PurposeTo evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre–Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images.MethodsRetrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist.ResultsIn total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57–0.91); precision, 0.67 (0.44–0.88); specificity, 0.45 (0.15–0.75); sensitivity, 0.92 (0.73–1.00); and AUC, 0.63 (0.52–0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance.ConclusionsThe MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model.Translational RelevanceMIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.