AIM: To elucidate the changes of different ganglion cell layer (GCL) thinning patterns between the optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: A prospective, observational study was conducted to evaluate the timing of GCL changes between acute ON and NAION using optical coherence tomography. RESULTS: Thinning on optical coherence tomography in the NAION group occurs as early as 11d after symptomatic onset of vision loss and follows an altitudinal pattern. The mean superior-inferior GCL thickness difference in the NAION cohort was clinically significant at 5.7 μm in the NAION cohort compared to controls of 0.8 μm (P=0.032), but not significant in the ON group compared to controls with both groups measuring 1.1 μm. Global thinning was significant for the ON group compared to controls at 7.2 μm (P=0.011) but not the NAION group compared to controls at 1.35 μm. CONCLUSION: These findings suggest that future treatments for NAION should be given early, and possibly before 11d in order to prevent GCL and irreversible vision loss.