A deep learning model for novel systemic biomarkers in photographs of the external eye: a retrospective study

Background Photographs of the external eye were recently shown to reveal signs of diabetic retinal disease and elevated glycated haemoglobin. This study aimed to test the hypothesis that external eye photographs contain information about additional systemic medical conditions. Methods We developed a deep learning system (DLS) that takes external eye photographs as input and predicts systemic parameters, such as those related to the liver (albumin, aspartate aminotransferase [AST]); kidney (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [ACR]); bone or mineral (calcium); thyroid (thyroid stimulating hormone); and blood (haemoglobin, white blood cells [WBC], platelets). This DLS was trained using 123 130 images from 38 398 patients with diabetes undergoing diabetic eye screening in 11 sites across Los Angeles county, CA, USA. Evaluation focused on nine prespecified systemic parameters and leveraged three validation sets (A, B, C) spanning 25 510 patients with and without diabetes undergoing eye screening in three independent sites in Los Angeles county, CA, and the greater Atlanta area, GA, USA. We compared performance against baseline models incorporating available clinicodemographic variables (eg, age, sex, race and ethnicity, years with diabetes). Findings Relative to the baseline, the DLS achieved statistically significant superior performance at detecting AST >36.0 U/L, calcium <8.6 mg/dL, eGFR <60.0 mL/min/1.73 m(2), haemoglobin <11.0 g/dL, platelets <150.0 x 10(3)/mu L, ACR =300 mg/g, and WBC <4.0 x 10(3)/mu L on validation set A (a population resembling the development datasets), with the area under the receiver operating characteristic curve (AUC) of the DLS exceeding that of the baseline by 5.3-19.9% (absolute differences in AUC). On validation sets B and C, with substantial patient population differences compared with the development datasets, the DLS outperformed the baseline for ACR =300.0 mg/g and haemoglobin <11.0 g/dL by 7.3-13.2%. Interpretation We found further evidence that external eye photographs contain biomarkers spanning multiple organ systems. Such biomarkers could enable accessible and non-invasive screening of disease. Further work is needed to understand the translational implications. Funding Google. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.