This thesis describes a series of investigations into the use of optic nerve head (ONH) imaging in primary open-angle glaucoma (POAG), and its relation to visual function. Accurate diagnosis is a key issue in POAG, particularly the difficult task of separating those with early disease from those healthy individuals who display signs of POAG. The purpose of this work is to improve diagnostic methods in glaucoma through use of ONH imaging and its relationship with visual field (VF) loss. First, the performance of a group of expert clinicians evaluating ONH photographs for glaucomatous damage was investigated. The results showed that even when their assessments are combined discrimination between eyes with and without POAG (based on VF loss) is far from perfect, highlighting the need for improvements in diagnosis. The possibility of combining structural and functional data to aid diagnosis was then considered. This requires VF loss and ONH damage to be strongly topographically related. The strength of this relationship was evaluated in 185 patients with POAG. 10,000 computer-generated maps between the ONH and VF were tested and the topographic relationship measured with each of these was compared to that using a published structure-based map. The weak topographic relationships found suggest that the application of these maps to individual patients is limited with current measures. The next chapter describes how a multispectral imaging (MSI, also called hyperspectral imaging) system was set-up for spatial evaluation of ONH oxygenation using a Beer-Lambert law model. Test-retest repeatability was tested and found to be acceptable for the purposes of the following studies. The MSI system was then used for an investigation of the relationship between ONH oxygenation and VF loss. 33 eyes of 18 patients underwent VF testing, MSI and HRT3 imaging. Superior-inferior asymmetries in VF sensitivity were compared to superior-inferior asymmetries in ONH oxygenation measured by MSI and in neuroretinal rim (NRR) area measured by HRT3. This way we take advantage of the typical progression of POAG and each eye acts as its own reference, negating the effect of a wide normal range and overlap between health and disease. This study found, for the first time, a strong association between ONH oxygenation and VF sensitivity. A re-analysis of the 33 ONH oxygenation maps was then performed to assess oxygenation only in the area of the NRR as defined by the HRT. Superior-inferior asymmetries in NRR oxygenation were then compared to superior-inferior asymmetries in VF loss, and the associations found were similarly strong. This study shows that MSI is capable of detecting areas of NRR deemed healthy tissue by structural imaging techniques, which are in fact poorly oxygenated and associated with VF defects. These findings show that NRR oxygenation measured by MSI is strongly related to VF loss. This important information complements existing technologies and may aid in the future diagnosis and management of patients with POAG.

Currently available methods for managing glaucoma, e.g. the planimetry on stereo disc photographs, involve a subjective component either by the patient or examiner. In addition, a few structures may overlap together on the essential 2-D images, which can decrease reproducibility. Spectral domain optical coherence tomography (SD-OCT) provides a 3-D, cross-sectional, microscale depiction of biological tissues. Given the wealth of volumetric information at microscale resolution available with SD-OCT, it is likely that better parameters can be obtained for measuring glaucoma changes that move beyond what is possible using fundus photography etc. The neural canal opening (NCO) is a 3-D single anatomic structure in SD-OCT volumes. It is proposed as a basis for a stable reference plane from which various optic nerve morphometric parameters can be derived. The overall aim of this Ph.D. project is to develop a framework to segment the 3-D NCO and its related structure retinal vessels using information from SD-OCT volumes and/or fundus photographs to aid the management of glaucoma changes. Based on the mutual positional relationship of the NCO and vessels, a multimodal 3-D scale-learning-based framework is developed to iteratively identify them in SD-OCT volumes by incorporating each other's pre-identified positional information. The algorithm first applies a 3-D wavelet-transform-learning-based layer segmentation and pre-segments the NCO using graph search. To aid a better NCO detection, the vessels are identified either using a SD-OCT segmentation approach incorporating the presegmented NCO positional information to the vessel classification or a multimodal approach combining the complementary features from SD-OCT volumes and fundus photographs (or a registered-fundus approach based on the original fundus vessel segmentation). The obtained vessel positional information is then used to help enhance the NCO segmentation by incorporating that to the cost function of graph search. Note that the 3-D wavelet transform via lifting scheme has been used to remove high frequency noises and extract texture properties in SD-OCT volumes etc. The graph search has been used for finding the optimal solution of 3-D multiple surfaces using edge and additionally regional information. In this work, the use of the 3-D wavelet-transform-learning-based cost function for the graph search is a further extension of the 3-D wavelet transform and graph search. The major contributions of this work include: 1) extending the 3-D graph theoretic segmentation to the use of 3-D scale-learning-based cost function, 2) developing a graph theoretic approach for segmenting the NCO in SD-OCT volumes, 3) developing a 3-D wavelet-transform-learning-based graph theoretic approach for segmenting the NCO in SD-OCT volumes by iteratively utilizing the pre-identified NCO and vessel positional information (from 4 or 5), 4) developing a vessel classification approach in SD-OCT volumes by incorporating the pre-segmented NCO positional information to the vessel classification to suppress the NCO false positives, and 5) developing a multimodal concurrent classification and a registered-fundus approach for better identifying vessels in SD-OCT volumes using additional fundus information.

