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

Boris Babenko, Ilana Traynis, Christina Chen, Preeti Singh, Akib Uddin, Jorge Cuadros, Lauren P. Daskivich, April Y. Maa, Ramasamy Kim, Eugene Yu Chuan Kang, Yossi Matias, Greg S. Corrado, Lily Peng, Dale R. Webster, Christopher Semturs, Jonathan Krause, Avinash V. Varadarajan, Naama Hammel*, Yun Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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 m2, haemoglobin <11·0 g/dL, platelets <150·0 × 103/μL, ACR ≥300 mg/g, and WBC <4·0 × 103/μL 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.

Original languageEnglish
Pages (from-to)e257-e264
JournalThe Lancet Digital Health
Issue number5
StatePublished - May 2023
Externally publishedYes


FundersFunder number
National Institutes of Health
U.S. Department of Veterans Affairs
National Center for Advancing Translational Sciences
GoogleUL1TR001855, UL1TR000130
Government of South Australia


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