Large language models (LLMs) have shown growing potential for Cognitive Behavioral Therapy (CBT) counseling. However, most existing approaches still formulate counseling as a local response generation problem, focusing on empathetic replies within short, text-only, or single-session interactions. We argue that this formulation fundamentally mismatches the nature of real psychotherapy. In clinical CBT, therapy is a longitudinal process in which therapists continuously infer, update, and intervene on evolving therapeutic states across sessions. Realistic CBT further involves multimodal inference and delayed cross-session intervention effects, requiring models to capture longitudinal therapeutic state evolution under partial observability. We propose DMT-CBT, a framework for Dynamic Modeling of evolving Therapeutic states in CBT counseling. DMT-CBT maintains structured therapeutic states across sessions while incorporating multimodal behavioral grounding and tool-augmented intervention to support adaptive therapeutic reasoning. Based on this framework, we construct DMTCorpus, a synthetic multi-session multimodal CBT counseling dataset featuring evolving therapeutic states, image-groun
Artificial intelligence has shown promise in medical imaging, yet most existing systems lack flexibility, interpretability, and adaptability - challenges especially pronounced in ophthalmology, where diverse imaging modalities are essential. We present EyeAgent, the first agentic AI framework for comprehensive and interpretable clinical decision support in ophthalmology. Using a large language model (DeepSeek-V3) as its central reasoning engine, EyeAgent interprets user queries and dynamically orchestrates 53 validated ophthalmic tools across 23 imaging modalities for diverse tasks including classification, segmentation, detection, image/report generation, and quantitative analysis. Stepwise ablation analysis demonstrated a progressive improvement in diagnostic accuracy, rising from a baseline of 69.71% (using only 5 general tools) to 80.79% when the full suite of 53 specialized tools was integrated. In an expert rating study on 200 real-world clinical cases, EyeAgent achieved 93.7% tool selection accuracy and received expert ratings of more than 88% across accuracy, completeness, safety, reasoning, and interpretability. In human-AI collaboration, EyeAgent matched or exceeded the p
Robust therapeutic relationships between counselors and clients are fundamental to counseling effectiveness. The assessment of therapeutic alliance is well-established in traditional face-to-face therapy but may not directly translate to text-based settings. With millions of individuals seeking support through online text-based counseling, understanding the relationship in such contexts is crucial. In this paper, we present an automatic approach using large language models (LLMs) to understand the development of therapeutic alliance in text-based counseling. We adapt a theoretically grounded framework specifically to the context of online text-based counseling and develop comprehensive guidelines for characterizing the alliance. We collect a comprehensive counseling dataset and conduct multiple expert evaluations on a subset based on this framework. Our LLM-based approach, combined with guidelines and simultaneous extraction of supportive evidence underlying its predictions, demonstrates effectiveness in identifying the therapeutic alliance. Through further LLM-based evaluations on additional conversations, our findings underscore the challenges counselors face in cultivating stron
The emergence of artificial intelligence (AI), particularly deep learning (DL), has marked a new era in the realm of ophthalmology, offering transformative potential for the diagnosis and treatment of posterior segment eye diseases. This review explores the cutting-edge applications of DL across a range of ocular conditions, including diabetic retinopathy, glaucoma, age-related macular degeneration, and retinal vessel segmentation. We provide a comprehensive overview of foundational ML techniques and advanced DL architectures, such as CNNs, attention mechanisms, and transformer-based models, highlighting the evolving role of AI in enhancing diagnostic accuracy, optimizing treatment strategies, and improving overall patient care. Additionally, we present key challenges in integrating AI solutions into clinical practice, including ensuring data diversity, improving algorithm transparency, and effectively leveraging multimodal data. This review emphasizes AI's potential to improve disease diagnosis and enhance patient care while stressing the importance of collaborative efforts to overcome these barriers and fully harness AI's impact in advancing eye care.
