Dissertationen zum Thema „Druskin“

Magistro darbe atlikta birių medžiagų barstymo proceso mokslinių darbų analizė. Apžvelgta Lietuvos kelius, žiemos metu, prižiūrinčių įmonių struktūra ir gamybinės sąlygos, įvertinant cheminių medžiagų barstymo proceso etapus, eiliškumą ir apimtis. Sudarytas barstytuvų technologinio proceso matematinis modelis, atliktas smėlio – druskos barstytuvų technologinio proceso kokybės tyrimas. Pasiūlyta eksperimentinė įranga ir eksperimento atlikimo metodika barstytuvų technologinio proceso kokybei įvertinti.
In this master work was reviewed analysis of spreading process. Reviewed the structure and industrial conditions of companie’s what during winter time are maintaining Lithuanian roads including the stages, priority and size of spreading process. Created mathematical model of spreading process and investigated the research of sand and salt spreader technological process. Suggested the experimental equipment and method to measure the quality of salt and sand spreading technological process.

Darbo tikslas: dviem metodais gauti azodažiklius iš aromatinių aminų diazonio druskų, nustatyti jų pKa reikšmes, įvertinti spektrines savybes bei pritaikyti kaip indikatorius. Darbo uždaviniai: Gauti azodažiklius iš metilanilinų ir 4-nitroanilino vykdant jų diazonio druskų hidrolizę arba jungiant su 1-naftoliu bei 2-naftoliu, apskaičiuoti gautų junginių išeigas, nustatyti jų pKa reikšmes, spektrines savybes, galimą kaip indikatorių pritaikymą. Metodai: Tyrimui atlikti naudojami du azodažiklių sintezės metodai. Apskaičiuotos abiem metodais gautų azodažiklių procentinės išeigos. ESC įvertintas junginių grynumas. Gautų azodažiklių pKa reikšmės bei pH ribos, kuriose keičiasi jų spalva, vertinamos atliekant potenciometrinį titravimą. Vandeniniai azodažiklių tirpalai vertinti spektrofotometriškai, matuojant tirpalų absorbcijos maksimumus ir optinius tankius. Rezultatai: Azodažikliai, atliekant aromatinių aminų diazonio druskų hidrolizę (hidrolizatas sudarytas iš 44 ml vandens ir 20 ml koncentruotos H2SO4), gaunami veikiant aminus koncentruota HCl, kai hidrolizato temperatūra pakeliama iki 104-110 oC. Atliekant tradicinę azodažiklių sintezę išeigos yra geros-labai geros (vidutinė išeiga yra 76,95 proc.), o vykdant diazonio druskų hidrolizę – vidutinės (junginiai gaunami su vidutine 41,44 proc. išeiga). Tradiciniu metodu gautų naftolinių azodažiklių pKa reikšmės yra 8,8-11,0 ribose, o fenolinių, gautų atliekant eksperimentinę sintezę, - 7,5 8,0. Spektrofotometrinis tyrimas parodė... [toliau žr. visą tekstą]
Aim of the work: synthesis of azo dyes from aromatic amines diazonium salts by two methods, determination of their pKa values, spectral features and applicability as indicators of produced azo dyes. Main objectives: to obtain azo dyes from methylanilines and 4-nitroaniline by hydrolysis of their diazonium salts or by binding with 1-naphtol and 2-naphtol, to calculate yields of obtained compounds, to determine their pKa values, spectral features and their possible application as indicators. Methods: Two methods of azo dyes synthesis are used to perform the assay. Percentage yields of synthesized compounds, obtained by both methods, are calculated. Purity of compounds is evaluated by HPLC. pKa values and range of pH where the colour changes of received compounds are evaluated by potentiometric titration. Aqueous solutions of azo dyes are assessed by measuring absorption peaks and optical densities with a spectrophotometer. Results: it is necessary to synthesise aromatic amines diazonium salts with conc. HCl and to perform hydrolysis in 104-110 oC temperature when hydrolysate consist of 44 ml water and 20 ml conc. H2SO4 in order to obtain azo dyes by experimental method. Yields of traditional method are good-very good (average yield is 76,95 proc.), yields of experimental method are moderate (average yield is 41,44 proc.). pKa values of naphtolic azo dyes which are obtained by traditional method are 8,8-11,0 and phenolic azo dyes – 7,5-8,0. Spectrophotometric studies showed that... [to full text]

