An investigation of the spectral reflectance of the fundus in normals and patients with common eye diseases was carried out using a multi wavelength scanning laser ophthalmoscope (SLO). With a knowledge of the spectral properties of the principal ocular pigments in the fundus, the appearance of the retina and choroid is predictable in normal subjects. The optic disc has a characteristic dark appearance when viewed with the SLO, and reasons for this may include a filtering effect of the confocal aperture to reduce the return of scattered light to the detector. In patients with macular exudates these features have a high reflectance in green-yellow light. An image processing method has been developed to quantify exudates and this was applied to SLO images and digitised colour slides of the same patients. Results show similar performance of processing in both image types with high accuracy (90% sensitivity for 95% specificity). A similar experiment was carried out on patients with macular drusen. These structures are of lower intensity than exudates and may have less well-defined borders. Again performance of the image processing methods showed broadly similar performance when comparing SLO images and digitised colour slides (60 to 68% sensitivity for 95% specificity). A study was carried out to assess the ability of the SLO to image the fundus in patients with cataract using a range of wavelengths. In conclusion the SLO offers the ability to image the fundus at selected wavelengths to enhance the desired features under investigation. As a fundus camera, used to generate digital images, it is unlikely to offer significant improvements over commercially available digital imaging CCD cameras. However, the SLO has properties which are likely to make it an ideal instrument for reflectometry, angiography and fundus topography. These applications are discussed in the final chapter.

No description available.

Age-related macular degeneration (AMD) is the leading cause of Government-registered blindness in the elderly of the Western world and has two forms: wet and dry. No current AMD therapies are curative, and most are provided after retinal damage from the disease has already occurred (to preserve what is left of the retina). We have constructed a multi-factorial Phase II randomized, controlled clinical trial, titled: “Omega-3 docosahexaenoic acid(DHA) and eicosapentaenoic acid (EPA) nutritional supplementation to delay the progression of age-related macular degeneration (AMD): The OMEGAlberta Study”. Each day, participants in the experimental arm of this study will receive 600mg DHA and 1200mg EPA, plus Vitalux AREDS antioxidant formula. Based on the physicochemical properties of DHA, EPA, and Vitalux, our aim is to delay the 5-year incident rate of progression of intermediate dry AMD to wet AMD. Several tests will be performed, not only to quantify the incident rate of progression of AMD, but also to gain insight of the physiological mechanisms behind the supplements being provided. If the supplements are proven to delay AMD progression, this knowledge should be implemented by changes in health services and policy relating to public education and the treatment of AMD.

Final publication is available at http://www.sciencedirect.com/science/article/pii/S0002939414000488 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19586号 / 医博第4093号 / 新制||医||1014(附属図書館) / 32622 / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 宮本 享, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Doctor of Philosophy (PhD) / BACKGROUND: The accumulation of abnormal extracellular deposits beneath the retinal pigment epithelium characterises the pathology of early age-related macular degeneration. However, the histopathological threshold at which age-related changes become early AMD is not defined, and the effect of each of the deposits (basal laminar deposit and membranous debris) on disease progression is poorly understood. Evidence suggests that macrophages play a key role in the development of AMD lesions, but the influence of basal laminar deposit (BLamD) and membranous debris on the recruitment and programming of local macrophages has not been explored. Although evidence also suggests that inflammation and innate immunity are involved in AMD, the significance of anti-retinal autoantibodies to disesase pathogenesis is not known. AIMS: (i) To determine the histopathological threshold that distinguishes normal