Automated Bruch’s Membrane Opening Segmentation in Cases of Optic Disc Swelling in Combined 2D and 3D SD-OCT Images Using Shape-Prior and Texture Information

When the optic disc is swollen, the visibility of the Bruch’s membrane opening (BMO) is often drastically reduced in spectral-domain optical coherence tomography (SD-OCT) volumes. Recent work pro- posed a semi-automated method to segment the BMO using combined information from 2D high-definition raster and 3D volumetric SD-OCT scans; however, manual placement of six landmark points was required. In this work, we propose a fully automated approach to segment the BMO from 2D high-definition and 3D volumetric SD-OCT scans. Using the topographic shape of the internal limiting membrane and textural information near Bruch’s membrane, two BMO points are first estimated in the high-definition central B-scan and then registered into the corresponding volumetric scan. Utilizing the information from both the high- definition BMO estimates and the standard-definition SD-OCT volume, the cost image was created. A graph-based algorithm with soft shape-based constraints is further applied to segment the BMO contour on the SD-OCT en-face image domain. Using a set of 23 volumes with reasonably centered raster scans and swelling larger than 14.42 mm3, the fully automated approach was significantly more accurate than a traditional approach utilizing information only from the SD-OCT volume (RMS error of 7.18 vs. 21.37 in pixels; p < 0.05) and had only a slightly higher (and not significantly different) error than the previously proposed semi-automated approach (RMS error of 7.18 vs. 5.30 in pixels; p = 0.08)

Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure: Effect of Image Acquisition Pattern and Image Analysis Method, a Preliminary Study

Background/Aims: High intracranial pressure (ICP) is associated with changes in peripapillary Bruch's membrane (pBM) shape on optical coherence tomography (OCT) images of the optic nerve head. It is not known if image acquisition pattern and analysis method impact this association.Materials and Methods: Cross sectional OCT scans of the optic nerve head were obtained at six angles using a radial scan pattern in 21 subjects immediately prior to ICP measurement via lumbar puncture. On each image, Bruch's membrane was manually segmented and defined by either 14 or 16 semi-landmarks and either rater identified, or distance identified boundaries. For each of these four image analysis strategies, geometric morphometric analysis identified the first principal component of Bruch's membrane shape for all images and for the set of images taken at each angle. Repeated measures ANOVA of the first principal component magnitude (PC1) for all images assessed for shape difference between image angles. Linear generalized estimating equation models assessed association between angle specific first principal component magnitudes (PC1) and ICP for each angle. Receiver operating characteristic analysis assessed angle specific PC1s' ability to differentiate elevated from normal ICP.Results: The first principal component represented deflection into the vitreous for all scan angles, but quantitatively differed across scan angles (p &lt; 0.005, repeated measures ANOVA). Angle specific first principal components were positively correlated with ICP (p &lt; 0.005 for all angles, generalized estimating equation models). All angle specific first principal components showed excellent ability to classify ICP (area under curve ≥ 0.8 for all). These results were independent from image analysis strategy.Discussion: Though qualitative changes in Bruch's membrane shape are similar regardless of cross-sectional angle of the 2-D OCT scan, they differ quantitatively between OCT scan angles, meaning that pBM is not axially symmetric and therefore PC1 extracted from different 2-D scan angles can't be compared between individuals. However, we do not identify an optimal scan angle for classification of ICP since there is a similarly strong linear relationship between the first principal component of shape and ICP and angle specific first principal components of Bruch's membrane shape showed similarly excellent ability to differentiate elevated from normal ICP. The results support development of Bruch's membrane shape extracted from 2-D cross sectional optic nerve head OCT scans as a biomarker of ICP and emphasize the importance of consistency of scan angle. This is relevant for developing diagnostic protocols that use OCT to detect high ICP states

Neue Methoden der Nachbearbeitung und Analyse retinaler optischer Kohärenztomografieaufnahmen bei neurologischen Erkrankungen

