Christopher Semturs
Christopher is a Research Lead at Google Health, working on AI projects to improve Health Outcomes, advancing research in Generative AI, Large Language Models, and Medical Imaging.
Born and raised in Austria, Christopher earned his MS in computer science at Technical University of Vienna. He joined Google in 2007 in the Zurich, Switzerland, office, and then moved to the United States in 2018 to join Google Health Research, where his team of engineers explores technology solutions for improving access to healthcare and healthcare information.
His work at Google Health allows him to be a part of the journey toward healthcare equity for all populations.
Authored Publications
Google Publications
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A Toolbox for Surfacing Health Equity Harms and Biases in Large Language Models
Heather Cole-Lewis
Nenad Tomašev
Liam McCoy
Leo Anthony Celi
Alanna Walton
Akeiylah DeWitt
Philip Mansfield
Sushant Prakash
Joelle Barral
Ivor Horn
Arxiv (2024) (to appear)
Preview abstract
Large language models (LLMs) hold immense promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. In this work, we present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, surfaces biases that may be missed via narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all.
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Towards Conversational Diagnostic AI
Anil Palepu
Khaled Saab
Jan Freyberg
Ryutaro Tanno
Amy Wang
Brenna Li
Nenad Tomašev
Le Hou
Albert Webson
Kavita Kulkarni
Sara Mahdavi
Juro Gottweis
Joelle Barral
Kat Chou
Arxiv (2024) (to appear)
Preview abstract
At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue.
AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.
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Crowdsourcing Dermatology Images with Google Search Ads: Creating a Diverse and Representative Dataset of Real-World Skin Conditions
Abbi Ward
Ashley Carrick
Dawn Siegel
Jay Hartford
Jimmy Li
Julie Wang
Justin Ko
Pradeep Kumar S
Renee Wong
Sriram Lakshminarasimhan
Steven Lin
Sunny Virmani
arXiv (2024)
Preview abstract
Background
Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets.
Methods
We used Google Search advertisements to solicit contributions of images of dermatology conditions, demographic and symptom information from internet users in the United States (US) over 265 days starting March 2023. With informed contributor consent, we described and released this dataset containing 10,106 images from 5058 contributions, with dermatologist labels as well as Fitzpatrick Skin Type and Monk Skin Tone labels for the images.
Results
We received 22 ± 14 submissions/day over 265 days. Female contributors (66.04%) and younger individuals (52.3% < age 40) had a higher representation in the dataset compared to the US population, and 36.6% of contributors had a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Image quality had no impact on dermatologist confidence in assigning a differential diagnosis. The dataset consists largely of short duration (54% with onset < 7 days ago) allergic, infectious, and inflammatory conditions. Fitzpatrick skin type distribution is well-balanced, considering the geographical origin of the dataset and the absence of enrichment for population groups or skin tones.
Interpretation
Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.
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Towards Generalist Biomedical AI
Danny Driess
Andrew Carroll
Chuck Lau
Ryutaro Tanno
Ira Ktena
Anil Palepu
Basil Mustafa
Simon Kornblith
Philip Mansfield
Sushant Prakash
Renee Wong
Sunny Virmani
Sara Mahdavi
Bradley Green
Ewa Dominowska
Joelle Barral
Pete Florence
NEJM AI (2024)
Preview abstract
BACKGROUND: Medicine is inherently multimodal, requiring the simultaneous interpretation and integration of insights between many data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence systems that flexibly encode, integrate, and interpret these data might better enable impactful applications ranging from scientific discovery to care delivery.
METHODS: To catalyze development of these models, we curated MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks, such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduced Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. To further probe the capabilities and limitations of Med-PaLM M, we conducted a radiologist evaluation of model-generated (and human) chest x-ray reports.
RESULTS: We observed encouraging performance across model scales. Med-PaLM M reached performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. In a side-by-side ranking on 246 retrospective chest x-rays, clinicians expressed a pairwise preference for Med-PaLM Multimodal reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility.
CONCLUSIONS: Although considerable work is needed to validate these models in real-world cases and understand if cross-modality generalization is possible, our results represent a milestone toward the development of generalist biomedical artificial intelligence systems.
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Health equity assessment of machine learning performance (HEAL): a framework and dermatology AI model case study
Terry Spitz
Malcolm Chelliah
Heather Cole-Lewis
Stephanie Farquhar
Qinghan Xue
Jenna Lester
Cían Hughes
Patricia Strachan
Fraser Tan
Peggy Bui
Craig Mermel
Lily Peng
Sunny Virmani
Ivor Horn
Cameron Chen
The Lancet eClinicalMedicine (2024)
Preview abstract
Background
Artificial intelligence (AI) has repeatedly been shown to encode historical inequities in healthcare. We aimed to develop a framework to quantitatively assess the performance equity of health AI technologies and to illustrate its utility via a case study.
