Plasma exchange for severe optic neuritis

Treatment of 10 patients
K. Ruprecht, MD; E. Klinker, MD; T. Dintelmann, MD; P. Rieckmann, MD; and R. Gold, MD

Abstract—The authors reviewed a series of 10 consecutive patients treated with plasma exchange (PE) for acute, severe
optic neuritis (ON) largely unresponsive to previous high-dose IV glucocorticosteroids. PE was associated with an improve-
ment of visual acuity according to the study criteria in 7 of 10 patients. On follow-up, three of these patients continued to
improve, two remained stable, and two had worsened again. PE may be beneficial as an escalating treatment in a subset
of patients with severe ON. A controlled trial is warranted.
NEUROLOGY 2004;63:1081–1083

Optic neuritis (ON) may occur in isolation or as a
manifestation of multiple sclerosis (MS). Although
visual recovery after ON is generally good, in some
patients, reduced visual acuity (VA) persists.1 Glu-
cocorticosteroids (GSs) are currently the only treat-
ment option for ON.1,2 In a recent randomized,
double-blind, sham-controlled crossover trial, plasma
exchange (PE) led to a functionally important neuro-
logic recovery in about 40% of patients with severe,
acute attacks of idiopathic inflammatory demyelinat-
ing diseases.3 In this study and in an extended re-
port on 59 patients treated at the same institution, a
wide spectrum of demyelinating syndromes was in-
cluded.3,4 However, the role of PE in the treatment of
severe isolated ON is not clear.
Patients and methods. Patients, diagnosis, and outcome mea-
sures. All patients treated with PE for isolated acute ON at the
Department of Neurology, University of Würzburg, were identi-
fied between January 2000 and March 2003 (n ⫽ 10). Diagnosis of
ON was based on clinical criteria and paraclinical tests.1 All pa-
tients were examined by a neurologist and an ophthalmologist
and underwent cranial MRI and lumbar puncture. Oligoclonal
bands in the CSF were present in all but one patient (Patient 5)
who was borderline positive. Visual evoked potentials (VEPs) were
obtained as described.5 Diagnosis of MS was established according
to the criteria of McDonald et al.6 Standardized determination of
VA (expressed as decimal equivalent) was performed with an oph-
thalmologic examination unit using number projection at a dis-
tance of 5 m. Vision below 0.02 was graded into finger counting,
perception of hand motions, light perception, and no light percep-
tion. VA data were transformed to the log MAR (log of the mini-
mum angle of resolution) notation, as suggested elsewhere.7
The primary outcome measure was improvement of VA of the
affected eye as determined within 4 days before and 5 days after
PE and on follow-up. A meaningful improvement of VA was de-
fined as a decrease of the log MAR equivalent of ⬎0.2, correspond-
ing to an improvement of more than two lines on a standard VA
chart.7 If baseline vision was no light perception, light perception,
hand motions, or counting fingers, any increase was regarded as
an improvement. VEP served as a secondary outcome measure.
PE. Informed consent was obtained from each patient prior to
PE. A median of 5 exchanges (range 2 to 5) per patient was
performed. A mean of 40.3 mL (range 27.6 to 49.9 mL) of plas-
ma/kg of body weight was exchanged by continuous-flow centrifu-
gation using a cell separation device. Approximately two-thirds of
the removed volume was replaced with 5% human serum albumin
and one-third with 500 mL of 6% hydroxyethyl starch and 500 mL
of 0.9% saline.
Results. All patients had been treated with at least two
courses of high-dose IV GSs prior to PE (table). Addition-
ally, two patients (Patients 3 and 8) had also been treated
with IV immunoglobulins (5 ⫻ 30 and 2 ⫻ 20 g) 3 weeks
before PE. In two patients (Patients 2 and 4), GS treat-
ment was associated with a certain improvement of vision
from no light perception to hand motions and 0.2 to 0.4. In
the remainder, neither GSs nor IV immunoglobulin ther-
apy was followed by a substantial improvement of VA.
None of the patients took any immunomodulatory or im-
munosuppressive treatment at the onset of ON. The me-
dian interval between symptom onset and start of PE was
34.5 days (range 11 to 73 days) and the median interval
between the last course of high-dose GSs and start of PE
2.5 days (range 0 to 19 days). Concomitant therapy during
PE consisted of either interferon-␤1a or -1b or oral GSs as
part of a taper following IV GSs.
Standardized reassessment of VA after the last PE was
performed a median of 10.5 days (range 6 to 19 days) after
the baseline VA measurement and demonstrated an im-
provement of VA according to the defined criteria in 7 of 10
patients. On follow-up, of these seven patients, three had
further improved, two remained stable, and two had dete-
riorated again. Of the three patients without short-term
improvement, one remained unchanged, whereas the other
two showed an improvement of VA, although the absolute
VA levels reached by these two patients were low.
Before PE, P100 was abnormal in two patients, whereas
in eight patients, no P100 could be detected on the affected
eye. VEP on follow-up essentially reflected the clinical
course of visual recovery.
There were no serious adverse events, and PE was over-
all well tolerated. Three patients experienced symptomatic

