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Os cães têm apresentado uma maior prevalência de DM nos últimos anos, sendo uma das endocrinopatias mais comuns. As complicações a curto e longo prazo incluem alterações retinianas, renais e neurológicas. Dentre as alterações mais evidentes podemos citar o desenvolvimento de cataratas e alterações nas vias visuais. As alterações das vias visuais são detectadas precocemente por testes eletrofisiológicos, métodos objetivos que independem da informação do paciente e necessitam de pouca colaboração para serem executados. Neste estudo utilizamos o PVE-F, que consiste em potenciais de baixa amplitude registrados quando a retina é submetida à estimulação visual adequada em uma cúpula de campo total, e avalia a integridade das vias ópticas desde a retina até o córtex occipital. Com este estudo objetivamos avaliar as alterações das vias visuais do PVE-F em cães diabéticos portadores de catarata, consoante os critérios da ISCEV. Para o projeto foram utilizados 59 cães, selecionados quanto aos melhores registros e com menor interferência, com idade variando entre 5 e 14 anos, de pequeno à médio porte (até 20kg) de diferentes raças, 46 fêmeas e 13 machos, encaminhados ao Serviço de Oftalmologia do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. Os animais foram divididos em 3 grupos: grupo normal (GN) cães adultos hígidos; grupo catarata (GC) cães apresentando catarata madura ou hipermadura; grupo diabético (GD) cães apresentando catarata madura ou hipermadura, com diabetes mellitus. Todos os grupos foram analisados quanto à latência (ms) e quanto à amplitude (V). O registro do PVE foi obtido por eletrodos de contato superficial utilizando o Sistema Eletrodiagnóstico Computadorizado Veris 2000 com frequência de 2Hz totalizando 180 estímulos. Os animais permaneceram com a cabeça introduzida no interior da cúpula geradora dos flashes de luz branca (Ganzfeld) durante todo o exame. Os potenciais foram registrados em ambos os olhos, no olho direito (ocluindo olho esquerdo) e posteriormente no olho esquerdo (ocluindo olho direito). Em relação ao pico P2 houve semelhança entre os olhos examinados, porém os valores das médias do GD foram maiores que os demais, com significância estatística ao GN (p=0,001) e ao GC (p=0,000). O GD apresentou valores de médias: AO 97,72ms; OD 98,10ms e OE 97,21ms. O GC apresentou valores de médias: AO 86,73ms; OD 86,27ms e OE 86,87ms. O GN apresentou valores de médias: AO 73,20ms; OD 74,53ms e OE 74,33ms. A amplitude (µV) dos intervalos N1-P1, P1-N2 e P2-N2 mostrou semelhança entre os grupos estudados (GN, GC e GD). Porém, os intervalos P1-N2 e N2-P2 apresentaram diferenças entre os olhos, com valores de médias de AO maiores em relação ao OD e OE estatísticamente significantes (p=0,000). No estudo realizado, os valores de glicemia estavam maiores no GD, com uma média de 202,79 mg/dl, enquanto que o GN apresentou média de 78,47 mg/dl e o GC 74,80 mg/dl. Conclui-se que as alterações nas vias visuais estão presentes nos cães diabéticos independentemente do tempo de DM, idade e controle glicêmico, e o PVE-F é um teste útil e importante capaz de detectar estas alterações. / Dogs have been frequently affected by Diabetes mellitus; nowadays, one of the commonest endocrinopathy in this specie. It causes short and long term complications in different organs, such as eyes, kidneys and nervous system. The most evident complication seen in DM dogs is the diabetic cataract and the alterations of the visual pathway. Most of the visual pathway alterations are early diagnosed by electrophysiological tests, objective methods which doesn´t need patient information and requires minimal co-operation to be performed. The aim of this study was to evaluate the integrity of the optic pathway, from the retina to the occipital cortex, in diabetic dogs with cataracts using the PVE-F test and the ISCEV standards. PVE-F is an electrophysiological test based on the registration of low amplitude potentials urged from the retina when stimulated by full field dome. The exam was performed at the Ophthalmology Service, of the Veterinary Hospital of the Veterinary College University of São Paulo in fifty-nine animals, including 46 female and 13 male dogs, with ages varying from 5 to 14 years and weighting less than 20kg. Dogs were divided in 3 groups: healthy dogs without ocular alterations (GN); healthy dogs with mature or hyper mature cataract (GC); diabetic dogs presenting mature or hyper mature