Non-arteritic anterior ischemic optic neuropathy (NA-AION) is considered the most frequent type of acute optic neuropathy. A 61-year-old woman presented with a NA-AION in her right eye within 24 h following an airplane flight. One year later, after driving for 10 days with a daily accumulated altitude of 1500 m, she developed a NA-AION in her left eye. Systemic disorders were investigated, and cerebral small vessel disease was observed via cranial computed tomography. An inadequate response to hypoxia, in a patient with individual susceptibility, could lead to reduced blood supply to the optic nerve head, which could represent an underlying cause of NA-AION.