Original Contribution
Long-Term Stability of Neuroaxonal Structure in
Alemtuzumab-Treated Relapsing–Remitting Multiple
Sclerosis Patients
Jillian K. Chan, MD, Elena Hernandez Martínez de Lapiscina, MD, Carolyn Taylor, MSc,
Ai-Lan Nguyen, MD, Salut Alba-Arbalat, OD, Virginia Devonshire, MD, Ana-Luiza Sayao, MD,
Robert Carruthers, MD, Fiona Costello, MD, Anthony Traboulsee, MD
Background: Patients with multiple sclerosis (MS) experi-
ence progressive thinning in optical coherence tomography
(OCT) measures of neuroaxonal structure regardless of
Department of Medicine (Neurology) (JKC, VD, A-LS, RC, AT),
University of British Columbia, Vancouver, Canada; Department of
Neurology (EHMdL, SA-A), Center of Neuroimmunology, Hospital
Clinic of Barcelona, Institut d’Investigacions Biomèdiques August Pi
Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain;
Department of Statistics (CT), University of British Columbia, Van-
couver, Canada; Department of Neruology (A-LN), University of
Melbourne, Melbourne, Australia; Royal Melbourne Hospital (A-LN),
Melbourne, Australia; and Departments of Clinical Neurosciences
and Surgery (Ophthalmology) (FC), University of Calgary, Clinician
Scientist with the Hotchkiss Brain Institute (HBI), Calgary, Canada.;
and Department of Neurology and Neurotherapeutics (SCB), Uni-
versity of Texas Southwestern Medical Center, Dallas, Texas.
Investigator add-on study to a Sanofi Genzyme–supported,
investigator-sponsored open-label treatment trial at the University of
British Columbia Hospital. The study was supported by the Instituto
de Salud Carlos III, Spain (JR16/0006) and Fondo Europeo de De-
sarrollo Regional (FEDER) to E. Hernandez Martínez de Lapiscina.
J. K. Chan received grant support from Biogen and consulted for Roche. E.
Hernandez Martínez de Lapiscina received grant support from Merck
(Grant for MS Innovation); consulting from Genzyme. Travel and
accommodation support from Roche and Genzyme. She is a member of
the IMSVISUAL consortium. A. L. Nguyen received research grants from
Novartis, Biogen, Merck-Serono, and MS Research Australia; speaker
honoraria and consulting fees from EMD Serono and Teva; and confer-
ence travel support from Genzyme-Sanofi, Biogen, and Roche. V. Dev-
onshire received honorarium for speaking from the following companies:
Sanofi, Biogen, Serono, Roche, and Novartis. A. L Sayao received speaker
honoraria from Merck-Serono, consulted for Merck-Serono, Novartis,
Biogen, Roche, and Genzyme. R. Carruthers is the site investigator for
studies funded by Novartis, MedImmune, and Roche and receives
research support from Teva Innovation Canada, Roche Canada, and
Vancouver Coastal Health Research Institute. He has done consulting
work and has received honoraria from Roche, EMD Serono, Sanofi,
Biogen, Novartis, and Teva. A. Traboulsee received research funding from
Biogen, Chugai, Novartis, Roche, and Sanofi Genzyme and consultancy
honoraria from Biogen, Roche, Sanofi Genzyme, and Teva Neuroscience.
The remaining authors report no conflicts of interest.
Address correspondence to Jillian K. Chan, MD, Division of Neu-
rology, UBC Hospital S213, 2211 Wesbrook Mall, Vancouver,
Canada V6T 2B5; E-mail: jillian.chan@ubc.ca
Chan et al: J Neuro-Ophthalmol 2020; 40: 37-43
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
optic neuritis history. Few prospective studies have inves-
tigated the effects of disease-modifying therapies on neu-
roaxonal degeneration in the retina. Alemtuzumab is
a monoclonal antibody shown to be superior to interferon
b-1a in treating relapsing–remitting MS (RRMS). The pur-
pose of this study was to assess the effects of alemtuzu-
mab and first-line injectable treatments on OCT measures of
neuroaxonal structure including peripapillary retinal nerve
fiber layer (RNFL) thickness and combined ganglion cell–
inner plexiform (GCIP) layer volume in RRMS patients fol-
lowed up over 5 years.
Methods: In this retrospective pilot study with prospectively
collected double cohort data, spectral domain OCT meas-
ures of RNFL thickness and GCIP volume were compared
between alemtuzumab-treated RRMS patients (N = 24) and
RRMS patients treated with either interferon-b or glatiramer
acetate (N = 21).
Results: Over a median of 60 months (range 42–60
months), the alemtuzumab cohort demonstrated a change
in the mean RNFL thickness (thinning from baseline) of
20.88 mm (95% confidence interval [CI] 22.63 to 0.86; P
= 0.32) and mean GCIP volume of +0.013 mm3 (95% CI
20.006 to 0.032; P = 0.18). Over the same time period,
the first-line therapy–treated cohort demonstrated greater
degrees of RNFL thinning (mean change in RNFL thickness
was 23.65 mm [95% CI 25.40 to 21.89; P = 0.0001]).
There was also more prominent GCIP volume loss relative to
baseline in the first-line therapy group (20.052 mm3 [95%
CI 20.070 to 20.034; P , 0.0001]).
Conclusions: Alemtuzumab-treated patients with RRMS
demonstrated relative stability of OCT-measured neuro-
axonal structure compared with RRMS patients treated with
either interferon-b or glatiramer acetate over a 5-year
period. These findings, along with previous demonstration
of improved brain atrophy rates, suggest that alemtuzumab
may offer long-term preservation of neuroaxonal structure in
patients with RRMS.
Journal of Neuro-Ophthalmology 2020;40:37–43
doi: 10.1097/WNO.0000000000000802
© 2019 by North American Neuro-Ophthalmology Society
37
 Original Contribution

