Abstract: The present disclosure is directed to systems and methods that leverage machine learning for detection of eye or non-eye (e.g., systemic) diseases from external anterior eye images. In particular, a computing system can include and use one or more machine-learned disease detection models to provide disease predictions for a patient based on external anterior eye images of the patient. Specifically, in some example implementations, a computing system can obtain one or more external images that depict an anterior portion of an eye of a patient. The computing system can process the one or more external images with the one or more machine-learned disease detection models to generate a disease prediction for the patient relative to one or more diseases, including, as examples, diseases which present manifestations in a posterior of the eye (e.g., diabetic retinopathy) or systemic diseases (e.g., poorly controlled diabetes).