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Background ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). Objective we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. Methods we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years (‘RetiAGE’) and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). Results in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42–1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69–3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31–1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14–1.69]) and 18% (HR = 1.18 [1.10–1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). Conclusions the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.

Purpose(1) To determine the independent association of dry eye symptoms with health-related quality of life (HRQoL) in the Singapore population and (2) to further investigate which factors mediate this association.MethodsIn this cross-sectional study, 7707 participants were included. The presence of dry eye symptoms was defined as experiencing at least one out of the six symptoms either ‘often’ or ‘all the time’. The EuroQoL-5 dimensions (EQ-5D) utility instrument (raw scores converted to UK time trade-off (TTO) values) was used to assess generic HRQoL and the overall score from the Visual Functioning Questionnaire for visual functioning. The association between dry eye symptoms and EQ-5D was investigated using multivariable linear regression, adjusting for demographic and socioeconomic information, comorbidities, systemic and ocular examinations results. Mediation analysis was used to determine whether certain factors mediated this association.ResultsAfter adjusting for relevant factors, those with dry eye symptoms had significantly lower HRQoL (difference in EQ-5D TTO: −0.062 (95% CI −0.073 to –0.050)), with the inability to open eyes affected the most (−0.101 (95% CI −0.161 to –0.042)), followed by a sandy sensation (−0.089 (95% CI −0.121 to –0.058)), a burning sensation (−0.070 (95% CI −0.105 to –0.036)), red eyes (−0.059 (95% CI −0.082 to –0.036)), a dry sensation (−0.058 (95% CI −0.072 to –0.044)) and crusting of eyelids (−0.040 (95% CI −0.071 to –0.008)). Visual functioning and the presence of recent falls accounted for 8.63% (4.98%–14.5%) and 2.93% (0.04%–5.68%) of the indirect relationship between dry eye and HRQoL, respectively.ConclusionDry eye symptoms were independently associated with poor HRQoL. Moreover, this was partly mediated by reduced visual functioning and experiencing recent falls. Our results suggest that efforts to reduce severity of dry eye symptoms are essential to optimise patients’ overall functioning and well-being.