Severe structural and functional visual system damage leads to profound loss of vision-related quality of life in patients with neuromyelitis optica spectrum disorders

doi:10.1016/j.msard.2016.11.008

Multiple Sclerosis and Related Disorders

Volume 11, January 2017, Pages 45-50

https://doi.org/10.1016/j.msard.2016.11.008 Get rights and content

Highlights

•
Vision-related quality of life in NMOSD is more severely impaired than in MS.
•
This is mostly caused by more devastating ON episodes in both eyes in NMOSD.
•
Structural damage is associated with lower vision-related quality of life in NMOSD.

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by devastating optic neuritis attacks causing more structural damage and visual impairment than in multiple sclerosis (MS). The objective of this study was to compare vision-related quality of life in NMOSD and MS patients and correlate it to structural retinal damage and visual function.

Methods

Thirty-one NMOSD and 31 matched MS patients were included. Vision-related quality of life was assessed with the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). All patients underwent retinal optical coherence tomography and visual acuity and contrast sensitivity measurements.

Results

Vision-related quality of life was reduced in NMOSD compared to MS patients. This difference was driven by a higher incidence of bilateral and more severe optic neuritis in the NMOSD group. Retinal thinning and visual impairment were significantly greater in the NMOSD cohort. Lower vision-related quality of life was associated with more retinal damage and reduced visual function as assessed by visual acuity and contrast sensitivity.

Conclusion

NMOSD-related bilateral ON-attacks cause severe structural damage and visual impairment that lead to severe loss of vision-related quality of life. The NEI-VFQ is a helpful tool to monitor vision-related quality of life in NMOSD patients.

Introduction

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune CNS conditions primarily presenting with longitudinally extensive transverse myelitis (LETM) and optic neuritis (ON), and to a lesser extent with area postrema, acute brainstem, diencephalic and cerebral syndromes (Wingerchuk et al., 2015). Initially thought to be a variant of multiple sclerosis (MS), the detection of serum autoantibodies targeting the water channel aquaporin-4 (AQP4-IgG) in up to 80% of cases established NMOSD as an own disease entity distinct from MS (Jarius et al., 2014, Zekeridou and Lennon, 2015). Recently, serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG) were found in a subset of AQP4-IgG negative NMOSD patients and in patients with recurrent optic neuritis, further extending the range of NMOSD (Jarius et al., 2016a, Jarius et al., 2016b, Jarius et al., 2016c, Pache et al., 2016).

Although pathogenically distinct, NMOSD and MS show a considerable overlap in clinical and paraclinical presentation, including involvement of the afferent visual system by acute ON (Wingerchuk et al., 2015). ON occurs in approximately 80% of NMOSD patients, in approximately 20% of the cases bilaterally, often involving the optic chiasm (Kleiter et al., 2016, Ramanathan et al., 2016). In contrast, ON in MS occurs in up to 70% of patients, is mainly unilateral and chiasm involving optic nerve lesions are rare (Costello, 2016, Toosy et al., 2014). In most cases, ON-associated damage is more severe in NMOSD patients than in MS patients, leading to more severe residual visual loss and structural damage (Bennett et al., 2015).

Visual function has great relevance for quality of life, affecting everyday tasks and vision-dependent activities like driving or social and role functioning. Consequently, in a previous study, MS patients rated vision as the second most important bodily function following lower limb function (Heesen et al., 2008). Further impact of vision-related quality of life has been previously investigated in MS patients and its association with retinal axonal and neuronal damage and reduced visual function shown (Mowry et al., 2009, Schinzel et al., 2014, Walter et al., 2012).

However, although NMOSD patients suffer from greater visual function loss than MS patients, vision-related quality of life has hitherto not been investigated in this condition. Thus, the goals of our study were to investigate vision-related quality of life in NMOSD compared to MS patients and to relate vision-related quality of life to structural damage and dysfunction of the visual system in patients with NMOSD.

Section snippets

Study participants and controls

Data for this cross-sectional study was derived from two on-going longitudinal observational studies following patients with NMOSD and MS. Thirty-six patients from the outpatient clinics of NeuroCure Clinical Research Center and from the Department of Neurology, Charité – Universitätsmedizin Berlin were screened for eligibility. Inclusion criteria were NMOSD according to the current diagnostic criteria (Wingerchuk et al., 2015) or MOG-IgG associated recurrent ON and age ≥18 and ≤70 years.

Results

Vision-related quality of life represented by the NEI-VFQ composite score was significantly lower in NMOSD patients (77.4±19.2) compared to MS patients (86.6±6.7, p=0.01) (Fig. 1). Patients with unilateral ON regularly displayed high vision-related quality of life, whereas patients with ON episodes in both eyes reported the strongest loss: A multivariate linear regression model showed that the severity of vision-related quality of life loss was driven by a higher incidence of bilateral in

Discussion

In this cross-sectional study we show that vision-related quality of life is more severely impaired in NMOSD than in MS patients. Key findings are, a) NEI-VFQ score was significantly reduced in NMOSD compared to MS patients; b) This effect is mostly attributable to the higher occurrence and stronger severity of ON episodes in both eyes in NMOSD patients whereas patients with unilateral ON showed only little loss of vision-related quality of life despite often-times severe structural and

Funding

This work was supported by Bundesministerium für Bildung und Forschung (Competence Network Multiple Sclerosis and N2-ADVISIMS), Deutsche Forschungsgemeinschaft (DFG Exc 257 to FrP), a limited research grant from Novartis Pharma, and the BIH-Charité Medical Student Research Program at Charité-Universitätsmedizin Berlin (to FCO).