cataract (GD). PVE-F was realized using Veris 2000 Computerized Electrodiagnostic System, adjusted for 2Hz flashes (180 flashes) while dogs, with superficial contact electrodes, were kept with their heads inside the generator dome of white light flashes (Ganzfeld). Registers were obtained from both eyes - AO; right eye - OD (occluding left eye) and left eye - OE (occluding right eye) and those with less interference were chosen. Latencies (ms) and amplitudes (V) in each group were analyzed separately. Similarity at peak P2 was observed in every examined eye, but mean values on GD were higher when compared to other groups, with statistically significance on GN (p=0,001) and GC (p=0,000) as shown: (GD): AO 97,72ms, OD 98,10ms and OE 97,21ms; (GC): AO 86,73ms, OD 86,27ms and OE 86,87ms; (GN) AO 73,20ms, OD 74,53ms and OE 74,33ms. Similarity at amplitude (µV) intervals N1-P1, P1-N2 and P2-N2 was observed in every studied group (GN, GC and GD). On the other hand, difference in P1-N2 and N2-P2 intervals registers were observed when comparing eyes: both eyes mean values were higher than OD and OE values, with statistically significance (p=0,000). Glycemic values were higher in GD, with mean values of 202,79 mg/dl, whereas GN was 78,47 mg/dl and GC 74,80 mg/dl. These study demonstrates that diabetic dogs presents alterations at the visual pathway function, independent of the DM time, age and glycemic control and that PVE-F is an important and useful test able to detect such alterations.

As disturbed binocular functions in small children may lead to severe amblyopia it is of interest to detect it as early as possible. Most tests for binocular functions, however, demand active cooperation and may be unreliable in children up to 4-5 years of age. This study therefore aims to employ visual evoked potentials (VEP) to enable the examiner to evaluate the binocular function in a subject without need of active cooperation from the subject. Initially we studied the relation of suprathreshold contrast to the latency of the transient pattern VEP (tpVEP). Although suprathreshold contrast independently influenced the tpVEP latency, interindividual variation was too large to suggest tpVEP as a possible method for objectively measuring contrast sensitivity in a subject. The tpVEP latency in normal and microstrabismic adult subjects was examined. It was significantly shorter with binocular viewing in normals, but not in the microstrabismic group. Contrast sensitivity and tpVEP latency was examined in adults, both with normal binocularity and with microstrabismus, using both luminance (black-and-white) contrast and colour contrast patterns. The tpVEP latency to colour contrast, like that to luminance contrast, is shorter in normal subjects who view the stimulus binocularly. Interindividual variation or overlap between the normal and microstrabismic groups did not improve with colour contrast. The most significant features of the tpVEP are amplitude and latency. Depending on stimulus conditions, the response may show variations in configuration, amplitude and, to a lesser degree, latency. To decrease the influence of such variations steady-state VEP (ssVEP) can be used. The stimulus is presented in a fast repetitive manner, yielding a VEP response shaped as a continuous curve. The frequency components of this curve can be analysed using Fast Fourier Analysis. Fast Fourier analysis of ssVEP in children aged 8-15 years with normal binocularity and with microstrabismus showed that the power of the second harmonic (the double frequency of stimulus frequency) of the response with binocular viewing was larger than with monocular viewing, both in normals and microstrabismic subjects. For higher stimulus frequencies, microstrabismic subjects showed a significantly lower power of the second harmonic compared with subjects with normal binocularity, when the stimulus was presented binocularly. Finally, Fast Fourier analysed ssVEP in pre-school children aged 4-5 years was studied. A normal group was compared with a group with microstrabismus and a group with significant amblyopia. Amblyopic subjects had significant interocular differences in the first harmonic. We confirmed the significant difference found between microstrabismic subjects and subjects with normal binocularity regarding the second harmonic’s power with higher temporal frequency binocular stimulation, although at a slightly lower frequency than for older children. A low power of the second harmonic in