Prediction of Cardiovascular Markers and Diseases Using Retinal Fundus Images and Deep Learning: A Systematic Scoping Review

Background: Cardiovascular risk prediction models based on sociodemographic factors and traditional clinical measurements have received significant attention. With rapid development in deep learning for image analysis in the last decade and the well-known association between micro- and macrovascular complications, some recent studies focused on the prediction of cardiovascular risk using retinal fundus images. The objective of this scoping review is to identify and describe studies using retinal fundus images and deep learning to predict cardiovascular risk markers and diseases. Methods: We searched MEDLINE and Embase for peer-reviewed articles on 17 November 2023. Abstracts and relevant full-text articles were independently screened by two reviewers. We included studies that used deep learning for the analysis of retinal fundus images to predict cardiovascular risk markers (e.g. blood pressure, coronary artery calcification, intima-media thickness) or cardiovascular diseases (prevalent or incident). Studies that used only predefined characteristics of retinal fundus images (e.g. tortuosity, fractal dimension) were not considered. Study characteristics were extracted by the first author and verified by the senior author. Results are presented using descriptive statistics. Results: We included 24 articles in the review, published between 2018 and 2023. Among these, 21 (88%) were cross-sectional studies and eight (33%) were follow-up studies with outcome of clinical CVD. Five studies included a combination of both designs. Most studies (n=23, 96%) used convolutional neural networks to process images. We found nine (38%) studies that incorporated clinical risk factors in the prediction and four (17%) that compared the results to commonly used clinical risk scores in a prospective setting. Three of these reported improved discriminative performance. External validation of models was rare (n=5, 21%). Only four (17%) studies made their code publicly available. Conclusions: There is an increasing interest in using retinal fundus images in cardiovascular risk assessment. However, there is a need for more prospective studies, comparisons of results to clinical risk scores and models augmented with traditional risk factors. Moreover, more extensive code sharing is necessary to make findings reproducible and more impactful beyond a specific study. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement LYL, AAI, BLJ, KF, and AH are employed at Steno Diabetes Center Aarhus which is partly funded by a donation from the Novo Nordisk Foundation (NNF17SA0031230). LYL, BLJ, and AH are supported by a Data Science Emerging Investigator grant (NNF22OC0076725) by the Novo Nordisk Foundation. SB, THA and ON are employed at the Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, which is partly funded by the Novo Nordisk Foundation. The funders had no role in the design of the study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://doi.org/10.6084/m9.figshare.25610088