Methods
Here, we propose a methodology to assess whether health AI technologies prioritise performance for patient populations experiencing worse outcomes, that is complementary to existing fairness metrics. We developed the Health Equity Assessment of machine Learning performance (HEAL) framework designed to quantitatively assess the performance equity of health AI technologies via a four-step interdisciplinary process to understand and quantify domain-specific criteria, and the resulting HEAL metric. As an illustrative case study (analysis conducted between October 2022 and January 2023), we applied the HEAL framework to a dermatology AI model. A set of 5420 teledermatology cases (store-and-forward cases from patients of 20 years or older, submitted from primary care providers in the USA and skin cancer clinics in Australia), enriched for diversity in age, sex and race/ethnicity, was used to retrospectively evaluate the AI model's HEAL metric, defined as the likelihood that the AI model performs better for subpopulations with worse average health outcomes as compared to others. The likelihood that AI performance was anticorrelated to pre-existing health outcomes was estimated using bootstrap methods as the probability that the negated Spearman's rank correlation coefficient (i.e., “R”) was greater than zero. Positive values of R suggest that subpopulations with poorer health outcomes have better AI model performance. Thus, the HEAL metric, defined as p (R >0), measures how likely the AI technology is to prioritise performance for subpopulations with worse average health outcomes as compared to others (presented as a percentage below). Health outcomes were quantified as disability-adjusted life years (DALYs) when grouping by sex and age, and years of life lost (YLLs) when grouping by race/ethnicity. AI performance was measured as top-3 agreement with the reference diagnosis from a panel of 3 dermatologists per case.
Findings
Across all dermatologic conditions, the HEAL metric was 80.5% for prioritizing AI performance of racial/ethnic subpopulations based on YLLs, and 92.1% and 0.0% respectively for prioritizing AI performance of sex and age subpopulations based on DALYs. Certain dermatologic conditions were significantly associated with greater AI model performance compared to a reference category of less common conditions. For skin cancer conditions, the HEAL metric was 73.8% for prioritizing AI performance of age subpopulations based on DALYs.
Interpretation
Analysis using the proposed HEAL framework showed that the dermatology AI model prioritised performance for race/ethnicity, sex (all conditions) and age (cancer conditions) subpopulations with respect to pre-existing health disparities. More work is needed to investigate ways of promoting equitable AI performance across age for non-cancer conditions and to better understand how AI models can contribute towards improving equity in health outcomes.
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Towards Accurate Differential Diagnosis with Large Language Models
Daniel McDuff
Anil Palepu
Amy Wang
Yash Sharma
Kavita Kulkarni
Le Hou
Sara Mahdavi
Sushant Prakash
Anupam Pathak
Shwetak Patel
Ewa Dominowska
Juro Gottweis
Joelle Barral
Kat Chou
Jake Sunshine
Arxiv (2023)
Preview abstract
An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.
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Towards Physician-Level Medical Question Answering with Large Language Models
Juro Gottweis
Le Hou
Kevin Clark
Heather Cole-Lewis
Amy Wang
Sami Lachgar
Philip Mansfield
Sushant Prakash
Bradley Green
Ewa Dominowska
Nenad Tomašev
Renee Wong
Sara Mahdavi
Joelle Barral
Arxiv (2023) (to appear)
Preview abstract
Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge.
Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach.
Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets.
We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations.
While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.
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Discovering novel systemic biomarkers in external eye photos
Ilana Traynis
Christina Chen
Akib Uddin
Jorge Cuadros
Lauren P. Daskivich
April Y. Maa
Ramasamy Kim
Eugene Yu-Chuan Kang
Lily Peng
Avinash Varadarajan
The Lancet Digital Health (2023)
Preview abstract
Background
Photographs of the external eye were recently shown to reveal signs of diabetic retinal disease and elevated glycated haemoglobin. This study aimed to test the hypothesis that external eye photographs contain information about additional systemic medical conditions.
Methods
We developed a deep learning system (DLS) that takes external eye photographs as input and predicts systemic parameters, such as those related to the liver (albumin, aspartate aminotransferase [AST]); kidney (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [ACR]); bone or mineral (calcium); thyroid (thyroid stimulating hormone); and blood (haemoglobin, white blood cells [WBC], platelets). This DLS was trained using 123 130 images from 38 398 patients with diabetes undergoing diabetic eye screening in 11 sites across Los Angeles county, CA, USA. Evaluation focused on nine prespecified systemic parameters and leveraged three validation sets (A, B, C) spanning 25 510 patients with and without diabetes undergoing eye screening in three independent sites in Los Angeles county, CA, and the greater Atlanta area, GA, USA. We compared performance against baseline models incorporating available clinicodemographic variables (eg, age, sex, race and ethnicity, years with diabetes).