M
and GCIP thinning between 2 independent RRMS cohorts
ultiple sclerosis (MS) is a chronic, immune-mediated
followed up over a median of 60 months (range 42–60
disease that affects the central nervous system (CNS)
months). The alemtuzumab cohort was recruited from the
and causes inflammation and neurodegeneration. Neuronal
University of British Columbia MS Clinic in Vancouver,
loss (for the purposes of this study, defined as thinning of the
Canada, and included 24 RRMS participants who received
ganglion cell–inner plexiform [GCIP] layer) and axonal
at least 2 courses of alemtuzumab. The second cohort
injury (defined as retinal nerve fiber layer [RNFL] thinning)
included 21 age- and sex-matched patients treated with
in the afferent visual pathway of the CNS can be quantified
first-line agents for at least 2 years from the MS Visual
noninvasively in vivo with optical coherence tomography
Pathway cohort at the Hospital Clinic in Barcelona, Spain
(OCT). As an endpoint, OCT has been validated as
(20). Informed, written consent was obtained from all
a reproducible measure of “neuroaxonal” (referring to GCIP
participants.
and RNFL values) structure in MS for both clinical and
research purposes (1,2). Reduced RNFL and GCIP meas- Inclusion Criteria
ures, as evidence of neuroaxonal injury captured in the reti- Patients (aged 18–55 years; disease duration up to 20 years)
nas of MS patients, correlate with worse visual outcomes, fulfilled 2005 McDonald criteria for MS (21) and had
reduced quality of life, MRI measures of brain atrophy, and Expanded Disability Status Scale scores of 5.0 or less. Exclusion
global disability. RNFL and GCIP loss are early phenomena criteria included a comorbid ophthalmological disorder. The
in MS and that retinal thinning may occur independent of alemtuzumab cohort could not have had exposure to cortico-
clinically overt episodes of optic neuritis (ON) (3–10). The steroids, IFN, or GA within 28 days. Eyes affected by ON #6
annual atrophy rates in RNFL thickness ranged from no months before baseline or during the study were excluded.
significant changes to 21.49 mm/year in MS patients (11).
Yearly, GCIP decreases from 20.34 to 20.55 mm Optical Coherence Tomography
(5,12,13), a rate that was 46% faster compared with healthy
Testing was performed at both sites at baseline and at
controls (3,8). Disease-modifying therapies may have differ-
Month 60 (±18 months). The alemtuzumab cohort was
ential effects on OCT-determined rates of retinal atrophy,
assessed with Heidelberg Spectralis-OCT (software version
supporting a potential utility for OCT as a surrogate end-
5.6.4; Heidelberg Engineering, Heidelberg, Germany) in
point to investigate the neuroprotective benefits of MS treat-
accordance with OSCAR-1B criteria (22). Peripapillary
ments (4). Natalizumab-treated patients exhibited the lowest
RNFL thickness was measured with ring scan of 12°/
rate of GCIP thinning (20.17 mm/year) over approximately
3.5-mm diameter centered on the optic nerve head with
3 years compared with patients receiving glatiramer acetate
1,536 A scans per B-scan high-resolution mode, quality
(GA) and interferon (IFN)-b-1a (14), whereas a prospective
$15. Macular volume was measured with a raster scan of
study by Zivadinov et al (15) showed that GA-treated pa-
6-mm diameter centered on the fovea with automatic real
tients had no significant change in RNFL thickness and total
time (ART) $9 using matrix size 30 · 25, 61 high-speed
macular volume over 24 months compared with healthy
B scans, 768 A scans per B scan, vertical acquisition. Mac-
controls.
ular layer segmentation was performed automatically using
Alemtuzumab, an anti-CD52 monoclonal antibody used
the algorithm included in the Viewer Mode (version
to treat relapsing–remitting MS (RRMS), has been shown
6.3.2.0). The first-line treatment cohort was tested with
to be superior to IFN-b-1a in clinical trials at reducing
Heidelberg Spectralis-OCT (software version 5.3.0; Hei-
relapse rate, disability progression, and radiological disease
delberg Engineering) following OSCAR-1B criteria. Peri-
activity including slowing of brain volume loss over 5 years
papillary RNFL measures were obtained with ring scan
(16–18). OCT measures demonstrating neurostability have
12°/3.5-mm diameter centered on the optic nerve head
been proposed as an additional criterion for no evidence of
with 1,536 A scans per B scan with an activated eye-
disease activity, in treating MS (19). The aim of this study
tracker, ART = 100. Macular volume was measured with
was to compare OCT measures of neuroaxonal structure in
a raster scan of 6-mm diameter centered on the fovea with
alemtuzumab-treated RRMS patients followed up over 5
ART $9 and a matrix size 20 · 20, 25 high-resolution B
years vs a convenience sample, independent, parallel, pro-
scans, 512 A scans per B scan, horizontal acquisition.
spective RRMS cohort treated with first-line injectable MS
Macular segmentation was performed automatically using
therapies.
Viewer Mode (version 6.0c).

