Statistical analysis of images from optical coherence tomography with retinal applications

V této práci je stručně popsána anatomie oka a struktura sítnice včetně jejích patologických změn. Práce se dále zabývá vlastnostmi a principem optické koherentní tomografie a její aplikací v oftalmologii ve spojení se statistickou analýzou snímků sítnice. Praktická část objasňuje vlastní problematiku statistické analýzy snímků sítnice s využitím histogramů představujících rozložení odstínů šedi a aproximačních funkcí, kterými jsou roztažná exponenciální funkce a Nakagamiho funkce. Vhodnou optimalizací jsou získány parametry, ze kterých jsou vytvořeny parametrické mapy, ilustrující distribuci odstínů šedi v různých oblastech zájmu.This work briefly describes the anatomy of the eye and retinal structure, including its pathological changes. The work is focused on the characteristics and the principle of optical coherence tomography and its application in ophthalmology in conjunction with statistical analysis of retinal images. The practical part explains problems of statistical analysis retinal images using histograms representing the distribution of gray shades and approximation of functions, which are stretched exponential function and Nakagami function. Suitable optimalization are obtained parameters, from which are formed parametric maps illustrating the distribution of gray levels in different areas of interest.

Task adapted reconstruction for inverse problems

The paper considers the problem of performing a task defined on a model parameter that is only observed indirectly through noisy data in an ill-posed inverse problem. A key aspect is to formalize the steps of reconstruction and task as appropriate estimators (non-randomized decision rules) in statistical estimation problems. The implementation makes use of (deep) neural networks to provide a differentiable parametrization of the family of estimators for both steps. These networks are combined and jointly trained against suitable supervised training data in order to minimize a joint differentiable loss function, resulting in an end-to-end task adapted reconstruction method. The suggested framework is generic, yet adaptable, with a plug-and-play structure for adjusting both the inverse problem and the task at hand. More precisely, the data model (forward operator and statistical model of the noise) associated with the inverse problem is exchangeable, e.g., by using neural network architecture given by a learned iterative method. Furthermore, any task that is encodable as a trainable neural network can be used. The approach is demonstrated on joint tomographic image reconstruction, classification and joint tomographic image reconstruction segmentation

Retromode imaging modality of epiretinal membranes

(1) Purpose: To determine the characteristics of macular epiretinal membranes (ERM) using non-invasive retromode imaging (RMI) and to compare retromode images with those acquired via fundus autofluorescence (FAF) and fundus photography. (2) Methods: Prospective observational case-series study including patients with macular ERM with no other ocular disease affecting their morphology and/or imaging quality. We compared RMI, FAF and fundus photography features by cropping and overlapping images to obtain topographic correspondence. (3) Results: In total, 21 eyes (21 patients) affected by ERM were included in this study. The mean area of retinal folds detected by RMI was significantly higher than that detected by FAF (11.85 ± 3.92 mm2 and 5.67 ± 2.15 mm2, respectively, p < 0.05) and similar to that revealed by fundus photography (11.85 ± 3.92 mm2 and 10.58 ± 3.45 mm2, respectively, p = 0.277). (4) Conclusions: RMI appears to be a useful tool in the evaluation of ERMs. It allows for an accurate visualization of the real extension of the retinal folds and provides a precise structural assessment of the macula before surgery. Clinicians should be aware of RMI's advantages and should be able to use them to warrant a wide range of information and, thus, a more personalized therapeutic approach

Clinical spectrum of lamellar macular defects including pseudoholes and pseudocysts defined by optical coherence tomography

Objective: To present the clinical spectrum of lamellar macular defects and describe the different subtypes based on their optical coherence tomography (OCT) configuration and visual prognosis.---- Methods: The retrospective observational case series reviewed OCT scans of 92 eyes with lamellar macular defects. Lamellar macular defects were categorised into subtypes of macular pseudohole (MPH), lamellar macular hole (LMH) and foveal pseudocyst (FP) according to their OCT morphology. The defects were quantitatively characterised in terms of base diameter, depth and central foveal thickness, and examined for the presence of associated epiretinal membranes (ERM).---- Results: Visual acuity (VA) was significantly correlated with the central foveal thickness and depth of the lamellar defect. MPH was associated with better VA compared with LMH and FP. MPH was of a smaller base diameter and had a greater central foveal thickness than that of LMH and FP. Fifty-per cent of all lamellar defects had an associated ERM.---- Conclusions: Different profiles of lamellar macular defects were characterised and quantified by OCT. Deeper and wider lamellar defects were associated with poorer visual outcome. Such objective parameters lamellar macular defects are of value when explaining to patients regarding their decreased acuity. Future prospective investigations are required to study the natural history of lamellar defects of different aetiology and surgical indications

