Predicting Drusen Regression from OCT in Patients with Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. The presence of drusen is the hallmark of early/intermediate AMD, and their sudden regression is strongly associated with the onset of late AMD. In this work we propose a predictive model of drusen regression using optical coherence tomography (OCT) based features. First, a series of automated image analysis steps are applied to segment and characterize individual drusen and their development. Second, from a set of quantitative features, a random forest classifiser is employed to predict the occurrence of individual drusen regression within the following 12 months. The predictive model is trained and evaluated on a longitudinal OCT dataset of 44 eyes from 26 patients using leave-one-patient-out cross-validation. The model achieved an area under the ROC curve of 0.81, with a sensitivity of 0.74 and a specificity of 0.73. The presence of hyperreflective foci and mean drusen signal intensity were found to be the two most important features for the prediction. This preliminary study shows that predicting drusen regression is feasible and is a promising step toward identification of imaging biomarkers of incoming regression

Methods for automated analysis of macular OCT data

Optical coherence tomography (OCT) is fast becoming one of the most important modalities for imaging the eye. It provides high resolution, cross-sectional images of the retina in three dimensions, distinctly showing its many layers. These layers are critical for normal eye function, and vision loss may occur when they are altered by disease. Specifically, the thickness of individual layers can change over time, thereby making the ability to accurately measure these thicknesses an important part of learning about how different diseases affect the eye. Since manual segmentation of the layers in OCT data is time consuming and tedious, automated methods are necessary to extract layer thicknesses. While a standard set of tools exist on the scanners to automatically segment the retina, the output is often limited, providing measurements restricted to only a few layers. Analysis of longitudinal data is also limited, with scans from the same subject often processed independently and registered using only a single landmark at the fovea. Quantification of other changes in the retina, including the accumulation of fluid, are also generally unavailable using the built-in software. In this thesis, we present four contributions for automatically processing OCT data, specifically for data acquired from the macular region of the retina. First, we present a layer segmentation algorithm to robustly segment the eight visible layers of the retina. Our approach combines the use of a random forest (RF) classifier, which produces boundary probabilities, with a boundary refinement algorithm to find surfaces maximizing the RF probabilities. Second, we present a pair of methods for processing longitudinal data from individual subjects: one combining registration and motion correction, and one for simultaneously segmenting the layers across all scans. Third, we develop a method for segmentation of microcystic macular edema, which appear as small, fluid-filled, cystoid spaces within the retina. Our approach again uses an RF classifier to produce a robust segmentation. Finally, we present the development of macular flatspace (MFS), a computational domain used to put data from different subjects in a common coordinate system where each layer appears flat, thereby simplifying any automated processing. We present two applications of MFS: inhomogeneity correction to normalize the intensities within each layer, and layer segmentation by adapting and simplifying a graph formulation used previously

An In-Depth Statistical Review of Retinal Image Processing Models from a Clinical Perspective

The burgeoning field of retinal image processing is critical in facilitating early diagnosis and treatment of retinal diseases, which are amongst the leading causes of vision impairment globally. Despite rapid advancements, existing machine learning models for retinal image processing are characterized by significant limitations, including disparities in pre-processing, segmentation, and classification methodologies, as well as inconsistencies in post-processing operations. These limitations hinder the realization of accurate, reliable, and clinically relevant outcomes. This paper provides an in-depth statistical review of extant machine learning models used in retinal image processing, meticulously comparing them based on their internal operating characteristics and performance levels. By adopting a robust analytical approach, our review delineates the strengths and weaknesses of current models, offering comprehensive insights that are instrumental in guiding future research and development in this domain. Furthermore, this review underscores the potential clinical impacts of these models, highlighting their pivotal role in enhancing diagnostic accuracy, prognostic assessments, and therapeutic interventions for retinal disorders. In conclusion, our work not only bridges the existing knowledge gap in the literature but also paves the way for the evolution of more sophisticated and clinically-aligned retinal image processing models, ultimately contributing to improved patient outcomes and advancements in ophthalmic care

CAD system for early diagnosis of diabetic retinopathy based on 3D extracted imaging markers.