Viele neurologische Krankheiten verursachen Veränderungen in der Netzhaut, die mit Hilfe der optischen Kohärenztomography (optical coherence tomography, OCT) dargestellt werden können. Dabei entstehen viele Bilddaten, deren Auswertung zeitintensiv ist und geschultes Personal erfordert. Ziel dieser Arbeit war die Entwicklung neuer Methoden zur Vorverarbeitung und Analyse retinaler OCT-Bilddaten, um Outcome-Parameter für Studien und diagnostische Marker für neurologische Erkrankungen zu verbessern. Dazu wurden Methoden für zwei wichtige Aufnahmebereiche der Netzhaut, den Sehnervenkopf (optic nerve head, ONH) und die Makula, entwickelt. Für den ONH-Bereich wurde eine automatische Segmentierung auf Basis aktiver Konturen entwickelt, die eine akkurate Segmentierung der inneren Grenzmembran auch bei komplexer Topografie ermöglicht. Für den Bereich um die Makula entstand eine intraretinale Schichtensegmentierungspipeline, die von der Auswahl der Bilddaten über die automatische Segmentierung sowie die manuelle Nachkorrektur bis zur Ausgabe verschiedener Schichtdicken in Tabellenform reicht. Für beide Aufnahmebereiche wurden mehrere Programme entwickelt, die auf einer gemeinsamen Basis zur Verarbeitung von OCT-Daten fußen. Eines dieser Programme bietet eine grafische Oberfläche zur manuellen Verarbeitung der Bilddaten. Mit dieser Software wurden Teile der Referenzdaten manuell erstellt, die innere Grenzmembran des ONH automatisch segmentiert sowie eine komfortable Nachbearbeitung von intraretinalen Segmentierungen vorgenommen. Dies ermöglichte die automatische Auswertung morphologischer Parameter des ONH, wovon einige signifikante Unterschiede zwischen Patienten mit neurologischen Krankheiten und gesunden Kontrollen zeigten. Weiter kam die Schichtensegmentierungspipeline beim Aufbau einer normativen Datenbank sowie in einer Studie zum Zusammenhang des retinalen Schadens mit der kritischen Flimmerfrequenz zum Einsatz. Ein Teil der Software wurde als freie und quelloffene Software (free and open-source software, FOSS) und der normative Datensatz für die Verwendung in anderen Studien freigegeben. Beides wird bereits in weiteren Studien eingesetzt und wird auch die Durchführung zukünftiger Studien vereinfachen sowie die Entwicklung neuer Methoden unterstützen.Many neurological diseases cause changes in the retina, which can be visualized using optical coherence tomography (OCT). This process produces large amounts of image data. Its evaluation is time-consuming and requires medically trained personnel. This dissertation aims to develop new methods for preprocessing and analyzing retinal OCT data in order to improve outcome parameters for clinical studies and diagnostic markers for neurological diseases. For this purpose, methods concerning the regions of two landmarks of the retina, the optic nerve head (ONH) and the macula, were developed. For the ONH, an automatic segmentation method based on active contours was developed, which allows accurate segmentation of the inner limiting membrane even in complex topography. For the macular region, an intraretinal layer segmentation pipeline from image data via automatic segmentation to manual post-correction and the output of different layer thicknesses in tabular form was developed. For both, ONH and macular region, several programs were developed, which share a common basis for processing OCT data. One of these programs offers a graphical user interface for the manual processing of image data. Parts of the reference data were created manually using this software. Moreover, the inner limiting membrane of the ONH was segmented automatically and post-processing of intraretinal segmentations was performed. This allowed for automatic evaluation of morphological parameters of the ONH, some of which showed significant differences between patients with neurological diseases and the healthy control group. Furthermore, the layer segmentation pipeline was utilized to create a normative database as well as to investigate the correlation of retinal damage and critical flicker frequency. Part of the software was released as free and open-source software (FOSS) and the normative data set was released for use in other studies. Both are already being used in further studies and will also aid in future studies, as well as support the development of new methods

