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
Restricted accessResearch articleFirst published online October, 2020
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
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.
WingerchukDMHogancampWFO’BrienPC, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology1999; 53(5): 1107–1114.
2.
MerleHOlindoSBonnanM, et al. Natural history of the visual impairment of relapsing neuromyelitis optica. Ophthalmology2007; 114(4): 810–815.
3.
LennonVAKryzerTJPittockSJ, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med2005; 202(4): 473–477.
4.
KitleyJWatersPWoodhallM, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: A comparative study. JAMA Neurol2014; 71(3): 276–283.
5.
SatoDKCallegaroDLana-PeixotoMA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology2014; 82: 474–481.
6.
ChenJJFlanaganEPJitprapaikulsanJ, et al. Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: Clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol2018; 195: 8–15.
7.
BennettJLdeSezeJLana-PeixotoM, et al. Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography. Mult Scler2015; 21(6): 678–688.
8.
GelfandJMNolanRSchwartzDM, et al. Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain2012; 135(Pt 6): 1786–1793.
9.
SaidhaSSotirchosESIbrahimMA, et al. Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: A retrospective study. Lancet Neurol2012; 11(11): 963–972.
10.
SotirchosESSaidhaSByraiahG, et al. In vivo identification of morphologic retinal abnormalities in neuromyelitis optica. Neurology2013; 80: 1406–1414.
11.
KaufholdFZimmermannHSchneiderE, et al. Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis. PLoS ONE2013; 8(8): e71145.
12.
GelfandJMCreeBANolanR, et al. Microcystic inner nuclear layer abnormalities and neuromyelitis optica. JAMA Neurol2013; 70(5): 629–633.
13.
HokariMYokosekiAArakawaM, et al. Clinicopathological features in anterior visual pathway in neuromyelitis optica. Ann Neurol2016; 79(4): 605–624.
14.
PacheFZimmermannHMikolajczakJ, et al. MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation2016; 13(1): 282.
15.
Martinez-LapiscinaEHSepulvedaMTorres-TorresR, et al. Usefulness of optical coherence tomography to distinguish optic neuritis associated with AQP4 or MOG in neuromyelitis optica spectrum disorders. Ther Adv Neurol Disord2016; 9: 436–440.
16.
HavlaJKumpfelTSchinnerR, et al. Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration. J Neurol2017; 264(1): 139–151.
17.
Stiebel-KalishHLotanIBrodyJ, et al. Retinal nerve fiber layer may be better preserved in MOG-IgG versus AQP4-IgG optic neuritis: A cohort study. PLoS ONE2017; 12(1): e0170847.
18.
ZhaoGChenQHuangY, et al. Clinical characteristics of myelin oligodendrocyte glycoprotein seropositive optic neuritis: A cohort study in Shanghai, China. J Neurol2018; 265(1): 33–40.
19.
WatersPWoodhallMO’ConnorKC, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm2015; 2(3): e89.
20.
PolmanCHReingoldSCBanwellB, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol2011; 69(2): 292–302.
21.
SycSBWarnerCVHiremathGS, et al. Reproducibility of high-resolution optical coherence tomography in multiple sclerosis. Mult Scler2010; 16(7): 829–839.
22.
TewariePBalkLCostelloF, et al. The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS ONE2012; 7(4): e34823.
23.
LangACarassAHauserM, et al. Retinal layer segmentation of macular OCT images using boundary classification. Biomed Opt Express2013; 4(7): 1133–1152.
24.
Cruz-HerranzABalkLJOberwahrenbrockT, et al. The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology2016; 86: 2303–2309.
25.
BenderRLangeS.Adjusting for multiple testing—When and how?J Clin Epidemiol2001; 54: 343–349.
WeberMSDerfussTMetzI, et al. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord2018; 11.
28.
PannickeTWurmAIandievI, et al. Deletion of aquaporin-4 renders retinal glial cells more susceptible to osmotic stress. J Neurosci Res2010; 88(13): 2877–2888.
29.
ShenWFruttigerMZhuL, et al. Conditional Müllercell ablation causes independent neuronal and vascular pathologies in a novel transgenic model. J Neurosci2012; 32: 15715–15727.
30.
OertelFCKuchlingJZimmermannH, et al. Microstructural visual system changes in AQP4-antibody-seropositive NMOSD. Neurol Neuroimmunol Neuroinflamm2017; 4(3): e334.
31.
GreenAJCreeBA.Distinctive retinal nerve fibre layer and vascular changes in neuromyelitis optica following optic neuritis. J Neurol Neurosurg Psychiatry2009; 80(9): 1002–1005.
32.
LucchinettiCFMandlerRNMcGavernD, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain2002; 125(Pt 7): 1450–1461.
33.
NaismithRTTutlamNTXuJ, et al. Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology2009; 72(12): 1077–1082.
34.
FitzGibbonTNestorovskiZ.Morphological consequences of myelination in the human retina. Exp Eye Res1997; 65(6): 809–819.
35.
OgdenTE.Nerve fiber layer of the primate retina: Thickness and glial content. Vision Res1983; 23(6): 581–587.
36.
SilvermanSMWongWT.Microglia in the retina: Roles in development, maturity, and disease. Annu Rev Vis Sci2018; 4: 45–77.
37.
PittockSJLennonVABakshiN, et al. Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis. JAMA Neurol2014; 71(11): 1433–1436.
38.
SycSBSaidhaSNewsomeSD, et al. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain2012; 135(Pt 2): 521–533.
39.
BeckRWClearyPABacklundJC.The course of visual recovery after optic neuritis. Ophthalmology1994; 101(11): 1771–1778.