ageing from early AMD; (ii) to determine the influence of BLamD and membranous debris on disease progression; (iii) to examine whether distinct early AMD phenotypes exist based on clinicopathological evidence; (iv) to determine the histopathological context in which Bruch’s membrane macrophages first found; (v) to examine the relationship between Bruch’s membrane macrophages and subclinical neovascularisation; (vi) to determine if the progressive accumulation of BLamD and membranous debris alters the immunophenotype of Bruch’s membrane macrophages and/or resident choroidal macrophages; (vii) to determine if the anti-retinal autoantibody profile differs significantly between normal individuals and those with early AMD, neovascular AMD or geographic atrophy; (viii) to examine whether baseline anti-retinal autoantibodies can predict progression to advanced AMD in individuals with early AMD; and (ix) to examine whether baseline anti-retinal autoantibodies can predict vision loss in individuals with neovascular AMD. METHODS:Clinicopathological studies were performed to correlate progressive accumulation of BLamD and membranous debris to fundus characteristics and visual acuity, as well as to sub-macular Bruch’s membrane macrophage count. Immunohistochemical studies were perfomed to determine whether the presence of BLamD and membranous debris altered the programming of Bruch’s membrane or resident choroidal macrophages. The presence of serum anti-retinal autoantibodies was determined by western blotting, and the association with disease progression examined in early and neovascular AMD. RESULTS: The presence of both basal linear deposit (BLinD) and a continuous layer of BLamD represents threshold early AMD histopathologically, which was seen clinically as a normal fundus in the majority of cases. Membranous debris accumulation appeared to influence the pathway of progression from early AMD to advanced AMD. Bruch’s membrane macrophages were first noted when a continuous layer of BLamD and clinical evidence of early AMD were present, and increased with the amount of membranous debris in eyes with thin BLamD. Eyes with subclinical CNV had high macrophage counts and there was some evidence of altered resident choroidal macrophage programming in the presence of BLamD and membranous debris. Serum anti-retinal autoantibodies were found in a higher proportion of early AMD participants compared with both controls and participants with neovascular AMD, and in a higher proportion of individuals with atrophic AMD compared to those with neovascular AMD. The presence of baseline anti-retinal autoantibodies in participants with early AMD was not associated with progression to advanced AMD. Participants with neovascular AMD lost more vision over 24 months if they had IgG autoantibodies at baseline compared to autoantibody negative participants. CONCLUSIONS: The finding that eyes with threshold early AMD appear clinically normal underscores the need to utilise more sophisticated tests to enable earlier disease detection. Clinicopathological evidence suggests two distinct early AMD phenotypes, which follow two pathways of AMD progression. Macrophage recruitment and programming may be altered by the presence of BLamD and membranous debris, highlighting the need to further characterise the biology of human resident choroidal macropahges. Anti-retinal autoantibodies can be found in both control and AMD sera, and future approaches that allow the examination of subtle changes in complex repertoires will determine whether they are involved in AMD disease pathogenesis.

Doctor of Philosophy (PhD) / BACKGROUND: The accumulation of abnormal extracellular deposits beneath the retinal pigment epithelium characterises the pathology of early age-related macular degeneration. However, the histopathological threshold at which age-related changes become early AMD is not defined, and the effect of each of the deposits (basal laminar deposit and membranous debris) on disease progression is poorly understood. Evidence suggests that macrophages play a key role in the development of AMD lesions, but the influence of basal laminar deposit (BLamD) and membranous debris on the recruitment and programming of local macrophages has not been explored. Although evidence also suggests that inflammation and innate immunity are involved in AMD, the significance of anti-retinal autoantibodies to disesase pathogenesis is not known. AIMS: (i) To determine the histopathological threshold that distinguishes normal ageing from early AMD; (ii) to determine the influence of BLamD and membranous debris on disease progression; (iii) to examine whether distinct early AMD phenotypes exist based on clinicopathological evidence; (iv) to determine the histopathological context in which Bruch’s membrane macrophages first found; (v) to examine the relationship between Bruch’s membrane macrophages and subclinical neovascularisation; (vi) to determine if the progressive accumulation of BLamD and membranous debris alters the immunophenotype of Bruch’s membrane macrophages and/or resident choroidal macrophages; (vii) to determine if the anti-retinal autoantibody profile differs significantly between normal individuals and those with early AMD, neovascular AMD or geographic atrophy; (viii) to examine whether baseline anti-retinal autoantibodies can predict progression to advanced AMD in individuals with early AMD; and (ix) to examine whether baseline anti-retinal autoantibodies can predict vision loss in individuals with neovascular AMD. METHODS:Clinicopathological studies were performed to correlate progressive accumulation of BLamD and membranous debris to fundus characteristics and visual acuity, as well as to sub-macular Bruch’s membrane macrophage count. Immunohistochemical studies were perfomed to determine whether the presence of BLamD and membranous debris altered the programming of Bruch’s membrane or resident choroidal macrophages. The presence of serum anti-retinal autoantibodies was determined by western blotting, and the association with disease progression examined in early and neovascular AMD. RESULTS: The presence of both basal linear deposit (BLinD) and a continuous layer of BLamD represents threshold early AMD histopathologically, which was seen clinically as a normal fundus in the majority of cases. Membranous debris accumulation appeared to influence the pathway of progression from early AMD to advanced AMD. Bruch’s membrane macrophages were first noted when a continuous layer of BLamD and clinical evidence of early AMD were present, and increased with the amount of membranous debris in eyes with thin BLamD. Eyes with subclinical CNV had high macrophage counts and there was some evidence of altered resident choroidal macrophage programming in the presence of BLamD and membranous debris. Serum anti-retinal autoantibodies were found in a higher proportion of early AMD participants compared with both controls and participants with neovascular AMD, and in a higher proportion of individuals with atrophic AMD compared to those with neovascular AMD. The presence of baseline anti-retinal autoantibodies in participants with early AMD was not associated with progression to advanced AMD. Participants with neovascular AMD lost more vision over 24 months if they had IgG autoantibodies at baseline compared to autoantibody negative participants. CONCLUSIONS: The finding that eyes with threshold early AMD appear clinically normal underscores the need to utilise more sophisticated tests to enable earlier disease detection. Clinicopathological evidence suggests two distinct early AMD phenotypes, which follow two pathways of AMD progression. Macrophage recruitment and programming may be altered by the presence of BLamD and membranous debris, highlighting the need to further characterise the biology of human resident choroidal macropahges. Anti-retinal autoantibodies can be found in both control and AMD sera, and future approaches that allow the examination of subtle changes in complex repertoires will determine whether they are involved in AMD disease pathogenesis.

This report contains a summation of a variety of articles that have been read and analysed. Each article describes different methods that can be used to detect lesions, optic disks, drusen and exudates in retinal images. I.e. diagnose e.g. Diabetic Retinopathy and Age-Related Macular Degeneration. A general approach is presented, which all methods more or less is based on. Methods to locate the optic disk The PCA  kNN Regression Hough Transform Fuzzy Convergence Vessel Direction Matched Filter Etc. The best method based on result, reliability, number of images and publisher is kNN regression. The result of this method is remarkably good and that brings some doubt about its reliability. Though the method was published at IEEE and that gives the method a more trustful look. A next best method which also is very useful is Vessel Direction Matched Filter. Methods to detect drusen – diagnose Age-Related Macular Degeneration PNN classifier Histogram approach Etc. The best method based on result, reliability, number of images and publisher is the PNN classifier. The method had a sensitivity of 94 % and a specificity of 95 %. 