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Background: Neuromyelitis spectrum disorder (NMOSD) is a rare autoimmune disorder previously thought to be a subtype of multiple sclerosis (MS). NMOSD is characterized by episodes of inflammation and damage to astrocytes that primarily results in damage to optic nerve and spinal cord. The objective of this exploratory study was to use optical coherence tomography (OCT) to measure axonal and neuronal health in NMOSD eyes over time. Methods: Nine patients with definite NMOSD were assessed at baseline and follow-up visits (time between visits: 35–55 months). OCT assessment involved a macular volume protocol and a retinal nerve fiber layer (RNFL) thickness scan. Results: The temporal, inferior, nasal, or superior quadrant and the mean global RNFL thickness, macular thickness, and volume of each NMOSD patient was unchanged compared with baseline for each eye separately and both together. There also was no change between the 2 time points for the OCT measures for eyes affected and unaffected by optic neuritis and all eyes together except for a significant change in the temporal RNFL quadrant when all NMOSD eyes were pooled together (mean = 2.88 μm, SD = 3.7, P = 0.021). Conclusions: Unlike in MS eyes, ongoing RNFL and macular thinning secondary to brain and optic nerve atrophy could not be observed in NMOSD eyes during an observation period of 4 years. This might be an additional marker to distinguish these 2 diseases. However, to confirm this finding, more long-term data are needed to compare these 2 diseases longitudinally. [ABSTRACT FROM AUTHOR]