Reticular pseudodrusen load is associated with an increased risk of stroke

BACKGROUND/AIMS: Reticular pseudodrusen (RPD) are increasingly recognised as a distinct phenotype in the age-related macular degeneration (AMD) disease spectrum. This study investigates the association between RPD and cardiovascular outcomes, specifically myocardial infarction (MI) and stroke in the UK Biobank (UKBB). METHODS: Retrospective analysis of UKBB participants (n=2010). A validated deep learning framework identified and quantified subjects with RPD, drusen and controls on optical coherence tomography. Five retina specialists validated the artificial intelligence findings. Multivariable logistic regression models assessed the association between RPD/drusen and stroke, MI and combined MI/stroke, adjusting for age, sex, high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ratio and smoking history. RESULTS: The study cohort included 71 subjects with pure RPD, 401 with pure drusen, 368 with both and 1170 controls. Univariable analysis showed that for every 20 RPD lesions, the OR for stroke increased by 1.02 (95% CI 1.00 to 1.04, p=0.028). The mean number of RPD per patient in this cohort was 199, indicating an increased stroke risk of 20%. Multivariable analysis showed a significant association between RPD load and stroke risk (OR 1.02, 95% CI 1.00 to 1.04, p=0.042) after adjustment for confounders. No significant association was found between drusen and stroke or between RPD/drusen and MI. CONCLUSION: Increased RPD load is associated with a higher risk of stroke, independent of traditional cardiovascular risk factors. Drusen did not have similar associations, suggesting that RPD may represent a distinct disease entity. Evaluating cardiovascular risk in patients with numerous RPD might be advisable. Further prospective studies are needed to validate these findings and explore the underlying mechanisms.