Internal limiting membrane peeling in macular hole

Macular hole (MH) is a full-thickness defect in the fovea, the central part of the neurosensory retina. As the fovea is the site responsible for central vision, the main clinical manifestation of MH is central visual field defect and metamorphopsia. Descriptions of MH in the medical literature are available since the 19th century. However, these only aroused renewed interest after Kelly and Wendel had shown that surgery of pars plana vitrectomy (PPV), combined with vitreous cortex detachment and fluid–gas exchange could close MH in a significant proportion of cases, although it was assumed that the retina would be unable to heal. With time, the success rate of MH surgery gradually increased and this surgery is now one of the most successful vitreoretinal surgeries. A recent innovation was the introduction of internal limiting membrane (ILM) peeling, which leads to a reduction in tangential traction and a higher rate of closure, with less recurrence. In the last 10 years, ILM peeling during MH surgery has thus become a routine step and is nowadays performed by most retinal surgeons. With the advent of modern spectral-domain (SD) optic coherence tomography (OCT), however, one can now see abnormal structural changes to the inner retinal surface after surgery with ILM peeling, suggesting that the procedure can cause retinal damage, even though vision improves. Moreover, some clinical studies found adverse functional events that have given rise to concerns regarding the safety of ILM peeling. The purpose of the present PhD thesis was to examine anatomical and functional effects of ILM peeling in MH surgery. We conducted a prospective study in 72 patients with MH, (stages 2, 3 and 4). MH surgery consisted in PPV, ILM peeling, intraocular gas and face down position. Morphologic and functional outcomes were assessed, 3, 6 and 12 months after surgery. The results reveal the presence of microstructural alterations in the different macular layers after MH surgery with ILM peeling, when compared to pre-operative measurements. Thinning of the Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL) on both sides of the fovea were the main structural alterations, in particular at the temporal region. In addition, nasal Internal Retinal Layer (IRL) thickening and shortening of papilo-macular distance could also be detected in cases of successful MH surgery with ILM peeling. Multifocal electroretinography (mf ERG) is a noninvasive method that analyses multiple retinal locations around macular area, and was used in this work to provide a topographic map of electrophysiological activity in central retina. Before surgery, mf ERG showed almost undetectable retinal response in foveal and parafoveal areas, in ring 1 and ring 2. After surgery, the improvement in the retinal response density of mf ERG in the same ring seems to be consequent to closure of the MH, with realignment of photoreceptor cells and glial cell activation. Resolution of the central scotoma could be attributed to anatomical repair and, in our study, we found a statistically significant increase in N1 and P1 in ring 1. This increase was dependent on the integrity of Outer Retina Layers (ORL), External Limiting Membrane (ELM) and Elipsoide Zone (EZ). To study the contribution of the peeled ILM to the outcome of MH surgery, the final position of the ILM after surgery was assessed. This analysis reveals that when the ILM flap ended buried into the hole after surgery, no realignment of external layers could be observed. In contrast, when the ILM flap remained over the hole, ELM and EZ were realigned, and vision was improved. In this study, duration of MH and ORL integrity were studied and we concluded that duration of symptoms of MH seem to relate to integrity to these layers. The ultrastructure and behavior of peeled ILM was studied by using light and transmission electron microscopy. We found that when both ILM vitreous sides are in apposition, there are signs of fibrotic activity, producing a basal membrane with collagen microfibrils between the two sides. This suggests that the two ILM surfaces may adhere, flanking the hole and establish a bridge that contributes to better hole closure after MH surgery. Based on the above findings, we conclude that ILM peeling performed in cases of FTMH surgery allows hole closure and vision improvement, even though anatomical differences as seen in OCT, reveals thinning of inner retinal layers and nasal displacement of the closed hole. Multifocal ERG revealed a functional alteration that is dependent on integrity of the ORL. Also, the position of ILM over the hole may have consequences on integrity of ORL and, consequently, BCVA.XIX