Darbo objektai: Virtų, karštai rūkytų dešrų gamyba, juslinių savybių ir mikrobiologinis dešrų įvertinimas. Darbo tikslas – Įvertinti natrio druskų mažinimo galimybes termiškai apdorotuose mėsos gaminiuose. Darbo užduotys: 1. Mokslinės literatūros apie natrio druskų mažinimo galimybes termiškai apdorotuose mėsos gaminiuose apibendrinimas. 2. Natrio druskų pakeitimo alternatyviais ingredientais virtose ir karštai rūkytose dešrose galimybių tyrimas. 3. Gaminių receptūrų sudarymas, gaminių gamyba, juslinis įvertinimas. 4. Gautų rezultatų statistinis apdorojimas, apibendrinimas, išvadų formulavimas. Darbo rengimo vieta: Tiriamasis darbas buvo atliktas Lietuvos sveikatos mokslų universitete Veterinarijos akademijoje Maisto saugos ir kokybės katedroje ir „X“ mėsos perdirbimo įmonėje. Tyrimai buvo atlikti Šiaulių Nacionalinio maisto ir veterinarijos rizikos vertinimo institute. Darbo apimtis: 46 puslapiai, 11 lentelės, 10 paveikslų, 4 priedai Raktažodžiai: virta dešra, karštai rūkyta dešra, natrio druska Išvados: 1. 50 proc. nitritinės druskos kiekio pakeitimas kalcio laktatu virtose dešrose ženkliai padidino aerobinių mikroorganizmų skaičių, todėl toks pakeitimas nėra tinkamas taikyti virtų dešrų gamyboje. Kiti tyrime tirti natrio nitrito pakaitalai virtose ir karštai rūkytose dešrose nežymiai padidino aerobinių mikroorganizmų skaičių; 2. Nitritinės druskos pakeitimas 50 proc. kalio chloridu ir 50 proc. kalcio laktatu turėjo nežymią įtaką virtų dešrų juslinėms savybėms bei... [toliau žr. visą tekstą]
Objects of the thesis: Production of cooked, smoked sausages, evaluation of sausages of organoleptic characteristics and microbiological. Aim of the thesis is to rate the possibilities of sodium salt reduction in the heat-treated meat products. Purpose of the thesis: 1. Summary of the scientific literature on possibilities of sodium salt reduction in the heat-treated meat products. 2. Research of possibilities of the change of the sodium salt by the alternative ingredients in the cooked and smoked sausages. 3. Formation of the products recipes, manufacture of the products and sensory evaluation. 4. Statistical processing of the obtained results, generalization, and formulation of conclusions. Work preparation place ant term: The research was performed at the Food Safety and Quality Department of the Veterinary Academy of the Lithuanian University of Health Sciences and at the company of meat processing “X”. The research was performed at the Šiauliai National Food and Veterinary Risk Assessment Institute. Work span: The thesis consists of: 46 pages, 11 tables, 10 pictures, 4 annexes Keywords: cooked sausage, smoked sausage, sodium salt Conclusions: 1. 50% nitric salt replacement to calcium lactate leads to increase of aerobic microorganisms in cooked sausages and it is therefore unsuitable for the production of cooked sausages. The other investigated nitric salt replacement variants do not show a significant increase of aerobic microorganisms in cooked and smoked... [to full text]

