Failing eyesight causes a dramatic change in life. The aim of this project is to help people with large central visual field loss to better utilize their remaining vision. Central visual field loss means that the person has to rely on peripheral vision since the direct vision is lost, often due to a dysfunctional macula. In these cases, a full restoration of vision would require replacement or repair of the damaged retinal tissue, which is not yet possible. Instead, the present study seeks to improve peripheral vision by enhancing the image quality on the remaining functional part of the retina by optical corrections. The off-axis optics of the human eye often suffers from large optical errors, which together with the lower sampling density of the retina explain the limited visual function in the periphery. The dominating aberrations are field curvature and oblique astigmatism, which induce an effective eccentric refractive error. However, the irregular character of the aberrations and the limited neural function in the periphery will make it difficult to find the optimal refractive correction; the conventional subjective refraction, for example, is not suitable for subjects with large central visual field loss. Within the work of this thesis a Hartmann-Shack wavefront sensor has been constructed for oblique aberration measurements. Wavefront sensing is an objective method to assess detailed information about the optical errors in the human eye. Theory and methods have been developed to allow accurate off-axis measurements of the large aberrations, enable eccentric fixation, and handle the elliptical pupil. The study has mainly concentrated on sphero-cylindrical correction of peripheral vision. Peripheral resolution and detection acuity thresholds have been evaluated for seven subjects with central visual field loss and ten control subjects with normal vision. Five of the subjects with field loss showed improved resolution acuity with eccentric refractive correction compared to their habitual central correction, whereas little change was found for the control subjects. These results demonstrate that correction of peripheral optical errors can be beneficial to people with large central visual field loss in situations where a normal healthy eye does not experience any improvements. In conclusion, it is worthwhile to investigate the peripheral refractive errors in low-vision rehabilitation of central visual field loss and prescribe spectacle correction when those errors are large. / QC 20100809

Les processus de plasticité cérébrale entrainés par la perte visuelle restent un domaine méconnu dans le champ des neurosciences. La vision centrale et périphérique, le meilleur compromis évolutionniste entre une bonne résolution spatiale et un volume d’espace échantillonné maximal, sont traitées par des régions différentes du cerveau. Par conséquent, étudier et comprendre l’impact de la perte visuelle centrale ou périphérique dans ces régions constitue une étape cruciale dans l’étude du cerveau visuel. Afin d’étudier ces processus, nous avons utilisé deux modèles de perte visuelle sélective de la vision centrale (la dystrophie maculaire de Stargardt) et périphérique (la rétinopathie pigmentaire), et nous avons évalué l’impact à terme de ces deux types de désafférentation sur la structure et la connectivité fonctionnelle du cerveau. 1. Plasticité structurelle induite par la perte sélective de la vision centrale ou périphérique. Nous avons étudié l’épaisseur corticale (EpCo) et de l’entropie corticale (EnCo, marquer de complexité synaptique) du lobe occipital, région pour laquelle nous disposons d’une cartographie complète des régions cytoarchitectoniques. Nous avons constaté que la perte de la vision centrale induit un amincissement des régions appartenant au flux dorsal, tandis que la perte de la vision périphérique occasionne un amincissement du cortex visuel primaire (CVP), ainsi que des régions du flux ventral et dorsal. Ces effets étaient inattendus si on se rapporte au modèle canonique qui associe la vision centrale au flux ventral et la vision périphérique au flux dorsal. La normalité de l’EnCo dans ces régions, suggère que la complexité synaptique est préservée dans les réseaux neuronaux résiduels. Nous avons identifié des modifications de l’EnCo seulement en cas de perte de la vison centrale, où l’augmentation de l’EnCo dans des régions impliquées dans la reconnaissance des objets pourrait traduire une réponse adaptative à la perte de la haute résolution spatiale de cette partie du champ visuel. Cette augmentation de la complexité synaptique pourrait compenser une éventuelle perte neuronale et être responsable de la normalité de l’EpCo dans ces régions. 2. Plasticité de la connectivité fonctionnelle des régions du cortex visuel primaire recevant les projections de la partie centrale » et périphérique champ visuel Dans cette étude, nous avons exploré et comparé la connectivité fonctionnelle des régions afférentées et desafférentées du CVP de sujets souffrant de dystrophie maculaire de Stargardt et retinitis pigmentosa, avec les régions afféréntées correspondantes du CVP de sujets avec une vision normale. Cette étude a révélé une réorganisation fonctionnelle distincte du CVP afférenté et désafférenté. Ainsi, le CVP qui reçoit les afférences visuelles résiduelles présente une connectivité fonctionnelle accrue avec des régions voisines, probablement afin de favoriser le traitement de l’information visuelle, tandis que le CVP désafférenté augmente sa connectivité fonctionnelle avec des régions plus éloignées, vraisemblablement pour contribuer aux fonctions supérieures et à des processus de type top-down. L’analyse comparative des données morphologiques et fonctionnelles suggère une correspondance des régions amincies du cortex visuel associatif avec des régions qui montrent une diminution de la connectivité fonctionnelle avec le CVP périphérique, et des régions présentant une augmentation de la complexité synaptique avec des régions qui montrent une