From the Clinical Research Unit for Multiple Sclerosis and Neuroimmunology (Drs. Ruprecht, Rieckmann, and Gold), Department of Neurology, and
Departments of Transfusion Medicine and Immunohematology (Dr. Klinker) and Ophthalmology (Dr. Dintelmann), Julius-Maximilians University, Würz-
burg, Germany.
Supported by the University Research Fund.
Received March 10, 2004. Accepted in final form May 21, 2004.
Address correspondence and reprint requests to Dr. K. Ruprecht, Department of Neurology, Julius-Maximilians University, Josef-Schneider Str. 11, 97080
Würzburg, Germany; e-mail: klemens.ruprecht@mail.uni-wuerzburg.de

Copyright © 2004 by AAN Enterprises, Inc. 1081

Table Clinical characteristics, treatment, and outcome

Cumulative Visual acuity Visual acuity

IV (methyl) within 4 d within 5 d Visual acuity P100 latency, ms/amplitude,
Patient ON in prednisolone Days from before first PE after last PE at follow-up ␮V, on affected side
no./gender/ setting of dose before symptom No. of Length of
age, y RRMS/CIS PE, g onset to PE PEs Decimal acuity (log MAR equivalent)* follow-up, d VEP before PE† VEP after PE‡

1/F/36 RRMS 8 41 5 LP HM (⫹3.0) HM (⫹3.0) 240 ND ND

2/F/24 RRMS 9 11 5 HM (⫹3.0) CF (⫹2.0) 1.0 (0.0) 125 ND 109.2/4.2

3/F/40 RRMS 6 33 5 CF (⫹2.0) 0.8 (⫹0.1) 0.5 (⫹0.3) 70 ND §

4/F/30 RRMS 10 36 3 0.4 (⫹0.4) 0.8 (0.1) 0.8 (⫹0.1) 666 108.0/1.3㛳 108.0/8.8¶

5/F/22 CIS 13 31 4 0.2 (⫹0.7) 0.5 (⫹0.3) 1.2 (⫺0.08) 153 117.6/3.8㛳 115.2/4.7

6/M/51 CIS 6 37 5 CF (⫹2.0) 0.2 (⫹0.7) 0.05 (⫹1.3) 320 ND ND

7/F/34 CIS 9 21 5 NLP 0.2 (⫹0.7) 0.9 (⫹0.05) 670 ND 99.6/6.2

8/F/30 CIS 11 50 2 CF (⫹2.0) HM (⫹3.0) 0.02 (⫹1.7) 774 ND ND

9/F/38 CIS 10 73 3 0.03 (⫹1.5) 0.05 (⫹1.3) 0.05 (⫹1.3) 700 ND ND

10/M/36 CIS 6 14 5 HM (⫹3.0) HM (⫹3.0) 0.03 (⫹1.5) 585 ND ND

9 (median) 34.5 (median) 5 (median) 452.5 (median)

*log MAR (log of the minimum angle of resolution) equivalents were calculated with the formula log MAR ⫽ ⫺ log (decimal acuity); the decimal equivalent
for CF was set at 0.01 and for HM at 0.001; NLP and LP were not transformed into log MAR equivalents (cf. ref. 7).
†VEP obtained within 1 wk before PE.
‡VEP at last follow-up visit.
§P100 questionably detectable.
㛳Amplitude (no. 4) or latency (no. 5) abnormal as compared with the unaffected eye.
¶VEP obtained in different electrophysiology unit from baseline VEP.

