Glaucoma is a common disease in the elderly population. Open-angle glaucoma (OAG) is the predominant form of glaucoma. Chronic simple glaucoma and capsular glaucoma, characterized by the occurrence of pseudoexfoliation in the anterior eye segment, are the most frequent types of OAG. The purpose of the present thesis was to study the epidemiology of OAG in the municipality of Tierp, whose population has a high exposure to pseudoexfoliation. In a case-finding study, the prevalence of known cases of OAG by December 31, 1983 was estimated to 1.4% in people ≥45 years of age. Sixty-three percent of all cases had capsular glaucoma. Patients with advanced glaucoma were older, had had the disease for longer, had higher mean initial intraocular pressure, and had more extensive visual field defects at the time of diagnosis. A population survey of people 65–74 years of age was conducted in 1984–86. The prevalence of OAG was 5.3%. Pseudoexfoliation was found in 17%, being more common in females. Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease (odds ratio = 16). In cases detected at the survey, an intraocular pressure ≥20 mmHg was a serious risk factor of having OAG (odds ratio = 9.7). In a 5-year follow-up study of participants in the population survey, increased intraocular pressure and pseudoexfoliation were recognized as independent risk factors for the development of OAG (standardized risk ratios = 3.4 and 9.8, respectively). Interaction between increased intraocular pressure and pseudoexfoliation was indicated. By May 2006, the incidence of OAG was estimated to 7.1 per 1,000 person-years. The incidence of capsular glaucoma was more than twice that of chronic simple glaucoma. The prevalence and incidence of OAG was higher than that reported from other studies conducted on Caucasian populations. The probable explanation for this finding is exposure to pseudoexfoliation.

L’examen PEV (Potentiel Évoqué Visuel) avec stimulation par balayage de fréquence spatiale est reconnu pour l’estimation de l’acuité visuelle (AV) chez le jeune enfant en raison de son objectivité et de sa faible durée d’examen. Néanmoins, plusieurs études ont souligné la variabilité des réponses et pour certains cas, des atténuations à certaines fréquences spatiales. Dans cette thèse, nous démontrons la relation entre la phase du signal et ces atténuations lorsque la transformée de Fourier à court terme (TFCT) est utilisée. Nous présentons une nouvelle méthode de traitement dusignal qui prend en compte les variations de phase, basée sur la transformée en ondelettes discrète stationnaire (TODS) pour le débruiter le signal et sur le filtre de Kalman étendu (FKE) pour l’estimer la réponse du système visuel. La nouvelle méthode est testée sur deux ensembles d’examens. Le premier provient du CHRU de Lille et le second de notre laboratoire. La TODS améliore le rapport signal sur bruit de 10.9 dB en moyenne (IC95 [6.3,15.6]) et réduit les artéfacts dus aux clignements et aux mouvements. Le FKE permet une estimation de la réponse du système visuel plus précise. Grâce à la prise en compte de la phase du signal, la forme de la réponse présente moins de variations. La dispersion entre les balayages est divisée par 1.4 en comparaison à la méthode actuelle. La corrélation entre l’AV ETDRS et l’estimation de l’acuité visuelle de la nouvelle méthode est meilleure (indice de Spearman=0.64, valeur-p=6 10-4, écart-type=0.34 logMAR) que celle de la méthode actuelle (indice de Spearman=0.57, valeur-p=1.1 10-3, écart type=0.45 logMAR). / Sweep VEP (visual evoked potentials) is known to be a valuable exam to estimate visual acuity (VA) in infants because of its objectivity and its rapidity. Nevertheless, several studies have pointed out the variability of the responses and sometimes attenuations at some spatial frequencies called “notches”. In this thesis, we demonstrate a relationship between the phase of the signal and these attenuations when the short-time discrete Fourier transform (STDFT) is used. We introduce a new method of signal processing which takes in account the phase shifting, based on stationary discrete wavelet transform (SDWT) for the denoising and on extended Kalman filtering (EKF) for the estimation of the visual system response. The new method is tested on two sets of exams. The first one comes from the CHRU of Lille and the second one from our laboratory. The SDWT improves the signal to noise ratio on average by 10.9 dB (CI95 [6.3,15.6]) and reduces artefacts caused by blinking or eyes movements. Thanks to the EKF, the estimation of the response of the visual system is more precise. By taking into account the phase of the signal, the shape of the reponse presentsless variations. The dispersion among the sweeps is divided by 1.4 compared to the DSTFT. The correlation between ETDRS VA and the VA estimation of the new method (Spearman’s correlation= 0.64, p-value=6 10-4, root mean squared error (RMSE)=0.34 logMAR) is better than that of the current method (Spearman’s correlation=0.58, p-value=1.1 10-3, RMSE=0.45 logMAR).

