Study Shows Risk Factors for Severe Vision Loss in Optic Neuritis

Patients with certain antibodies, those of older age at onset, and men are more likely to have worse outcomes.

In patients with optic neuritis (ON), severe vision loss is more prevalent in those with a seropositivity for aquaporin-4 immunoglobulin (AQP4-IgG), as well as several additional risk factors, according to a study published in the American Journal of Ophthalmology. The patients who experienced severe vision loss were also most commonly men older than 45 years with a nadir vision of 20/200 or worse, and had experienced a high number of recurrences, the report shows. 

Investigators looked at 3 groups of patients with ON divided by the presence of glial auto-antibodies. The groups included those with AQP4-IgG seropositivity, patients with ON who were seronegative, and those with myelin oligodendrocyte glycoprotein immunoglobulin (MOG-IgG)

“These findings may be of interest to further elucidate the etiology of the diseases and to plan immunomodulatory therapy,” researchers report.

The longitudinal observational cohort study looked at 529 patients with ON based on subgroups of autoantibody status and etiology of disease including: 291 who were AQP4-IgG seropositive; 112 who were MOG-IgG seropositive; and 126 who were double-seronegative with 1022 ON episodes (AQP4-IgG seropositive, n=550; MOG-IgG seropositive, n=254; double-seronegative, n=218). Researchers measured serum concentrations of glial autoantibodies consecutively, and longitudinally examined cases with three months of follow-up, at minimum. Multiple sclerosis and double seronegative results were excluded.

They found that prevalence of severe vision loss (best-corrected visual acuity (BCVA) ≤20/200 at the end of follow-up) was higher (P <.001) in the AQP4-IgG group (236/550;42.9%) than the seronegative group (68/218;31.2%) and the MOG-IgG group (15/254;5.9%). In contrast, the prevalence of good vision recovery (BCVA≥20/40) was higher (P <.001) in the MOG-IgG group (229/254;90.2%) than in the seronegative group (111/218:50.9%) and the AQP4-IgG group (236/550;42.9%). 

“In multivariable logistic analysis, higher prevalence of severe vision loss was associated with AQP4-IgG seropositivity (OR: 1.66; 95% CI: 1.14,2.43, P =.008), male sex (OR:1.97; 95% CI: 1.33, 2.93, P <.001), age at ON onset >45 years (OR: 1.93; 95% CI: 1.35, 2.77, P <.001), nadir vision ≤20/200 (OR: 14.11; 95% CI: 6.54, 36.93, P <.001) and higher number of recurrences (OR: 1.35; 95% CI: 1.14, 1.61, P =.001),” according to the study. “Higher prevalence of good vision outcome was associated with MOG-IgG seropositivity (OR: 8.13; 95% CI: 4.82, 14.2, P <.001), age at ON onset <18 years (OR: 1.78; 95% CI: 1.18, 2.71, P =.006), nadir visual acuity ≥20/40 (OR: 4.03; 95% CI: 1.45, 14.37, P =.015) and lower number of recurrences (OR: 0.60; 95% CI: 0.50, 0.72, P <.001).”

The study’s limitations include its recruitment of its study population, which was at third-referral hospital and not population-based. “The composition of the study sample including the proportions of the three antibody-defined subgroups may therefore not be representative. It holds true in particular since the study site is the largest neuroophthalmological department in China, so that patients with a severe course of the disease may preferably have been referred to the study site,” according to researchers. 

Another limitation: It’s recommended that patients begin immunosuppressive treatment when diagnosed with a NMOSD, but “in our study population, only 1/3 of the patients with an AQP4-ON received an immunosuppressive treatment directly after the first attack.” Additional limitations: Treatment wasn’t standardized, mean follow-up periods differed between subgroups in the study’s total population, which might have altered data, and they didn’t assess low contrast visual acuity, which has been found to be helpful for ON detection. Finally, the study was limited only to Chinese patients, so results might not be extrapolated to other ethnic groups (or should be with caution, they say).

But they do point out the study has strengths, including: “the relatively large study sample size, in particular for the AQP4-IgG seropositive group and MOG- IgG seropositive group, the relatively long follow-up time, and the assessment of risk factors for vision loss in dependence of the glial antibody status, including the parameters of age at ON onset and sex.”


Yang M, Wu Y, Song H, Lai M, Li H, et al. Vision prognosis and associated factors of optic neuritis in dependence of glial autoimmune antibodies. Am J Ophthalmol. 2022:S0002-9394(22)00016-2. doi:10.1016/j.ajo.2022.01.015