Deep learning-based improvement for the outcomes of glaucoma clinical trials

Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management. To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial

Imaging of physiological retinal structures in various raptor species using Optical Coherence Tomography (OCT)

Die Optische Kohärenztomografie (OCT) ist eine neue Technik, die vor kurzem in der Humanophthalmologie etabliert wurde und sich durch ihr Potential auszeichnet, Retinastrukturen in vivo und nicht-invasiv (ohne Augenkontakt) in einer Qualität vergleichbar mit der von Histologieschnitten darzustellen. Diese Technik ermöglicht es, minimale pathologische Veränderungen bei fast histologischer Auflösung darzustellen, sowie longitudinale Untersuchungen im Verlauf der Erkrankung oder Therapie durchzuführen. In der Tiermedizin, vor allem in der Vogel-Ophthalmologie, wurde bis jetzt OCT nur sehr selten angewendet. Das Hauptziel dieser Studie war es daher, die Eignung der OCT-Technik als eine Darstellungsmethode in der Vogel-Ophthalmologie zu evaluieren. Um dieses Ziel zu erreichen, fokussierte diese Studie auf die Darstellung der physiologischen Retinastrukturen von Greifvögeln. Des Weiteren wurde die Anwendung von OCT bei vielen verschiedenen Greifvogelarten evaluiert, um erste Hinweise auf Unterschiede zwischen unterschiedlichen Arten und auf innerartliche Unterschiede der Retinastruktur zu gewinnen. Die Ergebnisse der OCT-Augenuntersuchungen wurden mittels histologischer Untersuchungen validiert. Um die Möglichkeiten der Darstellung der physiologischen Retinastrukturen von Greifvögeln mittels OCT zu überprüfen, wurden 56 wilde Tag- und Nachtgreifvögel drei verschiedener Familien und 12 verschiedener Arten untersucht. Alle einbezogenen Vögel waren Patienten der Klinik für Vögel, Reptilien, Amphibien und Zierfische der Ludwig-Maximilians-Universität München und wurden meist mit Verdacht auf Trauma vorgestellt. Die OCT-Untersuchungen wurden an Augen und Retinaregionen durchgeführt, welche nach einer vorherigen ophthalmologischen Untersuchung als gesund erachtet wurden. Bei Vögeln, die aufgrund ethischer und Tierschutzgründen euthanasiert werden mussten, wurden die Augen zur Validierung der OCT-Technik histologisch untersucht. Zur Darstellung der Retina wurde in der vorliegenden Untersuchung das Modell Spectralis® HRA+OCT Plus (Heidelberg Engineering, Heidelberg, Germany) verwendet. Die Bearbeitung der Fotos wurde mit der Spectralis Software Heidelberg Eye Explorer® (HEYEX) version 5.4 (October 2011, Heidelberg Engineering, Heidelberg, Germany) durchgeführt. Abhängig von der zu erwartenden Stresstoleranz des Patienten erfolgte die OCT Untersuchung im wachen Zustand oder es wurde vor Beginn der Untersuchung eine Sedation mit Midazolam (2 mg/kg KM) oder eine Inhalationsnarkose durchgeführt. Bei der Untersuchung des Fundus wurden fünf unterschiedliche Areale einbezogen, und zwar eine Region unmittelbar superior des Pecten oculi einschließlich eines Teils des Ansatzes des Sehnervenkopfes, die sagitalste Region des retinalen Äquators und des Fundus superior sowie die am weitesten temporal und nasal gelegenen Bereiche des Äquators. Dickemessungen der Retinaschichten in unterschiedlichen Retinaabschnitten wurden durchgeführt, um potentielle Dickeunterschiede darzustellen. Die Messungen beinhalteten erstens die gesamte Retina-Dicke (TRT) von dem retinalen Pigmentepithel bis zur Membrana limitans interna, zweitens die Nervenfaserschicht und Ganglienzellschicht (RNFL+GCL), drittens die äußere Retina (OR), mit den Schichten zwischen dem retinalen Pigmentepithel und der innersten Grenze der äußeren Körnerschicht, und viertens die Schichten zwischen dem retinalen Pigmentepithel und der äußeren Grenzmembran (RPE-ELM). Die histologischen Schnitte der Augen wurden nach einem Standardprotokoll mittels Davison’s Lösung als Fixation und Haematoxylin & Eosin Färbung angefertigt. Mittels OCT-Technik konnte die physiologische Struktur der Greifvogelretina mit einer Auflösung, die nicht von anderen tomographischen Techniken erreicht wird, reproduzierbar dargestellt werden. Die TRT und die RNFL+GCL war bei allen Spezies in der Region superior des Pectens maximal und verminderte sich zu den peripheren Regionen hin. Im Gegensatz dazu blieben die OR und die RPE-ELM von gleicher Dicke. Zwischen den einzelnen Spezies variierten die gemessenen Werte. Die gesamte Retinadicke (TRT) war bei Taggreifvögeln höher als bei Nachtgreifvögeln. Die Werte für OR und RPE-ELM hingegen waren bei Nachtgreifvögeln höer als bei Taggreifvögeln. Bei Pernis apivorus, Asio otus und Aegolius funereus konnte die äußere Körnerschicht nicht differenziert werden. Die OCT-Untersuchung