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate delineation of retinal layers, enabling better understanding of the anatomical structure and more effective surgical interventions. Moreover, real-time guidance systems can be developed to assist surgeons during procedures, improving overall patient outcomes. The second contribution of this dissertation is the introduction of a novel computeraided diagnosis (CAD) system for precise identification of diabetic retinopathy. The CAD system utilizes 3D-OCT imaging and employs an innovative approach that extracts two distinct features: first-order reflectivity and 3D thickness. These features are then fused and used to train and test a neural network classifier. The proposed CAD system exhibits promising results, surpassing other machine learning and deep learning algorithms commonly employed in DR detection. This demonstrates the effectiveness of the comprehensive analysis approach employed by the CAD system, which considers both low-level and high-level data from the 3D retinal layers. The CAD system presents a groundbreaking contribution to the field, as it goes beyond conventional methods, optimizing backpropagated neural networks to integrate multiple levels of information effectively. By achieving superior performance, the proposed CAD system showcases its potential in accurately diagnosing DR and aiding in the prevention of vision loss. In conclusion, this dissertation presents novel approaches for the segmentation of retinal layers and the diagnosis of diabetic retinopathy. The proposed methods exhibit significant improvements in accuracy, speed, and performance compared to existing techniques, opening new avenues for clinical applications and advancements in the field of ophthalmology. By addressing future research directions, such as testing on larger datasets, exploring alternative algorithms, and incorporating user feedback, the proposed methods can be further refined and developed into robust, accurate, and clinically valuable tools for diagnosing and monitoring retinal diseases

Learn Single-horizon Disease Evolution for Predictive Generation of Post-therapeutic Neovascular Age-related Macular Degeneration

Most of the existing disease prediction methods in the field of medical image processing fall into two classes, namely image-to-category predictions and image-to-parameter predictions. Few works have focused on image-to-image predictions. Different from multi-horizon predictions in other fields, ophthalmologists prefer to show more confidence in single-horizon predictions due to the low tolerance of predictive risk. We propose a single-horizon disease evolution network (SHENet) to predictively generate post-therapeutic SD-OCT images by inputting pre-therapeutic SD-OCT images with neovascular age-related macular degeneration (nAMD). In SHENet, a feature encoder converts the input SD-OCT images to deep features, then a graph evolution module predicts the process of disease evolution in high-dimensional latent space and outputs the predicted deep features, and lastly, feature decoder recovers the predicted deep features to SD-OCT images. We further propose an evolution reinforcement module to ensure the effectiveness of disease evolution learning and obtain realistic SD-OCT images by adversarial training. SHENet is validated on 383 SD-OCT cubes of 22 nAMD patients based on three well-designed schemes based on the quantitative and qualitative evaluations. Compared with other generative methods, the generative SD-OCT images of SHENet have the highest image quality. Besides, SHENet achieves the best structure protection and content prediction. Qualitative evaluations also demonstrate that SHENet has a better visual effect than other methods. SHENet can generate post-therapeutic SD-OCT images with both high prediction performance and good image quality, which has great potential to help ophthalmologists forecast the therapeutic effect of nAMD

