Rapid Administration of High-Dose Intravenous Methylprednisolone Improves Visual Outcomes After Optic Neuritis in Patients With AQP4-IgG-Positive NMOSD

Abstract

Objective: The purpose of this study was to elucidate the rapid impact of high-dose intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) on the eventual visual prognosis in patients with serum anti-aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) who had an attack of optic neuritis (ON). Methods: Data from 32 consecutive NMOSD patients (1 male and 31 female) with at least one ON attack, involving a total of 36 ON-involved eyes, were evaluated. The following variables at ON onset were evaluated: sex, age at the first ON episode, visual acuity at nadir, visual acuity after 1 year, duration from ON onset to treatment for an acute ON attack, cycles of high-dose intravenous methylprednisolone pulse therapy for the ON attack, and cycles of plasmapheresis for the ON attack. Among the 36 ON-involved eyes, 27 eyes were studied using orbital MRI with a short-T1 inversion recovery sequence and gadolinium-enhanced fat-suppressed T1 imaging before starting treatment in the acute phase. Results: In univariate analyses, a shorter duration from ON onset to the initiation of high-dose intravenous methylprednisolone pulse therapy favorably affected the eventual visual prognosis 1 year later (Spearman's rho = 0.50, p = 0.0018). The lesion length on orbital MRI was also correlated with the eventual visual prognosis (rho = 0.68, p < 0.0001). Meanwhile, the days to steroid pulse therapy and lesion length on orbital MRI did not show a significant correlation. These findings suggest that the rapidness of steroid pulse therapy administration affects the eventual visual prognosis independent of the severity of ON. In multivariate analysis, a shorter time from ON onset to the start of acute treatment (p = 0.0004) and a younger age at onset (p = 0.0071) were significantly associated with better visual outcomes. Conclusions: Rapid initiation of high-dose intravenous methylprednisolone pulse therapy is essential to preserve the eventual visual acuity in patients with serum AQP4-IgG-positive NMOSD. Once clinicians suspect acute ON with serum AQP4-IgG, swift administration of steroid pulse therapy before confirming the positivity of serum AQP4-IgG would be beneficial for preserving visual function.

Keywords: neuromyelitis optica spectrum disorders; optic neuritis; steroid pulse therapy; timing; visual prognosis.

Figure 1

Flow diagram of the subgroup classification according to the acute therapies. A total of 32 AQP4-IgG (+) patients with a first episode of optic neuritis (ON; 36 ON-involved eyes) were enrolled. Three patients were untreated, and the remaining 29 patients (32 ON-involved eyes) were initially treated with intravenous methylprednisolone pulse therapy. A total of 19 patients (21 ON-involved eyes) were further treated with adjunctive plasma exchange. AQP4-IgG, anti-aquaporin-4 autoantibodies; IVMP, intravenous methylprednisolone pulse therapy; ON, optic neuritis; PLEX, plasma exchange; VA, visual acuity.

Figure 2

Correlations between treatment rapidity, optic neuritis (ON) severity, and visual prognosis. Scatter plots with visual prognosis and therapeutic rapidity (A), with visual prognosis and ON severity (B), and with ON severity and therapeutic rapidity (C). Note that the horizontal axes in panels (A,C) are log transformed. IVMP, intravenous methylprednisolone; logMAR, logarithmic minimum angle of resolution; ON, optic neuritis; VA, visual acuity.

Figure 3

A conceivable therapeutic strategy for patients suspected of having optic neuritis. AQP4-IgG, anti-aquaporin-4 autoantibodies; CRAO, central retinal artery occlusion; CRVO, central retinal vein occlusion; DDx, differential diagnosis; HIV, human immunodeficiency virus; IVMP, intravenous methylprednisolone; MS, multiple sclerosis; MOG-IgG, anti-myelin oligodendrocyte glycoprotein antibody; ON, optic neuritis; STIR, short T1 inversion recovery; T1WI, T1-weighted imaging.