Optical coherence tomography is a valuable tool for evaluating patients with neuro-ophthalmic disorders. In the acute phase of anterior optic neuritis (ON), peripapillary retinal nerve fiber layer (pRNFL) measurements can underestimate the amount of damage as axonal swelling could mask the true degree of RNFL loss. Contrary to pRNFL evaluation, we hypothesize that macular ganglion cell layer analysis could detect true neuronal loss before swelling resolution in anterior ON. We describe 4 patients with anterior ON in whom ganglion cell layer and inner plexiform layer (GCIPL) thinning was detected earlier than pRNFL loss. GCIPL analysis may provide more accurate information than pRNFL thickness and serve as an early structural indicator of irreversible neuronal loss.