Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms

OBJECTIVE: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). METHODS: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. RESULTS: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc (‘ntreeA’) was associated with both AAA (β = −0.36, P = 6.75e−10) and ICA (β = −0.11, P = 5.51e−06). In addition, the mean angles between each artery branch (‘curveangle_mean_a’) were commonly associated with 4 MFS genes (FBN1: β = −0.10, P = 1.63e−12; COL16A1: β = −0.07, P = 3.14e−09; LOC105373592: β = −0.06, P = 1.89e−05; C8orf81/LOC441376: β = 0.07, P = 1.02e−05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780–0.838], which was similar to the clinical risk model (0.806 [0.778–0.834]) but higher than the baseline model (0.739 [0.733–0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727–0.869) for the aneurysm-RVF model, 0.795 (0.718–0.871) for the clinical risk model and 0.719 (0.620–0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5–48.8], P = 1.02e−05). CONCLUSION: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.