Optical coherence tomography choroidal enhancement using generative deep learning.

Spectral-domain optical coherence tomography (SDOCT) is the gold standard of imaging the eye in clinics. Penetration depth with such devices is, however, limited and visualization of the choroid, which is essential for diagnosing chorioretinal disease, remains limited. Whereas swept-source OCT (SSOCT) devices allow for visualization of the choroid these instruments are expensive and availability in praxis is limited. We present an artificial intelligence (AI)-based solution to enhance the visualization of the choroid in OCT scans and allow for quantitative measurements of choroidal metrics using generative deep learning (DL). Synthetically enhanced SDOCT B-scans with improved choroidal visibility were generated, leveraging matching images to learn deep anatomical features during the training. Using a single-center tertiary eye care institution cohort comprising a total of 362 SDOCT-SSOCT paired subjects, we trained our model with 150,784 images from 410 healthy, 192 glaucoma, and 133 diabetic retinopathy eyes. An independent external test dataset of 37,376 images from 146 eyes was deployed to assess the authenticity and quality of the synthetically enhanced SDOCT images. Experts' ability to differentiate real versus synthetic images was poor (47.5% accuracy). Measurements of choroidal thickness, area, volume, and vascularity index, from the reference SSOCT and synthetically enhanced SDOCT, showed high Pearson's correlations of 0.97 [95% CI: 0.96-0.98], 0.97 [0.95-0.98], 0.95 [0.92-0.98], and 0.87 [0.83-0.91], with intra-class correlation values of 0.99 [0.98-0.99], 0.98 [0.98-0.99], and 0.95 [0.96-0.98], 0.93 [0.91-0.95], respectively. Thus, our DL generative model successfully generated realistic enhanced SDOCT data that is indistinguishable from SSOCT images providing improved visualization of the choroid. This technology enabled accurate measurements of choroidal metrics previously limited by the imaging depth constraints of SDOCT. The findings open new possibilities for utilizing affordable SDOCT devices in studying the choroid in both healthy and pathological conditions.

Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study.

Large language models (LLMs) underlie remarkable recent advanced in natural language processing, and they are beginning to be applied in clinical contexts. We aimed to evaluate the clinical potential of state-of-the-art LLMs in ophthalmology using a more robust benchmark than raw examination scores. We trialled GPT-3.5 and GPT-4 on 347 ophthalmology questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions. The performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p<0.05). LLMs are approaching expert-level knowledge and reasoning skills in ophthalmology. In view of the comparable or superior performance to trainee-grade ophthalmologists and unspecialised junior doctors, state-of-the-art LLMs such as GPT-4 may provide useful medical advice and assistance where access to expert ophthalmologists is limited. Clinical benchmarks provide useful assays of LLM capabilities in healthcare before clinical trials can be designed and conducted.

Cost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China.

Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.

Ethical and regulatory challenges of large language models in medicine.

With the rapid growth of interest in and use of large language models (LLMs) across various industries, we are facing some crucial and profound ethical concerns, especially in the medical field. The unique technical architecture and purported emergent abilities of LLMs differentiate them substantially from other artificial intelligence (AI) models and natural language processing techniques used, necessitating a nuanced understanding of LLM ethics. In this Viewpoint, we highlight ethical concerns stemming from the perspectives of users, developers, and regulators, notably focusing on data privacy and rights of use, data provenance, intellectual property contamination, and broad applications and plasticity of LLMs. A comprehensive framework and mitigating strategies will be imperative for the responsible integration of LLMs into medical practice, ensuring alignment with ethical principles and safeguarding against potential societal risks.

Medical education and physician training in the era of artificial intelligence.

ABSTRACT: With the rise of generative artificial intelligence (AI) and AI-powered chatbots, the landscape of medicine and healthcare is on the brink of significant transformation. This perspective delves into the prospective influence of AI on medical education, residency training and the continuing education of attending physicians or consultants. We begin by highlighting the constraints of the current education model, challenges in limited faculty, uniformity amidst burgeoning medical knowledge and the limitations in 'traditional' linear knowledge acquisition. We introduce 'AI-assisted' and 'AI-integrated' paradigms for medical education and physician training, targeting a more universal, accessible, high-quality and interconnected educational journey. We differentiate between essential knowledge for all physicians, specialised insights for clinician-scientists and mastery-level proficiency for clinician-computer scientists. With the transformative potential of AI in healthcare and service delivery, it is poised to reshape the pedagogy of medical education and residency training.

