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MS Study (CHAMPS),
6365
the Early Treatment of
MS (ETOMS) study
66
and the Betaferon
in Newly
Emerging MS For Initial Treatment (BENEFIT) study,
67
demonstrated that interferon beta increases the time
interval to a second MS-defining relapse in high-risk
patients at 15 years. Patients in the interferon group
also had significantly fewer lesions on brain MRI than
did those in the placebo group. This effect is identical
to the known effect of these treatments in relapsing-
remitting MS, where the number of relapses is reduced
by one-third, although here expressed as the time
interval between the first and second relapses. In
deciding whether or not to recommend such treatment
after a first episode of demyelinating ON it should be
remembered that over 40% of patients with abnormal
MRI scans at baseline will not go on to have a second,
MS-defining, episode at 10 years; also, these
treatments are only partially effective: the patient needs
to be treated for about 6 years in order to prevent one
relapse
68
and finally, the long-term visual prognosis is
favourable even if MS develops.
2
Practical Help and Advice
Despite the fact that many patients presenting with
ON for the first time will not develop MS, patients
should be made aware of this association by the
clinician. A fully informed discussion with the patient
about their individual risk of developing MS, together
with the availability of DMDs, can facilitate a
decision about whether to organize a brain MRI. It is
also crucial to emphasize that the patient may never
develop MS.
Despite evidence that the majority of patients
recover good vision based on objective parameters,
many patients commonly complain of residual deficits
in vision,
69
colour vision,
70
contrast sensitivity and
difficulty with depth and motion perception, the latter
due to the Pulfrich phenomenon. Symptomatic relief
The International MS Journal 2009; 16: 8289 87
G Optic Neuritis: A Review
can be afforded by spectacles with one tinted lens in
front of the unaffected eye to balance the delay in
conduction from the other side.
71
Patients can
alleviate Uhthoffs phenomenon by remaining indoors
on hot and humid days and drinking plenty of cool
fluids, but principally they need to be reassured that
Uhthoffs symptoms are entirely reversible and not
damaging to vision.
For patients who experience permanent visual
impairment following ON a wide range of low-vision
aids are available and formal psychological and
emotional support are offered for people coming to
terms with visual problems.
Conclusions
A thorough history-targeted ophthalmic and neurological
examination of a patient presenting with painful
unilateral visual loss should help to clinically identify those
with typical demyelinating ON. Conditions which mimic
demyelinating ON should be considered and atypical
features promptly investigated. Specific neuroimaging
and other laboratory studies must be directed by the
clinical history and examination. When rapid visual
recovery is desirable, intravenous methylprednisolone
can be considered after discussion of possible side-effects
and with the patient bearing in mind that treatment does
not alter the final visual outcome.
The presence of any number of white matter
lesions on brain MRI at first presentation in acute
demyelinating ON can identify those at high risk of
developing MS in the future; it may be appropriate
to offer these individuals DMDs as prophylaxis,
according to local protocols and following full
discussion with the patient. Other high-risk clinical
characteristics and natural-history information can aid
in estimating a patients individual 10-year risk for
MS being the final diagnosis, bearing in mind that
even when MRI lesions are present 40% will not
develop CDMS within 10 years.
Conflicts of Interest
No conflicts of interest were declared in relation to
this article.
Address for Correspondence
Gordon T Plant, Box 93,
The National Hospital for Neurology &
Neurosurgery, London WC1N 3BG, UK
E-mail: gordon@plant.globalnet.co.uk
Received: 26 May 2008
Accepted: 5 December 2008
References
88 The International MS Journal 2009; 16: 8289
Optic Neuritis: A Review G
1. Beck RW, Trobe JD, Moke PS
et al. High- and low-risk profiles
for the development of multiple
sclerosis within 10 years after
optic neuritis: experience of the
optic neuritis treatment trial. Arch
Ophthalmol 2003; 121:
944949.
2. Optic Neuritis Study Group.
Visual function 15 years after
optic neuritis: a final follow-up
report from the Optic Neuritis
Treatment Trial. Ophthalmology
2008; 115: 10791082.
3. Cleary PA, Beck RW, Anderson
MM et al. Design, methods, and
conduct of the Optic Neuritis
Treatment Trial. Control Clin
Trials 1993; 14: 123142.
4. Kidd DP: Inflammatory optic
neuropathies not associated with
multiple sclerosis. In: Neuro-
ophthalmology (Kidd DP,
Newman NJ, Biousse V, eds).
Boston: Butterworth Heinemann
2008; pp153190.