METHODS
Study Design
This retrospective (with prospectively collected parallel
data), pilot study comparing OCT-measured rates of RNFL
Statistical Analysis
A mixed-effects linear regression model was fit to each of the
OCT-measured rates (RNFL and GCIP) that included fixed
effects for the three 2-level categorical variables of time (baseline
and long-term follow-up), cohort (alemtuzumab and first-line
therapy), and history of ON (ON and no ON [NON]) along

38 Chan et al: J Neuro-Ophthalmol 2020; 40: 37-43

Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
 Original Contribution

TABLE 1. Baseline demographics for alemtuzumab-treated and first-line–treated cohorts

Characteristic Alemtuzumab-Treated Cohort (N = 24) First-Line–Treated Cohort (N = 21) P value

Age (yrs) 34.89 (±9.24) 35.23 (±8.24) 0.89*

Female gender (%) 20 (83%) 18 (86%) 1.00†
Disease duration (yrs) 5.21 (±3.89) 4.96 (±4.50) 0.84*
Eyes with a history of ON (%) 19 (41%) 14 (36%) 0.38‡
ARR 1.44 (±0.61) 0.74 (±0.38) ,0.0001*
Mean EDSS score 2.8 (±1.1) 1.6 (±0.9) 0.0003*

Plus–minus values are SD.

*The 2-sample t test for quantitative data.
†
The Fisher exact test for proportions.
‡
The 2-sample x 2 test for equality of proportions with continuity correction.
ARR, annualized relapse rate in 2 years before study entry; EDSS, Expanded Disability Status Scale; ON, optic neuritis.