the ssVEP to a binocular stimulus with high temporal frequency is a strong indicator of disturbed binocular function. / För att förhindra amblyopi (ensidig synsvaghet) hos barn är det viktigt att upptäcka störningar i samsynsfunktionerna så tidigt som möjligt. Samsynstester kräver dock aktiv medverkan och kan ge osäkra resultat hos barn upp till 4-5 års ålder. Den här avhandlingen studerar möjligheterna att utifrån tidsmässiga (temporala) egenskaper hos visual evoked potentials (VEP) undersöka samsynsfunktioner objektivt, utan att den undersökte behöver medverka aktivt. Första delstudien visar att ett synstimulus kontrastnivå i relation till kontrastkänslighetströskeln oberoende påverkar latensen i VEP, men variationer mellan individer gör metoden olämplig som objektiv kontrastkänslighetstest. Andra delstudien jämför latensen i VEP hos individer med normal samsyn med den hos personer med mikroskelning. Stimulering av båda ögonen gav signifikant kortare latens än stimulering av ett öga hos normala, men inte hos mikroskelare. I den tredje delstudien jämfördes känslighet för luminanskontrast och färgkontrast hos individer med normal samsyn och personer med mikroskelning. Både luminansmönster (svart-vita) och färgkontrastmönster upptäcktes vid lägre kontrast om båda ögonen stimulerades istället för ett i taget hos normalseende. Mikroskelare uppfattade mönstren sämre med båda ögonen än med ett öga (det dominanta). Latensen i VEP mättes i båda grupperna för både luminans- och färgkontrastmönster. Båda typerna av kontrast gav förkortning av latensen när båda ögonen stimulerades vid normal samsyn, men denna förkortning uteblev hos mikroskelare. Både luminans- och färgkontrast gav för varierande resultat för att utnyttja metoden för objektiv undersökning av samsynen. Fourier-analys innebär att en kurvform delas upp i sinuskurvor med olika frekvens, amplitud och fas. Om ett stimulus växlar hastigt får man ett steady-state VEP (ssVEP), dvs en kontinuerligt vågformad VEP-kurva, som kan delas upp i delsinuskurvor med Fourieranalys. Detta gör att man särskilt kan studera frekvenser som är relaterade till stimuleringsfrekvensen, till exempel grundton och övertoner (multipler av grundtonsfrekvensen). Barn 8-15 år gamla, med normal samsyn och med mikroskelning undersöktes med ssVEP i det fjärde delarbetet. Den första övertonen (= ”second harmonic”) var statistiskt signifikant svagare hos mikroskelare jämfört med normala individer, när stimuleringsfrekvensen var hög. Det femte och sista delarbetet undersökte ssVEP hos 4-5 år gamla förskolebarn på motsvarande sätt. I denna studie deltog också en grupp barn med amblyopi (synsvaghet) på ena ögat. På en något lägre stimuleringsfrekvens bekräftades den svagare första övertonen hos barnen med mikroskelning jämfört med barnen med normal samsyn. De amblyopa barnen visade tydligast förändringar vid lägre stimuleringsfrekvenser och i ssVEP:s grundtonsfrekvens (= ”first harmonic” eller ”fundamental harmonic”). Resultaten i de olika grupperna är så pass åtskilda att metoden verkar lämpa sig för objektiv undersökning av samsynsfunktioner, i det att en svag första överton i binokulärt ssVEP utlöst av hög stimuleringsfrekvens inger en stark misstanke om störd samsyn, medan en stor skillnad i grundtonens styrka i höger respektive vänster ögas ssVEP tyder på amblyopi.

Sensory adaptation to blur improves visual acuity under defocused conditions. This phenomenon has been successfully demonstrated using subjective measures of acuity and is known as blur adaptation. This study investigates aspects of the mechanism of blur adaptation in human vision using subjective and objective methods. Parafoveal visual acuity measured under defocused conditions demonstrates that blur adaptation is not limited to the fovea. The presence of the adaptive mechanism in the parafovea also suggests that the neural compensation that takes places under defocused conditions acts across a spatial range and is not limited to specific frequency bands. An evaluation of the contrast sensitivity function under defocus provides further evidence. Electrophysiological methods measure the effect of blur adaptation at the retina and at the visual cortex to provide objective evidence for the presence of the blur adaptation mechanism. Finally enhanced-depth imaging optical coherence tomography examines whether a period of prolonged defocus triggers any short-term changes in choroidal thickness in a similar manner to that reported in animal emmetropisation.

