Slow recruitment and an unexpectedly high proportion of AQP4-IgG-positive optic neuritis on masked feasibility review limited feasibility. No interim efficacy analysis was performed.

This pilot randomized, double-blind, placebo-controlled trial evaluated whether short-course adjunctive gypenosides, added to standard corticosteroid treatment, may preserve retinal structural outcomes in adults with acute optic neuritis.

This was a single-center, randomized, double-blind, placebo-controlled pilot trial in adults with a first episode of acute optic neuritis within 28 days of symptom onset. Participants received standard corticosteroid treatment and were randomized in a 1:1 ratio to adjunctive oral gypenosides 180 mg/day for 10 days or matching placebo.

The trial was designed as a pilot study to estimate structural treatment effects and variability for future neuroprotection trials in optic neuritis. The primary structural outcome was peripapillary retinal nerve fiber layer thickness in the prespecified index eye at Month 6 measured by spectral-domain OCT. Secondary outcomes included total macular volume, best-corrected visual acuity, visual evoked potentials, visual-field measures, and safety outcomes.

Macular ganglion cell-inner plexiform layer thickness was analyzed as an exploratory segmentation-derived macular structural endpoint.

Baseline aquaporin 4 immunoglobulin G serostatus was assessed. Myelin oligodendrocyte glycoprotein immunoglobulin G testing was not included in the original study design.

Inclusion criteria

1. Male and female Chinese patients aged ≥18 to ≤60 years
2. Patients with a first episode of optic neuritis in the eye of interest
3. First symptoms of optic neuritis ≤28 days prior to the first administration of investigational product
4. Best corrected visual acuity in the eye of interest ≤0.8

Exclusion criteria

1. Pre-existing multiple sclerosis MS or NMO
2. Refractive media opacity
3. Hyperopia >5 diopters, myopia <-5 diopters, or astigmatism >3 diopters
4. Active tuberculosis, hepatitis, renal insufficiency, uncontrolled hypertension, diabetes mellitus, infection with HIV or syphilis, or any other conditions potentially interfering treatment trial
5. Other autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, etc)
6. Existing other retina or optic nerve diseases
7. Pregnant or females who plan to be pregnant during study

Participants, treating clinicians, outcome assessors, and statisticians were masked to treatment assignment. Gypenosides and placebo capsules were prepared and packaged to maintain identical appearance and labeling.