OPTICAL COHERENCE TOMOGRAPHY FEATURES ASSOCIATED WITH VITREOMACULAR TRACTION RELEASE AND MACULAR HOLE SIZE PROGRESSION FOLLOWING TREATMENT WITH OCRIPLASMIN.

PURPOSE: To evaluate OCT features for vitreomacular traction (VMT) release and change in macular hole (MH) size after treatment with ocriplasmin. METHODS: Patients who had undergone treatment with ocriplasmin for VMT with or without MH ≤400 µm were included. The main outcomes were VMT release and changes in minimum linear diameter MH size at 4 weeks in MHs that persisted. OCT features evaluated were central retinal thickness, vitreomacular adhesion length, posterior vitreous cortex (PVC) insertion angles 500 µm from the insertion points, and minimum linear diameter size. RESULTS: Sixty patients were included: 37 had isolated VMT and 23 VMT with a MH. Four weeks after ocriplasmin injection, the overall VMT release rate was 66.7% (40/60); 64.9% (24/37) in eyes with isolated VMT and 69.6% (16/23) in eyes with MH. VMT release was associated with younger age (P = 0.02). Macular hole closure was achieved in 26.1% (6/23) and was associated with a smaller ratio of the temporal to the nasal PVC angle (P < 0.01). Of the 17 persistent MHs, 76.5% (13/17) increased in minimum linear diameter size from baseline 186 (±78) to 358 (±133) µm (P < 0.001). Progression in minimum linear diameter size showed a negative linear association with the size of the nasal PVC angle (R2 = 0.39, P = 0.002) and a positive linear association with the ratio of the temporal to nasal PVC angle (R2 = 0.39, P = 0.002). CONCLUSION: In patients with VMT-associated MHs, the risk of MH enlargement following ocriplasmin is negatively correlated with the nasal PVC angle size and is increased if the ratio of the temporal to nasal angle is >1.

Early detection of dementia through retinal imaging and trustworthy AI.

Alzheimer's disease (AD) is a global healthcare challenge lacking a simple and affordable detection method. We propose a novel deep learning framework, Eye-AD, to detect Early-onset Alzheimer's Disease (EOAD) and Mild Cognitive Impairment (MCI) using OCTA images of retinal microvasculature and choriocapillaris. Eye-AD employs a multilevel graph representation to analyze intra- and inter-instance relationships in retinal layers. Using 5751 OCTA images from 1671 participants in a multi-center study, our model demonstrated superior performance in EOAD (internal data: AUC = 0.9355, external data: AUC = 0.9007) and MCI detection (internal data: AUC = 0.8630, external data: AUC = 0.8037). Furthermore, we explored the associations between retinal structural biomarkers in OCTA images and EOAD/MCI, and the results align well with the conclusions drawn from our deep learning interpretability analysis. Our findings provide further evidence that retinal OCTA imaging, coupled with artificial intelligence, will serve as a rapid, noninvasive, and affordable dementia detection.

Artificial intelligence-based classification of cardiac autonomic neuropathy from retinal fundus images in patients with diabetes: The Silesia Diabetes Heart Study.

BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown. METHODS: This was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set. RESULTS: In an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74-0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86-1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73-1.00). CONCLUSIONS: AI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk. TRIAL REGISTRATION: This is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413).

AI-driven generalized polynomial transformation models for unsupervised fundus image registration.

We introduce a novel AI-driven approach to unsupervised fundus image registration utilizing our Generalized Polynomial Transformation (GPT) model. Through the GPT, we establish a foundational model capable of simulating diverse polynomial transformations, trained on a large synthetic dataset to encompass a broad range of transformation scenarios. Additionally, our hybrid pre-processing strategy aims to streamline the learning process by offering model-focused input. We evaluated our model's effectiveness on the publicly available AREDS dataset by using standard metrics such as image-level and parameter-level analyzes. Linear regression analysis reveals an average Pearson correlation coefficient (R) of 0.9876 across all quadratic transformation parameters. Image-level evaluation, comprising qualitative and quantitative analyzes, showcases significant improvements in Structural Similarity Index (SSIM) and Normalized Cross Correlation (NCC) scores, indicating its robust performance. Notably, precise matching of the optic disc and vessel locations with minimal global distortion are observed. These findings underscore the potential of GPT-based approaches in image registration methodologies, promising advancements in diagnosis, treatment planning, and disease monitoring in ophthalmology and beyond.