Os cães têm apresentado uma maior prevalência de DM nos últimos anos, sendo uma das endocrinopatias mais comuns. As complicações a curto e longo prazo incluem alterações retinianas, renais e neurológicas. Dentre as alterações mais evidentes podemos citar o desenvolvimento de cataratas e alterações nas vias visuais. As alterações das vias visuais são detectadas precocemente por testes eletrofisiológicos, métodos objetivos que independem da informação do paciente e necessitam de pouca colaboração para serem executados. Neste estudo utilizamos o PVE-F, que consiste em potenciais de baixa amplitude registrados quando a retina é submetida à estimulação visual adequada em uma cúpula de campo total, e avalia a integridade das vias ópticas desde a retina até o córtex occipital. Com este estudo objetivamos avaliar as alterações das vias visuais do PVE-F em cães diabéticos portadores de catarata, consoante os critérios da ISCEV. Para o projeto foram utilizados 59 cães, selecionados quanto aos melhores registros e com menor interferência, com idade variando entre 5 e 14 anos, de pequeno à médio porte (até 20kg) de diferentes raças, 46 fêmeas e 13 machos, encaminhados ao Serviço de Oftalmologia do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. Os animais foram divididos em 3 grupos: grupo normal (GN) cães adultos hígidos; grupo catarata (GC) cães apresentando catarata madura ou hipermadura; grupo diabético (GD) cães apresentando catarata madura ou hipermadura, com diabetes mellitus. Todos os grupos foram analisados quanto à latência (ms) e quanto à amplitude (V). O registro do PVE foi obtido por eletrodos de contato superficial utilizando o Sistema Eletrodiagnóstico Computadorizado Veris 2000 com frequência de 2Hz totalizando 180 estímulos. Os animais permaneceram com a cabeça introduzida no interior da cúpula geradora dos flashes de luz branca (Ganzfeld) durante todo o exame. Os potenciais foram registrados em ambos os olhos, no olho direito (ocluindo olho esquerdo) e posteriormente no olho esquerdo (ocluindo olho direito). Em relação ao pico P2 houve semelhança entre os olhos examinados, porém os valores das médias do GD foram maiores que os demais, com significância estatística ao GN (p=0,001) e ao GC (p=0,000). O GD apresentou valores de médias: AO 97,72ms; OD 98,10ms e OE 97,21ms. O GC apresentou valores de médias: AO 86,73ms; OD 86,27ms e OE 86,87ms. O GN apresentou valores de médias: AO 73,20ms; OD 74,53ms e OE 74,33ms. A amplitude (µV) dos intervalos N1-P1, P1-N2 e P2-N2 mostrou semelhança entre os grupos estudados (GN, GC e GD). Porém, os intervalos P1-N2 e N2-P2 apresentaram diferenças entre os olhos, com valores de médias de AO maiores em relação ao OD e OE estatísticamente significantes (p=0,000). No estudo realizado, os valores de glicemia estavam maiores no GD, com uma média de 202,79 mg/dl, enquanto que o GN apresentou média de 78,47 mg/dl e o GC 74,80 mg/dl. Conclui-se que as alterações nas vias visuais estão presentes nos cães diabéticos independentemente do tempo de DM, idade e controle glicêmico, e o PVE-F é um teste útil e importante capaz de detectar estas alterações. / Dogs have been frequently affected by Diabetes mellitus; nowadays, one of the commonest endocrinopathy in this specie. It causes short and long term complications in different organs, such as eyes, kidneys and nervous system. The most evident complication seen in DM dogs is the diabetic cataract and the alterations of the visual pathway. Most of the visual pathway alterations are early diagnosed by electrophysiological tests, objective methods which doesn´t need patient information and requires minimal co-operation to be performed. The aim of this study was to evaluate the integrity of the optic pathway, from the retina to the occipital cortex, in diabetic dogs with cataracts using the PVE-F test and the ISCEV standards. PVE-F is an electrophysiological test based on the registration of low amplitude potentials urged from the retina when stimulated by full field dome. The exam was performed at the Ophthalmology Service, of the Veterinary Hospital of the Veterinary College University of São Paulo in fifty-nine animals, including 46 female and 13 male dogs, with ages varying from 5 to 14 years and weighting less than 20kg. Dogs were divided in 3 groups: healthy dogs without ocular alterations (GN); healthy dogs with mature or hyper mature cataract (GC); diabetic dogs presenting mature or hyper mature cataract (GD). PVE-F was realized using Veris 2000 Computerized Electrodiagnostic System, adjusted for 2Hz flashes (180 flashes) while dogs, with superficial contact electrodes, were kept with their heads inside the generator dome of white light flashes (Ganzfeld). Registers were obtained from both eyes - AO; right eye - OD (occluding left eye) and left eye - OE (occluding right eye) and those with less interference were chosen. Latencies (ms) and amplitudes (V) in