Structure-Function Correlation of the Human Central Retina

The impact of retinal pathology detected by high-resolution imaging on vision remains largely unexplored. Therefore, the aim of the study was to achieve high-resolution structure-function correlation of the human macula in vivo.To obtain high-resolution tomographic and topographic images of the macula spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO), respectively, were used. Functional mapping of the macula was obtained by using fundus-controlled microperimetry. Custom software allowed for co-registration of the fundus mapped microperimetry coordinates with both SD-OCT and cSLO datasets. The method was applied in a cross-sectional observational study of retinal diseases and in a clinical trial investigating the effectiveness of intravitreal ranibizumab in macular telangietasia type 2. There was a significant relationship between outer retinal thickness and retinal sensitivity (p<0.001) and neurodegeneration leaving less than about 50 µm of parafoveal outer retinal thickness completely abolished light sensitivity. In contrast, functional preservation was found if neurodegeneration spared the photoreceptors, but caused quite extensive disruption of the inner retina. Longitudinal data revealed that small lesions affecting the photoreceptor layer typically precede functional detection but later cause severe loss of light sensitivity. Ranibizumab was shown to be ineffective to prevent such functional loss in macular telangietasia type 2.Since there is a general need for efficient monitoring of the effectiveness of therapy in neurodegenerative diseases of the retina and since SD-OCT imaging is becoming more widely available, surrogate endpoints derived from such structure-function correlation may become highly relevant in future clinical trials

RETINAL OCT IMAGE ANALYSIS USING DEEP LEARNING

Optical coherence tomography (OCT) is a noninvasive imaging modality which uses low-coherence light waves to take cross-sectional images of optical scattering media. OCT has been widely used in diagnosing retinal and neural diseases by imaging the human retina. The thicknesses of retinal layers are important biomarkers for neurological diseases like multiple sclerosis (MS). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIP) thickness can be used to assess the global disease progression of MS patients. Automated OCT image analysis tools are critical for quantitatively monitoring disease progression and exploring biomarkers. With the development of more powerful computational resources, deep learning based methods have achieved much better performance in accuracy, speed, and algorithm flexibility for many image analysis tasks. However, without task-specific modifications, these emerging deep learning methods are not satisfactory if directly applied to tasks like retinal layer segmentation. In this thesis, we present a set of novel deep learning based methods for OCT image analysis. Specifically, we focus on automated retinal layer segmentation from macular OCT images. The first problem we address is that existing deep learning methods do not incorporate explicit anatomical rules and cannot guarantee the layer segmentation hierarchy~(pixels of the upper layers should have no overlap or gap with pixels of layers beneath it). To solve this, we developed an efficient fully convolutional network to generate structured layer surfaces with correct topology that is also able to perform retinal lesion~(cysts or edema) segmentation. The second problem we addressed is that the segmentation uncertainty reduces the sensitivity of detecting mild retinal changes in MS patients over time. To solve this, we developed a longitudinal deep learning pipeline that considers both inter-slice and longitudinal segmentation priors to achieve a more consistent segmentation for monitoring patient-specific retinal changes. The third problem we addressed is that the performance of the deep learning models will degrade when test data is generated from different scanners~(domain shift). We address this problem by developing a novel test-time domain adaptation method. Different from existing solutions, our model can dynamically adapt to each test subject during inference without time-consuming retraining. Our deep networks achieved state-of-the-art segmentation accuracy, speed, and flexibility compared to the existing methods

Segmentation of the Retinal Vasculature within Spectral-Domain Optical Coherence Tomography Volumes of Mice

Automated approaches for the segmentation of the retinal vessels are helpful for longitudinal studies of mice using spectral-domain optical coherence tomography (SD-OCT). In the SD-OCT volumes of human eyes, the retinal vasculature can be readily visualized by creating a projected average intensity image in the depth direction. The created projection images can then be segmented using standard approaches. However, in the SD-OCT volumes of mouse eyes, the creation of projection images from the entire volume typically results in very poor images of the vasculature. The purpose of this work is to present and evaluate three machine-learning approaches, namely baseline, single-projection, and all-layers approaches, for the automated segmentation of retinal vessels within SD-OCT volumes of mice. Twenty SD-OCT volumes (400 × 400 × 1024 voxels) from the right eyes of twenty mice were obtained using a Bioptigen SD-OCT machine (Morrisville, NC) to evaluate our methods. The area under the curve (AUC) for the receiver operating characteristic (ROC) curves of the all-layers approach, 0.93, was significantly larger than the AUC for the single-projection (0.91) and baseline (0.88) approach with p < 0.05