A new SARS-CoV-2-related systemic inflammatory disorder has appeared, with symptom onset approximately a month after exposure to the virus — unique from other pediatric inflammatory syndromes. Researchers have now demonstrated that Multisystemic Inflammatory Syndrome in Children (MIS-C) can lead to subclinical changes in the microvascular system of the retina and choroid, according to their data published in Eye. Previous studies have found that patients’ endothelial cells may be injured from the virus itself or from a barrage of cytokines, but no definitive etiology has yet been defined.  

What is known is that conjunctivitis occurs in close to half of patients with MIS-C, and there is a lack of research on the impact of this post-acute illness on retinal microvasculature. The current prospective observational study was conducted at Kocaeli University in Turkey, between March and June 2021. Investigators performed dilated examinations, as well as optical coherence tomography angiography (OCT-A) for 34 right eyes of 34 patients diagnosed with MIS-C, and compared data with 36 eyes of 36 age- and sex-matched healthy control individuals. Mean age of patients was 10.94±3.08 years. 

In the case cohort, all were SARS-CoV-2 PCR negative, but returned IgG- or IgM-positive tests. The median acute-stage hospitalization was 9.12±2.84 days with average time from diagnosis to ophthalmic exam approximately 37.5 days. All macular superficial capillary plexus (SCP) vessel density variables were significantly reduced in participants with MIS-C compared with control individuals. Also, case participants had considerably lower density in FD-300, a 300 µm radius around the foveal avascular zone (P =.024). Outer retinal flow in 1 mm, 2 mm, and 3 mm radii; and choriocapillaris flow area at 1 mm, and 2 mm were significantly decreased, as well.


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Deep capillary plexus (DCP) and optic nerve head (ONH) vessel density parameters were lower in those with MIS-C, but not significantly so (all P >.05). Similarly, foveal avascular zone in overall retinal vasculature, foveal avascular zone in SCP, and zone perimeter did not display significant differences between cohorts (all P >.05). Choriocapillaris flow area at 3 mm radius was slightly lower but comparable, as well.

Finding reductions of vessel density for “all segments in SCP and flow of outer retina and choriocapillaris in an otherwise healthy cohort using OCT-A is quite remarkable,” the study explains, adding that because all participants exhibited best corrected visual acuity of 20/20 or better and were otherwise in good ocular and general health, outcomes are more clearly associated with MIS-C.

A number of prior studies of adults with COVID-19 have found mean macular SCP or DCP vessel densities are significantly decreased, although other investigations show no large differences in SCP and DCP compared with control sets. Another trial which considered microcirculation in 3 macular capillary layers found vessel density of SCP and DCP of recovered COVID-19 patients not significantly different from control individuals, but intermediate capillary plexus (ICP) density was substantially decreased.

The current analysis was limited by being conducted at a single center, and participants did not undergo long-term follow-up. The sample was small, but showed sufficient power, and this is the first study to explore these retinal microcirculatory changes. 

“Management of SARS-CoV-2 related MIS-C should include retinal assessment, with a close follow-up,” the researchers report.

Reference

Yılmaz Tuğan B, Sönmez HE, Atay K, Başar EZ, Özkan B, Karabaş L. Quantitative analysis of preclinical ocular microvascular changes in Multisystemic Inflammatory Syndrome in Children (MIS-C) detected by optical coherence tomography angiography. Eye. Published online April 29, 2022. doi:10.1038/s41433-022-02081-8