each group were analyzed separately. Similarity at peak P2 was observed in every examined eye, but mean values on GD were higher when compared to other groups, with statistically significance on GN (p=0,001) and GC (p=0,000) as shown: (GD): AO 97,72ms, OD 98,10ms and OE 97,21ms; (GC): AO 86,73ms, OD 86,27ms and OE 86,87ms; (GN) AO 73,20ms, OD 74,53ms and OE 74,33ms. Similarity at amplitude (µV) intervals N1-P1, P1-N2 and P2-N2 was observed in every studied group (GN, GC and GD). On the other hand, difference in P1-N2 and N2-P2 intervals registers were observed when comparing eyes: both eyes mean values were higher than OD and OE values, with statistically significance (p=0,000). Glycemic values were higher in GD, with mean values of 202,79 mg/dl, whereas GN was 78,47 mg/dl and GC 74,80 mg/dl. These study demonstrates that diabetic dogs presents alterations at the visual pathway function, independent of the DM time, age and glycemic control and that PVE-F is an important and useful test able to detect such alterations.

Sensory adaptation to blur improves visual acuity under defocused conditions. This phenomenon has been successfully demonstrated using subjective measures of acuity and is known as blur adaptation. This study investigates aspects of the mechanism of blur adaptation in human vision using subjective and objective methods. Parafoveal visual acuity measured under defocused conditions demonstrates that blur adaptation is not limited to the fovea. The presence of the adaptive mechanism in the parafovea also suggests that the neural compensation that takes places under defocused conditions acts across a spatial range and is not limited to specific frequency bands. An evaluation of the contrast sensitivity function under defocus provides further evidence. Electrophysiological methods measure the effect of blur adaptation at the retina and at the visual cortex to provide objective evidence for the presence of the blur adaptation mechanism. Finally enhanced-depth imaging optical coherence tomography examines whether a period of prolonged defocus triggers any short-term changes in choroidal thickness in a similar manner to that reported in animal emmetropisation. / Engineering and Physical Sciences Research Council

Medimos a acuidade visual em crianças com paralisia cerebral do tipo espástica, classificadas em tetraplégicas, diplégicas e hemiplégicas, de acordo com o seu prejuízo motor, pelo método dos potenciais visuais evocados de varredura. Encontramos uma redução na acuidade visual em todos as crianças com tetraplegia e diplegia e em 94% das crianças com hemiplegia. Ambliopia foi identificada em 16% das crianças. Uma alta correlacão entre o prejuízo motor e a redução da acuidade visual foi encontrada para todas as classes. Concluímos que a acuidade visual está reduzida na paralisia cerebral espástica e que esta é de origem cortical, uma vez que o exame oftalmológico de todas as crianças era normal. / We measured the visual acuity in children with spastic cerebral palsy classified as tetraplegic, diplegic and hemiplegic according to their motor impairment by the sweep visual evoked potential method. We found a reduction in the visual acuity of all tetraplegic and diplegic and in 94% of the hemiplegic children. Ambliopia was found in 16% of children. A high correlation was found between the motor impairment and the reduction in the visual acuity. We conclude that the visual acuity was reducted in the spastic cerebral palsy and the origins are presumed to be cortical since the ophthalmological exam in all children was normal.

Medimos a acuidade visual em crianças com paralisia cerebral do tipo espástica, classificadas em tetraplégicas, diplégicas e hemiplégicas, de acordo com o seu prejuízo motor, pelo método dos potenciais visuais evocados de varredura. Encontramos uma redução na acuidade visual em todos as crianças com tetraplegia e diplegia e em 94% das crianças com hemiplegia. Ambliopia foi identificada em 16% das crianças. Uma alta correlacão entre o prejuízo motor e a redução da acuidade visual foi encontrada para todas as classes. Concluímos que a acuidade visual está reduzida na paralisia cerebral espástica e que esta é de origem cortical, uma vez que o exame oftalmológico de todas as crianças era normal. / We measured the visual acuity in children with spastic cerebral palsy classified as tetraplegic, diplegic and hemiplegic according to their motor impairment by the sweep visual evoked potential method. We found a reduction in the visual acuity of all tetraplegic and diplegic and in 94% of the hemiplegic children. Ambliopia was found in 16% of children. A high correlation was found between the motor impairment and the reduction in the visual acuity. We conclude that the visual acuity was reducted in the spastic cerebral palsy and the origins are presumed to be cortical since the ophthalmological exam in all children was normal.

