Corneal nerve loss associated with nitrous oxide neurotoxicity

Nitrous oxide is an inhaled anaesthetic used recreationally that is neurotoxic. Corneal nerve parameters were assessed in patients with nitrous oxide toxicity. Four individuals underwent clinical, electrophysiological and corneal confocal microscopy assessment. Corneal images were analysed with automated software and compared to healthy controls. Two patients had prolonged heavy use of nitrous oxide ≥ two years. In both patients, there was a reduction in inferior whorl corneal nerve fibre length (6.3 mm/mm2 of cornea, 9.8 mm/mm2 of cornea, respectively versus healthy controls: mean 19.4 ± 9.0 mm/mm2 of cornea), and reduced inferior whorl corneal nerve fibre density (8.3 fibres/mm2 cornea, 2.5 fibres/mm2 of cornea, respectively versus healthy controls: mean 27.5 ± 11.1 fibres/mm2 of cornea. Conversely, patients three and four had shorter, intense exposure and normal corneal nerve parameters (inferior whorl corneal nerve fibre density 20.8 fibres/mm2 of cornea and 23.4 fibres/mm2 of cornea, and corneal nerve fibre length 14.5 fibres/mm2 of cornea and 19.6 fibres/mm2 of cornea, respectively). We demonstrated corneal nerve changes with long-term use of nitrous oxide, but preservation of corneal nerve indices with shorter duration of exposure. Corneal nerve assessment may be a marker of neurological injury from nitrous oxide.