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Yih-Chung Tham

Publications and source records attributed to Yih-Chung Tham.

13 recordsLinked to original sources

Toward Federated Large Language Models in Medicine: A Parameter-Efficient Framework for Privacy-Preserving, Multi-Institutional Adaptation

Large language models (LLMs) are increasingly adapted for medical applications, but most are trained using data from a single institution because privacy and governance constraints prevent multi-institutional data sharing. As a result, these models often generalize poorly across heterogeneous healthcare systems. We address this gap by introducing Fed-MedLoRA and Fed-MedLoRA+, a parameter-efficient federated framework for collaborative LLM adaptation across healthcare institutions. Fed-MedLoRA transmits only low-rank adapters rather than full model weights, reducing communication overhead. We also evaluate a privacy-preserving variant that applies Gaussian perturbation to transmitted adapter updates. Fed-MedLoRA+ further incorporates adaptive aggregation to better address cross-site heterogeneity in patient populations, annotation practices, and disease distributions. We evaluate the framework on clinical information extraction across five independent patient cohorts totaling 42,198 entities and 41,570 relations, and compare it with zero-shot and fine-tuned LLMs, domain-specific BERT models, and federated baselines. Across all settings, the proposed methods consistently improve extraction performance and generalize better to heterogeneous cohorts. In a real-world case study using clinical notes from the Yale New Haven Health System, the framework demonstrates strong performance under low-resource new-site deployment. These results suggest that federated, parameter-efficient LLM adaptation is feasible, scalable, and effective for multi-institutional clinical deployment.

cs.CL

Memorization in Large Language Models in Medicine: Prevalence, Characteristics, and Implications

Large Language Models (LLMs) have demonstrated significant potential in medicine, with many studies adapting them through continued pre-training or fine-tuning on medical data to enhance domain-specific accuracy and safety. However, a key open question remains: to what extent do LLMs memorize medical training data. Memorization can be beneficial when it enables LLMs to retain valuable medical knowledge during domain adaptation. Yet, it also raises concerns. LLMs may inadvertently reproduce sensitive clinical content (e.g., patient-specific details), and excessive memorization may reduce model generalizability, increasing risks of misdiagnosis and making unwarranted recommendations. These risks are further amplified by the generative nature of LLMs, which can not only surface memorized content but also produce overconfident, misleading outputs that may hinder clinical adoption. In this work, we present a study on memorization of LLMs in medicine, assessing its prevalence (how frequently it occurs), characteristics (what is memorized), volume (how much content is memorized), and potential downstream impacts (how memorization may affect medical applications). We systematically analyze common adaptation scenarios: (1) continued pretraining on medical corpora, (2) fine-tuning on standard medical benchmarks, and (3) fine-tuning on real-world clinical data, including over 13,000 unique inpatient records from Yale New Haven Health System. The results demonstrate that memorization is prevalent across all adaptation scenarios and significantly higher than that reported in the general domain. Moreover, memorization has distinct characteristics during continued pre-training and fine-tuning, and it is persistent: up to 87% of content memorized during continued pre-training remains after fine-tuning on new medical tasks.

cs.CL

Resolving the bias-precision paradox with stochastic causal representation learning for personalized medicine

Estimating individualized treatment effects from longitudinal observational data is central to data-driven medicine, yet existing methods face a fundamental limitation: reducing confounding bias often suppresses clinically informative heterogeneity, degrading patient-specific predictions. Here, we identify this tension as a bias-precision paradox in causal representation learning and introduce sampling-based maximum mean discrepancy (sMMD), a stochastic alignment strategy that replaces global adversarial balancing with subset-level matching. We instantiate this approach in a framework for counterfactual outcome prediction with attribution-grounded interpretability. Across two large-scale ICU cohorts (n = 27,783), our framework improves accuracy under distribution shift, reducing error by up to 11.5% and substantially increasing recall in high-risk tasks. Mechanistic analyses show that sMMD selectively preserves clinically decisive variables. In human-AI evaluation, our method outperforms clinicians-in-training and large language models, and improves clinician accuracy by 14.7% while reducing decision time, enabling interpretable, real-time clinical decision support.

cs.AI

Human-like Content Analysis for Generative AI with Language-Grounded Sparse Encoders

The rapid development of generative AI has transformed content creation, communication, and human development. However, this technology raises profound concerns in high-stakes domains, demanding rigorous methods to analyze and evaluate AI-generated content. While existing analytic methods often treat images as indivisible wholes, real-world AI failures generally manifest as specific visual patterns that can evade holistic detection and suit more granular and decomposed analysis. Here we introduce a content analysis tool, Language-Grounded Sparse Encoders (LanSE), which decompose images into interpretable visual patterns with natural language descriptions. Utilizing interpretability modules and large multimodal models, LanSE can automatically identify visual patterns within data modalities. Our method discovers more than 5,000 visual patterns with 93\% human agreement, provides decomposed evaluation outperforming existing methods, establishes the first systematic evaluation of physical plausibility, and extends to medical imaging settings. Our method's capability to extract language-grounded patterns can be naturally adapted to numerous fields, including biology and geography, as well as other data modalities such as protein structures and time series, thereby advancing content analysis for generative AI.

