COVID-19 and Retinal Layer Thickness: A bidirectional Mendelian
Randomization Study
Abstract
Observational studies have reported that COVID-19 is associated with
alterations in retinal layer thickness, including changes in the
ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber
layer (RNFL). However, observational studies are susceptible to
confounding factors and reverse causality. Therefore, we assessed the
direction and strength of the causal relationship between COVID-19
patient phenotypes (susceptibility, hospitalization, and severity) and
GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian
randomization (MR) design. The inverse-variance weighted (IVW) method is
the primary approach used to estimate causal effects. MR Egger, weighted
median, weighted mode, MR Egger (bootstrap), and penalized weighted
median methods were applied. In addition, we performed sensitivity
analyses using RadialMR, MRPRESSO, MR Egger regression, Cochran’s Q
statistic, and Leave-one-out analysis. Forward MR analysis revealed that
genetically identified COVID-19 susceptibility significantly increased
the risk of GCIPL thickness (OR: 2.428, 95% confidence
interval[CI]:1.493-3.947, PIVW=3.579 ×10
-4) and RNFL thickness (OR: 1.735,95%CI:1.198-2.513,
PIVW=3.580×10 -3). The results
after excluding MRPRESSO and RadialMR to identify outliers and SNPs
associated with confounding factors showed RNFL
thickness(OR:1.800,95%CI: 1.192-2.717,
PIVW=5.147×10 -3).Reverse MR
analysis did not indicate a significant causal association between GCIPL
and RNFL thicknesses and COVID-19 phenotypes. In conclusion, the host
genetic liability to COVID-19 susceptibility was causally associated
with increased GCIPL and RNFL thicknesses. Documenting this association
increases our understanding of the pathophysiological mechanisms
underlying COVID-19 susceptibility in retinopathy.