Association of Retinal Biomarkers With the Subtypes of Ischemic Stroke and an Automated Classification Model.

Purpose: Retinal microvascular changes are associated with ischemic stroke, and optical coherence tomography angiography (OCTA) is a potential tool to reveal the retinal microvasculature. We investigated the feasibility of using the OCTA image to automatically identify ischemic stroke and its subtypes (i.e. lacunar and non-lacunar stroke), and exploited the association of retinal biomarkers with the subtypes of ischemic stroke. Methods: Two cohorts were included in this study and a total of 1730 eyes from 865 participants were studied. A deep learning model was developed to discriminate the subjects with ischemic stroke from healthy controls and to distinguish the subtypes of ischemic stroke. We also extracted geometric parameters of the retinal microvasculature at different retinal layers to investigate the correlations. Results: Superficial vascular plexus (SVP) yielded the highest areas under the receiver operating characteristic curve (AUCs) of 0.922 and 0.871 for the ischemic stroke detection and stroke subtypes classification, respectively. For external data validation, our model achieved an AUC of 0.822 and 0.766 for the ischemic stroke detection and stroke subtypes classification, respectively. When parameterizing the OCTA images, we showed individuals with ischemic strokes had increased SVP tortuosity (B = 0.085, 95% confidence interval [CI] = 0.005-0.166, P = 0.038) and reduced FAZ circularity (B = -0.212, 95% CI = -0.42 to -0.005, P = 0.045); non-lacunar stroke had reduced SVP FAZ circularity (P = 0.027) compared to lacunar stroke. Conclusions: Our study demonstrates the applicability of artificial intelligence (AI)-enhanced OCTA image analysis for ischemic stroke detection and its subtypes classification. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of ischemic stroke and its subtypes.

Systematic Review and Meta-Analysis of Prehospital Machine Learning Scores as Screening Tools for Early Detection of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction. METHODS AND RESULTS: Six bibliographic databases were searched from inception until October 10, 2023. Meta-analyses pooled the model performance using area under the curve (AUC), sensitivity, specificity, and summary receiver operating characteristic curve. Of 1544 studies screened, 8 retrospective studies were eligible, including 32 prehospital stroke scales and 21 ML models. Of the 9 prehospital scales meta-analyzed, the Rapid Arterial Occlusion Evaluation had the highest pooled AUC (0.82 [95% CI, 0.79-0.84]). Support Vector Machine achieved the highest AUC of 9 ML models included (pooled AUC, 0.89 [95% CI, 0.88-0.89]). Six prehospital stroke scales and 10 ML models were eligible for summary receiver operating characteristic analysis. Pooled sensitivity and specificity for any prehospital stroke scale were 0.72 (95% CI, 0.68-0.75) and 0.77 (95% CI, 0.72-0.81), respectively; summary receiver operating characteristic curve AUC was 0.80 (95% CI, 0.76-0.83). Pooled sensitivity for any ML model for LVO was 0.73 (95% CI, 0.64-0.79), specificity was 0.85 (95% CI, 0.80-0.89), and summary receiver operating characteristic curve AUC was 0.87 (95% CI, 0.83-0.89). CONCLUSIONS: Both prehospital stroke scales and ML models demonstrated varying accuracies in predicting LVO. Despite ML potential for improved LVO detection in the prehospital setting, application remains limited by the absence of prospective external validation, limited sample sizes, and lack of real-world performance data in a prehospital setting.

Research progress on the application of anti-gravity treadmill in the rehabilitation of Parkinson's disease patients: a mini review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. It is the second most common chronic progressive neurodegenerative disease. PD still lacks a known cure or prophylactic medication. Current treatments primarily address symptoms without halting the progression of PD, and the side effects of dopaminergic therapy become more apparent over time. In contrast, physical therapy, with its lower risk of side effects and potential cardiovascular benefits, may provide greater benefits to patients. The Anti-Gravity Treadmill is an emerging rehabilitation therapy device with high safety, which minimizes patients' fear and allows them to focus more on a normal, correct gait, and has a promising clinical application. Based on this premise, this study aims to summarize and analyze the relevant studies on the application of the anti-gravity treadmill in PD patients, providing a reference for PD rehabilitation practice and establishing a theoretical basis for future research in this area.

Predicting multifaceted risks using machine learning in atrial fibrillation: insights from GLORIA-AF study.

