Marshall-Goebel K, Macias BR, Kramer LA, et al. - In this cohort study, researchers explored the connection between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight. This investigation involved healthy International Space Station crew members (n = 19; 5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years) before and immediately after long-duration spaceflight. Analyses showed a positive, although not definitive, connection between spaceflight-induced changes in total retinal thickness and lateral ventricle volume. There were no associations found between spaceflight-induced changes in total retinal thickness and white matter volume or brain tissue plus cerebrospinal fluid volume, which is an estimate of intracranial volume. Such findings contribute to the understanding of the spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes on the central nervous system during spaceflight. The possibly weak relationship between increased total retinal thickness and lateral ventricle volume suggests that, while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be unrelated to changes in the intracranial compartment.