Applicability of oculomics for individual risk prediction: Repeatability and robustness of retinal Fractal Dimension using DART and AutoMorph

Purpose: To investigate whether Fractal Dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness. Methods: We used two datasets: Caledonia, healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 colour fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE, thus it provides a pessimistic lower-bound as vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and Intraclass Correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter {\lambda} which is within-eye Standard Deviation (SD) of FD measurements in units of between-eyes SD. Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all p<0.0001). Median {\lambda} in Caledonia without exclusions was 3.55\% for DART and 12.65\% for AutoMorph, and improved to up to 1.67\% and 6.64\% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with {\lambda} (Pearson 0.5350-0.7550, depending on dataset and method, all p<0.0001). Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods.

Choroidalyzer: An open-source, end-to-end pipeline for choroidal analysis in optical coherence tomography

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5,600 OCT B-scans (233 subjects, 6 systemic disease cohorts, 3 device types, 2 manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep-learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centred region of interest. We analysed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error (MAE)) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703) and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal) / 0.9831, 0.9779, 0.7948 (external), respectively (all p<0.0001). Choroidalyzer's agreement with graders was comparable to the inter-grader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully-automatic methods like Choroidalyzer could provide objectivity and standardisation.

QuickQual: Lightweight, convenient retinal image quality scoring with off-the-shelf pretrained models

Image quality remains a key problem for both traditional and deep learning (DL)-based approaches to retinal image analysis, but identifying poor quality images can be time consuming and subjective. Thus, automated methods for retinal image quality scoring (RIQS) are needed. The current state-of-the-art is MCFNet, composed of three Densenet121 backbones each operating in a different colour space. MCFNet, and the EyeQ dataset released by the same authors, was a huge step forward for RIQS. We present QuickQual, a simple approach to RIQS, consisting of a single off-the-shelf ImageNet-pretrained Densenet121 backbone plus a Support Vector Machine (SVM). QuickQual performs very well, setting a new state-of-the-art for EyeQ (Accuracy: 88.50% vs 88.00% for MCFNet; AUC: 0.9687 vs 0.9588). This suggests that RIQS can be solved with generic perceptual features learned on natural images, as opposed to requiring DL models trained on large amounts of fundus images. Additionally, we propose a Fixed Prior linearisation scheme, that converts EyeQ from a 3-way classification to a continuous logistic regression task. For this task, we present a second model, QuickQual MEga Minified Estimator (QuickQual-MEME), that consists of only 10 parameters on top of an off-the-shelf Densenet121 and can distinguish between gradable and ungradable images with an accuracy of 89.18% (AUC: 0.9537). Code and model are available on GitHub: https://github.com/justinengelmann/QuickQual . QuickQual is so lightweight, that the entire inference code (and even the parameters for QuickQual-MEME) is already contained in this paper.

Efficient and fully-automatic retinal choroid segmentation in OCT through DL-based distillation of a hand-crafted pipeline

Retinal vascular phenotypes, derived from low-cost, non-invasive retinal imaging, have been linked to systemic conditions such as cardio-, neuro- and reno-vascular disease. Recent high-resolution optical coherence tomography (OCT) allows imaging of the choroidal microvasculature which could provide more information about vascular health that complements the superficial retinal vessels, which current vascular phenotypes are based on. Segmentation of the choroid in OCT is a key step in quantifying choroidal parameters like thickness and area. Gaussian Process Edge Tracing (GPET) is a promising, clinically validated method for this. However, GPET is semi-automatic and thus requires time-consuming manual interventions by specifically trained personnel which introduces subjectivity and limits the potential for analysing larger datasets or deploying GPET into clinical practice. We introduce DeepGPET, which distils GPET into a neural network to yield a fully-automatic and efficient choroidal segmentation method. DeepGPET achieves excellent agreement with GPET on data from 3 clinical studies (AUC=0.9994, Dice=0.9664; Pearson correlation of 0.8908 for choroidal thickness and 0.9082 for choroidal area), while reducing the mean processing time per image from 34.49s ($\pm$15.09) to 1.25s ($\pm$0.10) on a standard laptop CPU and removing all manual interventions. DeepGPET will be made available for researchers upon publication.