der Greifvogel-Retina kann zusammenfassend als eine wertvolle Methode in der Vogelophthalmologie beurteilt werden. Diese Studie bietet die Grundlage für die Interpretation von OCT-Ergebnissen hinsichtlich pathologischer Veränderungen der Retina von Greifvögeln, sowie die Basis für eine in vivo Kontrolle von Krankheitsverläufen der Retina und die Beurteilung von Behandlungserfolgen über die Zeit.Optical coherence tomography (OCT) is a new technique which has recently been established for routine human ophthalmology, focusing on its potential to visualize retinal structures in vivo and non-invasive, without eye contact, in a quality close to histological sections. This technique therefore permits to detect ocular disorders at almost (interpolated) histological resolution and, to be pointed out, longitudinal investigations on the course of disease or therapy. In veterinary medicine, especially in avian ophthalmology, until now, OCT has been applied only very scarcely. The main purpose of the present study was to evaluate OCT technique as an adequate imaging method at the avian retina. The study focused on the visualization of the physiological retinal architecture in raptors. Secondly, the application of OCT was evaluated in a broad range of raptor species in order to get first indications of interspecific variations in retinal structure revealed by OCT. Finally, the results of OCT eye examination were validated using histology. In order to test the potential of OCT to visualize the physiological retinal architecture in raptors, 56 diurnal and nocturnal wild raptors belonging to 3 orders and 12 species, underwent OCT examination. All these birds were patients of the Clinic for Birds, Reptiles, Amphibians and Ornamental Fish of the University Ludwig Maximilian (Munich) and were brought to the clinic mainly with a history of trauma. The OCT examination was performed on eyes and retinal regions considered healthy based on a previous ophthalmoscopical examination. The eyes of the patients euthanized due to humanitarian reasons were destined to histology in order to validate the technique. A Spectralis® HRA+OCT Plus (Heidelberg Engineering, Heidelberg, Germany) was used to image and evaluate the retina of the patients. The processing of the pictures was made with the software Spectralis Software Heidelberg Eye Explorer® (HEYEX) version 5.4 (October 2011, Heidelberg Engineering, Heidelberg, Germany). Depending on the expected stress tolerance, the OCT examination was performed with the patient awake, under sedation with Midazolam (2 mg/kg BW) or under general anaesthesia with isoflurane inhalation anaesthesia. The areas of the fundus considered were the superior portion of the Pecten oculi including a part of the optical nerve head (ONH), the most sagittal area of the retinal equator, the most sagittal area of the superiorly visualized fundus, the most temporal equatorial fundus area and the most nasal equatorial fundus area. Thickness measurements of retinal layers in the different retinal areas were performed in order to record potential thickness variations. Measurements included first, the total retinal thickness, from the retinal pigment epithelium up to the internal limiting membrane; second, the retinal nerve fiber layer and ganglion cell layer; third, the outer retina, which included the layers between the retinal pigment epithelium up to the innermost border of the outer nuclear layer; and fourth, the layers between the retinal pigment epithelium and the external limiting membrane. The histological processing of the eyes followed a conventional method to obtain histological sections of the retina in birds, using the Davison’s solution as fixation solution, and haematoxylin & eosin staining. The physiological architecture of the raptor retina imaged could be visualized with reproduceable results, and at a resolution not available to date. Regarding the intraspecific variations, the total retinal thickness (TRT) and the retinal nerve fiber layer and anglion cell layer (RNFL+GCL) were maximal at the region cranial to the pecten and decreased to the peripheral regions in all the species. On the contrary, the outer retina (OR) and the layers between the retinal pigment epithelium and external limiting membrane (RPE-ELM) maintained their size along the whole retina. Between species, the thickness of the different retinal measurements varied. The TRT was higher in diurnal species than in nocturnal species. By contrast, OR and RPE-ELM showed higher measurements in the nocturnal species than in the diurnal species. In the species Pernis apivorus, Asio otus, and Aegolius funereus, the outer nuclear layer (ONL) could not be distinguished. In