Cecilia S. Lee

Zixuan Liu, Hanwen Xu, Addie Woicik et al.

We present OCTCube-M, a 3D OCT-based multi-modal foundation model for jointly analyzing OCT and en face images. OCTCube-M first developed OCTCube, a 3D foundation model pre-trained on 26,685 3D OCT volumes encompassing 1.62 million 2D OCT images. It then exploits a novel multi-modal contrastive learning framework COEP to integrate other retinal imaging modalities, such as fundus autofluorescence and infrared retinal imaging, into OCTCube, efficiently extending it into multi-modal foundation models. OCTCube achieves best performance on predicting 8 retinal diseases, demonstrating strong generalizability on cross-cohort, cross-device and cross-modality prediction. OCTCube can also predict cross-organ nodule malignancy (CT) and low cardiac ejection fraction as well as systemic diseases, such as diabetes and hypertension, revealing its wide applicability beyond retinal diseases. We further develop OCTCube-IR using COEP with 26,685 OCT and IR image pairs. OCTCube-IR can accurately retrieve between OCT and IR images, allowing joint analysis between 3D and 2D retinal imaging modalities. Finally, we trained a tri-modal foundation model OCTCube-EF from 4 million 2D OCT images and 400K en face retinal images. OCTCube-EF attains the best performance on predicting the growth rate of geographic atrophy (GA) across datasets collected from 6 multi-center global trials conducted in 23 countries. This improvement is statistically equivalent to running a clinical trial with more than double the size of the original study. Our analysis based on another retrospective case study reveals OCTCube-EF's ability to avoid false positive Phase-III results according to its accurate treatment effect estimation on the Phase-II results. In sum, OCTCube-M is a 3D multi-modal foundation model framework that integrates OCT and other retinal imaging modalities revealing substantial diagnostic and prognostic benefits.

Meng Wang, Tian Lin, Aidi Lin et al.

Previous foundation models for fundus images were pre-trained with limited disease categories and knowledge base. Here we introduce a knowledge-rich vision-language model (RetiZero) that leverages knowledge from more than 400 fundus diseases. For RetiZero's pretraining, we compiled 341,896 fundus images paired with texts, sourced from public datasets, ophthalmic literature, and online resources, encompassing a diverse range of diseases across multiple ethnicities and countries. RetiZero exhibits remarkable performance in several downstream tasks, including zero-shot disease recognition, image-to-image retrieval, AI-assisted clinical diagnosis,few-shot fine-tuning, and internal- and cross-domain disease identification. In zero-shot scenarios, RetiZero achieves Top-5 accuracies of 0.843 for 15 diseases and 0.756 for 52 diseases. For image retrieval, it achieves Top-5 scores of 0.950 and 0.886 for the same sets, respectively. AI-assisted clinical diagnosis results show that RetiZero's Top-3 zero-shot performance surpasses the average of 19 ophthalmologists from Singapore, China, and the United States. RetiZero substantially enhances clinicians' accuracy in diagnosing fundus diseases, in particularly rare ones. These findings underscore the value of integrating the RetiZero into clinical settings, where various fundus diseases are encountered.

Joanne C. Wen, Cecilia S. Lee, Pearse A. Keane et al.

Purpose: To determine if deep learning networks could be trained to forecast a future 24-2 Humphrey Visual Field (HVF). Participants: All patients who obtained a HVF 24-2 at the University of Washington. Methods: All datapoints from consecutive 24-2 HVFs from 1998 to 2018 were extracted from a University of Washington database. Ten-fold cross validation with a held out test set was used to develop the three main phases of model development: model architecture selection, dataset combination selection, and time-interval model training with transfer learning, to train a deep learning artificial neural network capable of generating a point-wise visual field prediction. Results: More than 1.7 million perimetry points were extracted to the hundredth decibel from 32,443 24-2 HVFs. The best performing model with 20 million trainable parameters, CascadeNet-5, was selected. The overall MAE for the test set was 2.47 dB (95% CI: 2.45 dB to 2.48 dB). The 100 fully trained models were able to successfully predict progressive field loss in glaucomatous eyes up to 5.5 years in the future with a correlation of 0.92 between the MD of predicted and actual future HVF (p < 2.2 x 10 -16 ) and an average difference of 0.41 dB. Conclusions: Using unfiltered real-world datasets, deep learning networks show an impressive ability to not only learn spatio-temporal HVF changes but also to generate predictions for future HVFs up to 5.5 years, given only a single HVF.

Cecilia S. Lee, Ariel J. Tyring, Yue Wu et al.

Despite significant advances in artificial intelligence (AI) for computer vision, its application in medical imaging has been limited by the burden and limits of expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures perfusion of the retinal vasculature, to train an AI algorithm to generate vasculature maps from standard structural optical coherence tomography (OCT) images of the same retinae, both exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer perfusion of microvasculature from structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). OCTA suffers from need of specialized hardware, laborious acquisition protocols, and motion artifacts; whereas our model works directly from standard OCT which are ubiquitous and quick to obtain, and allows unlocking of large volumes of previously collected standard OCT data both in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed and accurate inferences of tissue function from structure imaging.

Cecilia S. Lee, Doug M. Baughman, Aaron Y. Lee

Objective: The advent of Electronic Medical Records (EMR) with large electronic imaging databases along with advances in deep neural networks with machine learning has provided a unique opportunity to achieve milestones in automated image analysis. Optical coherence tomography (OCT) is the most commonly obtained imaging modality in ophthalmology and represents a dense and rich dataset when combined with labels derived from the EMR. We sought to determine if deep learning could be utilized to distinguish normal OCT images from images from patients with Age-related Macular Degeneration (AMD). Methods: Automated extraction of an OCT imaging database was performed and linked to clinical endpoints from the EMR. OCT macula scans were obtained by Heidelberg Spectralis, and each OCT scan was linked to EMR clinical endpoints extracted from EPIC. The central 11 images were selected from each OCT scan of two cohorts of patients: normal and AMD. Cross-validation was performed using a random subset of patients. Area under receiver operator curves (auROC) were constructed at an independent image level, macular OCT level, and patient level. Results: Of an extraction of 2.6 million OCT images linked to clinical datapoints from the EMR, 52,690 normal and 48,312 AMD macular OCT images were selected. A deep neural network was trained to categorize images as either normal or AMD. At the image level, we achieved an auROC of 92.78% with an accuracy of 87.63%. At the macula level, we achieved an auROC of 93.83% with an accuracy of 88.98%. At a patient level, we achieved an auROC of 97.45% with an accuracy of 93.45%. Peak sensitivity and specificity with optimal cutoffs were 92.64% and 93.69% respectively. Conclusions: Deep learning techniques are effective for classifying OCT images. These findings have important implications in utilizing OCT in automated screening and computer aided diagnosis tools.