Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning

Abstract

Background: Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited. Objective: To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON). Methods: In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed. Results: AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (−22.3 ± 3.9 letters; p < 0.001) and MS-ON eyes (−21.7 ± 4.0 letters; p < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (−9.1 ± 2.0 µm; p < 0.001) and MOG-ON (−7.6 ± 2.2 µm; p = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (−16.5 ± 1.5 letters per 10 µm decrease; p < 0.001) and MS-ON eyes (−8.5 ± 2.3 letters per 10 µm decrease; p < 0.001), but not in MOG-ON eyes (−5.2 ± 3.8 letters per 10 µm decrease; p = 0.17), and these relationships differed between the AQP4-ON and other ON groups ( p < 0.01 for interaction). Conclusion: AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.

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

“…Interestingly, and in line with our prior observations ( 8 ), we found that, despite a similar severity of pRNFL and GCIPL thinning in AQP4-ON and MOG-ON, visual outcomes clearly diverged between these two entities, with MOG-ON eyes having relatively preserved visual acuity, whereas AQP4-ON eyes experienced markedly worse visual outcomes compared to both MOG-ON and MS-ON. The biological underpinnings of this observation remain unclear.…”

“…Of these, 202 articles were selected and assessed for eligibility at the full-text level. After careful evaluation, 35 studies were included that met the inclusion criteria ( 8 , 29 , 30 , 33 , 36 , 39 , 41 , 45 , 47 , 48 , 51 – 54 , 57 , 59 , 63 , 65 , 66 , 68 , 69 , 71 , 72 , 74 – 85 ). The detailed flow chart is presented in Supplementary Figure 9 .…”

“…Early recognition of the underlying etiology of ON has important therapeutic implications, given that treatment approaches vary between these conditions, and therapies that are efficacious in MS may exacerbate or be ineffective in AQP4-IgG- or MOG-IgG-associated disease ( 4 , 5 ). Furthermore, visual prognosis appears to differ between these conditions, with AQP4-IgG-associated ON (AQP4-ON) typically characterized by worse visual outcomes in comparison to MS-associated ON (MS-ON) and MOG-IgG-associated ON (MOG-ON) ( 6 – 8 ). In patients presenting with classic neuromyelitis optica (NMO) or acute disseminated encephalomyelitis (ADEM)-like phenotypes, clinical suspicion for AQP4-IgG- or MOG-IgG-associated disease is high, but diagnosis may be challenging and delayed in limited forms, such as isolated ON.…”

“…Optical coherence tomography (OCT) is an imaging technique that utilizes near-infrared light to obtain high-resolution images of the retina in vivo and enables the quantitative evaluation of individual retinal layers, allowing assessment of the integrity of the RGC axons [peri-papillary RNFL thickness (pRNFL)] and RGC cell bodies [composite thickness of the macular ganglion cell + inner plexiform layer (GCIPL)] ( 11 , 12 ). OCT studies have generally demonstrated increased severity of pRNFL and GCIPL thinning following AQP4-ON or MOG-ON, as compared to MS-ON ( 8 ). However, given the rarity of AQP4-IgG- and MOG-IgG-associated disease, OCT studies have examined relatively small numbers of participants, not permitting an in-depth characterization and comparison of the retinal neuro-axonal injury that occurs in these conditions.…”

Recurrent visual loss in a 64-year-old man

“…Optic neuritis is commonly associated with multiple sclerosis (MS); however, bilateral optic neuritis is unusual in adult-onset MS, and inflammatory relapses are uncommon in people with MS aged over 60 years. By contrast, NMO does manifest with bilateral optic neuritis, and with inflammatory relapses in older people; however, NMO-related optic neuritis is usually severe, with marked visual impairment and incomplete recovery 1. Anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a strong possibility as it frequently presents with recurrent optic neuritis and good recovery after attacks 2.…”