summary, the optical coherence examination of the raptor retina may be considered as an invaluable tool in the avian ophthalmology. This study provides a basis to perform a more accurate interpretation of pathological findings observed with OCT in the retina of birds of prey.La tomografía de coherencia óptica (OCT) es una técnica recientemente establecida en oftalmología humana de rutina, centrándose en la visualización de las estructuras de la retina en vivo, de forma no invasiva, sin contacto con el paciente y en una calidad cercana a la histología. Por ello esta técnica permite detectar desordenes oculares mínimos y de forma longitudinal, con lo que se puede seguir el curso de la enfermedad y la evolución de la terapia. En medicina veterinaria, especialmente en oftalmología aviar, esta técnica se ha aplicado de forma escasa. El objetivo principal del presente estudio fue evaluar la técnica de la OCT como método adecuado en oftalmología aviar. Para alcanzar este propósito el estudio se centró en la visualización de la arquitectura fisiológica de la retina en rapaces. Para ello se evaluó la aplicación de la OCT en un gran rango de especies de rapaces para obtener los primeros indicios de variaciones intraespecíficas en la estructura de la retina reveladas con la OCT. Para finalizar, los resultados se validarían utilizando histología. Como materiales y métodos para evaluar el potencial de la OCT se examinaron 56 aves rapaces, diurnas y nocturnas, de 3 órdenes y 12 especies. Los pacientes fueron en todos los casos de la Clínica de Aves, Reptiles, Anfibios y Peces Ornamentales de la Universidad Ludwig-Maximilian de Munich, prácticamente todos ellos a causa de un traumatismo. La OCT se llevó a cabo en los ojos y en las zonas de la retina consideradas sanas tras un previo examen oftalmoscópico. Los ojos de las aves que debieron eutanasiarse por razones de bienestar animal se destinaron a la validación de la técnica por medio de histología. El aparato utilizado para visualizar la retina de los pacientes fue el Spectralis® HRA+OCT Plus (Heidelberg Engineering, Heidelberg, Alemania) y el procesamiento de las imágenes a través del software Spectralis Software Heidelberg Eye Explorer® (HEYEX) versión 5.4 (Octubre 2011, Heidelberg Engineering, Heidelberg, Alemania). Dependiendo de la tolerancia demostrada por el paciente, la OCT se realizó con el paciente despierto, en sedación con midazolam (2 mg/Kg. MC) o bajo anestesia inhalatoria general. Las áreas del fondo de ojo consideradas en el estudio fueron la porción superior del Pecten oculi, incluyendo una parte de la cabeza del nervio óptico, las zonas más sagitales del ecuador y de la zona más superior visualizada y las zonas ecuatoriales más temporales y nasales visualizadas. En cada sección de cada área se llevaron a cabo medidas del grosor de las capas de la retina tales como el grosor de la retina total (TRT), la capa de fibras nerviosas de la retina junto con la capa de células ganglionares (RNFL+GCL), la retina externa (OR), y por último las capas comprendidas entre el epitelio pigmentario retiniano y la membrana limitante externa (RPE-ELM). Posteriormente los ojos a disposición de los pacientes eutanasiados se sometieron al procesado histológico utilizando como solución fijadora la solución de Davidson, y una tinción convencional de hematoxilina & eosina. La arquitectura fisiológica de la retina se visualizó de manera fiable con la técnica de la OCT, alcanzando resoluciones no posibles de alcanzar mediante otras técnicas topográficas. Entre las variaciones intraespecíficas observadas, se obtuvo como resultado que el TRT y el RNFL+GCL alcanzan valores máximos en el área craneal al pecten, y mínimos en las zonas de la retina excéntrica en todas las especies del estudio. Por el contrario, la OR y el RPE-ELM se mantuvieron constantes en grosor a lo largo de toda la retina. Se observaron grandes variaciones interespecíficas, entre los diferentes órdenes, y entre especies diurnas y nocturnas. El TRT es mayor en las especies diurnas que en las nocturnas. En cambio la OR y el RPE-ELM revelaron medidas más grandes en las especies nocturnas que en las diurnas. Una peculiaridad observada fue que en ciertas especies como Pernis apivorus, Asio otus, y Aegolius funereus, no se pudo observar la capa nuclear externa. Para finalizar, la tomografía ce coherencia óptica en cuanto al examen de la retina de las aves rapaces puede considerarse como una herramienta de incalculable valor en la oftalmología aviar. Este estudio proporciona la base para llevar a cabo una interpretación más exacta y adecuada de los hallazgos patológicos observados con la técnica de OCT en la retina de las aves rapaces

