Nasal-Predominant Ganglion Cell-Inner Plexiform Layer Thinning Distinguishes Early-Stage Leber Hereditary Optic Neuropathy From Acute Optic Neuritis

Clin Exp Ophthalmol. 2026 May 15. doi: 10.1111/ceo.70130. Online ahead of print.

ABSTRACT

BACKGROUND: To compare acute-phase macular ganglion cell-inner plexiform layer (GCIPL) thickness on optical coherence tomography (OCT) between Leber hereditary optic neuropathy (LHON) and optic neuritis (ON), and to evaluate the diagnostic performance of nasal GCIPL thickness.

METHODS: In this retrospective single-centre study, OCT (CIRRUS HD-OCT; Carl Zeiss Meditec, Dublin) acquired within 45 days of symptom onset was analysed. Sectoral GCIPL thickness was compared between LHON and ON-including double-seronegative (DN-ON), aquaporin-4 antibody-positive (AQP4-ON) and myelin oligodendrocyte glycoprotein antibody-positive (MOG-ON) subtypes-using linear mixed-effects models adjusted for age, sex and onset-to-OCT interval. Receiver operating characteristic (ROC) analyses evaluated nasal GCIPL thickness (average of superonasal and inferonasal sectors) alone and combined with clinical covariates.

RESULTS: LHON showed significantly thinner GCIPL than ON in the superonasal (adjusted mean difference -12.1 μm) and inferonasal (-12.4 μm) sectors in the acute phase (FDR-adjusted q = 0.02 and 0.01, respectively). The nasal GCIPL difference was evident versus DN-ON and MOG-ON, whereas separation from AQP4-ON was less apparent. Nasal GCIPL thickness alone discriminated LHON from ON with an area under the curve (AUC) of 0.88 (Youden-optimal cut-off 72.5 μm; sensitivity 0.93, specificity 0.82); a multivariable model including age, sex and onset-to-OCT category increased the AUC to 0.94.

CONCLUSION: Acute-phase OCT reveals nasal-predominant GCIPL thinning in LHON. This pattern differentiates LHON from DN-ON and MOG-ON but is less distinct from AQP4-ON. Nasal GCIPL thickness, alone or combined with clinical covariates, may aid differential diagnosis in acute presentations.

PMID:42140845 | DOI:10.1111/ceo.70130