculaire (DSO). Or, les méthodes de mesure du DSO utilisées jusqu'à maintenant présentent de nombreux désavantages et limites, ce qui rend difficile leur usage clinique. De récents développements dans le domaine des investigations non-invasives des paramètres sanguins oculaires proposent un modèle capable de mesurer en temps réel la concentration en oxygène, un autre paramètre important du métabolisme rétinien. Dans le cadre de la présente étude, ce nouveau modèle est utilisé afin de mesurer les effets d’un effort physique dynamique sur la concentration d’oxygène dans les capillaires de la tête du nerf optique (COTNO) de sujets jeunes et en santé. Six jeunes hommes non fumeurs ont participé à l’étude. L’effort physique dynamique consistait en une séance de bicyclette stationnaire de 15 minutes menant à une augmentation du pouls à 160 battements par minute. La COTNO était mesurée avant et immédiatement après la séance d’exercice. La pression artérielle (PA) et la PIO étaient mesurées ponctuellement alors que le pouls et la saturation sanguine en oxygène (SpO2) au niveau digital étaient mesurés tout au long de l’expérience. L’effort physique a entrainé une réduction de la PIO chez tous les sujets, une réduction de la COTNO chez tous les sujets sauf un tandis que la SpO2 demeura constante chez tous les sujets. Une corrélation quadratique entre les variations de la PIO et de la COTNO a pu être notée. Ces résultats suggèrent une corrélation directe entre les variations de la COTNO et celles de la PPO et de la PA. Les résultats de la présente étude suggèrent que les variations de la COTNO chez un sujet en santé suite à un effort physique dynamique pourraient représenter sa capacité à compenser un tel effort. De plus, les changements métaboliques sanguins induits par l’effort physique dynamique pourraient représenter une cause commune aux variations de la PIO et de la COTNO. / It is generally accepted that ocular vascular beds have the ability to autoregulate their blood flow to counter balance the variations in the ocular perfusion pressure (OPP). Many studies have tried to evaluate this mechanism by quantifying the effects of a variation in OPP on the ocular blood flow (OBF). This was induced by either exercise or scleral suction which increases intra-ocular pressure (IOP). However, the methods used for these measurements have many disadvantages and limitations, which deters their clinical use. Recent developments in the field of non-invasive investigation of ocular blood parameters propose a model for the measurement, in real-time, of oxygen concentration in the blood streams, another important parameter of the retinal metabolism. In the present study, this new model is used to evaluate the effects of dynamic physical efforts on the blood oxygenation in the optic nerve head capillary structures (BOONH) in young healthy subjects. Six non-smoking young men participated in the study. 15-minute sessions of stationary bicycle leading to a heart rate of 160bpm were performed as dynamic physical effort. The BOONH was measured before and immediately after the exercise. The blood pressure (BP) and the IOP were measured periodically while the heart rate and the oxygen saturation in blood (SpO2) were measured in a finger throughout the exercise. The physical effort led to a reduction of the IOP in all subjects, a decrease in the BOONH in all but one subjects and a constant SpO2 in all subjects. A quadratic correlation was observed between the variations in IOP and in BOONH. These results suggest a direct correlation between the variations in BOONH and those of the OPP and the BP. The results of the present study suggest that the variations in BOONH in a healthy subject following a physical dynamic effort could indicate his/her capacity to compensate for such an effort. Moreover, the metabolic changes in the blood due to physical dynamic efforts could be a common cause of the variations in IOP and BOONH.

Tato práce popisuje přehled standardních a pokročilých metod používaných k diagnose glaukomu v ranném stádiu. Na základě teoretických poznatků je implementován internetově orientovaný informační systém pro oční lékaře, který má tři hlavní cíle. Prvním cílem je možnost sdílení osobních dat konkrétního pacienta bez nutnosti posílat tato data internetem. Druhým cílem je vytvořit účet pacienta založený na kompletním očním vyšetření. Posledním cílem je aplikovat algoritmus pro registraci intenzitního a barevného fundus obrazu a na jeho základě vytvořit internetově orientovanou tři-dimenzionální vizualizaci optického disku. Tato práce je součásti DAAD spolupráce mezi Ústavem Biomedicínského Inženýrství, Vysokého Učení Technického v Brně, Oční klinikou v Erlangenu a Ústavem Informačních Technologií, Friedrich-Alexander University, Erlangen-Nurnberg.

Indiana University-Purdue University Indianapolis (IUPUI) / Epigenetic alterations have been shown to control cell type specification and differentiation leading to the changes in chromatin structure and organization of many genes. HDACs have been well documented to play an important role in both neurogenesis and gliogenesis in ganglionic eminence and cortex-derived cultures. However, the role of HDACs in glial cell type specification and differentiation in the optic nerve has not been well described. As a first step towards understanding their role in glial cell type specification, we have examined histone acetylation and methylation levels as well as the expression levels and patterns of the classical HDACs in both murine and chick optic nerve. Analysis of mRNA and protein levels in the developing optic nerve indicated that all 11 members of the classical HDAC family were expressed, with a majority declining in expression as development proceeded. Based on the localization pattern in both chick and murine optic nerve glial cells, we were able to group the classical HDACs: predominantly nuclear, nuclear and cytoplasmic, predominantly cytoplasmic. Nuclear expression of HDACs during different stages of development studied in this project in both murine and chick optic nerve glial cells suggests that HDACs play a role in stage-dependent changes in gene expression that accompany differentiation of astrocytes and oligodendrocytes. Examination of localization pattern of the HDACs is the first step towards identifying the specific HDACs involved directly in specification and differentiation of glia in optic nerve.

Background: Methanol poisoning is a life-threatening condition which induces acute toxic optic neuropathy with possible long-term visual sequelae in survivors. Aim: To study the prevalence, character, dynamics, and key determinants of chronic morphological and functional visual pathway changes during 4 years after methanol-induced optic neuropathy. Methods: A total of 55 patients with confirmed methanol poisoning with mean age 46.7 ± 3.6 years (46 males and 9 females), and 41 controls were included in this prospective longitudinal cohort study. The patients were examined 4.9 ± 0.6, 25.0 ± 0.6, and 49.9 ± 0.5 months after discharge. The following tests were performed: visual evoked potential (VEP), optical coherence tomography with retinal nerve fiber layer (RNFL) measurement, brain magnetic resonance imaging (MRI), complete ocular examination, biochemical tests, and apolipoprotein E (ApoE) genotyping. Results: Of 42/55 patients with all three consecutive examinations, abnormal RNFL thickness was registered in 13 (31%) and chronic axonal loss during the observation period was found in 10 (24%) patients. The risk estimate of chronic global RNFL loss for arterial blood pH<7.3 at admission was: 11.65 (1.91-71.12; 95% CI) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated...