Multiple Sclerosis Resource Centre

Welcome to the Multiple Sclerosis Resource Centre. This website is intended for international healthcare professionals with an interest in Multiple Sclerosis. By clicking the link below you are declaring and confirming that you are a healthcare professional

You are here

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

Multiple Sclerosis and Related Disorders, Volume 11, January 2017, Pages 45 - 50



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.


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.


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.


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.


  • 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.

Keywords: Neuromyelitis optica spectrum disorder, Vision related quality of life, Optic neuritis, Retinal nerve fibre layer, Visual function, Optical coherence tomography.

1. 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 and 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, and 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 and 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 and 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, and 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.

2. Patients and methods

2.1. 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. Exclusion criteria were any eye or retina diseases other than ON, acute ON or disease relapse within three months prior to examination or refractive errors greater than±6dpt. Five screened patients were not included in the study: two due to cataract, one due to diabetic retinopathy, one due to retinal detachment and one due to age over 70 years. From the 31 included patients, 20 had an AQP4-IgG positive NMOSD diagnosis according to the revised diagnostic criteria (Wingerchuk et al., 2015). Seven patients fulfilled the criteria for AQP4-IgG negative NMOSD, among them three patients with positive MOG-IgG serology and 4 patients both negative for AQP4-IgG and MOG-IgG. Another four patients tested positive for serum MOG-IgG and had at least one ON episode, but did not formally fulfil the 2015 NMOSD criteria (Wingerchuk et al., 2015). Clinically, 16 out of 31 patients showed a typical NMOSD phenotype (ON + LETM). Twenty-three patients had at least one event of ON and 13 patients had ON in both eyes (either consecutive or simultaneously bilateral). Eight patients had LETM only. One patient presented with LETM and area postrema syndrome. Twenty-nine patients were Caucasian, one patient Asian and one African.

Thirty-one age-matched (p=0.97) and sex-matched (p=0.51) MS patients from the NeuroCure Clinical Research Center's database were compared with the data of the NMOSD patients (Schinzel et al., 2014). Twenty-four MS patients with relapsing remitting (RR), 3 patients with secondary progressive (SP) MS and 3 patients with clinically isolated syndrome (CIS) according to standard clinical and neuroimaging criteria were randomly selected (Polman et al., 2011). The patients matched 1:1 for an event of ON (23 events of ON, eight times no event of ON). Disease duration was longer in MS patients, however the difference was not significant.

Demographic and clinical features are summarized in Table 1.

Table 1

Demographic and clinical characteristics of NMOSD and MS patients.


Subjects (n) 31 31
Age, years, mean±SD (Min-Max) 44.9±13.1 (21–67) 44.8±12.8 (19–64) MWU: p=0.97
Sex (f/m) 27/4 24/7 Chi2: p=0.51
Disease duration, months mean±SD (Min-Max) 84.6±60.2 (4–268) 120.6±76.9 (17–281) MWU: p=0.07
EDSS median (range) 3.5 (0.0–6.0) 2.0 (0.0–7.0) MWU: p=0.03
ON status (no ON/unilateral ON/ ON in both eyes) 8/10/13 4/16/11 Chi2: p=0.24
Prevalence of macular microcysts (eyes) 4 1 Chi2: p=0.36
AQP4-IgG + 20 not tested
MOG-IgG + 7 not tested

Abbreviations: AQP4= aquaporin-4, Chi2=chi-square test, EDSS=expanded disability status scale, f=female, MOG=myelin oligodendrocyte glycoprotein, m=male, min=minimum, max=maximum, MWU=Mann-Whitney-U-test, n=number, ON=optic neuritis, SD=standard deviation

2.2. Ethics statement

The study was approved by the Charité ethics committee and was conducted in accordance to the Declaration of Helsinki in its currently applicable version and applicable German laws. All participants gave written informed consent to participate in the study.