Conflict of interest

The authors declare that they have no conflict of interest.

Declaration of interest

F. Schmidt reports personal fees from Genzyme, outside the submitted work; H. Zimmermann reports personal fees from Teva, personal fees from Bayer, outside the submitted work; J. Mikolajczak reports personal fees from TEVA, personal fees from Biogen, outside the submitted work; . F. Oertel has nothing to disclose. F. Pache reports personal fees from Genzyme, outside the submitted work; . M. Weinhold reports personal fees from TEVA, outside the submitted work; J. Schinzel has nothing to

Acknowledgements

We thank Ivonne Hinz and Brian Dommisch for excellent technical assistance.

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Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), autoimmune inflammatory diseases of the central nervous system, affect the optic nerve and brain. A lumbar puncture to obtain biomarkers is highly invasive. Serum biomarkers and optical coherence tomography angiography (OCTA) are more accessible and less expensive than magnetic resonance imaging and provide reliable, reproducible measures of neuroaxonal damage. This study investigated the association between serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and OCTA metrics. Serum sNfL and sGFAP levels, OCTA values, and clinical characteristics were compared among 91 patients with NMOSD, 81 patients with MS, and 34 healthy controls (HCs) at baseline and 1-year follow-up.
sNfL and sGFAP levels were higher while the sGFAP/sNfL quotients were significantly lower in NMOSD and MS patients than those in HCs. At baseline, the average thicknesses of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGC-IPL) were significantly smaller in NMOSD and MS patients than those in HCs (pRNFL: MS 92.0 [80.2; 101] μm, NMOSD 80.0 [59.0; 95.8] μm, vs HC 99.0 [92.0; 104] μm, p < 0.001; mGC-IPL: MS 74.5 [64.2; 81.0] μm, NMOSD 68.0 [56.0; 81.0] μm, vs HC 83.5 [78.0; 88.0] μm, p < 0.001). The vessel density (VD) and perfusion density (PD) were increased in MS patients without optic neuritis compared to HCs (VD: MS 16.7 [15.6; 17.9] HC 15.3 [13.4; 16.9], p = 0.008; PD: MS 0.41 [0.38; 0.43], HC 0.37 [0.32; 0.41], p = 0.017). In NMOSD patients without optic neuritis, sNfL was significantly associated with PD at baseline (r = 0.329, q = 0.041). The baseline and follow-up values of the sNfL level and average pRNFL and mGC-IPL thicknesses in MS patients showed significant differences. NMOSD patients showed significant differences between baseline and follow-up sNfL and sGFAP levels but not OCTA metrics.
Changes in retinal microvasculature might occur earlier than those in retinal structure and may therefore serve as a promising diagnostic marker for early NMOSD. The combination of serum markers and OCTA metrics could be used to evaluate and differentiate between MS and NMOSD.
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Optic neuritis (ON) is an immune-mediated optic neuropathy associated with multiple immune-mediated neurological conditions. Our aim was to characterize the clinical and diagnostic features of first or initial episodes of ON associated with multiple sclerosis (MS)-associated (typical) and antibody-related (atypical) ON.
Retrospective, single institution, medical record review. We analyzed demographic, clinical, laboratory, and radiographic findings of 139 patients who presented with first episodes of MS-associated ON (MS-ON), aquaporin 4 antibody–associated ON (AQP4-ON), and myelin oligodendrocyte glycoprotein antibody–associated ON (MOG-ON) between January 2015 and October 2019 without preceding diagnosis. Simple hypothesis testing assessed differences between groups were performed.
Of 139 patients (109 [79 %] women; 29 [21 %] men; mean age 47 [SD, 14] years), 106 had MS-ON, 25 had AQP4-ON, and 8 had MOG-ON. Patients with MOG-ON had the highest recurrence rate (88 %) relative to MS-ON (28 %) and AQP4-ON (56 %) patients (P < .001). Patients with AQP4-ON had the highest mean visual functional system scores (4.3 [SD, 1.8]) relative to MS-ON (2.0 [SD, 1.9]) and MOG-ON patients (2.8 [SD, 2.0]) (P < .001).
Patients presenting with initial episodes of ON exhibit a range radiographic and laboratory feature depending on the underlying associated disease. Understanding the variable characteristics of typical (MS-associated) and atypical (antibody-associated) ON may help physicians accurately diagnose and effectively treat ON.
Comparisons of clinical phenotype, radiological and laboratory features, and therapy of neuromyelitis optica spectrum disorder by regions: update and challenges
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Citation Excerpt :
In a nationwide multi-center retrospective study from South Korea, the proportion of wheelchair-bound patients was 15.6% [55], while it was 35.1% in NMOSD patients with LETM in Mayo Clinic and the median time to reach the nadir was by 8.5 days (range: 2-63 days)[70]. Severe structural and functional impairment of the visual system in NMOSD-related ON (NMOSD-ON) patients resulted in serious loss of vision-related quality of life evaluated by the 39-item National Eye Institute Visual Function Questionnaire [71]. The factors impacting disability profile are summarized as follows.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) associated with autoantibody (ab) to aquaporin-4 (AQP4). There is obvious variation between regions and countries in the epidemiology, clinical features and management in NMOSD. Based on published population-based observation and cohort studies, the different clinical pattern of NMOSD has been seen in several geographical regions and some of these patients with NMOSD-like features do not fully meet the current diagnostic criteria, which is needed to consider the value of recently revised diagnostic criteria. At present, all treatments applied in NMOSD have made great progress, however, these treatments failed in AQP4 ab negative and refractory patients. Therefore, it is necessary to turn into an innovative idea and to open a new era of NMOSD treatment to develop novel and diverse targets and effective therapeutic drugs in NMOSD and to conduct the trails in large clinical samples and case-control studies to confirm their therapeutic effects on NMOSD in the future, which still remain a challenge.
Reduced quality of life in a pediatric-onset Neuromyelitis optica spectrum disorders cohort
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Neuromyelitis optica spectrum disorders (NMOSD) is a severe condition associated with high disability and low quality of life (QoL) in adults. Since this evaluation had been rarely perfomed in children, this study aimed to describe QoL in pediatric-onset NMOSD with positive aquaporin4 antibody (AQP4-IgG) patients.
This was a cross-section evaluation of patients and parents’ proxy QoL from individuals enrolled in a longitudinal cohort of AQP4-IgG positive NMOSD with onset ≤ 18 years of age.
Eighteen patients were included, sixteen girls. The mean (SD) age at disease onset was 11.5 (3.6) years. Eleven of patients experienced disability during a mean (SD) of 8.3 (5.3) years of follow-up. NMOSD had impact in QoL in 10 patients, being associated with higher EDSS and poor academic performance at last follow-up. Results from the PedsQL inventory for 13 patients and 10 parents disclosed low QoL specially in emotional functioning.
This study indicates impaired quality of life, high disability and high impact of the disease in daily life of adolescents and young adults with pediatric onset NMOSD.
Neuromyelitis optica spectrum disorders
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The disease concept of Neuromyelitis Optica Spectrum Disorders(NMOSD) has undergone a significant change over the last two decades including the detection of Myelin Oligodendrocyte Glycoprotein(MOG) antibody in patients who are seronegative for aquaporin-4 antibody. Aquaporin-4 antibody positive NMOSD is now regarded as an immune astrocytopathy. Conversely, MOG antibody associated disease is known to target myelin rather than astrocytes, leading to an NMOSD syndrome with distinct clinical and radiological features. Incorporation of clinical features like area postrema syndrome, brainstem syndrome, diencephalic syndrome and cortical manifestations as core clinical characteristics into the revised diagnostic criteria has widened the clinical spectrum of NMOSD. With the development of these criteria, it is possible to make the diagnosis at an earlier stage so that effective immunosuppression can be instituted promptly for a better long-term prognosis. Newer therapeutic agents have been introduced for aquaporin-4 seropositive NMOSD disease; however, challenges remain in treating seronegative disease because of limited treatment options.
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View all citing articles on Scopus