Federated machine learning in healthcare: A systematic review on clinical applications and technical architecture.

Federated learning (FL) is a distributed machine learning framework that is gaining traction in view of increasing health data privacy protection needs. By conducting a systematic review of FL applications in healthcare, we identify relevant articles in scientific, engineering, and medical journals in English up to August 31st, 2023. Out of a total of 22,693 articles under review, 612 articles are included in the final analysis. The majority of articles are proof-of-concepts studies, and only 5.2% are studies with real-life application of FL. Radiology and internal medicine are the most common specialties involved in FL. FL is robust to a variety of machine learning models and data types, with neural networks and medical imaging being the most common, respectively. We highlight the need to address the barriers to clinical translation and to assess its real-world impact in this new digital data-driven healthcare scene.

Geometric Correspondence-Based Multimodal Learning for Ophthalmic Image Analysis.

Color fundus photography (CFP) and Optical coherence tomography (OCT) images are two of the most widely used modalities in the clinical diagnosis and management of retinal diseases. Despite the widespread use of multimodal imaging in clinical practice, few methods for automated diagnosis of eye diseases utilize correlated and complementary information from multiple modalities effectively. This paper explores how to leverage the information from CFP and OCT images to improve the automated diagnosis of retinal diseases. We propose a novel multimodal learning method, named geometric correspondence-based multimodal learning network (GeCoM-Net), to achieve the fusion of CFP and OCT images. Specifically, inspired by clinical observations, we consider the geometric correspondence between the OCT slice and the CFP region to learn the correlated features of the two modalities for robust fusion. Furthermore, we design a new feature selection strategy to extract discriminative OCT representations by automatically selecting the important feature maps from OCT slices. Unlike the existing multimodal learning methods, GeCoM-Net is the first method that formulates the geometric relationships between the OCT slice and the corresponding region of the CFP image explicitly for CFP and OCT fusion. Experiments have been conducted on a large-scale private dataset and a publicly available dataset to evaluate the effectiveness of GeCoM-Net for diagnosing diabetic macular edema (DME), impaired visual acuity (VA) and glaucoma. The empirical results show that our method outperforms the current state-of-the-art multimodal learning methods by improving the AUROC score 0.4%, 1.9% and 2.9% for DME, VA and glaucoma detection, respectively.

Artificial intelligence, ChatGPT, and other large language models for social determinants of health: Current state and future directions.

This perspective highlights the importance of addressing social determinants of health (SDOH) in patient health outcomes and health inequity, a global problem exacerbated by the COVID-19 pandemic. We provide a broad discussion on current developments in digital health and artificial intelligence (AI), including large language models (LLMs), as transformative tools in addressing SDOH factors, offering new capabilities for disease surveillance and patient care. Simultaneously, we bring attention to challenges, such as data standardization, infrastructure limitations, digital literacy, and algorithmic bias, that could hinder equitable access to AI benefits. For LLMs, we highlight potential unique challenges and risks including environmental impact, unfair labor practices, inadvertent disinformation or "hallucinations," proliferation of bias, and infringement of copyrights. We propose the need for a multitiered approach to digital inclusion as an SDOH and the development of ethical and responsible AI practice frameworks globally and provide suggestions on bridging the gap from development to implementation of equitable AI technologies.

Large language models and their impact in ophthalmology.

The advent of generative artificial intelligence and large language models has ushered in transformative applications within medicine. Specifically in ophthalmology, large language models offer unique opportunities to revolutionise digital eye care, address clinical workflow inefficiencies, and enhance patient experiences across diverse global eye care landscapes. Yet alongside these prospects lie tangible and ethical challenges, encompassing data privacy, security, and the intricacies of embedding large language models into clinical routines. This Viewpoint highlights the promising applications of large language models in ophthalmology, while weighing up the practical and ethical barriers towards their real-world implementation. This Viewpoint seeks to stimulate broader discourse on the potential of large language models in ophthalmology and to galvanise both clinicians and researchers into tackling the prevailing challenges and optimising the benefits of large language models while curtailing the associated risks.