The validated German translation of the 39-item version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) was answered by all participants (Franke et al., 1998). The NEI-VFQ is an established scoring method that is widely used in ophthalmologic research and clinical trials (Mangione et al., 1960). The NEI-VFQ consists of 12 individual subscales measuring general health, general vision, ocular pain, near activities, distance activities, driving, colour vision, peripheral vision and vision specific social functioning, mental health, role difficulties and dependency. Scores range from 0 to 100 with lower scores indicating worse vision related quality of life. Averaging all subscale scores excluding the general health item generates a final composite score. The questionnaire was answered self-administered whenever possible. If patients were not able to read the questionnaire due to blindness, it was filled in by interview.

2.4. Optical coherence tomography

Each participant underwent retinal examination with optical coherence tomography (Spectralis SD-OCT, Heidelberg Engineering, Heidelberg, Germany) with automatic real time (ART) function for image averaging. Peripapillary retinal nerve fibre layer (pRNFL) was evaluated using a 3.4 mm ring scan around the optic nerve head (12°, 1536 A-scans 16≤ART≤100). The combined ganglion cell and inner plexiform layer thickness (GCIP) and inner nuclear layer (INL) thickness (only available for NMOSD patients) were derived from a 6 mm diameter cylinder around the fovea from a macular volume scan (25°×30°, 61 vertical B-scans, 768 A-scans per B-scan, ART=15). Retinal layers were segmented automatically by the device's software (Eye Explorer with viewing module and reviewed for scan quality and segmentation errors by an experienced grader. Segmentation errors were corrected whenever necessary prior to analysis.

2.5. Visual function

Visual function was tested monocularly under best corrected or habitually corrected conditions with the Functional Vision Analyzer Optec 6500 P system (Stereo Optical Co., Chicago, Illinois) with a simulated distance of 20 ft. High-contrast visual acuity was tested using the device's Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Contrast sensitivity was tested using the device's Functional Acuity Contrast Test (FACT) under photopic (85 cd/m2) conditions without glare. Contrast sensitivity was calculated as the area under the curve (AUC) as previously described (Bock et al., 2012).

2.6. Data analysis

Statistical analyses were performed with R version 3.3.0 using the packages geepack and ggplot2.(R Development Core Team, n.d.) Differences in demographics and clinical data between the cohorts were tested with Pearson's Chi2 test for sex and Mann-Whitney U test for age, disease duration and EDSS). Group comparisons of NEI-VFQ composite score between the NMOSD and MS cohorts were performed with linear regression models for simple group analysis and multivariate linear regression models with NEI-VFQ items set as dependent variable, accounting for influences of diagnosis (NMOSD or MS), ON status (no ON, unilateral ON, bilateral ON), and an interaction effect of diagnosis and ON status. The results of the twelve NEI-VFQ subscores were only investigated descriptively to avoid multiple testing errors in this study with low sample size. NEI-VFQ items of NMOSD patients were also compared to published control data using t-tests (Franke et al., 1998). OCT and visual function data was compared between groups using generalized estimating equation models (GEE) accounting for within-subject inter-eye dependencies. GEE models included effects for eye-specific ON status of the respective eye (yes/no) and an interaction effect of diagnosis and ON status. GEE results are provided with regression coefficient (B), standard error (SE) and p-value (p). GEE models were further applied to analyse correlations between the NEI-VFQ composite score and OCT data and visual assessments in the NMOSD cohort. Here, OCT data and visual function data were set as the dependent variables due to method-specific constraints. Additionally, a linear regression model was employed for obtaining R2 values for correlations. Statistical significance was established at p<0.05.

3. 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 combination with more severe ON in the NMOSD group (B=−25.0, SE=8.2, p=0.003). In contrast, NMOSD in combination with unilateral ON (B=−7.1, SE=8.1, p=0.38), bilateral ON alone (B=−2.6, SE=6.5, p=0.69), unilateral ON alone (B=4.7, SE=6.8, p=0.49) or diagnosis alone (B=4.7, SE=6.8, p=0.49) did not reveal a significant difference (Supplementary Fig 1).

Fig. 1

Fig. 1

Group differences of the NEI-VFQ composite score and its subscales for Neuromyelitis Optica (NMOSD) and Multiple Sclerosis (MS) patients. The group comparison for the composite score was analyzed with an univariate linear regression model.


Compared to published reference data from healthy controls, the NEI-VFQ composite score and all subscales except role difficulties, dependency and colour vision were significantly reduced in the NMOSD cohort (Supplementary Table 1). Fifteen (48.3%) NMOSD patients had reduced (outside one standard deviation) vision-related quality of life in comparison to this normative data. The 16 patients in normal range were seven patients with only LETM and eight patients with strictly unilateral ON. In contrast, only 3 (9.7%) MS patients had reduced vision-related quality of life, significantly less than in NMOSD (Chi2 p=0.002).

In line with previous reports, NMOSD patients showed more profound neuro-axonal damage and loss of visual function than MS patients (Table 2) (Bennett et al, 2015 and Schneider et al, 2013).

Table 2

Visual system data of NMOSD and MS patients.


NMOSD MS GEE Diagnosis (NMOSD) GEE ON GEE Interaction effect (NMOSD * ON)
NON Eyes ON Eyes NON Eyes ON Eyes B SE p B SE p B SE p
Visual acuity/logMAR −0.04±0.16 0.44±0.77 −0.01±0.15 0.04±0.23 0.04 0.05 0.40 0.06 0.03 0.084 0.30 0.12 0.013
Contrast sensitivity/AULCSF 1.84±0.27 1.18±0.87 1.88±0.25 1.81±0.38 −0.13 0.09 0.14 −0.08 0.06 0.15 −0.43 0.15 0.005
pRNFL/µm 93.5±15.7 56.8±20.5 89.4±13.7 78.7±14 0.15 4.82 0.98 −8.32 2.83 0.003 −19.5 5.5 <0.001
GCIP/µm 66.6±7.6 50.8±8.8 n.d. n.d.
INL/µm 32.2±2.9 34.6±3.6 n.d. n.d.

Analyses were performed with GEE models. Bold font indicates significant p-values (p<0.05)

Abbreviations: AULCSF=Area under the log contrast sensitivity function, B=correlation coefficient, GCIP=combined ganglion cell and inner plexiform layer thickness, GEE=generalized estimating equation, INL=inner nuclear layer thickness, logMAR=Logarithm of the minimum angle of resolution, n.d.=no data available, p= p-value, pRNFL= peripapillary retinal nerve fibre layer thickness, SE=standard error. All visual system data is presented in mean±standard deviation.

Lower NEI-VFQ composite scores were significantly associated with lower visual acuity and contrast sensitivity in NMOSD patients. Retinal neuro-axonal damage measured as pRNFL and GCIP thinning was associated with lower NEI-VFQ scores. Additionally, worse NEI-VFQ scores correlated with INL thickening in NMOSD patients (Fig. 2).

Fig. 2

Fig. 2

Correlations of NEI-VFQ composite score to structural and functional parameters. R2 was derived from uncorrected linear regression. A) High contrast visual acuity. B) Contrast sensitivity. C) Peripapillary nerve fibre layer (pRNFL). D) Retinal ganglion cell and inner plexiform layer (GCIP). E) Inner nuclear layer (INL). Abbreviations: GEE=Generalized estimation equations, B=coefficient, SE=standard error, ON=Optic neuritis..


There was no significant difference in any OCT, visual function or vision-related quality of life parameter between patients with AQP4- and MOG-IgG (data not shown).

4. 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 functional damage; c) Structural retinal damage and visual impairment were significantly greater in the NMOSD cohort than in the MS cohort; and d) worse OCT measurements and visual function were associated with worse vision-related quality of life in NMOSD.

The NEI-VFQ was introduced in 1998 and is an extensively validated and reproducible instrument to measure vision-related quality of life in patients with eye diseases. Several studies have previously investigated vision-related quality of life using the NEI-VFQ in patients with MS and have shown a moderate reduction compared to healthy controls that is associated with neuro-axonal and visual function loss (Mowry et al, 2009, Schinzel et al, 2014, and Walter et al, 2012). We did not include healthy controls in our study, thus we compared the NEI-VFQ results of the NMOSD patients with published reference values of healthy individuals (Franke et al., 1998).

To our knowledge, vision-related quality of life has not been previously studied in NMOSD patients. In our study, the NEI-VFQ questionnaire delivered valid and meaningful results as shown by correlations to structural retinal damage and visual function.

The strong loss of vision-related quality of life in NMOSD patients was driven by patients with severe bilateral ON attacks: NMOSD patients suffer more in comparison to MS patients from a loss of vision-related quality of life because of the high occurrence of bilateral ON in combination with a higher ON-associated damage. Interestingly the occurrence of unilateral ON had only little effect on vision-related quality of life, both in the MS and NMOSD groups. Both patient groups seem to be able to compensate even severe unilateral vision loss rather well. However, upon affection of the second eye, MS patients seem to lose vision-related quality of life only moderately. In contrast, NMOSD patients suffer from a much greater loss based on the greater severity of NMOSD associated ON damage, regularly leading to profound visual function loss or even blindness.

Progressive afferent visual system damage independent of apparent clinical optic neuritis attacks is known to occur in MS patients (Oberwahrenbrock et al, 2012 and Petzold et al, 2010), whereas damage in NMOSD patients seems to be mainly related to ON attacks (Ratchford et al, 2009 and Schneider et al, 2013).

OCT is the method of choice to determine structural retinal damage in NMOSD and MS patients; and pRNFL and GCIP have been established as the two main parameters to measure axonal (pRNFL) and neuronal (GCIP) damage both in MS (Zimmermann et al., 2014) and NMOSD (Bennett et al., 2015). Many studies have shown that ON in NMOSD causes more severe pRNFL and GCIP thinning (Bennett et al., 2015). Furthermore, macular microcysts occur as a correlate of ON severity more frequently in NMOSD than in MS (Kaufhold et al., 2013). Located in the INL they regularly lead to INL thickening in the aftermath of severe ON (Brandt et al., 2014). An association of macular microcysts and INL thickening with disease severity and progression has been reported in MS (Saidha et al., 2012). In our study, pRNFL and GCIP thickness were significantly correlated with vision-related quality of life in NMOSD patients, while there was an inverse correlation for INL. These findings establish structural damage measurements by OCT as appropriate correlates of vision-related quality of life also in NMOSD patients. In patients with CIS, INL thickness inversely correlated with prospective MRI disease activity (Knier et al., 2016). In our data, prevalence of macular microcysts was higher in the NMOSD group, though this difference was not significant (Table 1). If INL thickness holds any additional e.g. prognostic value over the more commonly used pRNFL and GCIP measurements in NMOSD remains to be shown.

Loss of vision-related quality of life was significantly associated with loss of high contrast visual acuity and contrast sensitivity in our study. This is in contrast to MS, where high contrast visual acuity regularly fails to detect subtle progressive or mild ON-associated vision loss, also reflected by a weak or missing association with vision-related quality of life (Schinzel et al., 2014). In contrast, low contrast visual acuity (comparable to contrast sensitivity in our study (Bock et al., 2012)) is able to detect subtle vision loss and structural damage and is associated nicely with loss of vision-related quality of life in MS patients (Mowry et al., 2009). Our study suggests that the larger measurement range of high contrast visual acuity while avoiding flooring effects due to blindness might be an appropriate correlate of vision-related quality of life in NMOSD patients.

We included MOG-IgG positive patients within the NMOSD group in our study. Patients with clinical and neuroimaging features of NMOSD associated with other biomarkers like MOG-IgG are currently investigated and discussed as a different disease entity displaying a similar clinical phenotype (Dalmau, 2015). In our study, there were no apparent differences between MOG-IgG positive, AQP4-IgG positive and AQP4-IgG negative patients regarding visual function and vision related quality of life.

In summary, our study introduces the NEI-VFQ as a helpful tool to detect and monitor vision-related quality of life in NMOSD patients. NMOSD related ON-attacks lead to more severe and persisting visual impairment and structural damage that results in a greater loss of vision-related quality of life. Early and effective therapeutic strategies are therefore important to prevent irreversible structural visual damage and preserve the quality of life for NMOSD patients. We suggest implementing the NEI-VFQ in longitudinal clinical studies in NMOSD patients to reflect drug efficacy on vision-related quality of life.


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 disclose. J. Bellmann-Strobl reports non-financial support from Biogen, non-financial support from Bayer, personal fees and non-financial support from TEVA, outside the submitted work; K. Ruprecht reports grants from BMBF, during the conduct of the study; grants and personal fees from Novartis Pharma, personal fees from Roche, grants and personal fees from Biogen, grants and personal fees from Merck Serono, grants and personal fees from Bayer Schering, personal fees from Teva, outside the submitted work; F. Paul reports grants from BMBF, grants from BMBF, grants from DFG, grants from GJCF, grants from Novartis, during the conduct of the study; personal fees from Bayer, personal fees from Teva, personal fees from Genzyme, personal fees from Merck, personal fees from MedImmune, personal fees from Novartis, outside the submitted work; .

A. Brandt reports personal fees from Motognosis, grants and personal fees from Novartis, personal fees from Biogen, personal fees from Teva, outside the submitted work.


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

Appendix A. Supplementary material

Download file


Supplementary Fig. 1: Group differences of the NEI-VFQ composite score and its subscales for Neuromyelitis Optica spectrum disorders (NMOSD) and Multiple Sclerosis (MS) patients, accounting for the influence of a history of optic neuritis unilaterally or in both eyes. A) NEI-VFQ composite score. Analysis was performed with multivariate linear regressions. B) NEI-VFQ subscores. No statistical analysis was performed for group comparisons to avoid multiple testing artifacts. Abbreviations: NON: no history of optic neuritis; UON: unilateral optic neuritis; BON: optic neuritis in both eyes.



Download file


Supplementary material




  • Bennett et al., 2015 J.L. Bennett, J. de Seze, M. Lana-Peixoto, J. Palace, A. Waldman, S. Schippling, et al., GJCF-ICC&BR. Neuromyelitis optica and multiple sclerosis: seeing differences through optical coherence tomography. Mult. Scler. J.. 2015;21:678-688 10.1177/1352458514567216 Crossref
  • Bock et al., 2012 M. Bock, A.U. Brandt, J. Kuchenbecker, J. Dörr, C.F. Pfueller, N. Weinges-Evers, et al. 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.. 2012;96:62-67 10.1136/bjo.2010.193581 Crossref
  • Brandt et al., 2014 A.U. Brandt, T. Oberwahrenbrock, E.M. Kadas, W.A. Lagrèze, F. Paul. Dynamic formation of macular microcysts independent of vitreous traction changes. Neurology. 2014; 10.1212/WNL.0000000000000545
  • Costello, 2016 F. Costello. Vision disturbances in multiple sclerosis. Semin. Neurol.. 2016;36:185-195 10.1055/s-0036-1579692
  • Dalmau, 2015 J. Dalmau. Observations on the evolving fields of neuroimmunology and neuroinflammation. Neurol. Neuroimmunol. Neuroinflamm.. 2015;2:e67 10.1212/NXI.0000000000000067 Crossref
  • Franke et al., 1998 G.H. Franke, J. Esser, A. Voigtländer, N. Mähner. 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.. 1998;7:178-184
  • Heesen et al., 2008 C. Heesen, J. Böhm, C. Reich, J. Kasper, M. Goebel, S.M. Gold. Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable. Mult. Scler. J.. 2008;14:988-991 10.1177/1352458508088916 Crossref
  • Jarius et al., 2016a S. Jarius, K. Ruprecht, I. Kleiter, N. Borisow, N. Asgari, K. Pitarokoili, et al., B. Wildemann, M. Reindl. 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.. 2016; 10.1186/s12974-016-0717-1
  • Jarius et al., 2016b S. Jarius, K. Ruprecht, I. Kleiter, N. Borisow, N. Asgari, K. Pitarokoili, et al. 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.. 2016; 10.1186/s12974-016-0718-0
  • Jarius et al., 2016c S. Jarius, I. Kleiter, K. Ruprecht, N. Asgari, K. Pitarokoili, N. Borisow, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: MOG-IgG-associated brainstem encephalitis. J. Neuroinflamm.. 2016; 10.1186/s12974-016-0719-z
  • Jarius et al., 2014 S. Jarius, B. Wildemann, F. Paul. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin. Exp. Immunol.. 2014;176:149-164 10.1111/cei.12271 Crossref
  • Kaufhold et al., 2013 F. Kaufhold, H. Zimmermann, E. Schneider, K. Ruprecht, F. Paul, T. Oberwahrenbrock, et al. Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis. PLoS ONE. 2013;8:e71145 10.1371/journal.pone.0071145 Crossref
  • Kleiter et al., 2016 I. Kleiter, A. Gahlen, N. Borisow, K. Fischer, K.-D. Wernecke, B. Wegner, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann. Neurol.. 2016;79:206-216 10.1002/ana.24554
  • Knier et al., 2016 B. Knier, A. Berthele, D. Buck, P. Schmidt, C. Zimmer, M. Mühlau, et al. Optical coherence tomography indicates disease activity prior to clinical onset of central nervous system demyelination. Mult. Scler. J.. 2016;22:893-900 10.1177/1352458515604496
  • Mangione et al., 1960 C.M. Mangione, P.P. Lee, P.R. Gutierrez, K. Spritzer, S. Berry, R.D. Hays. National Eye Institute Visual Function Questionnaire field test Investigators, 2001. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch. Ophthalmol. Chic. Ill.. 1960;119:1050-1058
  • Mowry et al., 2009 E.M. Mowry, M.J. Loguidice, A.B. Daniels, D.A. Jacobs, C.E. Markowitz, S.L. Galetta, et al. Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity. J. Neurol. Neurosurg. Psychiatry. 2009;80:767-772 10.1136/jnnp.2008.165449 Crossref
  • Oberwahrenbrock et al., 2012 T. Oberwahrenbrock, S. Schippling, M. Ringelstein, F. Kaufhold, H. Zimmermann, N., Y. Keser, et al. Retinal damage in multiple sclerosis disease subtypes measured by high-resolution optical coherence tomography. Mult. Scler. Int.. 2012;:530305 10.1155/2012/530305
  • Pache et al., 2016 F. Pache, H. Zimmermann, J. Mikolajczak, S. Schumacher, A. Lacheta, F.C. Oertel, 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. Neuroinflamm.. 2016; 10.1186/s12974-016-0720-6
  • Petzold et al., 2010 A. Petzold, J.F. de Boer, S. Schippling, P. Vermersch, R. Kardon, A. Green, et al. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol.. 2010;9:921-932 10.1016/S1474-4422(10)70168-X Crossref
  • Polman et al., 2011 C.H. Polman, S.C. Reingold, B. Banwell, M. Clanet, J.A. Cohen, M. Filippi, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann. Neurol.. 2011;69:292-302 10.1002/ana.22366 Crossref
  • R Development Core Team, R Development Core Team, n.d. R: A language and Environment for Statistical Computing.
  • Ramanathan et al., 2016 S. Ramanathan, K. Prelog, E.H. Barnes, E.M. Tantsis, S.W. Reddel, Henderson, et al. Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis. Mult. Scler. J.. 2016;22:470-482 10.1177/1352458515593406
  • Ratchford et al., 2009 J.N. Ratchford, M.E. Quigg, A. Conger, T. Frohman, E. Frohman, L.J. Balcer, et al. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies. Neurology. 2009;73:302-308 10.1212/WNL.0b013e3181af78b8 Crossref
  • Saidha et al., 2012 S. Saidha, E.S. Sotirchos, M.A. Ibrahim, C.M. Crainiceanu, J.M. Gelfand, Sepah, et al. Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study. Lancet Neurol.. 2012;11:963-972 10.1016/S1474-4422(12)70213-2 Crossref
  • Schinzel et al., 2014 J. Schinzel, H. Zimmermann, F. Paul, K. Ruprecht, K. Hahn, A.U. Brandt, et al. Relations of low contrast visual acuity, quality of life and multiple sclerosis functional composite: a cross-sectional analysis. BMC Neurol.. 2014;14:31 10.1186/1471-2377-14-31 Crossref
  • Schneider et al., 2013 E. Schneider, H. Zimmermann, T. Oberwahrenbrock, F. Kaufhold, E.M. Kadas, A. Petzold, et al. Optical coherence tomography reveals distinct patterns of retinal damage in neuromyelitis optica and multiple sclerosis. PloS One. 2013;8:e66151 10.1371/journal.pone.0066151 Crossref
  • Toosy et al., 2014 A.T. Toosy, D.F. Mason, D.H. Miller. Optic neuritis. Lancet Neurol.. 2014;13:83-99 10.1016/S1474-4422(13)70259-X Crossref
  • Walter et al., 2012 S.D. Walter, H. Ishikawa, K.M. Galetta, R.E. Sakai, D.J. Feller, S.B. Henderson, et al. Ganglion cell loss in relation to visual disability in multiple sclerosis. Ophthalmology. 2012;119:1250-1257 10.1016/j.ophtha.2011.11.032
  • Wingerchuk et al., 2015 D.M. Wingerchuk, B. Banwell, J.L. Bennett, P. Cabre, W. Carroll, T. Chitnis, et al., International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85:177-189 10.1212/WNL.0000000000001729 Crossref
  • Zekeridou and Lennon, 2015 A. Zekeridou, V.A. Lennon. Aquaporin-4 autoimmunity. Neurol. Neuroimmunol. Neuroinflamm.. 2015;:2 10.1212/NXI.0000000000000110
  • Zimmermann et al., 2014 H. Zimmermann, T. Oberwahrenbrock, A.U. Brandt, F. Paul, J.-M. Dörr. Optical coherence tomography for retinal imaging in multiple sclerosis. Degen. Neurol. Neuromuscul. Dis.. 2014;:153 10.2147/DNND.S73506 Crossref


a NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin, Germany

b Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany

c Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany

Corresponding author.

1 Equally contributing first authors in alphabetical order.

Search this site

Stay up-to-date with our monthly e-alert

If you want to regularly receive information on what is happening in MS research sign up to our e-alert.

Subscribe »

About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

This online Resource Centre has been made possible by a donation from EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.

Note that EMD Serono, Inc., has no editorial control or influence over the content of this Resource Centre. The Resource Centre and all content therein are subject to an independent editorial review.

The Grant for Multiple Sclerosis Innovation
supports promising translational research projects by academic researchers to improve understanding of multiple sclerosis (MS) for the ultimate benefit of patients.  For full information and application details, please click here

Journal Editor's choice

Recommended by Prof. Brenda Banwell

Causes of death among persons with multiple sclerosis

Gary R. Cutter, Jeffrey Zimmerman, Amber R. Salter, et al.

Multiple Sclerosis and Related Disorders, September 2015, Vol 4 Issue 5