Intracranial hypertension in syndromic craniosynostosis:Prevalence, detection, pathophysiology and treatment

This thesis highlights several aspects regarding the clinical course and treatment of syndromic craniosynostosis. First, we evaluate the prevalence of (syndromic) craniosynostosis: how many children are born with this rare condition in the Netherlands? Thereafter, we focus on the detection of (risk factors for) elevated intracranial pressure: can we use the head circumference as a reliable indicator of the intracranial volume? Can we improve the detection of intracranial hypertension by adding retina scans to the follow-up protocol? Also, the consequences of raised intracranial pressure are assessed: do we see changes in brain cortical thickness? Or in the retinal thickness and/or visual acuity? Finally, we evaluated the treatment protocol for Muenke and Saehtre-Chotzen syndrome: how do we prevent and treat raised intracranial pressure in these syndromes? Should we focus on intracranial hypertension only?<br/

Intracranial hypertension in syndromic craniosynostosis:Prevalence, detection, pathophysiology and treatment

This thesis highlights several aspects regarding the clinical course and treatment of syndromic craniosynostosis. First, we evaluate the prevalence of (syndromic) craniosynostosis: how many children are born with this rare condition in the Netherlands? Thereafter, we focus on the detection of (risk factors for) elevated intracranial pressure: can we use the head circumference as a reliable indicator of the intracranial volume? Can we improve the detection of intracranial hypertension by adding retina scans to the follow-up protocol? Also, the consequences of raised intracranial pressure are assessed: do we see changes in brain cortical thickness? Or in the retinal thickness and/or visual acuity? Finally, we evaluated the treatment protocol for Muenke and Saehtre-Chotzen syndrome: how do we prevent and treat raised intracranial pressure in these syndromes? Should we focus on intracranial hypertension only?<br/