Aims: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke and death. While anticoagulants are effective at reducing these risks, they increase the risk of bleeding. Current clinical risk scores only perform modestly in predicting adverse outcomes, especially for the outcome of death. We aimed to test the multi-label gradient boosting decision tree (ML-GBDT) model in predicting risks for adverse outcomes in a prospective global AF registry. Methods and results: We studied patients from phase II/III of the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation registry between 2011 and 2020. The outcomes were all-cause death, ischaemic stroke, and major bleeding within 1 year following the AF. We trained the ML-GBDT model and compared its discrimination with the clinical scores in predicting patient outcomes. A total of 25 656 patients were included [mean age 70.3 years (SD 10.3); 44.8% female]. Within 1 year after AF, ischaemic stroke occurred in 215 (0.8%), major bleeding in 405 (1.6%), and death in 897 (3.5%) patients. Our model achieved an optimized area under the curve in predicting death (0.785, 95% CI: 0.757-0.813) compared with the Charlson Comorbidity Index (0.747, P = 0.007), ischaemic stroke (0.691, 0.626-0.756) compared with CHA2DS2-VASc (0.613, P = 0.028), and major bleeding (0.698, 0.651-0.745) as opposed to HAS-BLED (0.607, P = 0.002), with improvement in net reclassification index (10.0, 12.5, and 23.6%, respectively). Conclusion: The ML-GBDT model outperformed clinical risk scores in predicting the risks in patients with AF. This approach could be used as a single multifaceted holistic tool to optimize patient risk assessment and mitigate adverse outcomes when managing AF.

Multi-granularity learning of explicit geometric constraint and contrast for label-efficient medical image segmentation and differentiable clinical function assessment.

Automated segmentation is a challenging task in medical image analysis that usually requires a large amount of manually labeled data. However, most current supervised learning based algorithms suffer from insufficient manual annotations, posing a significant difficulty for accurate and robust segmentation. In addition, most current semi-supervised methods lack explicit representations of geometric structure and semantic information, restricting segmentation accuracy. In this work, we propose a hybrid framework to learn polygon vertices, region masks, and their boundaries in a weakly/semi-supervised manner that significantly advances geometric and semantic representations. Firstly, we propose multi-granularity learning of explicit geometric structure constraints via polygon vertices (PolyV) and pixel-wise region (PixelR) segmentation masks in a semi-supervised manner. Secondly, we propose eliminating boundary ambiguity by using an explicit contrastive objective to learn a discriminative feature space of boundary contours at the pixel level with limited annotations. Thirdly, we exploit the task-specific clinical domain knowledge to differentiate the clinical function assessment end-to-end. The ground truth of clinical function assessment, on the other hand, can serve as auxiliary weak supervision for PolyV and PixelR learning. We evaluate the proposed framework on two tasks, including optic disc (OD) and cup (OC) segmentation along with vertical cup-to-disc ratio (vCDR) estimation in fundus images; left ventricle (LV) segmentation at end-diastolic and end-systolic frames along with ejection fraction (LVEF) estimation in two-dimensional echocardiography images. Experiments on nine large-scale datasets of the two tasks under different label settings demonstrate our model's superior performance on segmentation and clinical function assessment.

Linking Vascular Structure and Function: Image-Based Virtual Populations of the Retina.

Purpose: This study explored the relationship among microvascular parameters as delineated by optical coherence tomography angiography (OCTA) and retinal perfusion. Here, we introduce a versatile framework to examine the interplay between the retinal vascular structure and function by generating virtual vasculatures from central retinal vessels to macular capillaries. Also, we have developed a hemodynamics model that evaluates the associations between vascular morphology and retinal perfusion. Methods: The generation of the vasculature is based on the distribution of four clinical parameters pertaining to the dimension and blood pressure of the central retinal vessels, constructive constrained optimization, and Voronoi diagrams. Arterial and venous trees are generated in the temporal retina and connected through three layers of capillaries at different depths in the macula. The correlations between total retinal blood flow and macular flow fraction and vascular morphology are derived as Spearman rank coefficients, and uncertainty from input parameters is quantified. Results: A virtual cohort of 200 healthy vasculatures was generated. Means and standard deviations for retinal blood flow and macular flow fraction were 20.80 ± 7.86 µL/min and 15.04% ± 5.42%, respectively. Retinal blood flow was correlated with vessel area density, vessel diameter index, fractal dimension, and vessel caliber index. The macular flow fraction was not correlated with any morphological metrics. Conclusions: The proposed framework is able to reproduce vascular networks in the macula that are morphologically and functionally similar to real vasculature. The framework provides quantitative insights into how macular perfusion can be affected by changes in vascular morphology delineated on OCTA.