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-2
Purpose: To evaluate the accuracy and reasoning ability of DeepSeek-R1 and three other recently released large language models (LLMs) in bilingual complex ophthalmology cases. Methods: A total of 130 multiple-choice questions (MCQs) related to diagnosis (n = 39) and management (n = 91) were collected from the Chinese ophthalmology senior professional title examination and categorized into six topics. These MCQs were translated into English using DeepSeek-R1. The responses of DeepSeek-R1, Gemini 2.0 Pro, OpenAI o1 and o3-mini were generated under default configurations between February 15 and February 20, 2025. Accuracy was calculated as the proportion of correctly answered questions, with omissions and extra answers considered incorrect. Reasoning ability was evaluated through analyzing reasoning logic and the causes of reasoning error. Results: DeepSeek-R1 demonstrated the highest overall accuracy, achieving 0.862 in Chinese MCQs and 0.808 in English MCQs. Gemini 2.0 Pro, OpenAI o1, and OpenAI o3-mini attained accuracies of 0.715, 0.685, and 0.692 in Chinese MCQs (all P<0.001 compared with DeepSeek-R1), and 0.746 (P=0.115), 0.723 (P=0.027), and 0.577 (P<0.001) in English MCQ
Metabolic disorders, particularly type 2 diabetes mellitus (T2DM), represent a significant global health burden, disproportionately impacting genetically predisposed populations such as the Pima Indians (a Native American tribe from south central Arizona). This study introduces a novel machine learning (ML) framework that integrates predictive modeling with gene-agnostic pathway mapping to identify high-risk individuals and uncover potential therapeutic targets. Using the Pima Indian dataset, logistic regression and t-tests were applied to identify key predictors of T2DM, yielding an overall model accuracy of 78.43%. To bridge predictive analytics with biological relevance, we developed a pathway mapping strategy that links identified predictors to critical signaling networks, including insulin signaling, AMPK, and PPAR pathways. This approach provides mechanistic insights without requiring direct molecular data. Building upon these connections, we propose therapeutic strategies such as dual GLP-1/GIP receptor agonists, AMPK activators, SIRT1 modulators, and phytochemical, further validated through pathway enrichment analyses. Overall, this framework advances precision medicine by
While large language models (LLMs) excel at open-ended dialogue, effective psychotherapy requires structured progression and adherence to clinical protocols, making the design of psychotherapist chatbots challenging. We investigate how different LLM-based designs shape perceived therapeutic dialogue in a chatbot grounded in the Self-Attachment Technique (SAT), a novel self-administered psychotherapy rooted in attachment theory. We compare three architectural variants: (1) a multi-agent system utilizing finite state machine aligned with therapeutic stages and a shared long-term memory, (2) a single-agent using identical knowledge-base and the same prompts, and (3) an unguided LLM. In an eight-day randomized controlled trial (RCT) with N=66 Farsi-speaking participants, balanced across the three chatbots, the multi-agent system is perceived as significantly more natural and human-like than the other variants and achieves higher ratings across most other metrics. These findings demonstrate that for therapeutic AI, architectural orchestration is as critical as prompt engineering in fostering natural, engaging dialogue.
We report the design, fabrication and characterization of evanescent mid-infrared germanium-on-silicon waveguide sensors for therapeutic drug monitoring (TDM). TDM requires rapid and accurate quantification of serum drug levels but existing clinical assays rely on laboratory-based instrumentation that limits point-of-care deployment. In this work, tunable diode laser absorption spectroscopy was used to analyze dried samples of the anti-seizure medication phenytoin in the spectral region of $λ$ = 5.6 - 6.0 $μ$m. A limit of detection of 2.20 mg/L was achieved for extracted samples, where phenytoin was first added to human serum and subsequently isolated using liquid-liquid extraction. This limit is significantly below the therapeutic window of 10 - 20 mg/L for phenytoin, enabling detection of sub-therapeutic concentrations. At the same time, the sensor maintains a consistent dose-dependent response up to 40 mg/L, demonstrating its capability to quantify concentrations across the therapeutic window and above the upper therapeutic limit. This validates the use of silicon photonics for biomedical infrared spectroscopy for patients undergoing drug therapy, whether the serum-drug concentr