Ocular rigidity : a previously unexplored risk factor in the pathophysiology of open-angle glaucoma : assessment using a novel OCT-based measurement method

Le glaucome est la première cause de cécité irréversible dans le monde. Bien que sa pathogenèse demeure encore nébuleuse, les propriétés biomécaniques de l’oeil sembleraient jouer un rôle important dans le développement et la progression de cette maladie. Il est stipulé que la rigidité oculaire (RO) est altérée au travers les divers stades de la maladie et qu’elle serait le facteur le plus influent sur la réponse du nerf optique aux variations de la pression intraoculaire (PIO) au sein du glaucome. Pour permettre l’investigation du rôle de la RO dans le glaucome primaire à angle ouvert (GPAO), la capacité de quantifier la RO in vivo par l’entremise d’une méthode fiable et non-invasive est essentielle. Une telle méthode n’est disponible que depuis 2015. Basée sur l'équation de Friedenwald, cette approche combine l'imagerie par tomographie par cohérence optique (TCO) et la segmentation choroïdienne automatisée afin de mesurer le changement de volume choroïdien pulsatile (ΔV), ainsi que la tonométrie dynamique de contour Pascal pour mesurer le changement de pression pulsatile correspondant. L’objectif de cette thèse est d’évaluer la validité de cette méthode, et d’en faire usage afin d’investiguer le rôle de la RO dans les maladies oculaires, particulièrement le GPAO. Plus spécifiquement, cette thèse vise à : 1) améliorer la méthode proposée et évaluer sa validité ainsi que sa répétabilité, 2) investiguer l’association entre la RO et le dommage neuro-rétinien chez les patients glaucomateux, et ceux atteints d’un syndrome de vasospasticité, 3) évaluer l’association entre la RO et les paramètres biomécaniques de la cornée, 4) évaluer l’association entre la RO et les pics de PIO survenant suite aux thérapies par injections intravitréennes (IIV), afin de les prédire et de les prévenir chez les patients à haut risque, et 5) confirmer que la RO est réduite dans les yeux myopes. D’abord, nous avons amélioré le modèle mathématique de l’oeil utilisé pour dériver ΔV en le rendant plus précis anatomiquement et en tenant compte de la choroïde périphérique. Nous avons démontré la validité et la bonne répétabilité de cette méthodologie. Puis, nous avons effectué la mesure des coefficients de RO sur un large éventail de sujets sains et glaucomateux en utilisant notre méthode non-invasive, et avons démontré, pour la première fois, qu'une RO basse est corrélée aux dommages glaucomateux. Les corrélations observées étaient comparables à celles obtenues avec des facteurs de risque reconnus tels que la PIO maximale. Une forte corrélation entre la RO et les dommages neuro-rétiniens a été observée chez les patients vasospastiques, mais pas chez ceux atteints d'une maladie vasculaire ischémique. Cela pourrait potentiellement indiquer une plus grande susceptibilité au glaucome due à la biomécanique oculaire chez les patients vasospastiques. Bien que les paramètres biomécaniques cornéens aient été largement adoptés dans la pratique clinique en tant que substitut pour la RO, propriété biomécanique globale de l'oeil, nous avons démontré une association limitée entre la RO et ces paramètres, offrant une nouvelle perspective sur la relation entre les propriétés biomécaniques cornéennes et globales de l’oeil. Seule une faible corrélation entre le facteur de résistance cornéenne et la RO demeure après ajustement pour les facteurs de confusion dans le groupe des patients glaucomateux. Ensuite, nous avons présenté un modèle pour prédire l'amplitude des pics de PIO après IIV à partir de la mesure non-invasive de la RO. Ceci est particulièrement utile pour les patients à haut risque atteints de maladies rétiniennes exsudatives et de glaucome qui nécessiteraient des IIV thérapeutiques, et pourrait permettre aux cliniciens d'ajuster ou de personnaliser le traitement pour éviter toute perte de vision additionnelle. Enfin, nous avons étudié les différences de RO entre les yeux myopes et les non-myopes en utilisant cette technique, et avons démontré une RO inférieure dans la myopie axiale, facteur de risque du GPAO. Dans l'ensemble, ces résultats contribuent à l’avancement