Artificial intelligence-enhanced electrocardiogram analysis for identifying cardiac autonomic neuropathy in patients with diabetes.

AIM: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). MATERIALS AND METHODS: We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). RESULTS: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81). CONCLUSION: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.

Exosomal Proteomics: Unveiling Novel Insights into Lung Cancer.

Although significant progress has been made in early lung cancer screening over the past decade, it remains one of the most prevalent and deadliest forms of cancer worldwide. Exosomal proteomics has emerged as a transformative field in lung cancer research, with the potential to redefine diagnostics, prognostic assessments, and therapeutic strategies through the lens of precision medicine. This review discusses recent advances in exosome-related proteomic and glycoproteomic technologies, highlighting their potential to revolutionise lung cancer treatment by addressing issues of heterogeneity, integrating multiomics data, and utilising advanced analytical methods. While these technologies show promise, there are obstacles to overcome before they can be widely implemented, such as the need for standardization, gaps in clinical application, and the importance of dynamic monitoring. Future directions should aim to overcome the challenges to fully utilize the potential of exosomal proteomics in lung cancer. This promises a new era of personalized medicine that leverages the molecular complexity of exosomes for groundbreaking advancements in detection, prognosis, and treatment.

Investigation of inter-rater and test-retest reliability of Y balance test in college students with flexible flatfoot.

BACKGROUND: The Lower Quarter Y Balance Test (YBT-LQ) has been widely used to assess dynamic balance in various populations. Dynamic balance in flexible flatfoot populations is one of the risk factors for lower extremity injuries, especially in college populations in which more exercise is advocated. However, no study has demonstrated the reliability of the YBT-LQ in a college student flexible flatfoot population. METHODS: A cross-sectional observational study. 30 college students with flexible flatfoot were recruited from Beijing Sports University. They have been thrice assessed for the maximal reach distance of YBT under the support of the lower limb on the flatfoot side. Test and retest were performed with an interval of 14 days. The outcome measures using the composite score and normalized maximal reach distances in three directions (anterior, posteromedial, and posterolateral). The relative reliability was reported as the Intraclass Correlation Coefficient (ICC). Minimal Detectable Change (MDC), Smallest worthwhile change (SWC), and Standard Error of Measurement (SEM) were used to report the absolute reliability. RESULTS: For inter-rater reliability, the ICC values for all directions ranged from 0.84 to 0.92, SEM values ranged from 2.01 to 3.10%, SWC values ranged from 3.67 to 5.12%, and MDC95% values ranged from 5.58 to 8.60%. For test-retest reliability, the ICC values for all directions ranged from 0.81 to 0.92, SEM values ranged from 1.80 to 2.97%, SWC values ranged from 3.75 to 5.61%, and MDC95% values ranged from 4.98 to 8.24%. CONCLUSIONS: The YBT-LQ has "good" to "excellent" inter-rater and test-retest reliability. It appears to be a reliable assessment to use with college students with flexible flatfoot. TRIAL REGISTRATION: This trial was prospectively registered at the Chinese Clinical Trial Registry with the ID number ChiCTR2300075906 on 19/09/2023.

Using Deep Learning to Segment Retinal Vascular Leakage and Occlusion in Retinal Vasculitis.

PURPOSE: Retinal vasculitis (RV) is characterised by retinal vascular leakage, occlusion or both on fluorescein angiography (FA). There is no standard scheme available to segment RV features. We aimed to develop a deep learning model to segment both vascular leakage and occlusion in RV. METHODS: Four hundred and sixty-three FA images from 82 patients with retinal vasculitis were used to develop a deep learning model, in 60:20:20 ratio for training:validation:testing. Parameters, including deep learning architectures (DeeplabV3+, UNet++ and UNet), were altered to find the best binary segmentation model separately for retinal vascular leakage and occlusion, using a Dice score to determine the reliability of each model. RESULTS: Our best model for vascular leakage had a Dice score of 0.6279 (95% confidence interval (CI) 0.5584-0.6974). For occlusion, the best model achieved a Dice score of 0.6992 (95% CI 0.6109-0.7874). CONCLUSION: Our RV segmentation models could perform reliable segmentation for retinal vascular leakage and occlusion in FAs of RV patients.