with 2 random intercept effects for patients and eyes within
patients. The 2 random effects allow for separate effects to be
estimated for each patient and for each eye within a patient;
therefore, differences between patients and eyes within patients
were taken into account along with the dependency of the
repeated measures that were taken on each eye over time. Of all
the interactions included, only the interaction between time
and cohort was found to be significant and was therefore kept
in the final model. The effect of each eye, baseline age, gender,
and disease duration were added to the model separately but
were not strongly significant and were therefore not included in
the final model. The final model was used to calculate the least
square means and 95% confidence intervals [CIs] for each
cohort at each time period (averaged over the ON and NON
eyes) as well as the difference between long-term follow-up and
baseline. Similarly, mixed-effects models and estimates were
done for the ON and NON eyes separately. Models were fit to
all the available data, and the estimates for change over time
from these models were based on those subjects who had results
at both baseline and long-term follow-up. It was assumed that
missing data occurred at random in that those subjects with
missing data were no different from those with full data. Given
the exploratory nature of this study, all significant P values
based on a significance level of 0.05 are viewed as possibly
indicating significance and were not adjusted for multiple test-
ing. All analyses were conducted using R version 3.4.3 (2017-
11-30).
RESULTS
Alemtuzumab Cohort
There were 24 participants in the alemtuzumab cohort,
with baseline demographics displayed in Table 1. The

FIG. 1. Alemtuzumab-treated cohort RNFL and GCIP change over 60 months: The mean change in RNFL thickness and GCIP
volume is shown for all eyes (N = 48), ON eyes (N = 19), and NON eyes (N = 29) in the alemtuzumab-treated cohort. Each
data point is the value for an individual patient at baseline with a line tracking to his/her mean value at 60 months. The
horizontal line is the mean value for the cohort at baseline and at 60 months. GCIP, ganglion cell–inner plexiform layer; LTF,
long term follow-up; NON, no optic neuritis; ON, optic neuritis; RNFL, retinal nerve fiber layer.

Chan et al: J Neuro-Ophthalmol 2020; 40: 37-43 39

Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
 Original Contribution

annualized relapse rate (ARR) 2 years before treatment

0.0021

,0.0001

,0.0001
P value*

0.029

0.040
0.96
was 1.44 (±0.61). Before study entry, 9 (38%) partici-
pants were treatment-naive and 14 participants were
treated with first-line injectable therapies. Follow-up
OCT occurred at a median of 60 months (mean 57.6,

0.0001

,0.0001

,0.0001

,0.0001
P value

0.020
range 42–60 months). There were 48 eyes scanned in

0.20
total, and 2 eyes were excluded because of ON within 6
months of baseline. Thirteen participants received an
TABLE 2. Change in RNFL thickness and GCIP volume over 60 months in alemtuzumab-treated cohort and first-line–treated cohort

additional course, and 1 participant received 2 additional

courses of alemtuzumab.

20.037 (20.068 to 20.0064)

20.060 (20.083 to 20.037)
20.05 (20.070, 20.034)
First-Line–Treated Cohort (N = 21)

23.65 (25.40 to 21.89)

24.43 (26.42 to 22.44)

22.23 (25.68 to 1.21)

First-Line–Treated Cohort
Change (95% CI)

The convenience sample, parallel cohort included 21

patients (Table 1). The ARR 2 years before treatment
CI, confidence interval; GCIP, ganglion cell–inner plexiform layer; NON, no optic neuritis; ON, optic neuritis; RNFL, retinal nerve fiber layer.
was 0.74 ± 0.37. There were a total of 39 eyes after
excluding 3 because of an episode of ON during the
study. These patients received first-line injectable med-
ications including IFN b-1b, IFN b-1a (subcutaneous
and intramuscular), and GA for at least 24 months.
Thirteen patients remained on first-line therapy.
Three patients discontinued disease-modifying thera-
1.77
1.62
1.87
89.48
81.13
95.10
5 yrs

pies; 2 patients switched to teriflunomide, and 1 each

to dimethyl fumarate, fingolimod, natalizumab, and
rituximab.
Baseline

1.82
1.66
1.93
93.13
83.37
99.54

Longitudinal Optical Coherence Tomography

Analysis: Alemtuzumab Cohort
ON and NON eyes of MS patients were grouped together;
0.32
0.20
0.89

0.18
0.53
0.25

the mean RNFL thickness was 88.88 mm at baseline and

P

87.99 mm at long-term follow-up (median 60 months,

mean 57.6 months), corresponding to a total mean change
0.013 (20.0061 to 0.032)

of 20.88 mm (95% CI 22.63 to 0.86; P = 0.32). The

0.014 (20.010 to 0.038)

*P: comparison between alemtuzumab-treated and first-line–treated cohorts.

Alemtuzumab-Treated Cohort (N = 24)

All significant P values based on a significance level of 0.05 are in italics.

0.010 (20.023, 0.043)

mean GCIP volume at baseline was 1.77 and 1.78 mm3 at

20.88 (22.63 to 0.86)
22.11 (25.42 to 1.20)
0.14 (21.87 to 2.16)
Change (95% CI)

long-term follow-up with a total mean change of

+0.013 mm3 (95% CI 20.006 to 0.032; P = 0.18). Both
the RNFL and GCIP were not significantly decreased over
this longitudinal follow-up period (Fig. 1). Analyzing ON
and NON eyes separately in individual groups did not
show any significant change over this same time period
(Table 2).

Longitudinal Optical Coherence Tomography

1.78
1.69
1.86
87.99
81.66
94.40
5 yrs

Analysis: First-Line Therapy Cohort

All eyes were included; the RNFL thickness at baseline
was 93.13 and 89.48 mm at 60 months of follow-up.
Baseline

1.77
1.68
1.85
88.88
83.77
94.26

The estimated mean change in RNFL thickness for all

eyes was 23.65 mm (95% CI 25.40 to 21.89; P =
0.0001). The GCIP volume was 1.82 mm 3 at baseline
and 1.77 mm 3 at 60 months of follow-up. The esti-
NON eyes

NON eyes

mated mean change in GCIP volume was

ON eyes

ON eyes
GCIP (mm3)

20.052 mm 3 (95% CI 20.070 to 20.034; P ,

RNFL (mm)
All eyes

All eyes

0.0001). Both the RNFL thickness and GCIP volume

in the first-line therapy cohort showed a significant
decrease from baseline to follow-up at 60 months.

40 Chan et al: J Neuro-Ophthalmol 2020; 40: 37-43

Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
 Original Contribution

FIG. 2. Change in RNFL thickness and GCIP volume over 60 months in alemtuzumab-treated and first-line–treated cohorts:
Boxplot whiskers present minimum and maximum values. The dark line represents median change, and the top and bottom
plots represent the first and third quartile changes. All eyes, optic neuritis (ON) eyes, and no ON (NON) eyes are displayed for
the first-line–treated group (N = 21) and alemtuzumab-treated group (N = 24). GCIP, ganglion cell–inner plexiform layer; RNFL,
retinal nerve fiber layer.

DISCUSSION change in macular volume was noted for non–

The results of this exploratory study support the hypothesis
that alemtuzumab facilitates neurostability in MS. Over a 5-
year period, alemtuzumab-treated MS patients demon-
strated no significant loss of RNFL thickness or GCIP
volume in contrast to a comparative cohort of MS patients
receiving first-line therapies (Fig. 2). The latter demon-
strated significant RNFL thinning and GCIP volume loss
(Table 2), indicating accrued neuroaxonal damage in the
afferent visual pathway. In addition, the first-line therapy
cohort showed 2.76 mm more thinning in RNFL thickness
and 0.065 mm3 more loss of GCIP volume for all eyes
included in the study, relative to MS patients treated with
alemtuzumab. These observations were noteworthy because
alemtuzumab-treated patients had worse measures of MS
disease activity and disability at study entry and would have
been expected to demonstrate more severe neuroaxonal
injury, compared with their MS counterparts receiving
first-line therapies over 5 years. Clinically, earlier and greater
loss of neuroaxonal substrate translates to poorer neurolog-
ical outcomes (4,23).
OCT measures need to be interpreted with caution
in MS because they may reflect underlying mechanisms
of disease pathobiology or, alternatively, drug effects. In
a previous study by Nolan et al (24), comparing
fingolimod-treated MS patients with MS patients
receiving other therapies, OCT measures were com-
pared between groups over a follow-up period of 5–6
months. There was a mean increase of 0.025 mm3 in
macular volume in the fingolimod group, whereas no
fingolimod-treated patients. Although increased macu-
lar volume could be viewed as “neuroprotective” (24),
these findings could alternatively be interpreted to
demonstrate an increased propensity to develop micro-
cystic macular edema, which is known to affect MS
patients treated with fingolimod. This confounder limits
the utility of total macular volume as a surrogate marker
for neuroprotection in MS patients using this therapy
(24,25). In the current study, the follow-up interval of 5
years allowed a sufficient period to capture significant
decreases in OCT measures of neuroaxonal structure in
MS patients. Moreover, patients with a history of non-
MS-related optic nerve pathology and previous treat-
ment with fingolimod were excluded. OCT measures
observed were confined to the RNFL and GCIP, and
eyes with an acute ON within 6 months of OCT were
excluded. The latter exclusion criterion aimed to elim-
inate eyes with transient axoplasmic stasis as a result of
acute ON leading to edema in the RNFL that could
falsely elevate these measurements (26).
Neuroaxonal injury occurs in MS patients, with or
without a history of ON, and is believed to be due to both
anterograde and retrograde transsynaptic neurodegeneration
(27). This irreversible process occurs early in the disease
course of MS patients (12). Monitoring peripapillary
RNFL– and macular GCIP–segmented retinal layers in
MS has previously been shown to be robust in detecting
neurodegeneration longitudinally (11). Based on 6 longi-
tudinal studies, RNFL atrophy is at least 1 mm every 1–2