Abstract Glaucoma is a group of eye diseases characterized by a chronic, progressive optic neuropathy. During the disease process, the axon damage of the retinal ganglion cells leads to changes in the retinal nerve fiber layer, causing optic nerve head, and visual field defects typical of glaucoma. The Heidelberg Retina Tomograph (HRT) is a confocal scanning laser imaging device acquiring and analysing three-dimensional data of the ocular fundus wit good accuracy and reproducibility. Conventional planimetric measurements were compared to those taken with the HRT in a pilot study of 12 eyes with early glaucomatous optic disc, retinal nerve fiber layer and/or visual field abnormalities. The neuroretinal rim area measurements and cup-to-disc area ratio did not differ statistically from each other when using these two different methods. The effect of four different reference levels on the HRT parameter measurement values was tested in two separate studies. In the first study there were 67 eyes, 40 of the eyes were healthy and 27 eyes had glaucoma of different stages. Then, 279 eyes, 180 of which were non-glaucomatous and 99 glaucoma eyes, were included in another study. The flexible reference level gave the most reliable HRT parameter measurement values in both non-glaucomatous and glaucomatous eyes. The ability of the HRT parameters to separate between non-glaucomatous and glaucomatous eyes was tested in 77 eyes, 40 of the eyes were non-glaucomatous, 10 ocular hypertensives and 27 eyes had different stages of glaucoma. The reference level dependent HRT parameters cup-to-disc area ratio, vertical linear cup-to-disc ratio, mean retinal nerve fiber layer thickness (RNFLt) and rim volume as well as the reference level non-dependent HRT parameter, cup shape measure (CSM), separated best between the clinical groups. The best combination of the HRT and other structural and functional parameters in separating between non-glaucomatous and glaucomatous eyes was studied in 55 eyes. There were 32 non-glaucomatous eyes and 23 eyes with ocular hypertension or glaucoma. CSM, RNFLt, together with age- and lens coloration-corrected mean deviation of the B/Y perimetry showed good discrimination (ROC area 0.91) between non-glaucomatous and glaucomatous eyes. / Tiivistelmä Glaukooma koostuu joukosta hitaasti eteneviä näköhermon rappeumasairauksia. Sairausprosessin aikana verkkokalvon gangliosolujen aksonivaurio johtaa muutoksiin verkkokalvon hermosäiekerroksessa ja näköhermon päässä aiheuttaen glaukoomalle tyypillisiä näkökenttämuutoksia. The Heidelberg Retina Tomograph (HRT) on konfokaali laserskanneritekniikkaan perustuva kuvantamislaite, joka tuottaa ja analysoi silmänpohjasta saatua kolmiulotteista mittaustietoa tarkasti ja toistettavasti. Tavanomaisen planimetrian antamia mittaustuloksia verrattiin HRT:n antamiin tuloksiin 12:ssa silmässä, joissa oli todettu varhaisia glaukoomamuutoksia. Näköhermon pään hermoreunan (rim) pinta-ala ja keskuskuopan suhde papillan läpimittaan eivät poikenneet tilastollisesti toisistaan näitä kahta menetelmää käytettäessä. Neljän eri referenssitason vaikutusta HRT-parametrien mittausarvoihin testattiin kahdessa eri tutkimuksessa. Ensimmäisen tutkimusaineisto koostui yhteensä 67:stä silmästä, joista 40 oli terveitä ja 27:ssä eriasteisia glaukoomamuutoksia. Toisessa tutkimuksessa oli yhteensä 279 silmää, joista 180 oli terveitä ja 99:llä oli glaukooma. Papillomakulaarisäikeisiin tukeutuva, fleksiibeli referenssitaso antoi luotettavimmat HRT-parametrien mittaustulokset sekä terveissä että glaukoomasilmissä. HRT-parametrien kykyä erottaa terveet silmät glaukomatoottisista testattiin yhteensä 77:ssä silmässä, joista 40 oli terveitä, 10 oli korkeapaineisia ilman glaukoomamuutoksia, ja 27:ssä oli glaukoomamuutoksia. Referenssitasosta riippuvaiset HRT-parametrit, keskuskuopan suhde papillan läpimittaan, vertikaali-lineaarinen keskuskuopan suhde papillan läpimittaan, keskimääräinen verkkokalvon hermosäiekerroksen paksuus (RNFLt) ja `rim´:in tilavuus samoin kuin referenssitasosta riippumaton keskuskuopan ´vinous´-mitta (CSM) erottelivat parhaiten nämä kliiniset ryhmät toisistaan. Terveitä ja glaukoomasilmiä erottelevaa HRT:n ja muiden rakenteellisten ja toiminnallisten parametrien kombinaatiota etsittiin 55:n silmän aineistosta. Silmistä 32 oli terveitä ja 23 korkeapaineisia ja/tai glaukoomavaurioisia. CSM ja RNFLt, yhdessä iän ja mykiövärjäytymisen suhteen korjatun sinikeltaperimetrian keskipoikkeaman kanssa osoittivat hyvää erottelukykyä (ROC area 0.91) terveiden ja glaukoomasilmien välillä.

Optic nerve head and macula are important structures in fundus images. Detection and measurement plays crucial role in several diagnosis methods of optic disease. This work is focused on the detection of the central point of macula and optic nerve head, where the inner border is detected too. There are many methods for extracting this structure in retinal images. Due to the unique properties of each acquisition technique, a single generally acknowledged detection algorithm does not exist. The whole detection process is described from preprocessing through segmentation towards postprocessing. Presented methods are based on the combination of correlation techniques, Hough transform, active contours and morphological operations. The detected contours of the optic nerve head are evaluated and quantitatively compared with the contour drawn by experienced ophthalmologist. The master thesis contains quantity of images that help to describe detection methods.

The main target of this work is a design of the program for border localization of the optic disc in OCT data. Part of this program is also localization of the „optic cup“ and calculation of several values that characterize optic disc. The work is also dealing with a description of the optical coherence tomography principle which is used in ophthalmology. One chapter describes some published methods of optic cup localization. Success of the program and its comparison with OCT Zeiss Stratus 3000 is evaluated at the end of the work.

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

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

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