A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

Automatic Classification of Bright Retinal Lesions via Deep Network Features

The diabetic retinopathy is timely diagonalized through color eye fundus images by experienced ophthalmologists, in order to recognize potential retinal features and identify early-blindness cases. In this paper, it is proposed to extract deep features from the last fully-connected layer of, four different, pre-trained convolutional neural networks. These features are then feeded into a non-linear classifier to discriminate three-class diabetic cases, i.e., normal, exudates, and drusen. Averaged across 1113 color retinal images collected from six publicly available annotated datasets, the deep features approach perform better than the classical bag-of-words approach. The proposed approaches have an average accuracy between 91.23% and 92.00% with more than 13% improvement over the traditional state of art methods.Comment: Preprint submitted to Journal of Medical Imaging | SPIE (Tue, Jul 28, 2017

Retinal vessel segmentation using textons

Segmenting vessels from retinal images, like segmentation in many other medical image domains, is a challenging task, as there is no unified way that can be adopted to extract the vessels accurately. However, it is the most critical stage in automatic assessment of various forms of diseases (e.g. Glaucoma, Age-related macular degeneration, diabetic retinopathy and cardiovascular diseases etc.). Our research aims to investigate retinal image segmentation approaches based on textons as they provide a compact description of texture that can be learnt from a training set. This thesis presents a brief review of those diseases and also includes their current situations, future trends and techniques used for their automatic diagnosis in routine clinical applications. The importance of retinal vessel segmentation is particularly emphasized in such applications. An extensive review of previous work on retinal vessel segmentation and salient texture analysis methods is presented. Five automatic retinal vessel segmentation methods are proposed in this thesis. The first method focuses on addressing the problem of removing pathological anomalies (Drusen, exudates) for retinal vessel segmentation, which have been identified by other researchers as a problem and a common source of error. The results show that the modified method shows some improvement compared to a previously published method. The second novel supervised segmentation method employs textons. We propose a new filter bank (MR11) that includes bar detectors for vascular feature extraction and other kernels to detect edges and photometric variations in the image. The k-means clustering algorithm is adopted for texton generation based on the vessel and non-vessel elements which are identified by ground truth. The third improved supervised method is developed based on the second one, in which textons are generated by k-means clustering and texton maps representing vessels are derived by back projecting pixel clusters onto hand labelled ground truth. A further step is implemented to ensure that the best combinations of textons are represented in the map and subsequently used to identify vessels in the test set. The experimental results on two benchmark datasets show that our proposed method performs well compared to other published work and the results of human experts. A further test of our system on an independent set of optical fundus images verified its consistent performance. The statistical analysis on experimental results also reveals that it is possible to train unified textons for retinal vessel segmentation. In the fourth method a novel scheme using Gabor filter bank for vessel feature extraction is proposed. The ii method is inspired by the human visual system. Machine learning is used to optimize the Gabor filter parameters. The experimental results demonstrate that our method significantly enhances the true positive rate while maintaining a level of specificity that is comparable with other approaches. Finally, we proposed a new unsupervised texton based retinal vessel segmentation method using derivative of SIFT and multi-scale Gabor filers. The lack of sufficient quantities of hand labelled ground truth and the high level of variability in ground truth labels amongst experts provides the motivation for this approach. The evaluation results reveal that our unsupervised segmentation method is comparable with the best other supervised methods and other best state of the art methods

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruchs membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates

Adaptive Super-Candidate Based Approach for Detection and Classification of Drusen on Retinal Fundus Images

Identification and characterization of drusen is essential for the severity assessment of age-related macular degeneration (AMD). Presented here is a novel super-candidate based approach, combined with robust preprocessing and adaptive thresholding for detection of drusen, resulting in accurate segmentation with the mean lesion-level overlap of 0.75, even in cases with non-uniform illumination, poor contrast and con- founding anatomical structures. We also present a feature based lesion- level discrimination analysis between hard and soft drusen. Our method gives sensitivity of 80% for high specificity above 90% and high sensitivity of 95% for specificity of 70% on representative pathological databases (STARE and ARIA) for both detection and discrimination

Advanced image processing techniques for detection and quantification of drusen

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 TechnologyDrusen 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

Detection of macular atrophy in age-related macular degeneration aided by artificial intelligence

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development. AREAS COVERED: Artificial Intelligence (AI) has demonstrated great impact in detection of retinal diseases, especially with its robust ability to analyze big data afforded by ophthalmic imaging modalities, such as color fundus photography (CFP), fundus autofluorescence (FAF), near-infrared reflectance (NIR), and optical coherence tomography (OCT). Among these, OCT has been shown to have great promise in identifying early MA using the new criteria in 2018. EXPERT OPINION: There are few studies in which AI-OCT methods have been used to identify MA; however, results are very promising when compared to other imaging modalities. In this paper, we review the development and advances of ophthalmic imaging modalities and their combination with AI technology to detect MA in AMD. In addition, we emphasize the application of AI-OCT as an objective, cost-effective tool for the early detection and monitoring of the progression of MA in AMD