Há muitos agentes terapêuticos comercializados sob forma racêmica. Os enantiômeros podem apresentar diferenças significativas nos perfis farmacocinético e farmacodinâmico. O uso do enantiômero puro em formulações farmacêuticas pode resultar em melhor ajuste de dose e menos efeitos adversos. A atropina, um alcalóide natural da Atropa belladonna, é a mistura racêmica de l-hiosciamina e d-hiosciamina. Este fármaco é principalmente utilizado para dilatar a pupila e como um antiespasmódico. Para quantificar estes enantiômeros, foram desenvolvidos métodos analíticos utilizando a cromatografia líquida de alta eficiência (CLAE) com as fases estacionárias quirais Chiralcel-OD® e Chiral-AGP®. Para quantificar estes enantiômeros em soluções oftálmicas, foi realizada a validação com sucesso de um método por CLAE, empregando uma coluna Chiral-AGP®, a 20°C. A fase móvel foi uma solução tampão fosfato (contendo 10 mM de 1-octanosulfonato de sódio e 7,5 mM de trietilamina, ajustada para pH 7,0 com ácido fosfórico) e acetonitrila (99:1 v/v). A vazão foi de 0,6 mL/min, com detecção ultravioleta em 205 nm. No intervalo de concentração de 14,0 µg/mL a 26,0 µg/mL, o método é linear (r > 0,9999), exato (100,1% - 100,5%) e preciso (RSDsistema ≤ 0,6%; RSDintra-dia ≤ 1,1%; RSDentre-dias ≤ 0,9%). O método é específico e os testes de validação asseguram que as soluções de padrão e amostra são estáveis até 72 horas. O planejamento fatorial assegura a robustez com variação de ±10% nos componentes da fase móvel e 2°C na temperatura da coluna. / There are many therapeutic agents commercialized under racemic form. The enantiomers can show significant differences in the pharmacokinetic and pharmacodynamic profiles. The use of pure enantiomer in pharmaceutical formulations can result in better adjustment of dose and less adverse effects. Atropine, an alkaloid of the Atropa belladonna, is a racemic mixture of l-hyoscyamine and d-hyoscyamine. This drug is mainly used to dilate the pupil and as an antispasmodic agent. To quantify these enantiomers analytical methods were developed, using high performance liquid chromatography (HPLC) with chiral stationary phases Chiralcel OD® and Chiral AGP®. To quantify these enantiomers in ophthalmic solutions the validation of a HPLC method was performed using a Chiral AGP® column at 20°C. The mobile phase consisted of a buffered phosphate solution (containing 10 mM 1-octanesulfonic acid sodium salt and 7.5 mM triethylamine, adjusted to pH 7.0 with ortho-phosphoric acid) and acetonitrile (99:1 v/v). The flow rate was 0.6 mL/min, with ultraviolet detection at 205 nm. In the concentration range from 14.0 mg/mL to 26.0 mg/mL, the method is linear (r > 0.9999), exact (100.1% - 100.5%) and precise (RSDsystem ≤ 0.6%; RSDintra-day ≤ 1.1%; RSDinter day ≤ 0.9%). The method is specific and the validation tests assure that standard and sample solutions are stable for up to 72 hours. The factorial design assures the robustness with variation of ± 10% in the mobile phase components and 2°C of column temperature.