Findings
Relative to the baseline, the DLS achieved statistically significant superior performance at detecting AST >36.0 U/L, calcium <8.6 mg/dL, eGFR <60.0 mL/min/1.73 m2, haemoglobin <11.0 g/dL, platelets <150.0 × 103/μL, ACR ≥300 mg/g, and WBC <4.0 × 103/μL on validation set A (a population resembling the development datasets), with the area under the receiver operating characteristic curve (AUC) of the DLS exceeding that of the baseline by 5.3–19.9% (absolute differences in AUC). On validation sets B and C, with substantial patient population differences compared with the development datasets, the DLS outperformed the baseline for ACR ≥300.0 mg/g and haemoglobin <11.0 g/dL by 7.3–13.2%.
Interpretation
We found further evidence that external eye photographs contain biomarkers spanning multiple organ systems. Such biomarkers could enable accessible and non-invasive screening of disease. Further work is needed to understand the translational implications.
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Large Language Models Encode Clinical Knowledge
Sara Mahdavi
Jason Wei
Hyung Won Chung
Nathan Scales
Ajay Tanwani
Heather Cole-Lewis
Perry Payne
Martin Seneviratne
Paul Gamble
Abubakr Abdelrazig Hassan Babiker
Nathanael Schaerli
Philip Mansfield
Dina Demner-Fushman
Katherine Chou
Juraj Gottweis
Nenad Tomašev
Alvin Rajkomar
Joelle Barral
Nature (2023)
Preview abstract
Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA. We propose a human evaluation framework for model answers along multiple axes including factuality, comprehension, reasoning, possible harm and bias. In addition, we evaluate Pathways Language Model (PaLM, a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA and Measuring Massive Multitask Language Understanding (MMLU) clinical topics), including 67.6% accuracy on MedQA (US Medical Licensing Exam-style questions), surpassing the prior state of the art by more than 17%. However, human evaluation reveals key gaps. To resolve this, we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, knowledge recall and reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal limitations of today’s models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLMs for clinical applications.
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Using generative AI to investigate medical imagery models and datasets
Charles Lau
Chloe Nichols
Doron Yaya-Stupp
Heather Cole-Lewis
Ilana Traynis
https://arxiv.org/ (2022)
Preview abstract
AI models have shown promise in performing many medical imaging tasks. However, our ability to explain what signals these models learn from the training data is severely lacking. Explanations are needed in order to increase the trust of doctors in AI-based models, especially in domains where AI prediction capabilities surpass those of humans. Moreover, such explanations could enable novel scientific discovery by uncovering signals in the data that aren’t yet known to experts. In this paper, we present a method for automatic visual explanations that can help achieve these goals by generating hypotheses of what visual signals in the images are correlated with the task. We propose the following 4 steps: (i) Train a classifier to perform a given task to assess whether the imagery indeed contains signals relevant to the task; (ii) Train a StyleGAN-based image generator with an architecture that enables guidance by the classifier (“StylEx”); (iii) Automatically detect and extract the top visual attributes that the classifier is sensitive to. Each of these attributes can then be independently modified for a set of images to generate counterfactual visualizations of those attributes (i.e. what that image would look like with the attribute increased or decreased); (iv) Present the discovered attributes and corresponding counterfactual visualizations to a multidisciplinary panel of experts to formulate hypotheses for the underlying mechanisms with consideration to social and structural determinants of health (e.g. whether the attributes correspond to known patho-physiological or socio-cultural phenomena, or could be novel discoveries) and stimulate future research. To demonstrate the broad applicability of our approach, we demonstrate results on eight prediction tasks across three medical imaging modalities – retinal fundus photographs, external eye photographs, and chest radiographs. We showcase examples where many of the automatically-learned attributes clearly capture clinically known features (e.g., types of cataract, enlarged heart), and demonstrate automatically-learned confounders that arise from factors beyond physiological mechanisms (e.g., chest X-ray underexposure is correlated with the classifier predicting abnormality, and eye makeup is correlated with the classifier predicting low hemoglobin levels). We further show that our method reveals a number of physiologically plausible novel attributes for future investigation (e.g., differences in the fundus associated with self-reported sex, which were previously unknown). While our approach is not able to discern causal pathways, the ability to generate hypotheses from the attribute visualizations has the potential to enable researchers to better understand, improve their assessment, and extract new knowledge from AI-based models. Importantly, we highlight that attributes generated by our framework can capture phenomena beyond physiology or pathophysiology, reflecting the real world nature of healthcare delivery and socio-cultural factors, and hence multidisciplinary perspectives are critical in these investigations. Finally, we release code to enable researchers to train their own StylEx models and analyze their predictive tasks of interest, and use the methodology presented in this paper for responsible interpretation of the revealed attributes.