Sumário A retina é um tecido neuronal transparente composto de várias camadas e que forra os dois terços posteriores do globo ocular. A mácula, responsável pela visão central, visão de cores e de alta resolução, está situada no chamado polo posterior, entre as arcadas vasculares da retina. Tem um diâmetro de cerca de 5,5mm estando o seu centro a 3,5 mm do bordo do disco óptico e 1mm abaixo do centro do disco, em olhos emétropes. A fóvea corresponde ao centro da mácula. Na retina encontramos duas camadas básicas, a mais posterior, camada de epitélio pigmentar e a interna, camada neurossensorial. Esta retina neurossensorial é composta por 9 camadas, sendo do lado vítreo para o lado coroideu: Membrana limitante interna (MLI) Camada de células nervosas (CCN) Camada de Células ganglionares (CCG) Camada plexiforme interna (CPI) Camada nuclear interna (CNI) Camada plexiforme externa (CPE) Camada nuclear externa (núcleo dos fotorreceptores) Membrana limitante externa (MLE) Camada de fotorreceptores (zona elipsoide, ZE) Assim, a retina neurossensorial é composta de 3 camadas de corpos celulares neuronais e duas camadas de sinapses. A camada nuclear externa contém corpos celulares dos cones e bastonetes, a camada nuclear interna contém corpos celulares das células bipolares, horizontais e amácrinas. A camada de células nervosas é constituída por células ganglionares e algumas células amácrinas. Entre estas camadas de células neuronais, existem as camadas plexiformes em que ocorrem contactos sinápticos. Na camada plexiforme externa, ocorrem contactos entre cones, bastonetes e células bipolares e células horizontais. A camada plexiforme interna, permite a comunicação entre células XX bipolares e células ganglionares, assim como informações das células amácrinas e horizontais sobre as células ganglionares. A membrana limitante interna é camada mais interna da retina e faz fronteira com o humor vítreo pelo que forma uma barreira de difusão entre a retina neuronal e humor vítreo. É considerada a membrana basal das células de Müller, formada pelos podócitos destas células, colagénio e proteoglicanos, que permite a adesão da MLI à retina e adesão do vítreo cortical à MLI. A membrana limitante externa forma a barreira para o espaço subretiniano, onde se projectam as porções internas e externas dos fotorreceptores para permitir associação com a camada de epitélio pigmentado atrás e a própria retina neuronal. O Buraco Macular é um defeito retiniano na fóvea, zona central da retina neurossensorial. Sendo a fóvea responsável pela visão central, o buraco macular pode originar metamorfopsia e defeito central nos campos visuais. O diagnóstico de Buraco Macular existe desde o século 19. No entanto, o seu interesse tem sido maior desde que Kelly e Wendell revelaram que era possível a resolução cirúrgica do buraco macular com vitrectomia via pars plana, descolamento posterior do vítreo e trocas fluido/ar. Apesar de se considerar que a retina não tivesse capacidade regenerativa, esta técnica permitia encerrar os Buracos Maculares em grande parte dos doentes. A taxa de sucesso no encerramento do Buraco Maculares foi gradualmente melhorando e, hoje em dia, é considerada a patologia vítreo-retiniana com maior sucesso cirúrgico. Com a introdução de delaminação da MLI, reduziu-se a tracção tangencial o que permitiu uma maior taxa de encerramento do buraco e menos recidivas. Nos últimos 10 anos a delaminação da MLI na cirurgia de buraco macular tornou-se rotina e é praticada pela maioria de cirurgiões vítreo-retinianos. Com o advento da Tomografia de Coerência Óptica (OCT) de domínio espectral (SD), conseguem-se observar alterações estruturais da retina interna com a delaminação, sugerindo possível lesão retiniana, mesmo que se verifique que o buraco encerre e a visão melhore. Por outro lado, a maior ou menor integridade da MLE e ZE observados no OCT após encerramento do buraco, parecem ter relação com a recuperação da função visual. No entanto, alguns estudos revelaram alterações adversas que originaram preocupação sobre a segurança desta manobra. O objectivo da presente tese foi observar efeitos anatómicos e funcionais desta delaminação na cirurgia do buraco macular. Fizemos um estudo prospectivo em 72 doentes com buraco macular de estadio 2, 3 ou 4, submetidos a cirurgia de vitrectomia via pars plana, delaminação da membrana limitante interna, trocas fluído/ar, gaz e decúbito ventral. Os resultados pós-operatórios foram registados aos 3, 6 e 12 meses após a cirurgia. Quanto a alterações anatómicas, os resultados revelaram alterações microestruturais nas diferentes camadas maculares após delaminação da MLI na cirurgia de buraco macular comparativamente aos dados pré-operatórios. Um