Le traitement de l’épilepsie chez le jeune enfant représente un enjeu majeur pour le développement de ce dernier. Chez la grande majorité des enfants atteints de spasmes infantiles et chez plusieurs atteints de crises partielles complexes réfractaires, le vigabatrin (VGB) représente un traitement incontournable. Cette médication, ayant démontré un haut taux d’efficacité chez cette population, semble toutefois mener à une atteinte du champ visuel périphérique souvent asymptomatique. L’évaluation clinique des champs visuels avec la périmétrie chez les patients de moins de neuf ans d’âge développemental est toutefois très difficile, voire impossible. Les études électrophysiologiques classiques menées auprès de la population épileptique pédiatrique suggèrent l’atteinte des structures liées aux cônes de la rétine. Les protocoles standards ne sont toutefois pas spécifiques aux champs visuels et les déficits soulignés ne concordent pas avec l’atteinte périphérique observée. Cette thèse vise donc à élaborer une tâche adaptée à l’évaluation des champs visuels chez les enfants en utilisant un protocole objectif, rapide et spécifique aux champs visuels à partir des potentiels évoqués visuels (PEVs) et à évaluer, à l’aide de cette méthode, les effets neurotoxiques à long terme du VGB chez des enfants épileptiques exposés en bas âge. La validation de la méthode est présentée dans le premier article. La stimulation est constituée de deux cercles concentriques faits de damiers à renversement de phase alternant à différentes fréquences temporelles. La passation de la tâche chez l’adulte permet de constater qu’une seule électrode corticale (Oz) est nécessaire à l’enregistrement simultané des réponses du champ visuel central et périphérique et qu’il est possible de recueillir les réponses électrophysiologiques très rapidement grâces l’utilisation de l’état-stationnaire (steady-state). La comparaison des données d’enfants et d’adultes normaux permet de constater que les réponses recueillies au sein des deux régions visuelles ne dépendent ni de l’âge ni du sexe. Les réponses centrales sont aussi corrélées à l’acuité visuelle. De plus, la validité de cette méthode est corroborée auprès d’adolescents ayant reçu un diagnostic clinique d’un déficit visuel central ou périphérique. En somme, la méthode validée permet d’évaluer adéquatement les champs visuels corticaux central et périphérique simultanément et rapidement, tant chez les adultes que chez les enfants. Le second article de cette thèse porte sur l’évaluation des champs visuels, grâce à la méthode préalablement validée, d’enfants épileptiques exposés au VGB en jeune âge en comparaison avec des enfants épileptiques exposés à d’autres antiépileptiques et à des enfants neurologiquement sains. La méthode a été bonifiée grâce à la variation du contraste et à l’enregistrement simultané de la réponse rétinienne. On trouve que la réponse corticale centrale est diminuée à haut et à moyen contrastes chez les enfants exposés au VGB et à haut contraste chez les enfants exposés à d’autres antiépileptiques. Le gain de contraste est altéré au sein des deux groupes d’enfants épileptiques. Par contre, l’absence de différences entre les deux groupes neurologiquement atteints ne permet pas de faire la distinction entre l’effet de la médication et celui de la maladie. De plus, la réponse rétinienne périphérique est atteinte chez les enfants épileptiques exposés au Sabril® en comparaison avec les enfants neurologiquement sains. La réponse rétinienne périphérique semble liée à la durée d’exposition à la médication. Ces résultats corroborent ceux rapportés dans la littérature. En somme, les résultats de cette thèse offrent une méthode complémentaire, rapide, fiable, objective à celles connues pour l’évaluation des champs visuels chez les enfants. Ils apportent aussi un éclairage nouveau sur les impacts à long terme possibles chez les enfants exposés au VGB dans la petite enfance. / Epilepsy control is a major issue for the normal development in children. For the vast majority of children with infantile spasms and for some with refractory complex partial seizures, vigabatrin (VGB) represents the main treatment. VGB, which have shown high efficiency rate in this population, may, however, induce a peripheral visual field deficit, often asymptomatic. Clinical visual field assessment with perimetry is practically impossible in patients less than nine years of developmental age. Electrophysiological studies in epileptic children suggest an impact on the retinal structures related to the cones. However, standard