Baigiamajame magistriniame darbe tirta Utenos nuotekų valymo įrenginių pirminio ir perteklinio veikliojo dumblo mišinio skirtingų polimerų ir geležies druskų anaerobiniam puvimo procesui įtaka. Analizėje nagrinėjama proceso metu išsiskiriančių biodujų tūris ir metano dujų koncentracija. Tyrime naudojamas anaerobinio pūdymo modelis „W8 Armfield Ltd“, kuris dirba kaip vienalaipsniai anaerobiniai reaktoriai su mezofiliniu režimu. Išbuvimo trukmė – 20 dienų, apkrova bepelenėmis sausomis medžiagomis (BSM) nuo 0,61–0,96 gBSM/l/d, tiekiamo dumblo mišinio sausų medžiagų kiekis (SM) – 4 %. Baigiamuoju darbu siekiama išanalizuoti dumblo tirštinimui naudojamo sintetinio arba natūralaus polimero ir dozuojamos druskos (geležies sulfato (Fe2(SO4)3) bei geležies chlorido (FeCl3)) įtaką anaerobiniam pūdymo procesui. Panaudojus anaerobinio pūdymo modelį buvo sukurtos anaerobinės sąlygos ir pūdomas iš Utenos nuotekų valyklos tiekiamas pirminio ir perteklinio dumblo mišinys. Naudojantis įrenginiu INCA 4000 T100 buvo kaupiamos biodujos ir analizuojama jų sudėtis. Darbe taip pat nagrinėjamas SM sumažėjimas ir BSM suskaidymas. Įvertinus visus analizuojamus kriterijus nustatomas efektyviausias metodas išsiskiriančių dujų efektyvumui ir kokybei pagerinti. Išanalizavus tyrimo rezultatus pateiktos išvados. Darbą sudaro šios dalys: įvadas, 4 skyriai, išvados, rekomendacijos, literatūros sąrašas. Darbo apimtis – 63 p. teksto be priedų, 32 paveikslai, 8 lentelės, 42 bibliografiniai šaltiniai.
Objective of this work was to investigate impact of different iron and polymer doses on anaerobic digestion process. Primary and waste activated sludge was obtained from Utena Wastewater treatment plant. Analysis shows the volume of biogas produced and percentage of methane. The work was carried out using high-rate anaerobic digestion model W8 (Armfied Ltd. UK) which operates in the mesophilic range. The solids retention time was 20 days. The volatile suspended solids loading rate ranged from 0.61 to 0.96 g VSS/l d.Sludge mixture feed concentration – 4%. The Purpose of this work is to analyse impact of synthetic and organic polymer also iron (III) sulphate (Fe2(SO4)3) and iron (III) chloride (FeCl3) on anaerobic digestion process. Primary and waste activated sludge was obtained from Utena Wastewater treatment plant. The biogas was collected and components were analysed using INCA 4000 T100 analyser. Analysis of TS reduction and VS destruction is also presented. The most effective method of improving off-gas efficiency and quality was determined considering all the criteria determined by analysis. Having analyzed the results of the research, conclusions have been made. This work consists of the following parts: pre-face, 3 sections, conculsions, recommendations, reference list. There are 63 pages of text without appendices, 32 figures, 8 tables and 42 bibliographical sources in this work.

Dissertation presented to obtain the degree of Doctor of Philosophy in Electrical Engineering, speciality on Perceptional Systems, by the Universidade Nova de Lisboa, Faculty of Sciences and Technology
Drusen are common features in the ageing macula, caused by accumulation of extracellular materials beneath the retinal surface, visible in retinal fundus images as yellow spots. In the ophthalmologists’ opinion, the evaluation of the total drusen area, in a sequence of images taken during a treatment, will help to understand the disease progression and effectiveness. However, this evaluation is fastidious and difficult to reproduce when performed manually. A literature review on automated drusen detection showed that the works already published were limited to techniques of either adaptive or global thresholds which showed a tendency to produce a significant number of false positives. The purpose for this work was to propose an alternative method to automatically quantify drusen using advanced digital image processing techniques. This methodology is based on a detection and modelling algorithm to automatically quantify drusen. It includes an image pre-processing step to correct the uneven illumination by using smoothing splines fitting and to normalize the contrast. To quantify drusen a detection and modelling algorithm is adopted. The detection uses a new gradient based segmentation algorithm that isolates drusen and provides basic drusen characterization to the modelling stage. These are then fitted by Gaussian functions, to produce a model of the image, which is used to compute the affected areas. To validate the methodology, two software applications, one for semi-automated (MD3RI) and other for automated detection of drusen (AD3RI), were implemented. The first was developed for Ophthalmologists to manually analyse and mark drusen deposits, while the other implemented algorithms for automatic drusen quantification.Four studies to assess the methodology accuracy involving twelve specialists have taken place. These compared the automated method to the specialists and evaluated its repeatability. The studies were analysed regarding several indicators, which were based on the total affected area and on a pixel-to-pixel analysis. Due to the high variability among the graders involved in the first study, a new evaluation method, the Weighed Matching Analysis, was developed to improve the pixel-to-pixel analysis by using the statistical significance of the observations to differentiate positive and negative pixels. From the results of these studies it was concluded that the methodology proposed is capable to automatically measure drusen in an accurate and reproducible process. Also, the thesis proposes new image processing algorithms, for image pre-processing, image segmentation,image modelling and images comparison, which are also applicable to other image processing fields.

