Aims To evaluate longitudinal retinal ganglion cell inner plexiform layer (GC-IPL) and macular retinal nerve fibre layer (mRNFL) thickness changes in acute Leber's hereditary optic neuropathy (LHON).

Methods Six eyes of four patients with LHON underwent SD-OCT (optical coherence tomography) at month 1, 3, 6 and 12 after visual loss. In two eyes, the examination was carried out in the presymptomatic stage. The relationship and curves for area under the receiver operator characteristic (AUROC) were generated to assess the ability of each parameter to detect ganglion cell loss.

Results Significant longitudinal thinning of GC-IPL and mRNFL was detected in LHON. GC-IPL thinning was detectable in the deviation map during the presymptomatic stage in the inner ring of the nasal sector and then it progressively extended following a centrifugal and spiral pattern. Similarly, mRNFL thinning began in the inferonasal sector and it progressively extended. No further statistically significant changes were detected after month 3. The highest level of AUROC values at 1 month were detected in the nasal sectors and inferonasal mRNFL thickness reached AUROC value=1. All the parameters were equally able to detect ganglion cell loss from month 2 to 12.

Conclusions The natural history of GC-IPL thinning follows a specific pattern of reduction, reflecting the anatomical course of papillomacular fibres. Month 6 represents the end of GC-IPL loss. GC-IPL and mRNFL thinning is detectable before onset of visual loss. These observations can help future therapeutic approaches for both LHON carriers at high risk of conversion and patients with acute early LHON.