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Longitudinal Screening for Diabetic Retinopathy in a Nationwide Screening Program: Comparing Deep Learning and Human Graders
Jirawut Limwattanayingyong
Variya Nganthavee
Kasem Seresirikachorn
Tassapol Singalavanija
Ngamphol Soonthornworasiri
Varis Ruamviboonsuk
Chetan Rao
Rajiv Raman
Andrzej Grzybowski
Lily Hao Yi Peng
Fred Hersch
Richa Tiwari, PhD
Dr. Paisan Raumviboonsuk
Journal of Diabetes Research (2020)
Preview abstract
Objective.
To evaluate diabetic retinopathy (DR) screening via deep learning (DL) and trained human graders (HG) in a longitudinal cohort, as case spectrum shifts based on treatment referral and new-onset DR.
Methods.
We randomly selected patients with diabetes screened twice, two years apart within a nationwide screening program. The reference standard was established via adjudication by retina specialists. Each patient’s color fundus photographs were graded, and a patient was considered as having sight-threatening DR (STDR) if the worse eye had severe nonproliferative DR, proliferative DR, or diabetic macular edema. We compared DR screening via two modalities: DL and HG. For each modality, we simulated treatment referral by excluding patients with detected STDR from the second screening using that modality.
Results.
There were 5,738 patients (12.3% STDR) in the first screening. DL and HG captured different numbers of STDR cases, and after simulated referral and excluding ungradable cases, 4,148 and 4,263 patients remained in the second screening, respectively. The STDR prevalence at the second screening was 5.1% and 6.8% for DL- and HG-based screening, respectively. Along with the prevalence decrease, the sensitivity for both modalities decreased from the first to the second screening (DL: from 95% to 90%, p=0.008; HG: from 74% to 57%, p<0.001). At both the first and second screenings, the rate of false negatives for the DL was a fifth that of HG (0.5-0.6% vs. 2.9-3.2%).
Conclusion.
On 2-year longitudinal follow-up of a DR screening cohort, STDR prevalence decreased for both DL- and HG-based screening. Follow-up screenings in longitudinal DR screening can be more difficult and induce lower sensitivity for both DL and HG, though the false negative rate was substantially lower for DL. Our data may be useful for health-economics analyses of longitudinal screening settings.
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Deep Learning and Glaucoma Specialists: The Relative Importance of Optic Disc Features to Predict Glaucoma Referral in Fundus Photographs
Sonia Phene
Carter Dunn
Naho Kitade
Derek Wu
Ashish Bora
Anita Misra
Abigail Huang
Arielle Spitze
Felipe Medeiros
April Maa
Monica Gandhi
Lily Peng
Ophthalmology (2019)
Preview abstract
Purpose
To develop and validate a deep learning (DL) algorithm that predicts referable glaucomatous optic neuropathy (GON) and optic nerve head (ONH) features from color fundus images, to determine the relative importance of these features in referral decisions by glaucoma specialists (GSs) and the algorithm, and to compare the performance of the algorithm with eye care providers.
Design
Development and validation of an algorithm.
Participants
Fundus images from screening programs, studies, and a glaucoma clinic.
Methods
A DL algorithm was trained using a retrospective dataset of 86 618 images, assessed for glaucomatous ONH features and referable GON (defined as ONH appearance worrisome enough to justify referral for comprehensive examination) by 43 graders. The algorithm was validated using 3 datasets: dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of GSs; dataset B (9642 images, 1 image/patient; 9.2% referable), images from a diabetic teleretinal screening program; and dataset C (346 images, 1 image/patient; 81.7% referable), images from a glaucoma clinic.
Main Outcome Measures
The algorithm was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for referable GON and glaucomatous ONH features.
Results
The algorithm’s AUC for referable GON was 0.945 (95% confidence interval [CI], 0.929–0.960) in dataset A, 0.855 (95% CI, 0.841–0.870) in dataset B, and 0.881 (95% CI, 0.838–0.918) in dataset C. Algorithm AUCs ranged between 0.661 and 0.973 for glaucomatous ONH features. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders (including 1 GS), while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels.
Conclusions
A DL algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.
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