Šiame magistro darbe tirta automobilių kelių infrastruktūros įtaka dirvožemio pH aplinkinėse teritorijose. Lietuvoje panašių tyrimų nėra atlikta. Pateiksiu pagrindinius tyrimo rezultatus: 1. Prie kelių, turinčių asfaltbetonio dangas, tiek paviršiniame, tiek gilesniame dirvožemio sluoksniuose, prie pat kelio sankasos, pastebėtas dirvožemio pH padidėjimas. Prie kelio su grunto danga dirvožemio pH padidėjimo nepastebėta. 2. Prie kelių su asfaltbetonio danga paviršinio dirvožemio sluoksnio mėginių rezultatai, paimti pirmaisiais mėnesiais, yra mažesni negu sekančių mėnesių. 3. Dirvožemio pH padidėjimą šalia kelių, padengtų asfaltbetonio danga, sieju su techninių druskų naudojimu. Jos gali spartinti kelio sankasos grunte esančių karbonatinių uolienų tirpimą.
My master project is devoted to influence of soil pH in the surrounding territories to road traffic transport. There are no comparable researching in Lithuania. I would like to introduce the main results of my project: 1. pH of soil increase are beholded in the soil of surface and in the deep of soil near the roads with blacktop. The soil pH is not behold near the unsurfaced road. 2. The soil of surface specimen’s results are taken from the previous month near the roads with blacktop. These results are less than during next month. 3. The soil pH increase near the roads with blacktop is related with technical soil using. Technical soil can be quickening by melting of carbonaceous rock in the priming of subgrade.

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.

Pour segmenter les images d'angiographie retinienne, notamment les images de drusen (taches jaunatres hyperfluorescentes), plusieurs methodes ont ete etudiees et proposees. Ces images presentent des difficultes d'analyse : du bruit, un contraste faible, parfois un nombre insuffisant de niveaux de gris et souvent une heterogeneite de certaines regions de l'image. Pour resoudre de tels problemes, nous proposons une methode de segmentation qui procede en deux etapes. La premiere etape concerne le rehaussement du contraste grace a un partitionnement optimal de l'image en trois classes : la premiere classe correspond aux drusen, qui apparaissent en clair, la deuxieme classe au fond de l'image et enfin la troisieme, nommee classe intermediaire, regroupant tous les pixels ambigus. Cette derniere classe est definie comme une region floue. La deuxieme etape de la methode de segmentation fait appel a la logique floue, qui est appliquee a la seule region floue. Elle consiste a attribuer a chaque niveau de gris un degre d'appartenance. Ensuite, l'application d'une methode iterative tenant compte du contexte spatial des pixels permet de decider de l'appartenance definitive d'un pixel a la classe drusen ou a la classe fond. Des etudes quantitatives sur des images de drusen de plusieurs patients ont permis d'effectuer deux types de comparaison : l'une avec une autre methode de segmentation, l'autre avec la detection manuelle faite par un praticien. La methode de segmentation proposee permet de quantifier de maniere objective les drusen au cours du temps ; les resultats obtenus confirment les donnees quantitatives connues en angiographie.

La segmentation de structures claires dans une image donnée est un problème très important dans la vision par ordinateur et particulièrement en imagerie biomédicale. En angiographie rétinienne la segmentation des drusen, taches jaunes un peu nuageuses situées au niveau de la rétine, constitue un enjeu très important dans le diagnostic et la prévention de complications graves. L'utilisation de méthodes classiques de segmentation de type seuillage, croissance de régions, extraction de contours ou contours actifs donne des résultats peu probants causés par l'imparfaite automatisation de ces méthodes. Nous présentons dans cette thèse une nouvelle approche de segmentation basée sur des transformations morphologiques nouvelles. Pour ceci nous définissons une classe particulière de composantes connexes de l'image : s'agit des maxima d'ordre p dont nous démontrons un certain nombre de propriétés. Ensuite à partir de ces composantes, nous construisons une fonction adaptative h(x), que nous utilisons comme fonction de contraste dans l'algorithme des h(x) maxima d'ordre r. Nous présentons des résultats expérimentaux d'extraction de drusen sur des images d'angiographie rétinienne. Nous avons aussi appliqué cette méthode de segmentation dans une séquence dynamique d'images pour les deux cas suivants : - suivi et évaluation de l'intensité moyenne d'un drusen dans une séquence d'image durant un examen à la fluorescéine. - comparaison des types et surfaces des drusen au cours du temps pour des examens différents.

