AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

Abstract

Background: Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease. However, the prevalence of AQP4-IgG seropositivity and MOG-IgG seropositivity in isolated ON is unclear, and studies comparing visual outcomes and optical coherence tomography (OCT)-derived structural retinal measures between MS-ON, AQP4-ON, and MOG-ON eyes are limited by small sample sizes. Objectives: (1) To assess the prevalence of AQP4-IgG and MOG-IgG seropositivity among patients presenting with isolated ON; (2) to compare visual outcomes and OCT measures between AQP4-ON, MOG-ON, and MS-ON eyes. Methods: In this systematic review and meta-analysis, a total of 65 eligible studies were identified by PubMed search. Statistical analyses were performed with random effects models. Results: In adults with isolated ON, AQP4-IgG seroprevalence was 4% in non-Asian and 27% in Asian populations, whereas MOG-IgG seroprevalence was 8 and 20%, respectively. In children, AQP4-IgG seroprevalence was 0.4% in non-Asian and 15% in Asian populations, whereas MOG-IgG seroprevalence was 47 and 31%, respectively. AQP4-ON eyes had lower peri-papillary retinal nerve fiber layer (pRNFL; −11.7 μm, 95% CI: −15.2 to −8.3 μm) and macular ganglion cell + inner plexiform layer (GCIPL; −9.0 μm, 95% CI: −12.5 to −5.4 μm) thicknesses compared with MS-ON eyes. Similarly, pRNFL (−11.2 μm, 95% CI: −21.5 to −0.9 μm) and GCIPL (−6.1 μm, 95% CI: −10.8 to −1.3 μm) thicknesses were lower in MOG-ON compared to MS-ON eyes, but did not differ between AQP4-ON and MOG-ON eyes (pRNFL: −1.9 μm, 95% CI: −9.1 to 5.4 μm; GCIPL: −2.6 μm, 95% CI: −8.9 to 3.8 μm). Visual outcomes were worse in AQP4-ON compared to both MOG-ON (mean logMAR difference: 0.60, 95% CI: 0.39 to 0.81) and MS-ON eyes (mean logMAR difference: 0.68, 95% CI: 0.40 to 0.96) but were similar in MOG-ON and MS-ON eyes (mean logMAR difference: 0.04, 95% CI: −0.05 to 0.14). Conclusions: AQP4-IgG- and MOG-IgG-associated disease are important diagnostic considerations in adults presenting with isolated ON, especially in Asian populations. Furthermore, MOG-IgG seroprevalence is especially high in pediatric isolated ON, in both non-Asian and Asian populations. Despite a similar severity of GCIPL and pRNFL thinning in AQP4-ON and MOG-ON, AQP4-ON is associated with markedly worse visual outcomes.

Efficacy of Low-Dose Rituximab on Neuromyelitis Optica-Associated Optic Neuritis

“…In a study of conventional-dose RTX for NMOSD, the reduction rate of ARR ranged from 25% to 100% ( 6 – 8 , 10 , 20 ). We considered that the studies with relatively low effectiveness of RTX have the following commonalities: (1) patients included in most of the studies were diagnosed with NMO or long segment myelitis, which had higher EDSS scores than our ON patients; (2) positive serum AQP4-Ab was not included in the inclusion criteria in many studies, and patients with negative AQP4-Ab may have different pathological mechanisms, such as myelin oligodendrocyte glycoprotein antibody or glial fibrillary acidic protein antibody mediated autoimmunity ( 21 – 23 ); and (3) in some studies, RTX was used in refractory NMO treatment. Patients uncontrolled by other immunosuppression therapies might have higher disease activity.…”

“…Although OCT has been used for the evaluation of ON in NMO or MS in many studies, longitudinal observation studies have been rare. It is reported that NMO-ON eyes have lower peri-papillary retinal nerve fiber layer and macular ganglion cell + inner plexiform layer thicknesses, as well as a “flater” disc when compared with MS-ON eyes ( 21 , 37 ). Moreover, while MS-ON mostly affected the small-diameter neurons in the temporal quadrant of the optic disc, NMO-ON more affected the nerve fibers above and below the optic disc ( 38 , 39 ), consistent with the results in this study.…”

Optical coherence tomography angiography helps distinguish multiple sclerosis from AQP4‐IgG‐seropositive neuromyelitis optica spectrum disorder

“…This result was consistent with a recent meta‐analysis study. (Filippatou et al., 2020) Patients with NMOSD had significantly smaller whole VD and PD areas than those with MS. A recent study showed that NMOSD + ON eyes were associated with worse visual outcomes than MS + ON eyes, even with similar severity of their macular GC‐IPL thinning. (Sotirchos et al., 2020) Our results confirm this finding.…”

“…The most common retinal abnormality during OCT assessments of the MS and NMOSD groups is a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell‐inner plexiform layer (GC‐IPL). (Bennett et al., 2015; Fernandes et al., 2013; Filippatou et al., 2020; Lange et al., 2013; Merle et al., 2008).…”

Practical recognition tools of immunoglobulin G serum antibodies against the myelin oligodendrocyte glycoprotein‐positive optic neuritis and its clinical implications

“…A recent meta‐analysis of the prevalence of AQP4‐IgG and MOG‐IgG ON reports a prevalence of AQP4‐IgG of 27% in the Asian population and 4% in non‐Asian adult patients with isolated ON, whereas MOG‐IgG seroprevalence was 20% in Asians and 8% in non‐Asians 55 …”