3D Segmentation & Measurement of Macular Holes

Macular holes are blinding conditions where a hole develops in the central part of retina, resulting in reduced central vision. The prognosis and treatment options are related to a number of variables including the macular hole size and shape. In this work we introduce a method to segment and measure macular holes in three-dimensional (3D) data. High-resolution spectral domain optical coherence tomography (SD-OCT) allows precise imaging of the macular hole geometry in three dimensions, but the measurement of these by human observers is time consuming and prone to high inter- and intra-observer variability, being characteristically measured in 2D rather than 3D. This work introduces several novel techniques to automatically retrieve accurate 3D measurements of the macular hole, including surface area, base area, base diameter, top area, top diameter, height, and minimum diameter. Specifically, it is introducing a multi-scale 3D level set segmentation approach based on a state-of-the-art level set method, and introducing novel curvature-based cutting and 3D measurement procedures. The algorithm is fully automatic, and we validate the extracted measurements both qualitatively and quantitatively, where the results show the method to be robust across a variety of scenarios. A segmentation software package is presented for targeting medical and biological applications, with a high level of visual feedback and several usability enhancements over existing packages. Specifically, it is providing a substantially faster graphics processing unit (GPU) implementation of the local Gaussian distribution fitting (LGDF) energy model, which can segment inhomogeneous objects with poorly defined boundaries as often encountered in biomedical images. It also provides interactive brushes to guide the segmentation process in a semi-automated framework. The speed of implementation allows us to visualise the active surface in real-time with a built-in ray tracer, where users may halt evolution at any timestep to correct implausible segmentation by painting new blocking regions or new seeds. Quantitative and qualitative validation is presented, demonstrating the practical efficacy of the interactive elements for a variety of real-world datasets. The size of macular holes is known to be one of the strongest predictors of surgical success both anatomically and functionally. Furthermore, it is used to guide the choice of treatment, the optimum surgical approach and to predict outcome. Our automated 3D image segmentation algorithm has extracted 3D shape-based macular hole measurements and described the dimensions and morphology. Our approach is able to robustly and accurately measure macular hole dimensions. This thesis is considered as a significant contribution for clinical applications particularly in the field of macular hole segmentation and shape analysis

Artificial intelligence and deep learning in ophthalmology

Artificial intelligence (AI) based on deep learning (DL) has sparked tremendous global interest in recent years. DL has been widely adopted in image recognition, speech recognition and natural language processing, but is only beginning to impact on healthcare. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography and visual fields, achieving robust classification performance in the detection of diabetic retinopathy and retinopathy of prematurity, the glaucoma-like disc, macular oedema and age-related macular degeneration. DL in ocular imaging may be used in conjunction with telemedicine as a possible solution to screen, diagnose and monitor major eye diseases for patients in primary care and community settings. Nonetheless, there are also potential challenges with DL application in ophthalmology, including clinical and technical challenges, explainability of the algorithm results, medicolegal issues, and physician and patient acceptance of the AI 'black-box' algorithms. DL could potentially revolutionise how ophthalmology is practised in the future. This review provides a summary of the state-of-the-art DL systems described for ophthalmic applications, potential challenges in clinical deployment and the path forward