Final publication is available at http://www.sciencedirect.com/science/article/pii/S0002939414000488
Kyoto University (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

Les DMLA (dégénérescences maculaires liées à l’âge) première cause de cécité après 50 ans dans les pays industrialisés sont un ensemble de maladies hétérogènes influencées par des facteurs environnementaux. Elles sont caractérisées par la présence de dépôts lipidiques (drusens) dans la membrane de Bruch. Nous avons montré une co-expression du récepteur aux HDL SR-BI et de l’enzyme clé de la stéroïdogénèse StAR dans la rétine de rat adulte. L’exploration du phénotype oculaire de la souris déficiente pour le gène SR-BI après 30 semaines de régime athérogène (cholestérol + cholate) a montré une accumulation de dépôts sous-rétiniens riches en lipides et en A2E, une dégénérescence des photorécepteurs, un électrorétinogramme altéré, une activation locale du système immunitaire ainsi qu’un transport anormal des vitamines A et E. Nous avons donc caractérisé un modèle connu d’atherosclérose susceptible de permettre une meilleure compréhension de la genèse des drusens et des DMLA

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

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.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016
Este trabalho aborda o tema "Drusen do disco óptico" - DDO. Ocorre em até 2,4% dos indivíduos apesar de muitos não serem identificados clinicamente. A sua patogénese não se encontra ainda bem esclarecida discutindo-se alguns dos possíveis mecanismos fisiopatológicos. É também abordada a história natural e a clínica dos DDO. Muitas vezes assintomáticos, podem passar despercebidos até que o exame oftalmológico os evidencie, devido ao quadro de instalação lento e progressivo, que pode progredir desprovido de sintomas, mesmo com perda do campo visual - CV. É importante o estabelecimento do diagnóstico diferencial, sobretudo com o papiledema. Vários exames complementares podem ser úteis, nomeadamente a Ecografia, a Angiografia fluoresceínica, a Tomografia computorizada orbitária, a Ressonância magnética e a Tomografia de coerência óptica - OCT. Os DDO podem complicar-se com neuropatia óptica isquémica anterior, neovasos subretinianos, oclusões vasculares e corioretinopatia central serosa peripapilar. Por vezes os DDO associam-se a outras patologias como a Retinite Pigmentar, o Pseudoxantoma elástico e estrias angióides ou o síndrome de Alargille. Não existe tratamento para os DDO, devendo no entanto as complicações ser tratadas. Documenta-se e discute-se o caso clínico de uma doente de 47 anos de idade sob terapêutica com hidroxicloroquina e quadro de pseudopapiledema por DDO.
This work addresses the theme Drusen of the optic disc. It occurs in up to 2.4% of the subjects even though many are not recognized clinically. As it's pathogenesis is not yet well understood we discuss some of the possible pathophysiological mechanisms. It is also addressed the natural history and clinics of DDO. Many asymptomatic patients can go unnoticed until eye examination, due to the slow and progressive installation frame, which can pass devoid of symptoms, even with loss of visual field. It is important to establish the differential diagnosis, especially with papilledema. Several complementary exams may be useful, including ultrasound, fluorescein angiography, orbital CT, MRI and OCT. The DDO can be complicated with anterior ischemic optic neuropathy, subretinal neovascularization, vascular occlusions, central serous peripapillary corioretinopathy. Sometimes DDO are associated with other pathologies such as retinitis pigmentosa, the elastic pseudoxanthoma and angioid streaks or the Alargille syndrome. There is no treatment for DDO, however complications must be approached. It is documented and discussed the case of a 47 old patient submitted to treatment with hydroxychloroquine and presenting pseudopapilledema due to DDO.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014
The drusen of the optic disc is an uncommon disease that's due to the abnormal accumulation of hyalin-like material in this structure, being itself a cause for pseudopapilledema. It affects 0,3-2,0% of the population, with major incidence on the caucasians, and it's just identifiable from the first decade of life on. It can be expressed by peripheral visual loss, sudden or progressively, and can also cause retinian hemorrhage. Its etiology isn't completely known, it is thought that the accumulation of calcified debris is caused by a defect on the axonal metabolism. On another hand, tilted disc is an anatomic variation which is responsible for refractive errors such as myopia and astigmatism, rarely being associated with drusen. Knowing the etiology, signs and symptoms, as well as the diagnostic plan, is essential for the clinical intervention. Therefore, there will be a theorical review and a clinical case discussion.