cs.CV

VOLMO: Versatile and Open Large Models for Ophthalmology

Vision impairment affects millions globally, and early detection is critical to preventing irreversible vision loss. Ophthalmology workflows require clinicians to integrate medical images, structured clinical data, and free-text notes to determine disease severity and management, which is time-consuming and burdensome. Recent multimodal large language models (MLLMs) show promise, but existing general and medical MLLMs perform poorly in ophthalmology, and few ophthalmology-specific MLLMs are openly available. We present VOLMO (Versatile and Open Large Models for Ophthalmology), a model-agnostic, data-open framework for developing ophthalmology-specific MLLMs. VOLMO includes three stages: ophthalmology knowledge pretraining on 86,965 image-text pairs from 26,569 articles across 82 journals; domain task fine-tuning on 26,929 annotated instances spanning 12 eye conditions for disease screening and severity classification; and multi-step clinical reasoning on 913 patient case reports for assessment, planning, and follow-up care. Using this framework, we trained a compact 2B-parameter MLLM and compared it with strong baselines, including InternVL-2B, LLaVA-Med-7B, MedGemma-4B, MedGemma-27B, and RETFound. We evaluated these models on image description generation, disease screening and staging classification, and assessment-and-management generation, with additional manual review by two healthcare professionals and external validation on three independent cohorts for age-related macular degeneration and diabetic retinopathy. Across settings, VOLMO-2B consistently outperformed baselines, achieving stronger image description performance, an average F1 of 87.4% across 12 eye conditions, and higher scores in external validation.

cs.CV

LEME: Open Large Language Models for Ophthalmology with Advanced Reasoning and Clinical Validation

The rising prevalence of eye diseases poses a growing public health burden. Large language models (LLMs) offer a promising path to reduce documentation workload and support clinical decision-making. However, few have been tailored for ophthalmology, and most evaluations focus mainly on knowledge-based QA without clinically relevant benchmarks or real-world validation. Here, we present LEME, a suite of open-weight LLMs developed through a two-stage process: (1) instruction tuning on 200,000 samples from clinical guidelines, textbooks, and case reports to enhance reasoning and task-following, and (2) reinforcement learning with ~30,000 preference labels to enhance accuracy and informativeness. LEME was evaluated on five curated zero-shot benchmarks spanning tasks such as patient QA, consultation, and treatment planning. It outperformed all seven baselines (all p < 0.004), exceeding GPT-4o by 3.32% (absolute ROUGE-L gain). It was further evaluated on three downstream tasks using deidentified patient data, reviewed by clinicians. In patient QA, LEME received the highest ratings from attending clinicians in 3 out of 4 criteria, with scores of 4.67 for factuality, 4.77 for specificity, 4.79 for completeness, and 4.88 for safety (1-5 scale). Its completeness score surpassed that of expert-written answers (4.79 vs. 4.56; p = 0.015). In visual acuity extraction, LEME achieved the highest F1, outperforming LLaMA-3 by 14.1% and Eye-LLaMA by 59.0%. In a pilot evaluation on assessment and treatment planning for diabetic retinopathy, AMD, and glaucoma, LEME received scores of 4.36 for factuality, 4.55 for specificity, 4.42 for completeness, and 4.36 for safety, approaching attending-level performance. All models, data, and code will be released to support further development and clinical translation, laying the groundwork for improved efficiency and patient care

cs.CL

EH-Benchmark Ophthalmic Hallucination Benchmark and Agent-Driven Top-Down Traceable Reasoning Workflow

Medical Large Language Models (MLLMs) play a crucial role in ophthalmic diagnosis, holding significant potential to address vision-threatening diseases. However, their accuracy is constrained by hallucinations stemming from limited ophthalmic knowledge, insufficient visual localization and reasoning capabilities, and a scarcity of multimodal ophthalmic data, which collectively impede precise lesion detection and disease diagnosis. Furthermore, existing medical benchmarks fail to effectively evaluate various types of hallucinations or provide actionable solutions to mitigate them. To address the above challenges, we introduce EH-Benchmark, a novel ophthalmology benchmark designed to evaluate hallucinations in MLLMs. We categorize MLLMs' hallucinations based on specific tasks and error types into two primary classes: Visual Understanding and Logical Composition, each comprising multiple subclasses. Given that MLLMs predominantly rely on language-based reasoning rather than visual processing, we propose an agent-centric, three-phase framework, including the Knowledge-Level Retrieval stage, the Task-Level Case Studies stage, and the Result-Level Validation stage. Experimental results show that our multi-agent framework significantly mitigates both types of hallucinations, enhancing accuracy, interpretability, and reliability. Our project is available at https://github.com/ppxy1/EH-Benchmark.