protocols are not field-specific and the deficits reported in the literature are not coherent with the peripheral deficit observed. Thus, this thesis aims to develop a fast and efficient electrophysiological protocol to examine the visual field’s integrity, which would be useful in pediatric testing and to assess the visual field long-term effects of the VGB in school-aged epileptic children exposed early in life. The first article concerns the method’s validation. The stimulation is made of two high-contrast radial checks reversing at two different temporal frequencies. Adult testing reveals that only one electrode (Oz) is needed to record simultaneously both central and peripheral visual fields and that steady-state use allows fast gathering of both electrophysiological responses. No effect of age or sex was found in the comparison of adult and child’ responses. Moreover, the visual acuity, as calculated by the binocular visual acuity index, was related to the central signal when comparing healthy participants with central visual impaired adolescents. Our method presents several advantages in evaluating visual fields integrity, as it is fast, reliable and efficient, and applicable in children. The aim of the second article of the thesis is the assessment of the long term visual effect on the visual field in children exposed to VGB in infancy in comparison to epileptic children exposed to other antiepileptics and with healthy children using the previously validated electrophysiology method with the addition of contrast variation and simultaneous recording of electroretinograms. Results reveal a cortical central deficit at high and mid-range contrast in VGB exposed-children and at high contrast in other antiepileptic exposed group. The contrast gain is also affected in both epileptic groups. The absence of difference between both epileptic groups does not allow distinguishing the impact of medication and/or seizure disorder. The peripheral retinal response is also altered in the VGB-exposed group in comparison to the healthy group. The peripheral retinal response is related to the exposition duration. This result concurs with previous studies in the literature. Finally, the results of the thesis offer an objective, fast, efficient and alternative method to assess visual fields in children. They also bring a new point of view on the likely long term impacts of the VGB in children exposed in infancy.

Objetivo: Avaliar os efeitos da desnutrição intra-uterina na acuidade visual (AV) de resolução de grades pelo Potencial Visual Evocado de Varredura (PVEv) e Cartões de Acuidade de Teller (CAT). Método: Avaliamos a AV de resolução de grades, binocularmente, de 41 recém-nascidos com idade estacional 37 semanas, destes 23 nasceram com o peso adequado para a idade gestacional (AIG - Idade: 14,3 ± 7,5 semanas) e 18 nasceram pequenos para a idade gestacional (PIG - Idade: 10,7 ± 4,1semanas). A AV foi determinada usando ambas as técnicas psicofísica (CAT) e eletrofisiológica (PVEv). Durante o teste dos CAT foram apresentados cartões contendo em um dos lados grades de ondas quadradas pretas e brancas com freqüência espacial entre 0,23 e 19 ciclos por grau de ângulo visual a 55 cm do participante. O teste iniciou com o cartão com a freqüência espacial mais baixa com orientação randômica desconhecida pelo experimentador. Cartões contendo freqüências espaciais mais altas foram apresentados gradativamente até que uma resposta incorreta ocorresse, então o cartão anterior era apresentado novamente. A AV foi definida pela média aritmética das freqüências espaciais contidas nos cartões para 4 reversões. Para o registro do PVEv, o sistema PowerDiva (Brosnahan et al., 1998) foi usado para gerar todos os estímulos e analisar as repostas provocadas. Estímulos de grades senoidais em reversão de fase em 3, 6 ou 10 Hz foram apresentados em monitor de vídeo monocromático de 21 polegadas com luminância média de 161,13 cd/m2. Registramos o eletroencefalograma com três eletrodos ativos (O1, Oz, O2) relacionados ao eletrodo de referência no vertex. Durante cada tentativa com duração de 10 segundos, resentávamos uma faixa de freqüência espacial que aumentava linearmente. Para cada condição (freqüência temporal - FT) foram usadas no mínimo três tentativas para estimar o limiar. Consideramos o canal que registrou a AV mais alta com boa razão sinal-ruído (SNR>3:1), fase constante e critério estatístico. Resultados: Não encontramos diferenças significativas na AV entre os grupos para nenhum dos métodos. Para o PVEv, não encontramos diferenças significativas