estreitamento da camada de células ganglionares (CCG) e camada plexiforme interna (CPI), em ambos os lados, nasal e temporal da fóvea, parecem ser as maiores alterações. Mas a diferença de estreitamento das camadas, em cada um dos lados, nasal e temporal, são igualmente importantes, sendo a espessura total nasal maior que a espessura total temporal. Encontrou-se, ainda, um aumento da espessura do sector interno das camadas internas da macula nasal, assim como um encurtamento da distância entre o disco óptico e a mácula, após cirurgia com pelagem da MLI e encerramento do buraco. Assim, o buraco macular encerra modificando a sua posição inicial, aproximando-se do disco óptico e aumentando a espessura nasal da mácula. Utilizou-se o ERG multifocal para estudo de alterações funcionais da mácula antes e depois da pelagem da MLI na cirurgia do buraco macular. Trata-se de um método não invasivo que seleciona múltiplas zonas à volta da área macular, de modo a permitir um mapa topográfico de actividade eletrofisiológica na retina central. Após cirurgia eficaz, passa a haver um buraco encerrado, com ou sem integridade da membrana limitante externa, zona elipsoide e epitélio pigmentado. Neste estudo funcional, o ERG multifocal revelou, antes da cirurgia, uma resposta retiniana indetectável na área foveal e parafoveal nos anéis 1 e 2. Após encerramento do buraco, a melhoria da resposta retiniana nos dois anéis referidos parecem ser consequência do encerramento do buraco com realinhamento dos fotorreceptores. A resolução do escotoma central parece ser devida a reparação anatómica do buraco. No nosso estudo houve um aumento das ondas N1 e P1 no anel 1. Este aumento foi dependente da integridade das camadas externas da mácula, MLE e EZ. Em buracos maculares de dimensão elevada, superior a 400 micras, a MLI é delaminada até ao bordo do BM, reservando uma porção maior que é dobrada sobre si própria e colocada sobre o buraco, permitido o seu encerramento. Comprovámos que o resultado funcional e a integridade dos fotorreceptores dependiam da posição final da porção de MLI sobre o BM. Neste estudo, verificámos que se um fragmento de MLI ficasse enterrada no buraco, havia encerramento do buraco, mas não realinhamento dos fotorreceptores. Se o fragmento de MLI se mantivesse sobre o BM, o BM encerrava e a camadas de fotorreceptores, traduzida pela membrana limitante externa e zona elipsoide, revelavam integridade em grande parte dos casos. Para esta integridade também tinha importância o tempo de evolução do BM. Quanto menor tempo de evolução do BM, melhor a taxa de realinhamento das camadas externas da macula. Sempre que possível, durante a cirurgia macular, depois da delaminação da MLI e de colocada uma porção evertida de MLI sobre o buraco, eram excisados dois outros pedaços de MLI e estes enviados para estudo. A ulta estrutura e o comportamento da membrana limitante interna excisada foram estudadas por microscopia óptica e electrónica. Verificou-se que, em meio rico, e estando as duas faces vítreas da MLI em contacto, havia sinais de actividade fibrótica com produção de membrana basal, o que permitia a aderência destas duas faces de MLI. Sugerimos no nosso estudo que células epiretinianas na MLI pudessem ter capacidade proliferativa, com formação de microfibrilhas entre as duas faces adjacentes de MLI. Este facto poderia explicar a aderência observada entre o folheto de ILM e os bordos do buraco macular, depois da cirurgia, o que contribuiria para o encerramento do BM. Baseados nos resultados encontrados, poderemos concluir que a delaminação de MLI em todos os casos de cirurgia de BM permite o encerramento do buraco e melhoria da visão, apesar de se verificar alterações importante na anatomia, medidas pela tomografia de coerência óptica, antes e depois da cirurgia. As alterações anatómicas mais importantes são diminuição da espessura das camadas internas da mácula, nasal e temporal, um aumento da espessura total da porção nasal da mácula e uma diminuição da espessura temporal. E, ainda, um desvio nasal do BM depois do seu encerramento. O ERG multifocal revela alterações funcionais na mácula depois de cirurgia com pelagem da MLI e, esta alteração, depende da integridade das camadas externas da mácula. A integridade das camadas externas, MLE, ZE e EP determinam a função visual final. Para ser possível esta integridade, a posição da porção de MLI sobre o BM é muito importante, dependendo se esta fica enterrada no meio do buraco ou se fica sobre o buraco. Por fim, na análise por microscopia electrónica da MLI excisada, encontrámos microfibrilhas de colagénio entre as duas faces vítreas da membrana, que poderão contribuir para o mecanismo de encerramento do Buraco macular