connectivité fonctionnelle accrue avec le CVP périphérique. Ces données suggèrent que la désafferentation sensorielle du CVP périphérique est plus propice au développement d’une réorganisation cérébrale. Synoptique : Ces travaux révèlent un aspect inattendu de la plasticité cérébrale induite une perte isolée de la vision centrale ou périphérique. La réorganisation s’avère plus complexe que le laisser présager le modèle canonique actuel, vraisemblablement trop simple. / Cerebral plasticity induced by visual loss represents a poorly understood field of neuroscience, with numerous questions that don’t yet have an answer. Central and peripheral vision, the evolutionary compromise between spatial resolution and the sampled space volume, are processed in distinct areas of the brain. Understanding the impact of vision loss in theses regions, is of utmost interest for the study of visual brain. Herein, in two models of retinal disorders affecting central and peripheral vision (namely Stargardt macular dystrophy and retinitis pigmentosa), we specifically investigated the effects of the central and peripheral visual loss on brain morphology and its functional connectivity. 1. Morphological plastic changes induced by central and peripheral visual loss. We explored the effects of visual loss on cortical thickness (CoTks) and cortical entropy (CoEn, marker of synaptic complexity) in the cytoarchytectonic regions of the occipital lobe. Central visual loss associated thinning in dorsal stream regions, while peripheral visual loss in early visual cortex (EVC) and regions belonging both to dorsal and ventral stream. Theses effects were unpredicted by the canonical view “central vision – ventral stream”, “peripheral vision – dorsal stream”. Normal CoEn in theses areas suggests that synaptic complexity is preserved in the remaining networks. Only central visual field loss presented CoEn alterations, namely an increase in areas involved in object recognition, that likely reflects a synaptic complexity enhancement in response to the loss of the high spatial resolution of central vision. The gain in synaptic complexity could mask neuronal loss due to deafferentation and may account for the CoTks normality. 2. Plastic changes in the functional connectivity of central and peripheral EVC. We explored and compared to normally afferented EVC, the functional connectivity of afferented and deafferented parts of EVC and found that central and peripheral visual loss induce different patterns of reorganization. Residually afferented early visual cortex reinforce local connections presumably to enhance the processing of altered visual input, while deafferented EVC strengthen long-range connections presumably to assist high-order functions. Combined structural and functional data indicate that areas with reduced CoTks superpose with several areas presenting reduced functional connectivity with the peripheral EVC and that areas with increased CoEn superpose with several areas presenting increased functional connectivity with afferented peripheral EVC. These data point that alterations of the sensory input to the peripheral field are more prone to induce plastic changes. Overview : Data in the current work provide an interesting perspective about the plasticity following central or peripheral visual field loss and show that it is more complex than the canonical model would have let to presume.

The loss of central vision subsequent to macular disease is often extremely debilitating. People with central field loss (CFL) must use other peripheral areas of the retina in order to see; areas with inferior resolution capacity, which are also affected by off-axis optical errors. The overall aim of the work encompassed by this thesis was to identify and evaluate methods of improving vision for people with CFL; with focus on the effects of off-axis optical correction and stimulus motion on resolution acuity and contrast sensitivity. Off-axis optical errors were measured using a commercially-available COAS-HD VR open-view aberrometer. We used adaptive psychophysical methods to evaluate grating resolution acuity and contrast sensitivity in the peripheral visual field; drifting gratings were employed to   measure the effect of motion on these two measures of visual performance. The effect of sphero-cylindrical correction and stimulus motion on visual performance in healthy eyes and in subjects with CFL was also studied; in addition, the effect of adaptive optics aberration correction was examined in one subject with CFL. The COAS-HD aberrometer provided rapid and reliable measurements of off-axis refractive errors. Correction of these errors gave improvements in low-contrast resolution acuity in subjects with higher amounts of oblique astigmatism. Optical correction also improved high-contrast resolution acuity in most subjects with CFL, but not for healthy subjects. Adaptive optics correction improved both high and low contrast resolution acuity in the preferred retinal locus of a subject with CFL. The effect of stimulus motion depended on spatial frequency; motion of 7.5 Hz improved contrast sensitivity for stimuli of low spatial frequency in healthy and CFL subjects. Motion of 15 Hz had little effect on contrast sensitivity for low spatial frequency but resulted in reduced contrast sensitivity for higher spatial frequencies in healthy subjects. Finally, high-contrast resolution acuity was relatively insensitive to stimulus motion in the periphery. This thesis has served to broaden the knowledge regarding peripheral optical errors, stimulus motion and their effects on visual function, both in healthy subjects and in people with CFL. Overall it has shown that correction of off-axis refractive errors is important for optimizing peripheral vision in subjects with CFL; the use of an open-view aberrometer simplifies the determination of these errors. In addition, moderate stimulus motion can have a beneficial effect on contrast sensitivity for objects of predominantly low spatial frequency.