na AV, amplitude, ruído ou SNR entre os grupos para nenhuma das FT. Análises intra-grupos mostraram que os valores de amplitude, SNR e ruído foram significativamente diferentes entre as freqüências temporais apenas para os PIG. Entretanto, os PIG até 8 semanas de idade mostraram uma tendência para amplitudes e SNR mais altas para a FT de 3 Hz comparadas aos AIG. Esses mesmos PIG mostraram uma tendência para valores de fase maiores respostas lentas) em comparação aos AIG. Entretanto, a taxa de desenvolvimento da fase foi maior para os PIG do que para os AIG em todas as FT. Conclusão. Não há alteração significativa na AV de recém-nascidos PIG, entretanto as informações de medidas supra-limiares são consistentes com a hipótese que a desnutrição intra-uterina torna as respostas visuais mais lentas entre a retina e o córtex visual. Os dados também sugerem de forma sutil que tais efeitos são passageiros afetando primariamente o grupo de recém-nascidos mais jovens e que o sistema visual dos PIG tem plasticidade suficiente para atingir rapidamente os níveis normais. Mais dados serão necessários para validar esta interpretação. / Objective: To evaluate the effects of intra-uterine malnutrition on grating visual acuity (VA) using Sweep VEP and Teller Acuity Cards (TAC). Method: Binocular grating acuity was evaluated in 41 newborns with gestational age 37 weeks. Twentythree were born with appropriate weight for gestational age (AGA age: 14.3 ± 7.5 weeks) and 18 were born small for gestational age (SGA age: 10.7 ± 4.1 weeks). Visual acuity was determined using both psychophysical (Teller Acuity Cards) and electrophysiological (sVEP) techniques. For the TAC evaluation, cards having calibrated black and white square waves gratings at spatial frequencies (SFs) between 0.23 and 19 cycles/degree were presented 55 cm from the subject. The test began with the lowest SF card in random orientation to which the experimenter was blind. Subsequent cards were presented in order of increasing SF until an incorrect response was made, at which time the prior (lower-SF) card was presented again. Visual acuity was defined as the average of the SF values for 4 reversals. For the sVEP recordings, the PowerDIVA VEP system (Brosnahan et al., 1998) was used to generate all stimuli and analyze the evoked responses. Stimuli were spatial luminance sinewave gratings presented on a 21-inch monochromatic high-resolution monitor (1600x1200 pixels) with an average luminance of 161.1 cd/m2. Gratings were phase-reversed at either 3, 6 or 10 Hz. The electroencephalogram was recorded using 3 active electrodes (O1,Oz,O2) related to the reference electrode at vertex. During each 10-sec sVEP trial a linear sweep of increasing SF was presented. Sweep ranges were selected according to the subjects age. For each condition (each TF), a minimum of 3 trials were used to estimate thresholds, but the majority of measures were the result of a vector average of 5 to 10 trials. For each condition, the acuity estimate used derived from the channel with the highest acuity with statistically significant signal-to-noise ratio (>3:1) and stable phase during the high-SNR portion of the response. Results: There were no statistical differences in visual acuity between the two groups (SGA and AGA) for either method (sVEP or TAC). For the sVEP, acuities were not statistically different for the different TFs. There were also no statistical differences between groups for the sVEP measures of amplitude, phase, noise or signal-to-noise ratio. Intra-group analysis of the sVEP measures at the three TFs revealed statistical differences for amplitude, noise and signal-to-noise ratio, but only for SGA group. However, the SGA subjects less than or equal to 8 weeks of age showed a tendency for higher amplitudes and SNR for 3Hz temporal frequency compared to AGA subjects, and these same SGA subjects showed tendency for larger phase values (slower responses) compared to AGA. However, phase development rate was faster for SGA than for AGA for all temporal frequencies. Conclusion: There were no significant alterations of visual acuity in SGA babies, but the data from suprathreshold measures are consistent with the hypothesis that intrauterine malnutrition results in slower visual responses between retina and cortex. The data obtained so far suggest that such affects are transient, affecting primarily the younger group of infants, and that the visual system in SGA infants has sufficient plasticity to recover rapidly to normal levels. More data is needed to validate this interpretation of the results.