The association between markers of inflammation and retinal microvascular parameters: A systematic review and meta-analysis

Abstract Background and aims Adverse changes to the microcirculation play an important role in the pathogenesis of cardiovascular disease (CVD), and inflammation is a key causal mechanism. We investigated the relationship between inflammatory markers and retinal microvascular parameters. Methods Studies up to April 2021 were identified in Medline, Embase and PubMed with the following terms: retinal microvascular parameters, inflammatory markers, and observational studies. Correlation coefficients of inflammatory markers and retinal vascular caliber were pooled using the random-effects model. Results Of 4783 studies identified, 36 met the inclusion criteria (general population 26, patients with diseases 10). C-reactive protein (CRP) and white blood cell count (WBC) were most frequently reported. We conducted meta-analysis with 12 CRP studies (22422 participants) and six WBC studies (15209 participants), and also performed a narrative review of all studies. There was consistent evidence of a modest association between CRP and venular caliber (r = 0.09, 95%CI 0.05 to 0.12), but little evidence of an association between CRP with retinal arteriolar caliber (r = 0.00, 95%CI -0.02 to 0.02). Similarly, WBC had stronger associations with venular (r = 0.18, 95%CI 0.05 to 0.31) than arteriolar caliber (r = 0.05, 95%CI 0.01 to 0.09). Narrative review of other inflammatory markers showed consistent findings. There was little evidence of associations between inflammation markers and other microvascular parameters, fractal dimension and tortuosity. Conclusions There was more evidence for an association of inflammation with retinal venular than with arterial caliber. The findings suggest a potential druggable mechanism contributing to microvascular damage that has been relatively overlooked in CVD pathogenesis and treatment.