Recent advances in reasoning-focused large language models (LLMs) mark a shift from general LLMs toward models designed for complex decision-making, a crucial aspect in medicine. However, their performance in specialized domains like ophthalmology remains underexplored. This study comprehensively evaluated and compared the accuracy and reasoning capabilities of four newly developed reasoning-focused LLMs, namely DeepSeek-R1, OpenAI o1, o3-mini, and Gemini 2.0 Flash-Thinking. Each model was assessed using 5,888 multiple-choice ophthalmology exam questions from the MedMCQA dataset in zero-shot setting. Quantitative evaluation included accuracy, Macro-F1, and five text-generation metrics (ROUGE-L, METEOR, BERTScore, BARTScore, and AlignScore), computed against ground-truth reasonings. Average inference time was recorded for a subset of 100 randomly selected questions. Additionally, two board-certified ophthalmologists qualitatively assessed clarity, completeness, and reasoning structure of responses to differential diagnosis questions.O1 (0.902) and DeepSeek-R1 (0.888) achieved the highest accuracy, with o1 also leading in Macro-F1 (0.900). The performance of models across the text-ge
Therapeutic art activities, such as expressive drawing and painting, require the synergy between creative visual production and interactive dialogue. Recent advancements in Multimodal Large Language Models (MLLMs) have expanded the capacity of computing systems to interpret both textual and visual data, offering a new frontier for AI-mediated therapeutic support. This work-in-progress paper introduces an MLLM-powered chatbot that analyzes visual creation in real-time while engaging the creator in reflective conversations. We conducted an evaluation with five experts in art therapy and related fields, which demonstrated the chatbot's potential to facilitate therapeutic engagement, and highlighted several areas for future development, including entryways and risk management, bespoke alignment of user profile and therapeutic style, balancing conversational depth and width, and enriching visual interactivity. These themes provide a design roadmap for designing the future AI-mediated creative expression tools.
Chatbots or conversational agents (CAs) are increasingly used to improve access to digital psychotherapy. Many current systems rely on rigid, rule-based designs, heavily dependent on expert-crafted dialogue scripts for guiding therapeutic conversations. Although advances in large language models (LLMs) offer potential for more flexible interactions, their lack of controllability and explanability poses challenges in high-stakes contexts like psychotherapy. To address this, we conducted two studies in this work to explore how aligning LLMs with expert-crafted scripts can enhance psychotherapeutic chatbot performance. In Study 1 (N=43), an online experiment with a within-subjects design, we compared rule-based, pure LLM, and LLMs aligned with expert-crafted scripts via fine-tuning and prompting. Results showed that aligned LLMs significantly outperformed the other types of chatbots in empathy, dialogue relevance, and adherence to therapeutic principles. Building on findings, we proposed ``Script-Strategy Aligned Generation (SSAG)'', a more flexible alignment approach that reduces reliance on fully scripted content while maintaining LLMs' therapeutic adherence and controllability. In
Virtual Reality (VR) offers promising avenues for innovative therapeutic interventions in populations with intellectual disabilities (ID). This paper presents the design, development, and evaluation of Space Exodus, a novel VR-based role-playing game specifically tailored for children with ID. By integrating immersive gameplay with therapeutic task design, Space Exodus aims to enhance concentration, cognitive processing, and fine motor skills through structured hand-eye coordination exercises. A six-week pre-test/post-test study was conducted with 16 children in Ecuador, using standardized assessments, the Toulouse-Pieron Cancellation Test, and the Moss Attention Rating Scale complemented by detailed observational metrics. Quantitative results indicate statistically significant improvements in concentration scores, with test scores increasing from 65.2 to 80.3 and 55.4 to 68.7, respectively (p < 0.01). Qualitative observations revealed reduced task attempts, enhanced user confidence, and increased active participation. The inclusion of a VR assistant provided consistent guidance that further boosted engagement. These findings demonstrate the potential of immersive, game-based le
The need for improved diagnostic methods in ophthalmology is acute, especially in the underdeveloped regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and underrepresented ophthalmic conditions. VisionUnit
The therapeutic working alliance is an important predictor of the outcome of the psychotherapy treatment. In practice, the working alliance is estimated from a set of scoring questionnaires in an inventory that both the patient and the therapists fill out. In this work, we propose an analytical framework of directly inferring the therapeutic working alliance from the natural language within the psychotherapy sessions in a turn-level resolution with deep embeddings such as the Doc2Vec and SentenceBERT models. The transcript of each psychotherapy session can be transcribed and generated in real-time from the session speech recordings, and these embedded dialogues are compared with the distributed representations of the statements in the working alliance inventory. We demonstrate, in a real-world dataset with over 950 sessions of psychotherapy treatments in anxiety, depression, schizophrenia and suicidal patients, the effectiveness of this method in mapping out trajectories of patient-therapist alignment and the interpretability that can offer insights in clinical psychiatry. We believe such a framework can be provide timely feedback to the therapist regarding the quality of the conve