¹: Equally contributing first authors in alphabetical order.

View full text

Severe structural and functional visual system damage leads to profound loss of vision-related quality of life in patients with neuromyelitis optica spectrum disorders

Highlights

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study participants and controls

Results

Discussion

Funding

Conflict of interest

Declaration of interest

Acknowledgements

Lancet Neurol.

Lancet Neurol.

Lancet Neurol.

Ophthalmology

Neuromyelitis optica and multiple sclerosis: seeing differences through optical coherence tomography

Mult. Scler. J.

Impairment of contrast visual acuity as a functional correlate of retinal nerve fibre layer thinning and total macular volume reduction in multiple sclerosis

Br. J. Ophthalmol.

Dynamic formation of macular microcysts independent of vitreous traction changes

Neurology

Vision disturbances in multiple sclerosis

Semin. Neurol.

Observations on the evolving fields of neuroimmunology and neuroinflammation

Neurol. Neuroimmunol. Neuroinflamm.

Der National Eye Institute Visual Function Questionnaire (NEI-VFQ) Erste Ergebnisse zur psychometrischen Ueberpruefung eines Verfahrens zur Erfassung der Lebensqualitaet bei Sehbeeintraechtigten

Z. Für Med. Psychol.

Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable

Mult. Scler. J.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin

J. Neuroinflamm.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment, and long-term outcome

J. Neuroinflamm.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: MOG-IgG-associated brainstem encephalitis

J. Neuroinflamm.

Neuromyelitis optica: clinical features, immunopathogenesis and treatment

Clin. Exp. Immunol.