O drusen do Disco Óptico (DO) é uma patologia incomum que se deve à acumulação anormal de material hialino nesta estrutura, sendo uma causa de pseudopapiledema. Afecta 0,3-2,0% da população, com maior incidência caucasiana, e apenas é identificável a partir da primeira década de vida. Poderá manifestar-se por perda de visão periférica súbita ou progressiva, podendo também provocar hemorragia retiniana. De etiologia não totalmente conhecida, pensa-se que a acumulação de detritos calcificados seja devido a um defeito no metabolismo axonal. O tilted disc, por sua vez, é uma variante anatómica que é responsável por erros de refracção como a miopia e o astigmatismo, estando raras vezes associado ao drusen. O conhecimento etiológico, os sinais e sintomas, bem como o plano diagnóstico, é essencial para a intervenção clínica. Assim, será feita uma revisão teórica e abordado um caso clínico.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Introdução: Drusen e pseudodrusen reticulares (RPD) são fatores de risco bem conhecidos de progressão para os estadios tardios da degenerescência macular relacionada com a idade (DMI). Contudo, o impacto preciso dos RPD e de características específicas dos drusen na taxa de conversão para esses estadios continua ainda por caracterizar. O nosso objetivo foi determinar, numa coorte a 5 anos, a influência dos RPD, tamanho, área e número de drusen nas taxas de conversão para as fases tardias da DMI no olho adelfo de pacientes com neovascularização coroideia (NVC). Métodos: Estudo retrospetivo de seguimento incluindo os olhos adelfos de DMI com NVC. No início, todos os olhos foram avaliados com base num extenso protocolo imagiológico, que permitiu uma identificação dos RPD e caracterização do número, área e dimensão dos drusen. Todos os olhos incluídos foram seguidos até à conversão ou pelo menos até se atingir os 5 anos de seguimento. Análises de sobrevivência univariadas e multivariadas foram usadas para analisar os fatores preditores de conversão. Resultados: Estudámos 63 olhos de 63 doentes (26 do sexo feminino) com uma idade media de 76.2 ± 6.6 anos e um seguimento médio de 45.8±26.8 meses. A prevalência de base de RPD foi de 55.6% (35). Não foi encontrada uma diferença estatisticamente significativa para idade (p=0.70) ou sexo (p=0.82) entre os grupos de doentes com e sem RPD. Quarenta e um olhos (65.1%) converteram para as fases tardias de DMI durante o seguimento: 7 (11.1%) para atrofia geográfica (AG) e 34 (54.0%) para NVC, após um tempo médio de 31.5±20.9 meses. O tempo médio até à conversão foi de 39.2±12.7 meses: 29.8±6.1 meses nos doentes com RPD e 79.2 meses nos doentes sem RPD. A presença de RPD (p<0.01) e drusen grandes (p=0.02) foram fatores estatisticamente significativos para conversão. A taxa de risco (TR) para conversão em pacientes com RPD foi de 2.64 (95% CI 1.35-5.16, p<0.01), 0.36 para área de drusen >700 µm (95% CI 0.17-0.79, p=0.01) e com drusen grandes de 4.96 (95% CI 1.96-12.53, p<0.01). Discussão e Conclusão: A conversão para os estadios tardios da DMI nos olhos adelfos de doentes com NVC ocorreu 2.64 vezes mais rapidamente na presença de RPD e 4.96 vezes quando drusen grandes estavam presentes. Uma área total de drusen aumentada esteve associada a um menor risco de conversão. Dada a sua influência na velocidade de conversão, é recomendado um seguimento metódico dos doentes que apresentem estas lesões, recorrendo às últimas técnicas de imagem multimodal disponíveis, de forma a possibilitar um diagnóstico e tratamento atempados.
Introduction: Drusen and reticular pseudodrusen (RPD) are well-known risk factors for progression to the late stages of age-related macular degeneration (AMD). However, the precise impact of RPD and specific drusen characteristics in the rate of conversion to those stages is not completely characterized. Our purpose was to determine, in a 5-year cohort, the influence of RPD, drusen size, area and number on the progression rates to late-stage AMD in the fellow eye of patients with unilateral choroidal neovascularization (CNV). Methods: Retrospective follow-up study including fellow eyes of AMD with CNV. At baseline all eyes were evaluated with a comprehensive imaging protocol, which allowed for RPD identification and characterization of drusen number, area and size. All eyes were followed up until conversion or until at least 5 years of follow up were attained. Univariate and multivariate survival analysis was used to assess predictors of conversion. Results: We studied 63 eyes of 63 patients (26 female) with a mean age of 76.2±6.6 years and a mean follow up of 45.8±26.8 months. Baseline prevalence of RPD was 55.6% (35 eyes). No statistically significant difference was found for age (p=0.70) or sex (p=0.82) between patients with and without RPD. Forty-one eyes (65.1%) converted to late-stage AMD during follow-up: 7 (11.1%) to geographic atrophy (GA) and 34 (54.0%) to CNV, after an average time of 31.5±20.9 months. The mean time until conversion was 39.2±12.7 months: 29.8±6.1 months for patients with RPD and 79.2 months for patients without RPD. RPD (p<0.01) and large drusen (p<0.02) were statistically significant for conversion. Hazard ratio (HR) for conversion in patients with RPD was 2.64 (95% CI 1.35-5.16, p<0.01), with drusen area >700 µm was 0.36 (95% CI 0.17-0.79, p=0.01) and 4.96 (95% CI 1.96-12.53, p< 0.01) for large drusen.Discussion & Conclusion: Conversion to late-stage AMD in fellow eyes of patients with CNV occurs 2.64 times faster when RPD are present and 4.96 times faster when large drusen are detected. Increased total drusen area was associated with a smaller risk of conversion. Given their influence in the speed of conversion, a strict follow-up of these patients with the latest available multi-modal imaging techniques available is recommended.