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Psychiatric Case Record

Bipolar Disorder-Mania: Patient was apparently normal one-month back, Then all of a sudden he developed sleep disturbances –mainly difficult in initiation of sleep. He also started abusing his family members for unwanted things. Subsequently, he started talking excessively and irritable. Sometimes he sings film songs and dances. He used to say that God Supreme exists in himself and so he has all the powers of Almighty. With that superior power he says that he can solve all the problems in this world. He also says that he has invented herbs to keep people young. For the past one week, he talks excessively without having an hour of sleep & wanders here and there & found excessively smoking. He becomes excessively spiritual and goes to near by villages for offering prayers to God. He takes only a little food everyday and he is very much keen in personal cleanliness. Paranoid Schizophrenia: She was apparently normal 8 months back, then she developed sleep disturbances in the form of difficult in falling asleep. She was found talking & smiling to herself at night & day with mirror gazing. She started saying that her neighbour & relatives are planning to kill herself by poisoning. In this context she had frequent quarrels with them and she refused to take food prepared by her mother in law. She left the home at night without informing any one and started wandering in the road side near her home. She was complaining that she hears voices as if her neighbour & relatives were talking about her among themselves She was not doing house hold activities for past 6 months and she was not taking care of her child. Her personal hygiene was very much deteriorated slowly as she used to take bath & brush, only if she was asked to do so. She started abusing & assaulting the strangers and family members. Generalised Anxiety Disorder: Six months back he was apparently normal. He is working as a system analyst in a private bank . He had once, made a mistake in his bank work for which he was given charges by his employer, followed this event he becomes very tense and afraid whenever his boss called him. He is very cautious that he should not commit any mistakes. Even though he is not doing so, he fears that he may commit some mistake in his work. At that moment he develops palpitation, giddiness, breathlessness, excessive sweating over palms and soles. Slowly these symptoms present through out the day even when he was not in his office, and he could not control his fearfulness. For the past 6 months he didn’t sleep well. His sleep is disturbed by bad dreams. Recurrent Depressive Disorder: Patient was apparently alright 2 months back. Then she developed sleep disturbances particularly early morning awakening, she use to wake up by 3.00 am and use to brood about herself and started crying. She was not doing her domestic work as before, as she felt excess tiredness and use to take frequent rests. She developed poor communication. She had lost her interest in pleasurable activities and was not interested in watching TV, and attending family gatherings. She stayed aloof most of the time & calm, quiet and withdrawn. She was expressing her helplessness and hopelessness about the future. She started to have decline in maintaining self care. 15 days back, she frequently expressed suicidal ideas and she had attempted suicide by hanging herself and was rescued by neighbours. 5 days back, she started talking in an irrelevant manner. She was smiling to self. She was assaulting her family members. She was suspicious that her neighbour had done black magic on her and also saying that people are talking about her. She reported hearing the voice of her neighbour scolding and threatening her. Organic Brain Syndrome – Dementia: Ten months back he was apparently alright. Then his relatives noticed himself frequently misplaces things inside his home. Then he started behaving aggressively. He was beating his wife without reason. He was roaming here and there, running out of home and wandering aimlessly. He was not able to come back home when he goes out. He was brought back to home by his relatives. Slowly he developed fearfulness and tremulousness while he was staying alone. He also started saying that his family members & neighbours were talking about himself, in this context he would make frequent quarrels with them. He also started hearing voices of known male voices abusing himself in third person. He sleeps for few hour only. He is passing urine and motion inside the house. He is asking about his brother and mother-in-law who were expired long back. He behaves abnormally such as pouring water in the plate while eating. And his relatives found the symptoms were worsened by evening. All these symptoms started insidiously, increased in severity through time and attained the present state. No history of loss of appetite / crying spells / suicidal tendencies / convulsions / fever / head injury

Identification of Surrogate Anatomic Identifiers of Disease Progression in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss in patients over 50 in the developed world. The visual impairment is due to either choroidal neovascularisation (wet AMD) or geographic atrophy (GA). Drusen is the hallmark of AMD but the presence of drusen does not inform progression to wet AMD. Although the disease is mostly bilateral, the rate of progression of disease in both eyes may not be simultaneous. If one eye is affected by wet AMD, the risk of progression of the fellow eye to wet AMD increases by 10% every year. However, there are no markers that inform the time of conversion to wet AMD. For this reason, there is an unmet need to identify biomarkers that can fully predict the progression to wet AMD in order to allow early intervention before permanent damage. My thesis aimed to assess whether changes in imaging characteristics can more precisely explain conversion. I studied various cohorts including (a) normal aging eyes (b) eyes with early/ intermediate AMD and (c) fellow eyes of unilateral wet AMD to study the conversion to wet AMD. Firstly, I evaluated longitudinally volume changes in inner and outer retinal layers of 71 eyes with early/intermediate AMD using optical coherence tomography (OCT). Our results showed that inner and outer retina layer volumes may differentiate AMD eyes from healthy eyes. When comparing those who progressed to wet AMD at year 2 to those who did not, we found that baseline volume of GCIPL may differentiate between the 2 groups. As it is an inner retinal change, I hypothesized that heritability of the retinal layers may influence the rate of retinal layer changes and that may in turn help understand the changes seen in aging and AMD. I worked with the TWIN Study database, in which OCT was done in eyes of twins of different age groups and OCT data were available on 364 eyes of 184 (92 pair) twins. I evaluated whether heritability was responsible for ageing changes of the retinal layers. I found that total retinal volume and inner retinal layer volumes may be affected by genetic factors