5. Kidd DP, Plant GT. Optic neuritis.
In: Neuro-ophthalmology (Kidd
DP, Newman NJ, Biousse V, eds).
Boston: Butterworth Heinemann
2008; pp134152.
6. Plant GT. Optic neuritis and
multiple sclerosis. Curr Opin
Neurol 2008; 21: 1621.
7. Beck RW, Gal RL, Bhatti MT et
al. Visual function more than
10 years after optic neuritis:
experience of the optic neuritis
treatment trial. Am J Ophthalmol
2004; 137: 7783.
8. Costello F, Coupland S, Hodge
W et al. Quantifying axonal loss
after optic neuritis with optical
coherence tomography. Ann
Neurol 2006; 59: 963969.
9. Fisher JB, Jacobs DA, Markowitz
CE et al. Relation of visual
function to retinal nerve fiber
layer thickness in multiple
sclerosis. Ophthalmology 2006;
113: 324332.
10. Trip SA, Schlottmann PG, Jones
SJ et al. Retinal nerve fiber layer
axonal loss and visual
dysfunction in optic neuritis. Ann
Neurol 2005; 58: 383391.
11. Henderson AP, Trip SA,
Schlottmann PG et al. An
investigation of the retinal nerve
fibre layer in progressive multiple
sclerosis using optical coherence
tomography. Brain 2008; 131:
277287.
12. Kurtzke JF. Optic neuritis or
multiple sclerosis. Arch Neurol
1985; 42: 704710.
13. Rodriguez M, Siva A, Cross SA
et al. Optic neuritis: a population-
based study in Olmsted County,
Minnesota. Neurology 1995;
45: 244250.
14. Phillips PH, Newman NJ, Lynn
MJ. Optic neuritis in African
Americans. Arch Neurol 1998;
55: 186192.
15. Kurtzke JF. Multiple sclerosis
among immigrants. Br Med J
1976; 1: 15271528.
16. Dean G, Elian M. Age at
immigration to England of Asian
and Caribbean immigrants and
the risk of developing multiple
sclerosis. J Neurol Neurosurg
Psychiatry 1997; 63: 565568.
17. Balcer LJ. Clinical practice. Optic
neuritis. N Engl J Med 2006;
354: 12731280.
18. Boomer JA, Siatkowski RM.
Optic neuritis in adults and
children. Semin Ophthalmol
2003; 18: 174180.
19. Brady KM, Brar AS, Lee AG
et al. Optic neuritis in children:
clinical features and visual
outcome. J AAPOS 1999; 3:
98103.
20. Morales DS, Siatkowski RM,
Howard CW et al. Optic neuritis
in children. J Pediatr Ophthalmol
Strabismus 2000; 37: 254259.
21. Lucchinetti CF, Kiers L, O'Duffy A
et al. Risk factors for developing
multiple sclerosis after childhood
optic neuritis. Neurology 1997;
49: 14131418.
22. Schneck ME, Haegerstrom-
Portnoy G. Color vision defect
type and spatial vision in the
optic neuritis treatment trial.
Invest Ophthalmol Vis Sci 1997;
38: 22782289.
The International MS Journal 2009; 16: 8289 89
G Optic Neuritis: A Review
23. Goldstein JE, Cogan DG.
Exercise and the optic neuropathy
of multiple sclerosis. Arch
Ophthalmol 1964; 72: 168170.
24. Optic Neuritis Study Group. The
clinical profile of optic neuritis.
Experience of the Optic Neuritis
Treatment Trial. Arch Ophthalmol
1991; 109: 16731678.
25. Beck RW, Cleary PA, Anderson
MM Jr et al. A randomized,
controlled trial of corticosteroids
in the treatment of acute optic
neuritis. The Optic Neuritis Study
Group. N Engl J Med 1992;
326: 581588.
26. Hickman SJ, Ko M, Chaudhry F
et al. Optic neuritis: An update
typical and atypical optic
neuritis. Neuroophthalmology
2008; 32: 237248.
27. Hickman SJ, Dalton CM, Miller
DH et al. Management of acute
optic neuritis. Lancet 2002; 360:
19531962.
28. Brass SD, Zivadinov R, Bakshi R.
Acute demyelinating optic
neuritis: a review. Front Biosci
2008; 13: 23762390.
29. Beck RW, Cleary PA, Trobe JD
et al. The effect of corticosteroids
for acute optic neuritis on the
subsequent development of
multiple sclerosis. The Optic
Neuritis Study Group. N Engl J
Med 1993; 329: 17641769.
