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Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m 2 . Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background To explore the role of microvascular pathology in migraine, we investigated the association between migraine and retinal microvascular damage. Methods We included 3270 participants (age ≥ 45 years, 63% women) from the population-based Rotterdam Study (2006-2009). Participants with migraine were identified using a validated questionnaire based on ICHD-II criteria (n = 562). Retinopathy signs were graded on fundus photographs. Retinal arteriolar and venular caliber were measured by semi-automatic assessment of fundus photographs. Associations of migraine with retinopathy and retinal microvascular calibers were examined using logistic and linear regression models, respectively, adjusting for age, sex, and cardiovascular risk factors. Results Migraine was not associated with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval (CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion vessel, persons with migraine did not differ in retinal arteriolar or venular caliber compared to persons without migraine (mean difference in standardized arteriolar caliber -0.05 (95%CI -0.13; 0.03); in standardized venular caliber -0.00 (95%CI -0.09; 0.08)). Migraine subtypes, including migraine with aura, were also not associated with retinal microvascular damage. Conclusions Our findings suggest that migraine is not associated with retinopathy or difference in retinal microvascular caliber. Further studies are needed to confirm these results.

Vitamin D has been linked to various cardiovascular risk factors including indices of large-vessel disease. However, it remains unclear whether vitamin D is also associated with microvascular damage. In a community-dwelling population, we studied associations between vitamin D serum levels and retinal microvascular damage defined as retinopathy signs, narrower arterioles, and wider venules.From the population-based Rotterdam Study, we included 5675 participants (age ≥45 years) with vitamin D data and gradable retinal photographs. Serum levels of vitamin D were measured using an antibody-based assay. Retinal exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages were graded on fundus photographs by experienced graders in the whole sample; retinal vascular calibers, that is, arteriolar and venular diameters, were semiautomatically measured in a subsample (n = 2973). We examined the cross-sectional association between vitamin D and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors.We found that persons with lower vitamin D levels were more likely to have retinopathy (adjusted odds ratio per standard deviation (SD) decrease of vitamin D = 1.30; 95% confidence interval (CI): = 1.12-1.49). Furthermore, lower vitamin D levels were associated with wider venular calibers (adjusted mean difference per SD decrease in vitamin D = 1.35; 95% CI = 0.64-2.06). This association was strongest among men (P for interaction = 0.023).Lower levels of vitamin D are associated with retinal microvascular damage, suggesting that the link with cardiovascular risk may partly run through changes in the microvasculature., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To investigate whether retinal microvascular damage is related to normal-appearing white matter microstructure on diffusion tensor MRI., Methods: We included 2,436 participants (age ≥45 years) from the population-based Rotterdam Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. White matter microstructure was assessed using diffusion tensor MRI. We used linear regression models to investigate the associations of retinal vascular calibers with markers of normal-appearing white matter microstructure, adjusting for age, sex, the fellow vascular caliber, and additionally for structural MRI markers and cardiovascular risk factors., Results: Narrower arterioles and wider venules were associated with poor white matter microstructure: adjusted difference in fractional anisotropy per SD decrease in arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and increase in venular caliber 0.047 (0.008-0.085). The associations for venules were more prominent in women., Conclusions: Retinal vascular calibers are related to normal-appearing white matter microstructure. This suggests that microvascular damage in the white matter is more widespread than visually detectable as white matter lesions., (© 2016 American Academy of Neurology.)

Background and Purpose: Perivascular enlargement in the brain is a putative imaging marker for microvascular brain damage, but this link has not yet been confirmed using direct in vivo visualization of small vessels. We investigated the relation between microvascular calibers on retinal imaging and enlarged perivascular spaces (ePVSs) on brain magnetic resonance imaging., Methods: We included 704 participants from the Rotterdam study. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. ePVSs were counted in the centrum semiovale, basal ganglia, hippocampus, and mesencephalon, using a standardized rating method. We determined the association between retinal microvascular calibers and ePVSs with negative binomial regression models, adjusting for age, sex, the other vascular caliber, structural brain magnetic resonance imaging markers, and cardiovascular risk factors., Results: Both narrower arteriolar and wider venular calibers were associated with more ePVSs in the centrum semiovale and hippocampal region. Rate ratios (95% confidence interval) for arterioles in the centrum semiovale and hippocampus were 1.07 (1.01-1.14) and 1.13 (1.04-1.22), respectively, and for venules 1.08 (1.01-1.16) and 1.09 (1.00-1.18), respectively. These associations were independent from other brain magnetic resonance imaging markers and cardiovascular risk factors., Conclusions: Retinal microvascular calibers are related to ePVSs, confirming the putative link between microvascular damage and ePVSs., (© 2016 American Heart Association, Inc.)

Retinal vascular diameters are associated with (sub)clinical cardiovascular disease and short-term cardiovascular mortality, but their association with long-term mortality is uncertain. We studied the association of retinal vascular diameters with cause-specific mortality in the general adult Dutch population during 25 years of follow-up. From 1990 to 1993, arteriolar and venular diameters were measured semiautomatically on digitized images in 5674 persons (mean age 68.0 years, 59% women) from the population-based Rotterdam study. Follow-up for mortality was complete till March 2015. Associations between vascular diameters and mortality were examined using Cox proportional hazards models, adjusting for age, sex, cardiovascular risk factors, and the fellow vessel diameter. During 85 770 person-years (mean±SD: 15.1±6.67), 3794 (66.8%) persons died, of whom 1034 due to cardiovascular causes. We found that narrower arterioles and wider venules were associated with higher risk of mortality (adjusted hazard ratio [95% confidence interval] per SD decrease 1.04 [1.00-1.08] and increase 1.07 [1.03-1.12], respectively). For arterioles, these associations were strongest for cardiovascular mortality, whereas venules showed consistent associations for cardiovascular and noncardiovascular mortality. Importantly, these associations remained unchanged after excluding the first 10 years of follow-up as immortal person-time. We found evidence for effect modification with stronger associations in persons <70 years (venules only) and smokers (P value for interaction<0.01). We replicated our findings in another independent cohort from the Rotterdam Study of 3106 persons with 19 880 person-years of follow-up and 144 deaths (hazard ratio for venules 1.22 [1.00-1.49]). Markers of retinal microvasculature are associated with long-term mortality in the general adult Dutch population., (© 2015 American Heart Association, Inc.)