The Role of Medical Image Modalities and AI in the Early Detection, Diagnosis and Grading of Retinal Diseases: A Survey.

Traditional dilated ophthalmoscopy can reveal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal tear, epiretinal membrane, macular hole, retinal detachment, retinitis pigmentosa, retinal vein occlusion (RVO), and retinal artery occlusion (RAO). Among these diseases, AMD and DR are the major causes of progressive vision loss, while the latter is recognized as a world-wide epidemic. Advances in retinal imaging have improved the diagnosis and management of DR and AMD. In this review article, we focus on the variable imaging modalities for accurate diagnosis, early detection, and staging of both AMD and DR. In addition, the role of artificial intelligence (AI) in providing automated detection, diagnosis, and staging of these diseases will be surveyed. Furthermore, current works are summarized and discussed. Finally, projected future trends are outlined. The work done on this survey indicates the effective role of AI in the early detection, diagnosis, and staging of DR and/or AMD. In the future, more AI solutions will be presented that hold promise for clinical applications

Astigmatism and Pseudoaccommodation in Pseudophakic Eyes

noAdvanced IOLs with circumferential zones of different power provide pseudoaccommodation. We investigated the potential for power variation with meridian, namely astigmatism, to provide pseudo-accommodation. With appropriate power and axis orientations, acceptable pseudo-accommodation can be achieved

Optical coherence tomography: evaluation and clinical application

The ability to examine the appearance of the retina is of paramount importance for the diagnosis and monitoring of ophthalmic disease and for the evaluation of treatment outcomes. Direct cross-sectional imaging of retinal structure could be useful for early diagnosis and more sensitive monitoring of a variety of retinal conditions such as macular oedema and glaucoma. The view of the fundus given by ophthalmoscopy provides very limited depth information and clinicians will often have to resort to additional techniques such as flourescein angiography or visual field testing for information on structural abnormalities within the retina. Other currently available imaging techniques do not provide sufficient depth resolution to produce useful cross-sectional images of retinal structure. Optical coherence tomography (OCT) is a new imaging technique which is capable of producing cross-sectional images of the retina with a resolution that surpasses that of conventional imaging techniques. This new technique has axial resolution of around 1 O.tm and can resolve individual retinal layers, thus providing information on retinal structure. In principle, OCT is very similar to ultrasound however it makes use of a light source rather than an acoustic one. The technique is non-contact and non-invasive and is generally well tolerated by patients. This thesis describes the evaluation of this new imaging technique with regards to its potential within routine clinical practice. A number of investigations were performed to fuffil this evaluation. Tests were carried out to experimentally measure the system's resolution and the accuracy and precision of measurements made from the OCT scans. A number of factors that could affect the quality of the scans were identified and their effects were minimised wherever possible. The software provided with the system was rigorously tested and potential sources of error were identified. Various studies were undertaken to quantify the repeatability and reproducibility of measurements made from scans and normative values were established. These results were used to assess the ability of the technique to detect and quantify several retinal disorders. The potential of the technique for corneal imaging was investigated - a scanning protocol was established and customised software for processing cornea! scans was developed. The relationship between OCT bands and retinal morphology was investigated by correlating scans from canine retina with corresponding light microscopy images and by observing the position of retinal abnormalities on scans from patients with a variety of conditions that affected different parts of the retina. Finally the clinical potential of OCT was investigated by carrying out various studies on a number of retinal conditions. Further clinical studies which combine anatomical information from OCT with functional information from electrophysiology are currently underway. Current developments are aimed at improving the imaging processing features and user interface so as to provide a more robust, user-friendly system for routine clinical use