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.

Tese de Doutoramento em Líderes para Indústrias Tecnológicas
The age-related macular degeneration (AMD) starts to manifest itself with the appearance of drusen. Progressively, the drusen increase in size and in number without causing alterations to vision. Nonetheless, their quantification is important because it correlates with the evolution of the disease to an advanced stage, which could lead to the loss of central vision. Manual quantification of drusen is impractical, since it is time-consuming and it requires specialized knowledge. Therefore, this work proposes a method for quantifying drusen automatically In this work, it is proposed a method for segmenting boundaries limiting drusen and another method for locating them through classification. The segmentation method is based on a multiple surface framework that is adapted for segmenting the limiting boundaries of drusen: the inner boundary of the retinal pigment epithelium + drusen complex (IRPEDC) and the Bruch’s membrane (BM). Several segmentation methods have been considerably successful in segmenting layers of healthy retinas in optical coherence tomography (OCT) images. These methods were successful because they incorporate prior information and regularization. However, these factors have the side-effect of hindering the segmentation in regions of altered morphology that often occur in diseased retinas. The proposed segmentation method takes into account the presence of lesion related with AMD, i.e., drusen and geographic atrophies (GAs). For that, it is proposed a segmentation scheme that excludes prior information and regularization that is only valid for healthy regions. Even with this segmentation scheme, the prior information and regularization can still cause the oversmoothing of some drusen. To address this problem, it is also proposed the integration of local shape priors in the form of a sparse high order potentials (SHOPs) into the multiple surface framework. Drusen are commonly detected by thresholding the distance among the boundaries that limit drusen. This approach misses drusen or portions of drusen with a height below the threshold. To improve the detection of drusen, Dufour et al. [1] proposed a classification method that detects drusen using textural information. In this work, the method of Dufour et al. [1] is extended by adding new features and performing multi-label classification, which allow the individual detection of drusen when these occur in clusters. Furthermore, local information is incorporated into the classification by combining the classifier with a hidden Markov model (HMM). Both the segmentation and detections methods were evaluated in a database of patients with intermediate AMD. The results suggest that both methods frequently perform better than some methods present in the literature. Furthermore, the results of these two methods form drusen delimitations that are closer to expert delimitations than two methods of the literature.
A degenerescência macular relacionada com a idade (DMRI) começa a manifestar-se com o aparecimento de drusas. Progressivamente, as drusas aumentam em tamanho e em número sem causar alterações à visão. Porém, a sua quantificação é importante porque está correlacionada com a evolução da doença para um estado avançado, levar à perda de visão central. A quantificação manual de drusas é impraticável, já que é demorada e requer conhecimento especializado. Por isso, neste trabalho é proposto um método para segmentar drusas automaticamente. Neste trabalho, é proposto um método para segmentar as fronteiras que limitam as drusas e outro método para as localizar através de classificação. O método de segmentação é baseado numa ”framework” de múltiplas superfícies que é adaptada para segmentar as fronteiras que limitam as drusas: a fronteira interior do epitélio pigmentar + complexo de drusas e a membrana de Bruch. Vários métodos de segmentação foram consideravelmente bem-sucedidos a segmentar camadas de retinas saudáveis em imagens de tomografia de coerência ótica. Estes métodos foram bem-sucedidos porque incorporaram informação prévia e