Robust and efficient computation of retinal fractal dimension through deep approximation

A retinal trait, or phenotype, summarises a specific aspect of a retinal image in a single number. This can then be used for further analyses, e.g. with statistical methods. However, reducing an aspect of a complex image to a single, meaningful number is challenging. Thus, methods for calculating retinal traits tend to be complex, multi-step pipelines that can only be applied to high quality images. This means that researchers often have to discard substantial portions of the available data. We hypothesise that such pipelines can be approximated with a single, simpler step that can be made robust to common quality issues. We propose Deep Approximation of Retinal Traits (DART) where a deep neural network is used predict the output of an existing pipeline on high quality images from synthetically degraded versions of these images. We demonstrate DART on retinal Fractal Dimension (FD) calculated by VAMPIRE, using retinal images from UK Biobank that previous work identified as high quality. Our method shows very high agreement with FD VAMPIRE on unseen test images (Pearson r=0.9572). Even when those images are severely degraded, DART can still recover an FD estimate that shows good agreement with FD VAMPIRE obtained from the original images (Pearson r=0.8817). This suggests that our method could enable researchers to discard fewer images in the future. Our method can compute FD for over 1,000img/s using a single GPU. We consider these to be very encouraging initial results and hope to develop this approach into a useful tool for retinal analysis.

Detection of multiple retinal diseases in ultra-widefield fundus images using deep learning: data-driven identification of relevant regions

Ultra-widefield (UWF) imaging is a promising modality that captures a larger retinal field of view compared to traditional fundus photography. Previous studies showed that deep learning (DL) models are effective for detecting retinal disease in UWF images, but primarily considered individual diseases under less-than-realistic conditions (excluding images with other diseases, artefacts, comorbidities, or borderline cases; and balancing healthy and diseased images) and did not systematically investigate which regions of the UWF images are relevant for disease detection. We first improve on the state of the field by proposing a DL model that can recognise multiple retinal diseases under more realistic conditions. We then use global explainability methods to identify which regions of the UWF images the model generally attends to. Our model performs very well, separating between healthy and diseased retinas with an area under the curve (AUC) of 0.9206 on an internal test set, and an AUC of 0.9841 on a challenging, external test set. When diagnosing specific diseases, the model attends to regions where we would expect those diseases to occur. We further identify the posterior pole as the most important region in a purely data-driven fashion. Surprisingly, 10% of the image around the posterior pole is sufficient for achieving comparable performance to having the full images available.

Global explainability in aligned image modalities

Deep learning (DL) models are very effective on many computer vision problems and increasingly used in critical applications. They are also inherently black box. A number of methods exist to generate image-wise explanations that allow practitioners to understand and verify model predictions for a given image. Beyond that, it would be desirable to validate that a DL model \textit{generally} works in a sensible way, i.e. consistent with domain knowledge and not relying on undesirable data artefacts. For this purpose, the model needs to be explained globally. In this work, we focus on image modalities that are naturally aligned such that each pixel position represents a similar relative position on the imaged object, as is common in medical imaging. We propose the pixel-wise aggregation of image-wise explanations as a simple method to obtain label-wise and overall global explanations. These can then be used for model validation, knowledge discovery, and as an efficient way to communicate qualitative conclusions drawn from inspecting image-wise explanations. We further propose Progressive Erasing Plus Progressive Restoration (PEPPR) as a method to quantitatively validate that these global explanations are faithful to how the model makes its predictions. We then apply these methods to ultra-widefield retinal images, a naturally aligned modality. We find that the global explanations are consistent with domain knowledge and faithfully reflect the model's workings.

Conditional Wasserstein GAN-based Oversampling of Tabular Data for Imbalanced Learning

Class imbalance is a common problem in supervised learning and impedes the predictive performance of classification models. Popular countermeasures include oversampling the minority class. Standard methods like SMOTE rely on finding nearest neighbours and linear interpolations which are problematic in case of high-dimensional, complex data distributions. Generative Adversarial Networks (GANs) have been proposed as an alternative method for generating artificial minority examples as they can model complex distributions. However, prior research on GAN-based oversampling does not incorporate recent advancements from the literature on generating realistic tabular data with GANs. Previous studies also focus on numerical variables whereas categorical features are common in many business applications of classification methods such as credit scoring. The paper propoes an oversampling method based on a conditional Wasserstein GAN that can effectively model tabular datasets with numerical and categorical variables and pays special attention to the down-stream classification task through an auxiliary classifier loss. We benchmark our method against standard oversampling methods and the imbalanced baseline on seven real-world datasets. Empirical results evidence the competitiveness of GAN-based oversampling.