Zwart SR, Laurie SS, Chen JJ, et al. - Since candidates exposed to carbon dioxide, 0.5%, for 30 days, showed development of optic disc edema and increased total retinal thickness in a recent strict 6° head-down tilt bed rest (HDTBR) study, researchers ascertained if peripapillary retinal thickness measures obtained from optical coherence tomography images during HDTBR and carbon dioxide, 0.5%, exposure were correlated with B vitamin status and single-nucleotide polymorphisms involved in folate-dependent and vitamin B12–dependent 1-carbon metabolism pathways. This research was carried out at the Institute of Aerospace Medicine at the German Aerospace Center in Cologne, Germany. The data presented in this work showed a greater increase in total retinal thickness and baseline retinal nerve fiber layer thickness during 30 days of head-down tilt bed rest with carbon dioxide, 0.5%, exposure, in correlation with the presence of more 5-methyltetrahydrofolate-homocysteine methyltransferase reductase 66G and serine hydroxymethyltransferase 1 1420C alleles. Furthermore, B vitamin status was identified as a contributing factor. Such results can help to explain the magnitude variability of optical disc edema observed during bed rest and spaceflight and thus enhance efforts to counteract this phenomenon.