Chan et al: J Neuro-Ophthalmol 2020; 40: 37-43 41

Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
 Original Contribution
years in MS patients with active disease and GCIP mea-
surement further improves detection of early atrophy fol-
lowing ON (11). The RNFL thickness in the alemtuzumab
cohort changed by 22.11 mm in ON eyes and +0.14 mm
in NON eyes after 5 years. This may suggest that treatment
has less of an effect on RNFL neurodegeneration after an
episode of ON compared with eyes without a history of
ON, supporting earlier initiation of higher efficacy treat-
ment. GCIP measures have been shown to provide better
reproducibility and reliability, improved structure–function
relationships (with visual outcomes), and more robust cor-
relations with brain atrophy over RNFL measures in addi-
tion to having less confounding elements, such as edema
during acute inflammation (5,8). The GCIP volume change
in the alemtuzumab cohort was +0.010 mm3 in ON eyes
and +0.014 mm3 in NON eyes. Treatment with a highly
effective immune therapy may be necessary to halt pro-
gressive neuronal loss and axonal damage.
Limitations in this study include small cohort sizes, lack
of serial OCT monitoring over time with clinical visual
outcomes, and the absence of a direct comparison cohort
to the alemtuzumab-treated group. Furthermore, baseline
measurements of RNFL thickness and GCIP volume in
the ON and NON eyes were not matched between
cohorts. The use of an independent, parallel cohort
receiving first-line therapies for at least 2 years was
implemented for indirect comparison. Both cohorts in
this study were scanned on different devices at separate
sites, which may account for measurement changes.
However, the same OCT device without adjustments
was used consistently at each site over time. Although the
cohorts did have differing OCT retinal layer thickness
segmentation measures (vertical vs horizontal), it has been
shown that these protocols compare well at a cohort level
(28). New MRI T2 lesions and clinical relapses were not
available longitudinally for both cohorts to better represent
disease activity beyond baseline comparison data. To bet-
ter investigate treatment effect on neuroaxonal integrity in
MS, future studies should ideally include a prospective,
longitudinal study comparing alemtuzumab with first-
line injectable medications using serial OCT, and MRI
measures of brain volume would help provide potential
support for neurostability.
OCT RNFL thickness and GCIP volume are measures
that reflect neuroaxonal health in the afferent visual
pathway, a functionally eloquent region of the CNS that
is frequently affected in MS. Degeneration of these
structures occurs in most MS patients, at varying rates.
Treatment with alemtuzumab demonstrated relative neu-
rostability of RNFL and GCIP measures over approxi-
mately 5 years, whereas treatment with first-line injectable
therapies was associated with significant RNFL thinning
and GCIP volume loss over a similar time period. The
extent to which induction-based, high-efficacy immune
42
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
therapies protect neuroaxonal structure in MS awaits
further study.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: A. Traboulsee, E. Hernandez
Martínez de Lapiscina, and A. L. Nguyen; b. Acquisition of data: A. L.
Nguyen, J. K. Chan, S. Alba-Arbalat, A. Traboulsee, E. Hernandez
Martínez de Lapiscina, R. Carruthers, V. Devonshire, and A. L. Sayao;
c. Analysis and interpretation of data: A. Traboulsee, E. Hernandez
Martínez de Lapiscina, J. K. Chan, C. Taylor, and F. Costello. Cate-
gory 2: a. Drafting the manuscript: J. K. Chan, A. Traboulsee, C.
Taylor, and F. Costello; b. Revising it for intellectual content: A.
Traboulsee, E. Hernandez Martínez de Lapiscina, J. K. Chan, and
F. Costello. Category 3: a. Final approval of the completed manu-
script: A. Traboulsee, J. K. Chan, F. Costello, R. Carruthers, V. Devon-
shire, and A. L. Sayao.
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