regularização. Contudo, estes fatores têm como efeito secundário dificultar a segmentação em regiões onde a morfologia da retina está alterada devido a doenças. O método de segmentação proposto toma em consideração a presença de lesões relacionadas com DMRI, .i.e., drusas e atrofia geográficas. Para isso, é proposto um esquema de segmentação que exclui informação prévia e regularização que são válidas apenas em regiões saudáveis da retina. Mesmo com este esquema de segmentação, a informação prévia e a regularização podem causar a suavização excessiva de algumas drusas. Para tentar resolver este problema, também é proposta a integração de informação prévia local sob a forma de potenciais esparsos de ordem elevada na ”framework” multi-superfície. As drusas são usalmente detetadas por ”thresholding” da distância entre as fronteiras que limitam as drusas. Esta abordagem falha drusas ou porções de drusas abaixo do ”threshold”. Para melhorar a deteção de drusas, Dufour et al. [1] propuseram um método de classificação que deteta drusas usando informação de texturas. Neste trabalho, o método de Dufour et al. [1] é estendido, adicionando novas características e realizando uma classificação com múltiplas classes, o que permite a deteção individual de drusas em aglomerados. Além disso, é incorporada informação local na classificação, combinando o classificador com um modelo oculto de Markov. Ambos os métodos de segmentação e deteção foram avaliados numa base de dados de pacientes com DMRI intermédia. Os resultados sugerem que ambos os métodos obtêm frequentemente melhores resultados que alguns métodos descritos na literatura. Para além disso, os resultados destes dois métodos formam delimitações de drusas que estão mais próximas das delimitações dos especialistas que dois métodos da literatura.
This work was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941. Furthermore, the Portuguese funding institution Fundação Calouste Gulbenkian has conceded me a Ph.D. grant for this work. For that, I wish to acknowledge this institution. Additionally, I want to thank one of its members, Teresa Burnay, for all her assistance with issues related with the grant, for believing that my work was worth supporting and for encouraging me to apply for the grant.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017
O papiledema é um achado oftalmológico que corresponde a edema do disco ótico secundário a aumento da pressão intracraniana, estando presente em condições potencialmente fatais. Diferenciar o papiledema de pseudopapiledema constitui um desafio na prática clínica, particularmente quando o grau de edema é baixo e estão ausentes sintomas típicos de hipertensão intracraniana. Torna-se também difícil na presença de drusens do disco ótico profundos, não observáveis à fundoscopia, tomando uma apresentação semelhante ao papiledema. A tomografia de coerência ótica destaca-se entre os exames complementares de diagnóstico, pela sua importância no diagnóstico diferencial, follow-up e determinação do prognóstico do doente. Através deste exame rápido e minimamente invasivo, consegue-se uma melhor orientação em cada caso clínico, evitando-se custos económicos desnecessários, ansiedade nos doentes e futilidade terapêutica.
Papilledema is an ophtalmologic finding used to describe optic disc edema due to increased intracranial pressure and it is a sign that appears in potentially life-threatening situations. Differentiating true papilledema from pseudopapilledema can be particularly challenging in the presence of mild papilledema or when symptoms of elevated intracranial pressure are absent. Furthermore, buried optic nerve head drusen can mimic the appearence of papilledema, as they cannot be easily seen on ophtalmoscopy. Optical coherence tomography has proven its value in the diagnostic dillema, monitoring response to treatment and determining the long-term visual outcome. It is a non-invasive and easily accessible exam that allows an effective management while decreasing patient anxiety and avoiding unnecessary healthcare costs.

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.

Validerat; 20131029 (global_studentproject_submitter)