300 images were used in the experiment which was published by the IEEE in 2011. Methods to detect exudates – diagnose Diabetic Retinopathy Morphological techniques Luv colour space, Wiener filter an Canny edge detector. The best method based on result, reliability, number of images and publisher is an experiment called “Feature Extraction”. The method includes the Luv colour space, Wiener filter (remove noise) and the Canny edge detector. / Den här rapporten innehåller en sammanfattning av ett flertal artiklar som har blivit studerade. Varje artikel har beskrivit en metod som kan användas för att upptäcka sjuka förändringar i ögonbottenbilder, det vill säga, åldersförändringar i gula fläcken och diabetisk retinopati. Metoder för att lokalisera blinda fläcken PCA kNN regression Hough omvandling Suddig konvergens Filtrering beroende på kärlens riktning Mm. Den bästa metoden baserat på resultat, pålitlighet, antal bilder och utgivare är kNN regression. De förvånansvärt goda resultaten kan inbringa lite tvivel på huruvida resultaten stämmer. Artikeln publicerades dock av IEEE och det gör artikeln mer trovärdig. Den näst bästa metoden är filtrering beroende på kärlens riktning. Metoder för att diagnosticera åldersförändringar i gula fläcken PNN klassificeraren Histogram Mm. Den bästa metoden baserat på resultat, pålitlighet, antal bilder och utgivare är PNN klassificeraren. Metoden hade en sensitivitet på 94 % och en specificitet på 95 %. 300 bilder användes i experimentet som publicerades av IEEE år 2011. Metoder att diagnosticera diabetisk retinopati Morfologiska tekniker Luv colour space, Wiener filter and Canny edge detector. Den bästa metoden baserat på resultat, pålitlighet, antal bilder och utgivare är ett experimentet som heter ”Feature Extraction”. Experimentet inkluderar Luv colour space, Wiener filter (brus borttagning) och Canny edge detector

Background: The relevance of drusen-like deposits (DLD) in patients with systemic lupus erythematosus (SLE) is to a large extent uncertain. Their genesis is proposed to be correlated to immune-complex and complement depositions in the framework of SLE. The intention of this study was to determine potential morphological differences in the choroid and retina as well as potential microvascular changes comparing two cohorts of SLE patients divergent in the presence or absence of DLD using multimodal imaging. Methods: Both eyes of 16 SLE patients with DLD were compared to an age- and sex-matched control-group consisting of 16 SLE patients without detectable DLD. Both cohorts were treated with hydroxychloroquine (HCQ) and did not differ in the treatment duration or dosage. Using spectral-domain optical coherence tomography (SD-OCT) choroidal volume measures, choroidal vascularity indices (CVI) and retinal layer segmentation was performed and compared. In addition, by the exploitation of optical coherence tomography angiography vascular density, perfusion density of superficial and deep retinal capillary plexuses and the choriocapillaris were analyzed. For the choroidal OCT-scans, a subset of 51 healthy individuals served as a reference-group. Results: CVI measures revealed a significant reduction in eyes with DLD compared to healthy controls (0.56 (0.54−0.59) versus 0.58 (0.57−0.59) (p = 0.018) and 0.56 (0.54−0.58) versus 0.58 (0.57−0.60) (p < 0.001)). The photoreceptor cell layer presented significant thinning in both eyes of subjects with DLD compared to control subjects without DLD (68.8 ± 7.7 µm vs. 77.1 ± 7.3 µm for right eyes, p = 0.008, and 66.5 ± 10.5 µm vs. 76.1 ± 6.3 µm for left eyes, p = 0.011). OCTA scans revealed no significant changes, yet there could be observed numerically lower values in the capillary plexuses of the retina in eyes with DLD than in eyes without DLD. Conclusions: Our results illustrated significant alterations in the choroidal and retinal analyzes, suggesting a correlation between DLD and the progression of inflammatory processes in the course of SLE leading to retinal degeneration. For this reason, DLD could serve as a biomarker for a more active state of disease.