30. Rolak LA, Beck RW, Paty DW
et al. Cerebrospinal fluid in acute
optic neuritis: experience of the
optic neuritis treatment trial.
Neurology 1996; 46: 368372.
31. Cole SR, Beck RW, Moke PS
et al. The predictive value of CSF
oligoclonal banding for MS 5
years after optic neuritis. Optic
Neuritis Study Group. Neurology
1998; 51: 885887.
32. Wu GF, Schwartz ED, Lei T et al.
Relation of vision to global and
regional brain MRI in multiple
sclerosis. Neurology 2007; 69:
21282135.
33. Balcer LJ, Baier ML, Cohen JA
et al. Contrast letter acuity as a
visual component for the Multiple
Sclerosis Functional Composite.
Neurology 2003; 61:
13671373.
34. Baier ML, Cutter GR, Rudick RA
et al. Low-contrast letter acuity
testing captures visual dysfunction
in patients with multiple sclerosis.
Neurology 2005; 64: 992995.
35. Beck RW: Optic neuritis. In:
Miller NR and Newman NJ.
Walsh and Hoyt's Clinical
Neuro-ophthalmology, 5th edn
(Miller NR, Newman JJ, eds).
Baltimore: Williams & Wilkins
1998; pp599647.
36. Beck RW, Trobe JD. What we
have learned from the Optic
Neuritis Treatment Trial.
Ophthalmology 1995; 102:
15041508.
37. Beck RW, Cleary PA. Recovery
from severe visual loss in optic
neuritis. Arch Ophthalmol 1993;
111: 300.
38. Kupersmith MJ, Gal RL, Beck RW
et al. Visual function at baseline
and 1 month in acute optic
neuritis: Predictors of visual
outcome. Neurology 2007; 69:
508514.
39. Brusaferri F, Candelise L. Steroids
for multiple sclerosis and optic
neuritis: a meta-analysis of
randomized controlled clinical
trials. J Neurol 2000; 247:
435442.
40. Wenning GK, Wietholter H,
Schnauder G et al. Recovery of
the hypothalamic-pituitary-
adrenal axis from suppression by
short-term, high-dose intravenous
prednisolone therapy in patients
with MS. Acta Neurol Scand
1994; 89: 270273.
41. Roed HG, Langkilde A,
Sellebjerg F et al. A double-blind,
randomized trial of IV
immunoglobulin treatment in
acute optic neuritis. Neurology
2005; 64: 804810.
42. Noseworthy JH, O'Brien PC,
Petterson TM et al. A randomized
trial of intravenous
immunoglobulin in inflammatory
demyelinating optic neuritis.
Neurology 2001; 56:
15141522.
43. Ruprecht K, Klinker E, Dintelmann
T et al. Plasma exchange for
severe optic neuritis: treatment of
10 patients. Neurology 2004;
63: 10811083.
44. Optic Neuritis Study Group. The
5-year risk of MS after optic
neuritis. Experience of the Optic
Neuritis Treatment Trial.
Neurology 1997; 49:
14041413.
45. Optic Neuritis Study Group.
Visual function 5 years after optic
neuritis: experience of the Optic
Neuritis Treatment Trial. Arch
Ophthalmol 1997; 115:
15451552.
46. Goodin DS. Perils and pitfalls in
the interpretation of clinical trials:
a reflection on the recent
experience in multiple sclerosis.
Neuroepidemiology 1999; 18:
5363.
47. Kaufman DI, Trobe JD,
Eggenberger ER et al. Practice
parameter: the role of
corticosteroids in the
management of acute
monosymptomatic optic neuritis.
Report of the Quality Standards
Subcommittee of the American
Academy of Neurology.
Neurology 2000; 54:
20392044.
48. Sellebjerg F, Nielsen HS,
Frederiksen JL et al. A
randomized, controlled trial of
oral high-dose
methylprednisolone in acute optic
neuritis. Neurology 1999; 52:
14791484.
49. Bhatti MT; Group ONS. The final
15-year follow-up report on the
neurological outcome of the
Optic Neuritis Treatment Trial.
34th Annual Meeting of the
North American Neuro-
Ophthalmology Society
(NANOS), Orlando, USA,
2008.
50. Rizzo JF 3rd, Lessell S. Risk of
developing multiple sclerosis after
uncomplicated optic neuritis: a
long-term prospective study.
Neurology 1988; 38: 185190.