des connaissances sur la physiopathologie du GPAO. Le développement de notre méthode permettra non seulement de mieux explorer le rôle de la RO dans les maladies oculaires, mais contribuera également à élucider les mécanismes et développer de nouveaux traitements ciblant la RO pour contrer la déficience visuelle liée à ces maladies.Glaucoma is the leading cause of irreversible blindness worldwide. While its pathogenesis is yet to be fully understood, the biomechanical properties of the eye are thought to be involved in the development and progression of this disease. Ocular rigidity (OR) is thought to be altered through disease processes and has been suggested to be the most influential factor on the optic nerve head’s response to variations in intraocular pressure (IOP) in glaucoma. To further investigate the role of OR in open-angle glaucoma (OAG) and other ocular diseases such as myopia, the ability to quantify OR in living human eyes using a reliable and non-invasive method is essential. Such a method has only become available in 2015. Based on the Friedenwald equation, the method uses time-lapse optical coherence tomography (OCT) imaging and automated choroidal segmentation to measure the pulsatile choroidal volume change (ΔV), and Pascal dynamic contour tonometry to measure the corresponding pulsatile pressure change. The purpose of this thesis work was to assess the validity of the methodology, then use it to investigate the role of OR in ocular diseases, particularly in OAG. More specifically, the objectives were: 1) To improve the extrapolation of ΔV and evaluate the method’s validity and repeatability, 2) To investigate the association between OR and neuro-retinal damage in glaucomatous patients, as well as those with concomitant vasospasticity, 3) To evaluate the association between OR and corneal biomechanical parameters, 4) To assess the association between OR and IOP spikes following therapeutic intravitreal injections (IVIs), to predict and prevent them in high-risk patients, and 5) To confirm that OR is lower in myopia. First, we improved the mathematical model of the eye used to derive ΔV by rendering it more anatomically accurate and accounting for the peripheral choroid. We also confirmed the validity and good repeatability of the method. We carried out the measurement of OR coefficients on a wide range of healthy and glaucomatous subjects using this non-invasive method, and were able to show, for the first time, that lower OR is correlated with more glaucomatous damage. The correlations observed were comparable to those obtained with recognized risk factors such as maximum IOP. A strong correlation between OR and neuro-retinal damage was found in patients with concurrent vasospastic syndrome, but not in those with ischemic vascular disease. This could perhaps indicate a greater susceptibility to glaucoma due to ocular biomechanics in vasospastic patients. While corneal biomechanical parameters have been widely adopted in clinical practice as surrogate measurements for the eye’s overall biomechanical properties represented by OR, we have shown a limited association between these parameters, bringing new insight unto the relationship between corneal and global biomechanical properties. Only a weak correlation between the corneal resistance factor and OR remained in glaucomatous eyes after adjusting for confounding factors. In addition, we presented a model to predict the magnitude of IOP spikes following IVIs from the non-invasive measurement of OR. This is particularly useful for high-risk patients with exudative retinal diseases and glaucoma that require therapeutic IVIs, and could provide the clinician an opportunity to adjust or customize treatment to prevent further vision loss. Finally, we investigated OR differences between non-myopic and myopic eyes using this technique, and demonstrated lower OR in axial myopia, a risk factor for OAG. Overall, these findings provide new insights unto the pathophysiology of glaucomatous optic neuropathy. The development of our method will permit further investigation of the role of OR in ocular diseases, contributing to elucidate mechanisms and provide novel management options to counter vision impairment caused by these diseases