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Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1\u2010carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences. Indeed, genetics and B vitamin status were significant predictors of ophthalmic issues. We now have developed a hypothesis regarding the mechanisms that link 1\u2010carbon pathway genetics and the condition that we suggest calling, \u201castronaut ophthalmic syndrome.\u201d We maintain that this condition is genetically predisposed and is associated with endothelial dysfunction that is induced by oxidative stress. Subsequent edema can hinder cerebrospinal fluid efflux and can lead to locally increased pressures in the subarachnoid space within the orbit, which impinges on the optic nerve and\/or eye in affected individuals. Confirming this hypothesis will help characterize the genetics of 1\u2010carbon pathway metabolism, homocysteine, oxidative stress, endothelial dysfunction, and cardiovascular and potentially other diseases.\u2014Zwart, S. R., Gibson, C. R., Gregory, J. F., Mader, T. H., Stover, P. J., Zeisel, S. H., Smith, S. M. Astronaut ophthalmic syndrome. FASEB J. 31, 3746\u20133756 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    \u2014Zwart, Sara R., Gibson, Charles R., Gregory, Jesse F., Mader, Thomas H., Stover, Patrick J., Zeisel, Steven H., Smith, Scott M., Astronaut ophthalmic syndrome. 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