Democratizing Artificial Intelligence Imaging Analysis With Automated Machine Learning: Tutorial.

Deep learning-based clinical imaging analysis underlies diagnostic artificial intelligence (AI) models, which can match or even exceed the performance of clinical experts, having the potential to revolutionize clinical practice. A wide variety of automated machine learning (autoML) platforms lower the technical barrier to entry to deep learning, extending AI capabilities to clinicians with limited technical expertise, and even autonomous foundation models such as multimodal large language models. Here, we provide a technical overview of autoML with descriptions of how autoML may be applied in education, research, and clinical practice. Each stage of the process of conducting an autoML project is outlined, with an emphasis on ethical and technical best practices. Specifically, data acquisition, data partitioning, model training, model validation, analysis, and model deployment are considered. The strengths and limitations of available code-free, code-minimal, and code-intensive autoML platforms are considered. AutoML has great potential to democratize AI in medicine, improving AI literacy by enabling "hands-on" education. AutoML may serve as a useful adjunct in research by facilitating rapid testing and benchmarking before significant computational resources are committed. AutoML may also be applied in clinical contexts, provided regulatory requirements are met. The abstraction by autoML of arduous aspects of AI engineering promotes prioritization of data set curation, supporting the transition from conventional model-driven approaches to data-centric development. To fulfill its potential, clinicians must be educated on how to apply these technologies ethically, rigorously, and effectively; this tutorial represents a comprehensive summary of relevant considerations.

Generative Artificial Intelligence Through ChatGPT and Other Large Language Models in Ophthalmology: Clinical Applications and Challenges.

The rapid progress of large language models (LLMs) driving generative artificial intelligence applications heralds the potential of opportunities in health care. We conducted a review up to April 2023 on Google Scholar, Embase, MEDLINE, and Scopus using the following terms: "large language models," "generative artificial intelligence," "ophthalmology," "ChatGPT," and "eye," based on relevance to this review. From a clinical viewpoint specific to ophthalmologists, we explore from the different stakeholders' perspectives-including patients, physicians, and policymakers-the potential LLM applications in education, research, and clinical domains specific to ophthalmology. We also highlight the foreseeable challenges of LLM implementation into clinical practice, including the concerns of accuracy, interpretability, perpetuating bias, and data security. As LLMs continue to mature, it is essential for stakeholders to jointly establish standards for best practices to safeguard patient safety. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artificial intelligence education: An evidence-based medicine approach for consumers, translators, and developers.

Current and future healthcare professionals are generally not trained to cope with the proliferation of artificial intelligence (AI) technology in healthcare. To design a curriculum that caters to variable baseline knowledge and skills, clinicians may be conceptualized as "consumers", "translators", or "developers". The changes required of medical education because of AI innovation are linked to those brought about by evidence-based medicine (EBM). We outline a core curriculum for AI education of future consumers, translators, and developers, emphasizing the links between AI and EBM, with suggestions for how teaching may be integrated into existing curricula. We consider the key barriers to implementation of AI in the medical curriculum: time, resources, variable interest, and knowledge retention. By improving AI literacy rates and fostering a translator- and developer-enriched workforce, innovation may be accelerated for the benefit of patients and practitioners.

Deep learning for precision medicine: Guiding laser therapy in ischemic retinal diseases.

In this issue of Cell Reports Medicine, Zhao and colleagues1 report a multi-tasking artificial intelligence system that can assist the whole process of fundus fluorescein angiography (FFA) imaging and reduce the reliance on retinal specialists in FFA examination.

A translational perspective towards clinical AI fairness.

