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

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.