cs.CL

BEnchmarking LLMs for Ophthalmology (BELO) for Ophthalmological Knowledge and Reasoning

Current benchmarks evaluating large language models (LLMs) in ophthalmology are limited in scope and disproportionately prioritise accuracy. We introduce BELO (BEnchmarking LLMs for Ophthalmology), a standardized and comprehensive evaluation benchmark developed through multiple rounds of expert checking by 13 ophthalmologists. BELO assesses ophthalmology-related clinical accuracy and reasoning quality. Using keyword matching and a fine-tuned PubMedBERT model, we curated ophthalmology-specific multiple-choice-questions (MCQs) from diverse medical datasets (BCSC, MedMCQA, MedQA, BioASQ, and PubMedQA). The dataset underwent multiple rounds of expert checking. Duplicate and substandard questions were systematically removed. Ten ophthalmologists refined the explanations of each MCQ's correct answer. This was further adjudicated by three senior ophthalmologists. To illustrate BELO's utility, we evaluated six LLMs (OpenAI o1, o3-mini, GPT-4o, DeepSeek-R1, Llama-3-8B, and Gemini 1.5 Pro) using accuracy, macro-F1, and five text-generation metrics (ROUGE-L, BERTScore, BARTScore, METEOR, and AlignScore). In a further evaluation involving human experts, two ophthalmologists qualitatively reviewed 50 randomly selected outputs for accuracy, comprehensiveness, and completeness. BELO consists of 900 high-quality, expert-reviewed questions aggregated from five sources: BCSC (260), BioASQ (10), MedMCQA (572), MedQA (40), and PubMedQA (18). A public leaderboard has been established to promote transparent evaluation and reporting. Importantly, the BELO dataset will remain a hold-out, evaluation-only benchmark to ensure fair and reproducible comparisons of future models.

cs.CL

LMOD: A Large Multimodal Ophthalmology Dataset and Benchmark for Large Vision-Language Models

The prevalence of vision-threatening eye diseases is a significant global burden, with many cases remaining undiagnosed or diagnosed too late for effective treatment. Large vision-language models (LVLMs) have the potential to assist in understanding anatomical information, diagnosing eye diseases, and drafting interpretations and follow-up plans, thereby reducing the burden on clinicians and improving access to eye care. However, limited benchmarks are available to assess LVLMs' performance in ophthalmology-specific applications. In this study, we introduce LMOD, a large-scale multimodal ophthalmology benchmark consisting of 21,993 instances across (1) five ophthalmic imaging modalities: optical coherence tomography, color fundus photographs, scanning laser ophthalmoscopy, lens photographs, and surgical scenes; (2) free-text, demographic, and disease biomarker information; and (3) primary ophthalmology-specific applications such as anatomical information understanding, disease diagnosis, and subgroup analysis. In addition, we benchmarked 13 state-of-the-art LVLM representatives from closed-source, open-source, and medical domains. The results demonstrate a significant performance drop for LVLMs in ophthalmology compared to other domains. Systematic error analysis further identified six major failure modes: misclassification, failure to abstain, inconsistent reasoning, hallucination, assertions without justification, and lack of domain-specific knowledge. In contrast, supervised neural networks specifically trained on these tasks as baselines demonstrated high accuracy. These findings underscore the pressing need for benchmarks in the development and validation of ophthalmology-specific LVLMs.

cs.CV

Are Traditional Deep Learning Model Approaches as Effective as a Retinal-Specific Foundation Model for Ocular and Systemic Disease Detection?

Background: RETFound, a self-supervised, retina-specific foundation model (FM), showed potential in downstream applications. However, its comparative performance with traditional deep learning (DL) models remains incompletely understood. This study aimed to evaluate RETFound against three ImageNet-pretrained supervised DL models (ResNet50, ViT-base, SwinV2) in detecting ocular and systemic diseases. Methods: We fine-tuned/trained RETFound and three DL models on full datasets, 50%, 20%, and fixed sample sizes (400, 200, 100 images, with half comprising disease cases; for each DR severity class, 100 and 50 cases were used. Fine-tuned models were tested internally using the SEED (53,090 images) and APTOS-2019 (3,672 images) datasets and externally validated on population-based (BES, CIEMS, SP2, UKBB) and open-source datasets (ODIR-5k, PAPILA, GAMMA, IDRiD, MESSIDOR-2). Model performance was compared using area under the receiver operating characteristic curve (AUC) and Z-tests with Bonferroni correction (P<0.05/3). Interpretation: Traditional DL models are mostly comparable to RETFound for ocular disease detection with large datasets. However, RETFound is superior in systemic disease detection with smaller datasets. These findings offer valuable insights into the respective merits and limitation of traditional models and FMs.

