Evidence of Microvascular Changes in the Retina following Kawasaki Disease

Abstract

It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 μm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 μm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults.

Association between Coronary Artery Measurements and Retinal Microvasculature in Children with New Onset of Kawasaki Disease

“…A previous study found that increment of coronary artery diameters was associated with wider retinal venules in paediatric KD patients with recurrent acute flares 5 . We found however, that retinal arteriolar changes, instead of retinal venular changes, were associated with coronary artery changes during the acute phase of new KD onset.…”

“…Both geometric parameters reflect an optimal blood circulation in the retina. Thus, altered fractal dimension and/or curvature tortuosity could reflect increased angiogenesis or oxidative stress in response to inflammatory-induced neuro-retinal hypoxia and endothelial dysfunction 5 . Although increased retinal tortuosity has been speculated to be related to increased blood flow and angiogenesis 13–15 , the true physiologic significance of increased retinal arteriolar tortuosity is still not fully understood.…”

“…Such systematic parameters mirror an “optimal state” of the retinal microcirculation, which may also reflect systemic microcirculation 4 . A previous cross-sectional study conducted on Singaporean and Australian chronic paediatric KD patients, who suffered relapses and were treated for years, found that wider retinal venules were associated with coronary artery abnormalities, such as giant coronary artery aneurysms 5 . However, it is still unknown whether such retinal vascular changes exist during the new-onset other than recurrent acute phase of KD.…”

Involvement of Nervous System in Kawasaki Disease

“…These changes may serve as key players in the pathophysiology of vascular damage outside cardiovascular system. 23 Although the number of children reported to present this complication is small and does not permit the identification of more risk factors, literature data imply that an early diagnosis and initiation of appropriate treatment prevent the appearance of this complication. 16…”

A case of Kawasaki disease complicated with retinal vasculitis

“…Recently, Chen et al . reported that the retinal venules of patients with KD at least 2 years after acute illness were larger in size than those of control participants after adjusting for traditional cardiovascular risk factors . Furthermore, an increase in the size of retinal venules was observed in patients with coronary artery abnormalities compared with control patients.…”