Artificial intelligence (AI) has demonstrated the ability to extract insights from data, but the fairness of such data-driven insights remains a concern in high-stakes fields. Despite extensive developments, issues of AI fairness in clinical contexts have not been adequately addressed. A fair model is normally expected to perform equally across subgroups defined by sensitive variables (e.g., age, gender/sex, race/ethnicity, socio-economic status, etc.). Various fairness measurements have been developed to detect differences between subgroups as evidence of bias, and bias mitigation methods are designed to reduce the differences detected. This perspective of fairness, however, is misaligned with some key considerations in clinical contexts. The set of sensitive variables used in healthcare applications must be carefully examined for relevance and justified by clear clinical motivations. In addition, clinical AI fairness should closely investigate the ethical implications of fairness measurements (e.g., potential conflicts between group- and individual-level fairness) to select suitable and objective metrics. Generally defining AI fairness as "equality" is not necessarily reasonable in clinical settings, as differences may have clinical justifications and do not indicate biases. Instead, "equity" would be an appropriate objective of clinical AI fairness. Moreover, clinical feedback is essential to developing fair and well-performing AI models, and efforts should be made to actively involve clinicians in the process. The adaptation of AI fairness towards healthcare is not self-evident due to misalignments between technical developments and clinical considerations. Multidisciplinary collaboration between AI researchers, clinicians, and ethicists is necessary to bridge the gap and translate AI fairness into real-life benefits.

Federated and distributed learning applications for electronic health records and structured medical data: a scoping review.

OBJECTIVES: Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations, and discusses potential innovations. MATERIALS AND METHODS: We searched 5 databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from 3 primary perspectives, including data quality, modeling strategies, and FL frameworks. RESULTS: Out of the 1193 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. CONCLUSIONS: The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research.

Explainable artificial intelligence in ophthalmology.

PURPOSE OF REVIEW: Despite the growing scope of artificial intelligence (AI) and deep learning (DL) applications in the field of ophthalmology, most have yet to reach clinical adoption. Beyond model performance metrics, there has been an increasing emphasis on the need for explainability of proposed DL models. RECENT FINDINGS: Several explainable AI (XAI) methods have been proposed, and increasingly applied in ophthalmological DL applications, predominantly in medical imaging analysis tasks. SUMMARY: We summarize an overview of the key concepts, and categorize some examples of commonly employed XAI methods. Specific to ophthalmology, we explore XAI from a clinical perspective, in enhancing end-user trust, assisting clinical management, and uncovering new insights. We finally discuss its limitations and future directions to strengthen XAI for application to clinical practice.

Artificial intelligence and digital health in global eye health: opportunities and challenges.

Global eye health is defined as the degree to which vision, ocular health, and function are maximised worldwide, thereby optimising overall wellbeing and quality of life. Improving eye health is a global priority as a key to unlocking human potential by reducing the morbidity burden of disease, increasing productivity, and supporting access to education. Although extraordinary progress fuelled by global eye health initiatives has been made over the last decade, there remain substantial challenges impeding further progress. The accelerated development of digital health and artificial intelligence (AI) applications provides an opportunity to transform eye health, from facilitating and increasing access to eye care to supporting clinical decision making with an objective, data-driven approach. Here, we explore the opportunities and challenges presented by digital health and AI in global eye health and describe how these technologies could be leveraged to improve global eye health. AI, telehealth, and emerging technologies have great potential, but require specific work to overcome barriers to implementation. We suggest that a global digital eye health task force could facilitate coordination of funding, infrastructural development, and democratisation of AI and digital health to drive progress forwards in this domain.

Synthetic artificial intelligence using generative adversarial network for retinal imaging in detection of age-related macular degeneration.

Introduction: Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale. Methods: To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively. Results and discussion: The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61-0.66) and Cohen's kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos.

Large language models in medicine.

Large language models (LLMs) can respond to free-text queries without being specifically trained in the task in question, causing excitement and concern about their use in healthcare settings. ChatGPT is a generative artificial intelligence (AI) chatbot produced through sophisticated fine-tuning of an LLM, and other tools are emerging through similar developmental processes. Here we outline how LLM applications such as ChatGPT are developed, and we discuss how they are being leveraged in clinical settings. We consider the strengths and limitations of LLMs and their potential to improve the efficiency and effectiveness of clinical, educational and research work in medicine. LLM chatbots have already been deployed in a range of biomedical contexts, with impressive but mixed results. This review acts as a primer for interested clinicians, who will determine if and how LLM technology is used in healthcare for the benefit of patients and practitioners.