Abstract: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.
Abstract:Cryo-electron microscopy (cryo-EM) offers near-atomic resolution imaging of macromolecules, but developing robust models for downstream analysis is hindered by the scarcity of high-quality annotated data. While synthetic data generation has emerged as a potential solution, existing methods often fail to capture both the structural diversity of biological specimens and the complex, spatially varying noise inherent in cryo-EM imaging. To overcome these limitations, we propose CryoCCD, a synthesis framework that integrates biophysical modeling with generative techniques. Specifically, CryoCCD produces multi-scale cryo-EM micrographs that reflect realistic biophysical variability through compositional heterogeneity, cellular context, and physics-informed imaging. To generate realistic noise, we employ a conditional diffusion model, enhanced by cycle consistency to preserve structural fidelity and mask-aware contrastive learning to capture spatially adaptive noise patterns. Extensive experiments show that CryoCCD generates structurally accurate micrographs and enhances performance in downstream tasks, outperforming state-of-the-art baselines in both particle picking and reconstruction.