51. Barkhof F, Filippi M, Miller DH
et al. Comparison of MRI criteria
at first presentation to predict
conversion to clinically definite
multiple sclerosis. Brain 1997;
120(Pt 11): 20592069.
52. Keltner J, Johnson C, Cello K
et al. A 15-year summary of
abnormal visual fields in the
Optic Neuritis Treatment Trial.
34th Annual Meeting of the
North American Neuro-
Ophthalmology Society
(NANOS), Orlando, USA,
2008.
53. Brex PA, Ciccarelli O, O'Riordan
JI et al. A longitudinal study of
abnormalities on MRI and
disability from multiple sclerosis.
N Engl J Med 2002; 346:
158164.
54. O'Riordan JI, Thompson AJ,
Kingsley DP et al. The prognostic
value of brain MRI in clinically
isolated syndromes of the CNS.
A 10-year follow-up. Brain 1998;
121(Pt 3): 495503.
55. Beck RW, Arrington J, Murtagh
FR et al. Brain magnetic
resonance imaging in acute optic
neuritis. Experience of the Optic
Neuritis Study Group. Arch
Neurol 1993; 50: 841846.
56. Beck RW, Smith CH, Gal RL et
al. Neurologic impairment 10
years after optic neuritis. Arch
Neurol 2004; 61: 13861389.
57. McDonald WI, Compston A,
Edan G et al. Recommended
diagnostic criteria for multiple
sclerosis: guidelines from the
International Panel on the
diagnosis of multiple sclerosis.
Ann Neurol 2001; 50:
121127.
58. Dalton CM, Brex PA, Miszkiel KA
et al. Application of the new
McDonald criteria to patients
with clinically isolated syndromes
suggestive of multiple sclerosis.
Ann Neurol 2002; 52: 4753.
59. Revesz T. Axonal lesions in
multiple sclerosis: an old story
revisited. Brain 2000; 123(Pt 2):
203204.
60. De Stefano N, Narayanan S,
Francis GS et al. Evidence of
axonal damage in the early
stages of multiple sclerosis and its
relevance to disability. Arch
Neurol 2001; 58: 6570.
61. Bermel RA, Puli SR, Rudick RA
et al. Prediction of longitudinal
brain atrophy in multiple sclerosis
by gray matter magnetic
resonance imaging T2
hypointensity. Arch Neurol 2005;
62: 13711376.
62. Frohman EM, Racke M, van Den
Noort S. To treat, or not to treat:
the therapeutic dilemma of
idiopathic monosymptomatic
demyelinating syndromes. Arch
Neurol 2000; 57: 930932.
63. CHAMPS Study Group.
Interferon beta-1a for optic
neuritis patients at high risk for
multiple sclerosis. Am J
Ophthalmol 2001; 132:
463471.
64. Beck RW, Chandler DL, Cole SR
et al. Interferon beta-1a for early
multiple sclerosis: CHAMPS trial
subgroup analyses. Ann Neurol
2002; 51: 481490.
65. Kinkel RP, Kollman C, O'Connor
P et al. IM interferon beta-1a
delays definite multiple sclerosis
5 years after a first
demyelinating event. Neurology
2006; 66: 678684.
66. Comi G, Filippi M, Barkhof F
et al. Effect of early interferon
treatment on conversion to
definite multiple sclerosis: a
randomised study. Lancet 2001;
357: 157615.82
67. Kappos L, Polman CH, Freedman
MS et al. Treatment with
interferon beta-1b delays
conversion to clinically definite
and McDonald MS in patients
with clinically isolated
syndromes. Neurology 2006;
67: 12421249.
68. Ghosh A, Kelly SP, Mathews J
et al. Evaluation of the
management of optic neuritis:
audit on the neurological and
ophthalmological practice in the
north west of England. J Neurol
Neurosurg Psychiatry 2002; 72:
119121.
69. Frederiksen JL, Sorensen TL,
Sellebjerg FT. Residual symptoms
and signs after untreated acute
optic neuritis. A one-year follow-
up. Acta Ophthalmol Scand
1997; 75: 544547.
70. Cleary PA, Beck RW, Bourque LB
et al. Visual symptoms after optic
neuritis. Results from the Optic
Neuritis Treatment Trial. J
Neuroophthalmol 1997; 17:
1823; Quiz, 2428.
71. Heron G, Thompson KJ, Dutton
GN. The symptomatic Pulfrich
phenomenon can be successfully
managed with a coloured lens in
front of the good eye--a long-term
follow-up study. Eye 2007; 21:
14691472.