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 revie
Large language models (LLMs) have shown significant promise across various medical applications, with ophthalmology being a notable area of focus. Many ophthalmic tasks have shown substantial improvement through the integration of LLMs. However, before these models can be widely adopted in clinical practice, evaluating their capabilities and identifying their limitations is crucial. To address this research gap and support the real-world application of LLMs, we introduce the OphthBench, a specialized benchmark designed to assess LLM performance within the context of Chinese ophthalmic practices. This benchmark systematically divides a typical ophthalmic clinical workflow into five key scenarios: Education, Triage, Diagnosis, Treatment, and Prognosis. For each scenario, we developed multiple tasks featuring diverse question types, resulting in a comprehensive benchmark comprising 9 tasks and 591 questions. This comprehensive framework allows for a thorough assessment of LLMs' capabilities and provides insights into their practical application in Chinese ophthalmology. Using this benchmark, we conducted extensive experiments and analyzed the results from 39 popular LLMs. Our evaluati
Deep learning has recently gained high interest in ophthalmology, due to its ability to detect clinically significant features for diagnosis and prognosis. Despite these significant advances, little is known about the ability of various deep learning systems to be embedded within ophthalmic imaging devices, allowing automated image acquisition. In this work, we will review the existing and future directions for "active acquisition" embedded deep learning, leading to as high quality images with little intervention by the human operator. In clinical practice, the improved image quality should translate into more robust deep learning-based clinical diagnostics. Embedded deep learning will be enabled by the constantly improving hardware performance with low cost. We will briefly review possible computation methods in larger clinical systems. Briefly, they can be included in a three-layer framework composed of edge, fog and cloud layers, the former being performed at a device-level. Improved edge layer performance via "active acquisition" serves as an automatic data curation operator translating to better quality data in electronic health records (EHRs), as well as on the cloud layer, f
Thanks to the increasing availability of genomics and other biomedical data, many machine learning approaches have been proposed for a wide range of therapeutic discovery and development tasks. In this survey, we review the literature on machine learning applications for genomics through the lens of therapeutic development. We investigate the interplay among genomics, compounds, proteins, electronic health records (EHR), cellular images, and clinical texts. We identify twenty-two machine learning in genomics applications across the entire therapeutics pipeline, from discovering novel targets, personalized medicine, developing gene-editing tools all the way to clinical trials and post-market studies. We also pinpoint seven important challenges in this field with opportunities for expansion and impact. This survey overviews recent research at the intersection of machine learning, genomics, and therapeutic development.
Vision impairment and blindness are a major global health challenge where gaps in the ophthalmology workforce limit access to specialist care. We evaluate AMIE, a medically fine-tuned conversational system based on Gemini with integrated web search and self-critique reasoning, using real-world clinical vignettes that reflect scenarios a general ophthalmologist would be expected to manage. We conducted two complementary evaluations: (1) a human-AI interactive diagnostic reasoning study in which ophthalmologists recorded initial differentials and plans, then reviewed AMIE's structured output and revised their answers; and (2) a masked preference and quality study comparing AMIE's narrative outputs with case author reference answers using a predefined rubric. AMIE showed standalone diagnostic performance comparable to clinicians at baseline. Crucially, after reviewing AMIE's responses, ophthalmologists tended to rank the correct diagnosis higher, reached greater agreement with one another, and enriched their investigation and management plans. Improvements were observed even when AMIE's top choice differed from or underperformed the clinician baseline, consistent with a complementary