Nonlocal Graph-PDEs and Riemannian Gradient Flows for Image Labeling

In this thesis, we focus on the image labeling problem which is the task of performing unique pixel-wise label decisions to simplify the image while reducing its redundant information. We build upon a recently introduced geometric approach for data labeling by assignment flows [ APSS17 ] that comprises a smooth dynamical system for data processing on weighted graphs. Hereby we pursue two lines of research that give new application and theoretically-oriented insights on the underlying segmentation task. We demonstrate using the example of Optical Coherence Tomography (OCT), which is the mostly used non-invasive acquisition method of large volumetric scans of human retinal tis- sues, how incorporation of constraints on the geometry of statistical manifold results in a novel purely data driven geometric approach for order-constrained segmentation of volumetric data in any metric space. In particular, making diagnostic analysis for human eye diseases requires decisive information in form of exact measurement of retinal layer thicknesses that has be done for each patient separately resulting in an demanding and time consuming task. To ease the clinical diagnosis we will introduce a fully automated segmentation algorithm that comes up with a high segmentation accuracy and a high level of built-in-parallelism. As opposed to many established retinal layer segmentation methods, we use only local information as input without incorporation of additional global shape priors. Instead, we achieve physiological order of reti- nal cell layers and membranes including a new formulation of ordered pair of distributions in an smoothed energy term. This systematically avoids bias pertaining to global shape and is hence suited for the detection of anatomical changes of retinal tissue structure. To access the perfor- mance of our approach we compare two different choices of features on a data set of manually annotated 3 D OCT volumes of healthy human retina and evaluate our method against state of the art in automatic retinal layer segmentation as well as to manually annotated ground truth data using different metrics. We generalize the recent work [ SS21 ] on a variational perspective on assignment flows and introduce a novel nonlocal partial difference equation (G-PDE) for labeling metric data on graphs. The G-PDE is derived as nonlocal reparametrization of the assignment flow approach that was introduced in J. Math. Imaging & Vision 58(2), 2017. Due to this parameterization, solving the G-PDE numerically is shown to be equivalent to computing the Riemannian gradient flow with re- spect to a nonconvex potential. We devise an entropy-regularized difference-of-convex-functions (DC) decomposition of this potential and show that the basic geometric Euler scheme for inte- grating the assignment flow is equivalent to solving the G-PDE by an established DC program- ming scheme. Moreover, the viewpoint of geometric integration reveals a basic way to exploit higher-order information of the vector field that drives the assignment flow, in order to devise a novel accelerated DC programming scheme. A detailed convergence analysis of both numerical schemes is provided and illustrated by numerical experiments

Functional outcome of retinal oedema and its standard treatment

Macular oedema is a pathological condition of fluid accumulation in the retinal tissues. It is a nonspecific sign of several retinal diseases that in the long term can lead to permanent vision loss. The clinical aspect of macular oedema treatment and vision recovery is reduction of the amount of fluid accumulated in the retina. Due to its complex pathophysiological mechanism, macular oedema has proven challenging to manage. Many unanswered questions remain in the ophthalmology world on this subject. The development of recent diagnostic tools such as optical coherence tomography allows better understanding of the morphological changes in the retina. Now we are able to detect retinal oedema and characterise it by location, depth, and amount of fluid. Further, clinicians are now able to assess therapeutic response by examining the anatomical structures of the retina. Yet, with techniques offering objective accuracy, emerging reports have shown discrepancies between clinically examined visual acuity, anatomical changes of the retina, and patients’ self-reported visual ability. The presence of such discrepancies is also supported by the fact that results achieved by randomised clinical trials rarely align with results attained in real-world settings. Today, functional vision testing can be performed with several different methods including questionnaires, colour vision tests, reading speed tests, contrast sensitivity tests etc. Nevertheless, none of these methods are widely used in clinical settings, and their predictive capabilities have yet to be explored. Establishing precise methodology for functional vision testing is likely to provide better understanding of patients’ treatment response. This thesis aims to investigate the potential predictive capabilities of functional vision tests and to compare these capabilities with those of well-established, routine ophthalmic examinations such as visual acuity and retinal thickness tests. In the current research, I focused on the following functional examinations: the visual function questionnaire (VFQ- 25), reading speed testing, and testing of the contrast sensitivity of the macula area (examined by microperimetry). These techniques allowed very specific and sensitive testing of the functionality of the retina. In addition, I explored functional vision tests and their association to the routine ophthalmic tests and their ability to detect sub-clinical changes in vision. I believe further research in this area will offer better understanding of the functional vision changes in patients with macular oedema and potentially will help in improving visionrelated quality of life

Clamp-assisted retractor advancement for lower eyelid involutional entropion

Scientific Poster 144PURPOSE: To describe a novel approach to internal repair of lower lid entropion using the Putterman clamp. METHODS: Retrospective, consecutive case series of patients with entropion who underwent retractor advancement using the clamp. RESULTS: Seven eyes of 6 patients (average age: 80; 4 women and 2 men) were analyzed. Complete resolution was achieved in 5 of the 6 patients (83.3%). The 1 patient with recurrence had 2 previous entropion surgeries on each eye over the past 4 years; there was lid laxity, and horizontal tightening was needed. No severe adverse events occurred in the patients. CONCLUSION: Clamp-assisted lower lid retractor advancement offers a safe and effective, minimally invasive approach to involutional entropion. Further study is needed to assess its role in recurrent entropion.postprin