Deep segmentation of OCTA for evaluation and association of changes of retinal microvasculature with Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study. METHODS: We defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects. RESULTS: In the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls. CONCLUSION: Our study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.

A Systematic Review on Retinal Biomarkers to Diagnose Dementia from OCT/OCTA Images.

Background: Traditional methods for diagnosing dementia are costly, time-consuming, and somewhat invasive. Since the retina shares significant anatomical similarities with the brain, retinal abnormalities detected via optical coherence tomography (OCT) and OCT angiography (OCTA) have been studied as a potential non-invasive diagnostic tool for neurodegenerative disorders; however, the most effective retinal changes remain a mystery to be unraveled in this review. Objective: This study aims to explore the relationship between retinal abnormalities in OCT/OCTA images and cognitive decline as well as evaluating biomarkers' effectiveness in detecting neurodegenerative diseases. Methods: A systematic search was conducted on PubMed, Web of Science, and Scopus until December 2022, resulted in 64 papers using agreed search keywords, and inclusion/exclusion criteria. Results: The superior peripapillary retinal nerve fiber layer (pRNFL) is a trustworthy biomarker to identify most Alzheimer's disease (AD) cases; however, it is inefficient when dealing with mild AD and mild cognitive impairment (MCI). The global pRNFL (pRNFL-G) is another reliable biomarker to discriminate frontotemporal dementia from mild AD and healthy controls (HCs), moderate AD and MCI from HCs, as well as identifing pathological Aß42/tau in cognitively healthy individuals. Conversely, pRNFL-G fails to realize mild AD and the progression of AD. The average pRNFL thickness variation is considered a viable biomarker to monitor the progression of AD. Finally, the superior and average pRNFL thicknesses are considered consistent for advanced AD but not for early/mild AD. Conclusions: Retinal changes may indicate dementia, but further research is needed to confirm the most effective biomarkers for early and mild AD.

Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

Development and external validation of a mixed-effects deep learning model to diagnose COVID-19 from CT imaging.

Background: The automatic analysis of medical images has the potential improve diagnostic accuracy while reducing the strain on clinicians. Current methods analyzing 3D-like imaging data, such as computerized tomography imaging, often treat each image slice as individual slices. This may not be able to appropriately model the relationship between slices. Methods: Our proposed method utilizes a mixed-effects model within the deep learning framework to model the relationship between slices. We externally validated this method on a data set taken from a different country and compared our results against other proposed methods. We evaluated the discrimination, calibration, and clinical usefulness of our model using a range of measures. Finally, we carried out a sensitivity analysis to demonstrate our methods robustness to noise and missing data. Results: In the external geographic validation set our model showed excellent performance with an AUROC of 0.930 (95%CI: 0.914, 0.947), with a sensitivity and specificity, PPV, and NPV of 0.778 (0.720, 0.828), 0.882 (0.853, 0.908), 0.744 (0.686, 0.797), and 0.900 (0.872, 0.924) at the 0.5 probability cut-off point. Our model also maintained good calibration in the external validation dataset, while other methods showed poor calibration. Conclusion: Deep learning can reduce stress on healthcare systems by automatically screening CT imaging for COVID-19. Our method showed improved generalizability in external validation compared to previous published methods. However, deep learning models must be robustly assessed using various performance measures and externally validated in each setting. In addition, best practice guidelines for developing and reporting predictive models are vital for the safe adoption of such models.

Predicting Acute and Post-Recovery Outcomes in Cerebral Malaria and Other Comas by Optical Coherence Tomography (OCT in CM) - A protocol for an observational cohort study of Malawian children.

Cerebral malaria (CM) remains a significant global health challenge with high morbidity and mortality. Malarial retinopathy has been shown to be diagnostically and prognostically significant in the assessment of CM. The major mechanism of death in paediatric CM is brain swelling. Long term morbidity is typically characterised by neurological and neurodevelopmental sequelae. Optical coherence tomography can be used to quantify papilloedema and macular ischaemia, identified as hyperreflectivity. Here we describe a protocol to test the hypotheses that quantification of optic nerve head swelling using optical coherence tomography can identify severe brain swelling in CM, and that quantification of hyperreflectivity in the macula predicts neurodevelopmental outcomes post-recovery. Additionally, our protocol includes the development of a novel, low-cost, handheld optical coherence tomography machine and artificial intelligence tools to assist in image analysis.