ON ⫽ optic neuritis; RRMS ⫽ relapsing–remitting multiple sclerosis; CIS ⫽ clinically isolated syndrome; PE ⫽ plasma exchange; NLP ⫽ no light percep-
tion; LP ⫽ light perception; HM ⫽ hand motions; CF ⫽ counting fingers; VEP ⫽ visual evoked potential; ND ⫽ not detectable.

hypotension, and five patients reported paresthesias. In
two patients, central IV catheter placement was necessary.
Four additional patients had local vein problems caused by
the peripheral venous access that led to premature termi-
nation of PE in one of them (Patient 8).
Discussion. In the short term, PE was associated
with an improvement of VA in a substantial number
of patients with severe ON who previously had not
recovered following high-dose IV GS therapy. This is
in accordance with the positive effects of PE in pa-
tients with other inflammatory demyelinating syn-
dromes, unresponsive to GS therapy, formerly
reported in a controlled trial,3 patient series,4 and
case reports.8,9 Although in two of the seven respond-
ing patients, improvement was not sustained on
follow-up, the redeteriorated VA in these patients
was still above the baseline levels before PE. Redete-
rioration occurred within 10 (Patient 3) and 16 (Pa-
tient 6) weeks after PE and may reflect a declining
treatment effect of PE or, alternatively, a new epi-
sode of ON.
Three of the 10 patients investigated (Patients 8
to 10) did not profit from PE in the short term. There
were no obvious demographic differences between
this group and the responders; however, two of the
nonresponders had the longest intervals between
symptom onset and initiation of PE in our series and
were administered a lower than average number of
PEs. In all three, the P100 potential was initially
absent, possibly indicating severe and irreversible
1082 NEUROLOGY 63 September (2 of 2) 2004
axonal damage. Although the low patient number
prohibits definitive conclusions concerning specific
differences between responders and nonresponders,
these features may be associated with a less favor-
able outcome.
This open study addressed the worst-case group
with ON. Although long-term follow-up data were
obtained prospectively, this work is limited by its
initially retrospective character and lack of a control
group. Taking into account the generally good prog-
nosis of ON,1,10 we cannot rule out that some of our
patients might have improved spontaneously or by
means of a delayed therapeutic effect of the GS ther-
apy. However, in the vast majority of patients, recov-
ery from uncomplicated ON begins within the first 2
weeks after onset of visual symptoms, and much of
the improvement has occurred by the end of 1
month.10 As the interval between symptom onset and
PE was ⬎2 weeks in 90% and ⬎1 month in 70% of
our patients, and all had repeated GS treatment,
which is expected to accelerate visual improvement
after ON,2 most patients in this series should have
had sufficient time to at least partly recover before
PE was started. Furthermore, the clear temporal as-
sociation of PE with improvement of VA over a rela-
tively short period of time in the responding patients
suggests a treatment effect of PE. An early treat-
ment effect of PE in patients who ultimately respond to
this therapy is also in keeping with results of a larger
patient series.4 We therefore favor the hypothesis that
PE had a therapeutic effect in our series and propose a
larger prospective controlled trial to readdress this.
Acknowledgment
The authors thank Prof. K.V. Toyka for stimulating discussion
and for reviewing the manuscript. They also thank Prof. K.H.
Reiners for providing VEP recordings.
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September (2 of 2) 2004 NEUROLOGY 63 1083
 Plasma exchange for severe optic neuritis: Treatment of 10 patients
K. Ruprecht, E. Klinker, T. Dintelmann, et al.
Neurology 2004;63;1081-1083
DOI 10.1212/01.WNL.0000138437.99046.6B

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