Optic Nerve Lesion Length at the Acute Phase of Optic Neuritis Is Predictive of Retinal Neuronal Loss

Abstract

Background and objectives: Acute optic neuritis (ON) is a classical presenting symptom of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and anti-MOG-associated disorders. The resulting visual impairment is variable and can be severe. Clinicians are in need of predictive biomarkers to optimize the management of acute ON. In this longitudinal study (IRMANO, NCT03651662), we evaluated the ability of optic nerve lesion length measured on MRI at the acute phase of ON to predict retinal neuro-axonal loss and visual impairment at a chronic stage.

Methods: We conducted a longitudinal study (IRMANO, NCT03651662) of patients who presented a clinical episode of ON (≤8 weeks). All patients underwent a retinal optical coherence tomography (OCT) and a brain/optic nerve MRI, including 3D double-inversion recovery (DIR) sequence at the acute phase of ON and 12 months later. Primary outcomes were optic nerve DIR hypersignal lesion length, macular ganglion cell-inner plexiform layer (GCIPL) volume measured on OCT, and low-contrast monocular visual acuity (LCMVA).

Results: The study group included 51 patients (33 women, mean age of 32.4 years ± 7.9). We recruited patients with a clinically isolated syndrome (n = 20), a relapsing-remitting MS (n = 23), an isolated ON (n = 6), and a first clinical episode of NMOSD (n = 2). Optic nerve DIR hypersignal was observed in all but 1 symptomatic optic nerves. At inclusion, the mean optic nerve lesion length (in mm) was 12.35 ± 5.98. The mean GCIPL volume (in mm³) significantly decreased between inclusion (1.90 ± 0.18) and M₁₂ (1.67 ± 0.21; p < 0.0001). Optic nerve lesion length at inclusion was significantly associated with GCIPL thinning (estimate ± SD; -0.012 ± 0.004; p = 0.0016) and LCMVA at M₁₂ (0.016 ± 0.003; p < 0.001). Optic nerve lesion length significantly increased at M₁₂ (15.76 ± 8.70; p = 0.0007). The increase in optic nerve lesion length was significantly associated with the GCIPL thinning between inclusion and M₁₂ (-0.012 ± 0.003; p = 0.0011).

Discussion: At the acute phase of ON, optic nerve lesion length is an imaging biomarker predictive of retinal neuro-axonal loss and chronic visual impairment, which can help to stratify future therapeutic strategies in acute ON.

Classification of evidence: This study provides Class I evidence that optic nerve lesion length measured on MRI during the acute phase of a first episode of ON is associated with long-term retinal neuro-axonal loss and visual impairment.

Figure 1. Optic Nerve MRI Findings in a Patient With CIS

(A) Patient with CIS presenting a left clinical episode of acute optic neuritis. A symptomatic optic nerve lesion (arrowhead) and a right asymptomatic optic nerve lesion (white arrow) were detected on 3D-Double-Inversion Recovery MR sequence. MRI reconstruction of left and right optic nerves showing symptomatic (arrowheads) and asymptomatic (white arrows) lesions in sagittal optic nerve planes (B) and coronal planes (C). CIS = clinically isolated syndrome

Figure 2. Flowchart of IRMANO Cohort and the Corresponding Eyes' Subgroups According to the Occurrence of an Acute ON, ON History, and Optic Nerve MRI Data

The authors recruited 51 patients presenting an acute episode of ON. One patient with acute ON did not present any optic nerve lesion on MRI. One patient with RRMS presented a bilateral acute ON. All eyes with a history of ON presented an optic nerve lesion. Some patients with CIS and RRMS presented an asymptomatic optic nerve lesion on the fellow eye. CIS = clinically isolated syndrome; DIR = double-inversion recovery; NMOSD = neuromyelitis optica spectrum disorders; ON = optic neuritis; RRMS = relapsing-remitting multiple sclerosis.

Figure 3. Optic Nerve MRI of a CIS Patient With Detection of a New Asymptomatic Optic Nerve Lesion During the Follow-up

Optic nerve MRI of a patient with CIS presenting a left acute optic neuritis. At inclusion, no lesion was detected on the right optic nerve. At M₁₂, a new right asymptomatic retrobulbar optic nerve DIR hypersignal was detected (white arrows). CIS = clinically isolated syndrome.