cs.CV

Enhancing Community Vision Screening -- AI Driven Retinal Photography for Early Disease Detection and Patient Trust

Community vision screening plays a crucial role in identifying individuals with vision loss and preventing avoidable blindness, particularly in rural communities where access to eye care services is limited. Currently, there is a pressing need for a simple and efficient process to screen and refer individuals with significant eye disease-related vision loss to tertiary eye care centers for further care. An ideal solution should seamlessly and readily integrate with existing workflows, providing comprehensive initial screening results to service providers, thereby enabling precise patient referrals for timely treatment. This paper introduces the Enhancing Community Vision Screening (ECVS) solution, which addresses the aforementioned concerns with a novel and feasible solution based on simple, non-invasive retinal photography for the detection of pathology-based visual impairment. Our study employs four distinct deep learning models: RETinal photo Quality Assessment (RETQA), Pathology Visual Impairment detection (PVI), Eye Disease Diagnosis (EDD) and Visualization of Lesion Regions of the eye (VLR). We conducted experiments on over 10 datasets, totaling more than 80,000 fundus photos collected from various sources. The models integrated into ECVS achieved impressive AUC scores of 0.98 for RETQA, 0.95 for PVI, and 0.90 for EDD, along with a DICE coefficient of 0.48 for VLR. These results underscore the promising capabilities of ECVS as a straightforward and scalable method for community-based vision screening.

eess.IV

Enhancing Large Language Models with Domain-specific Retrieval Augment Generation: A Case Study on Long-form Consumer Health Question Answering in Ophthalmology

Despite the potential of Large Language Models (LLMs) in medicine, they may generate responses lacking supporting evidence or based on hallucinated evidence. While Retrieval Augment Generation (RAG) is popular to address this issue, few studies implemented and evaluated RAG in downstream domain-specific applications. We developed a RAG pipeline with 70,000 ophthalmology-specific documents that retrieve relevant documents to augment LLMs during inference time. In a case study on long-form consumer health questions, we systematically evaluated the responses including over 500 references of LLMs with and without RAG on 100 questions with 10 healthcare professionals. The evaluation focuses on factuality of evidence, selection and ranking of evidence, attribution of evidence, and answer accuracy and completeness. LLMs without RAG provided 252 references in total. Of which, 45.3% hallucinated, 34.1% consisted of minor errors, and 20.6% were correct. In contrast, LLMs with RAG significantly improved accuracy (54.5% being correct) and reduced error rates (18.8% with minor hallucinations and 26.7% with errors). 62.5% of the top 10 documents retrieved by RAG were selected as the top references in the LLM response, with an average ranking of 4.9. The use of RAG also improved evidence attribution (increasing from 1.85 to 2.49 on a 5-point scale, P<0.001), albeit with slight decreases in accuracy (from 3.52 to 3.23, P=0.03) and completeness (from 3.47 to 3.27, P=0.17). The results demonstrate that LLMs frequently exhibited hallucinated and erroneous evidence in the responses, raising concerns for downstream applications in the medical domain. RAG substantially reduced the proportion of such evidence but encountered challenges.

cs.CL

Localizing Anatomical Landmarks in Ocular Images using Zoom-In Attentive Networks

Localizing anatomical landmarks are important tasks in medical image analysis. However, the landmarks to be localized often lack prominent visual features. Their locations are elusive and easily confused with the background, and thus precise localization highly depends on the context formed by their surrounding areas. In addition, the required precision is usually higher than segmentation and object detection tasks. Therefore, localization has its unique challenges different from segmentation or detection. In this paper, we propose a zoom-in attentive network (ZIAN) for anatomical landmark localization in ocular images. First, a coarse-to-fine, or "zoom-in" strategy is utilized to learn the contextualized features in different scales. Then, an attentive fusion module is adopted to aggregate multi-scale features, which consists of 1) a co-attention network with a multiple regions-of-interest (ROIs) scheme that learns complementary features from the multiple ROIs, 2) an attention-based fusion module which integrates the multi-ROIs features and non-ROI features. We evaluated ZIAN on two open challenge tasks, i.e., the fovea localization in fundus images and scleral spur localization in AS-OCT images. Experiments show that ZIAN achieves promising performances and outperforms state-of-the-art localization methods. The source code and trained models of ZIAN are available at https://github.com/leixiaofeng-astar/OMIA9-ZIAN.

eess.IV