The retina is a highly metabolically active tissue with large demands on the supply of nutrients. Disorders affecting the retina often include some vasculopathy with an impact on retinal circulation. Studies of retinal haemodynamics could thus help to detect, differentiate and diagnose diseases, to monitor changes in disease as well as progression and efficiency of the therapy. The present studies were an attempt to validate and determine the clinical usefulness of a newly developed technique for studying the retinal circulation in human eyes. We used different techniques to evaluate different parameters of retinal circulation. We examined how leukocyte velocity determined with Blue Field Simulation and transit times, mean transite time (MTT) and arterio-venous passage (AVP), and vessel diameter, determined from fluorescein angiograms, together reflects the retinal circulation. MTT was determined with a method based on an Impulse-Response technique, MTTIR. In a study on monkeys we compared our method, together with two conventional methods, with an absolute measurement of retinal blood flow (RBF) determined with labelled microspheres. There was a weak, but not statistically significant, correlation between retinal blood flow and MTTIR (r2 = -0.60, p = 0.06), but no useful correlation between retinal blood flow and either of the other two measures of transit times. In a study on healthy eyes we determined the effect of a physiological provocation, changes in arterial blood gases, on retinal circulation. Breathing pure oxygen or increased level of carbon dioxide in inspired air had no effect on MTT, but oxygen reduced leukocyte velocity and vessel diameter and carbon dioxide increased leukocyte velocity significantly. We concluded that unchanged transit time trough the retinal tissue was not due to a lack of effect of the gas provocation but a result due to concomitant changes in volume and flow. In a study on eyes of patients with diabetic retinopathy we investigated the relation between the extent of retinal circulation changes and the severity of the diabetes retinopathy (DRP). Transit times were relatively unaffected until proliferative DRP (PDRP) developed. In eyes with PDRP both MTTIR and AVP were increased. After panretinal photocoagulation treatment MTTIR returned to normal levels and vessel diameters tended to decrease while leukocyte velocity and AVP remained unchanged. We concluded that the increase in MTTIR in eyes with PDRP is at least partly explained by vessel dilation, causing an increased volume of the retinal vascular bed.

Há muitos agentes terapêuticos comercializados sob forma racêmica. Os enantiômeros podem apresentar diferenças significativas nos perfis farmacocinético e farmacodinâmico. O uso do enantiômero puro em formulações farmacêuticas pode resultar em melhor ajuste de dose e menos efeitos adversos. A atropina, um alcalóide natural da Atropa belladonna, é a mistura racêmica de l-hiosciamina e d-hiosciamina. Este fármaco é principalmente utilizado para dilatar a pupila e como um antiespasmódico. Para quantificar estes enantiômeros, foram desenvolvidos métodos analíticos utilizando a cromatografia líquida de alta eficiência (CLAE) com as fases estacionárias quirais Chiralcel-OD® e Chiral-AGP®. Para quantificar estes enantiômeros em soluções oftálmicas, foi realizada a validação com sucesso de um método por CLAE, empregando uma coluna Chiral-AGP®, a 20°C. A fase móvel foi uma solução tampão fosfato (contendo 10 mM de 1-octanosulfonato de sódio e 7,5 mM de trietilamina, ajustada para pH 7,0 com ácido fosfórico) e acetonitrila (99:1 v/v). A vazão foi de 0,6 mL/min, com detecção ultravioleta em 205 nm. No intervalo de concentração de 14,0 µg/mL a 26,0 µg/mL, o método é linear (r > 0,9999), exato (100,1% - 100,5%) e preciso (RSDsistema ≤ 0,6%; RSDintra-dia ≤ 1,1%; RSDentre-dias ≤ 0,9%). O método é específico e os testes de validação asseguram que as soluções de padrão e amostra são estáveis até 72 horas. O planejamento fatorial assegura a robustez com variação de ±10% nos componentes da fase móvel e 2°C na temperatura da coluna. / There are many therapeutic agents commercialized under racemic form. The enantiomers can show significant differences in the pharmacokinetic and pharmacodynamic profiles. The use of pure enantiomer in pharmaceutical formulations can result in better adjustment of dose and less adverse effects. Atropine, an alkaloid of the Atropa belladonna, is a racemic mixture of l-hyoscyamine and d-hyoscyamine. This drug is mainly used to dilate the pupil and as an antispasmodic agent. To quantify these enantiomers analytical methods were developed, using high performance liquid chromatography (HPLC) with chiral stationary phases Chiralcel OD® and Chiral AGP®. To quantify these enantiomers in ophthalmic solutions the validation of a HPLC method was performed using a Chiral AGP® column at 20°C. The mobile phase consisted of a buffered phosphate solution (containing 10 mM 1-octanesulfonic acid sodium salt and 7.5 mM triethylamine, adjusted to pH 7.0 with ortho-phosphoric acid) and acetonitrile (99:1 v/v). The flow rate was 0.6 mL/min, with ultraviolet detection at 205 nm. In the concentration range from 14.0 mg/mL to 26.0 mg/mL, the method is linear (r > 0.9999), exact (100.1% - 100.5%) and precise (RSDsystem ≤ 0.6%; RSDintra-day ≤ 1.1%; RSDinter day ≤ 0.9%). The method is specific and the validation tests assure that standard and sample solutions are stable for up to 72 hours. The factorial design assures the robustness with variation of ± 10% in the mobile phase components and 2°C of column temperature.