Optical Coherence Tomography (OCT) has been around for more than 30 years and is still being continuously improved. The department of ophthalmology is a part of Sahlgrenska Hospital that heavily uses OCT for helping people with the treatment of eye diseases. They are currently facing a problem where the time to go from an OCT scan to treatment is being increased due to having an overload of patient visits every day. Since it requires a trained expert to analyze each OCT scan, the increase of patients is too overwhelming for the few experts that the department has. It is believed that the next phase of this medical field will be through the adoption of machine learning technology. This thesis has been issued by Sahlgrenska University Hospital (SUH), and they want to address the problem that ophthalmology has by introducing the use of machine learning into their workflow. This thesis aims to determine the best suited CNN through training and testing of pre-trained models and to build a tool that a model can be integrated into for use in ophthalmology. Transfer learning was used to compare three different types of pre-trained models offered by Keras, namely VGG16, InceptionResNet50V2 and ResNet50V2. They were all trained on an open dataset containing 84495 OCT images categorized into four different classes. These include the three diseases Choroidal Neovascularization (CNV), Diabetic Macular Edema (DME), drusen and normal eyes. To further improve the accuracy of the models, oversampling, undersampling, and data augmentation were applied to the training set and then tested in different variations. A web application was built using Tensorflow.js and Node.js that the best-performed model later was integrated into. The VGG16 model performed the best with only oversampling applied out of the three. It yielded an average of 95% precision, 95% recall and got a 95% F1-score. The second was the Inception model with only oversampling applied that got an average of 93% precision, 93% recall and a 93% F1-score. Last came the ResNet model with an average of 93% precision, 92% recall and a 92% F1-score. The results suggest that oversampling is the overall best technique for this given dataset. The chosen data augmentation techniques only lead to models performing marginally worse in all cases. It also suggests that pre-trained models with more parameters, such as the VGG16 model, have more feature mappings and, therefore, achieve higher accuracy. On this basis, parameters and better mappings of features should be taken into account when using pre-trained models.

Before year 1895, the doctors could only make a probable diagnosis based on what the patient could tell and it was hurt and there was no discernable change to the outside of the body. With X-ray, it was possible to see inside the patient without first cutting it, you can say that the X-ray was the starting point for diagnostic imaging.The further development of X-ray gave CT (Computed Tomography), where X-ray tubes and detectors rotate around the patient while the patient table moves. Besides CT also developed MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) and Ultrasound. Common to these methods is that the produced 3D images.In 1990 a completely new approach for diagnostic imaging, OCT (optical coherence tomography), by measuring the phase shift and the intensity of reflected light, it provides real-time and non-destructive measurements (in vivo) a resolution of 1 to 15 microns, much higher than all other standard imaging techniques. You could say that OCT machine can be compared to ultrasound, which uses the reflection of sound waves to interpretation.The first OCT machines were of type TD (Time Domain), these had low resolution and low scanning speed. In 2005 came the SD-OCT, they had higher resolution and scanning speed, SD stands for spectral domain, SD-OCT is sometimes called FD-OCT as Fourier transformed signals and operating in the frequency domain.The development of OCT machines are only in their infancy, resolution, scanning speed and accuracy will increase all the time, this allows new uses and ways to diagnose developed. OCT can be used in such Oncology, MSD (Musculoskeletal disorders), cardiovascular medicine, teeth, nerves, but the largest field is the eye and then the back of the eye called the retina (retina).This thesis is limited to the eye, the purpose is to provide input to those who are likely to purchase an OCT-machine, but also show the measurement data OCT-machines are performing and how to use the OCT-machine more than to see age-related macular degeneration. Another aim is to increase understanding of the physics behind an OCT-machine for ease of understanding the output given.The manufacture/model that have selected for evaluation are Zeiss Cirrus 4000, Topcon 3D OCT-2000 and Heidelberg Spectralis, the reason is that there are only these three on the Swedish market and all are SD-OCT. The way to evaluate OCT-machines is to scan performance and what the various analysis programs can handle. Furthermore, each OCT-machine scans the macula and optic disk on a experimental person/ reference eye, in order to get the output of the precision, or if you want to call it repeatability, which is very important if one wants to follow a solitary disease course.The conclusion of this thesis is to OCT machines are quite similar. When it comes to ease of use when doing scans is the Cirrus is lightened by the use of the extra screen where you always look eye (iris camera), which makes it easy to adjust the sharpness and position of the mouse buttons. Topcon and Heidelberg is not difficult to use but requires more experience of the person making the OCT scans. Most measurement functions in the analysis program is Topcon and Heidelberg and best accuracy/repeatability is Heidelberg, both the macula and RFNL.OCT machine is a good tool to use on the anterior segment, but in the case the precision allows the precision used to monitor RNFL thickness changes in those with glaucoma. / <p>Validerat; 20131029 (global_studentproject_submitter)</p>