© 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.Purpose: To use optic coherence tomography (OCT) to evaluate idiopathic intracranial hypertension (IIH) patients with subclinical segmental optic atrophy despite being under apparently effective treatment. Methods: IIH patients underwent an OCT examination including the peripapillary retina never fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, focal loss volume (FLV) and global loss volume (GLV) of the GCC, and total macular thickness measurements at presentation and at 3, 6, 9, and 12 months after the diagnosis. The obtained data were compared with healthy subjects. Subjects with and without subclinical segmental atrophy at the 12th month were compared according to the demographics, clinical findings, and the OCT parameters recorded at the beginning of the disease. Results: Both eyes of 56 patients with papilledema due to IIH and 50 age- and sex-matched control subjects were included in this prospective case–control study. Regression of papilledema with regional axon loss on the peripapillary RNFL thickness map was found in 37 (33%) eyes in the IIH group. IIH patients with segmental atrophy had the following characteristics when compared to those without segmental atrophy at the beginning of the disease: higher CSF opening pressure, higher grade of papilledema, thicker mean peripapillary RNFL thickness, thinner GCC layer, greater FLV and GLV loss, and severe visual field loss. Conclusions: Axonal loss occurred in the patients despite apparent treatment. It would be appropriate to follow-up with aggressive medical treatment those patients who present with the following characteristics: higher CSF opening pressure, higher grade of papilledema, thicker mean peripapillary RNFL thickness, and thinner GCC.