Uveitis associated with multiple sclerosis

Clinical Research

Uveitis associated with multiple sclerosis: complications

and visual prognosis

1
Department of Geriatrics Medicine, Dokuz Eylul University, DOI:10.3980/j.issn.2222-3959.2014.06.18
Izmir 35340, Turkey
2
Department of Ophthalmology, Dokuz Eylul University, Kaya D, Kaya M, zakba S, Idiman E. Uveitis associated with
Izmir 35340, Turkey multiple sclerosis: complications and visual prognosis.
3
Department of Neurology, Dokuz Eylul University, Izmir 2014;7(6):1010-1013
35340, Turkey
Correspondence to: Derya Kaya. Department of Geriatrics INTRODUCTION
Medicine, Faculty of Medicine, Dokuz Eylul University,
M
ultiple sclerosis (MS) is a chronic inflammatory
Izmir 35340, Turkey. [email protected] disorder of the central nervous system (CNS) white
Received: 2013-11-24 Accepted:2014-02-17 matter and a common cause of neurological disability in
young adults [1,2]. Optic neuritis is the most frequent
Abstract ophthalmic manifestation of MS, however intraocular
AIM: To determine the frequency, subtype, inflammation may also occur. Uveitis is an intraocular
complications, treatment and visual prognosis of uveitis inflammation involving the uveal tract, retina or vitreous
in patients with multiple sclerosis (MS). body which appears unusually in MS [3]. The association
between MS and uveitis is unclear. In patients with MS, the
METHODS: A total of 1702 MS patients' medical
records were reviewed for a history of uveitis both with a
frequency of uveitis ranges from 0.4 to 26.9% and in patients
neurologist and an ophthalmologist. with uveitis, the prevalence of MS is 1% -2% [4,5]. The most
common type of uveitis has been reported to be intermediate
RESULTS: Nine patients (0.52% ) with uveitis were
uveitis which primarily involves the vitreous, peripheral
detected. Eight of them were female, one was male. The
retina and pars plana ciliaris [6]. Mild impairment in visual
mean age was 42.014.1y (range 22-66). Seven patients
were relapsing remitting MS, two were secondary acuity (VA) may be seen at the time of initial presentation in
progressive MS. The mean duration of MS was 10.8 patients with intermediate uveitis, in whom visual prognosis
10.3y, and the mean duration of uveitis 10.3 9.9y. The is related to the severity of the disease. Actually, macular
onset of uveitis preceded that of MS (four patients) by a involvement [cystoid macular edema (CME) and post-cystoid
mean of 5.04.3y (range 1-11). MS diagnosed prior to the degeneration] is the most important prognostic factor for
onset of uveitis (five patients) by an interval of 0.75-16y vision [7]. Patients with MS may also present with
(mean 4.95 6.24y). There were 16 affected eyes of nine
granulomatous anterior uveitis with development of extensive
patients. The most common types of uveitis were
posterior synechiae and "mutton fat" keratic precipitates, that
panuveitis and intermediate uveitis. Uveitis was bilateral
in most patients. The most common complications were
is highly suggestive of sarcoidosis [5,8-11]. Secondary changes
cataract and glaucoma, and patients with such due to uveitis such as cataract, CME, band keratopathy,
complications were surgically treated. The range of visual glaucoma, retinal detachment, retinoschisis, vitreous
acuity of affected eyes was 20/800 to 20/22, with only six hemorrhage and occlusive vasculitis may occur. Therefore,
of 16 affected eyes better than 20/40. After treatment, the the management could be often difficult to achive [12,13]. We
visual acuity of the affected eyes was better than 20/40 in present herein the frequency, clinical features, complications
11 of 16 eyes. and outcomes of uveitis in MS patients with a long follow-up.
CONCLUSION: Uveitis should be considered when SUBJECTS AND METHODS
assessing an MS patient with visual loss, as surgical The case records of 1702 consecutive patients with clinically
interventions other than medical treatments may be definite MS treated at the Department of Neurology in Dokuz
needed to improve visual function. Complications could Eylul University between February 1976 and December
be seen more often when posterior segment is involved.
2008, were reviewed for a history of uveitis. This research
KEYWORDS: complication; multiple sclerosis; uveitis; was carried out in accordance with the Declaration of
visual acuity Helsinki and after obtaining approval from The local
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Table 1 Demographic and clinical data of the patients
Age at onset of Type of
Patients Age (a)/sex Type/laterality of UV UV evolution Follow up (a)
UV (a) MS (a) MS
1 41/F 22 33 RR Panuveitis/ BL Chronic 3
2 22/M 17 20 RR Intermediate/ R Chronic 2
1
3 39/F 34 34 RR Panuveitis/ R Chronic 4
4 42/F 40 37 RR Intermediate/ BL Chronic 5
5 37/F 29 34 RR Posterior/ BL Chronic 3
6 63/F 45 42 SP Posterior/ BL Chronic 18
7 66/F 36 34 SP Panuveitis/ BL Chronic 32
8 30/F 24 25 RR Intermediate/ BL Chronic 5
9 38/F 37 21 RR Anterior/BL Acute 17
BL: Bilateral; MS: Multiple sclerosis; UV: Uveitis; 1The patient had uveitis after 9mo than MS onset.

University Hospital Medical Ethics Committee. Written cataract had developed or where the fundus view was
informed constent from patients was obtained. Patients who obscured due to lens opacity in patients with posterior
fulfilled the criteria of Poser [14]
for the diagnosis of segment inflammation. Cataract surgery technique was
clinically definite MS and who were examined for the extracapsular cataract extraction (ECCE) in our patients with
occurrence of visual symptoms both by a neurologist and by clinically significant cataract becuase they were performed
an expert ophthalmologist on uveal disorders were included before phacoemulsification surgery era. Elevated intraocular
into the study. All patients were of caucasian origin. Patients pressure (IOP) was treated by medical agents. Glaucoma
whose uveitis were attributed to systemic vasculitis, chronic surgery was undertaken when an IOP of <21 mm Hg could
bacterial or viral infections and patients who had history of not be attained by the medical treatment. Retinal
optic neuritis had been excluded. Also, records were neovascularization was treated by argon laser panretinal
checked if dermatological and urological examinations had photocoagulation.
revealed any evidence of aphthosis that is diagnostic for RESULTS
Behet's disease and if neurosarcoidosis had been ruled out Nine patients (0.52% ) with uveitis were identified out of
by chest X-ray, and angiotensin converting enzyme level in 1702 definite MS patients between February 1976 and
serum. After that, records were checked for a clinical December 2008. Eight of them were female, one was male.
opthalmological examination in order to determine clinical The mean age was 42.014.1y (range 22-66). Seven patients
and anatomical pattern of uveitis as well as the treatment were relapsing remitting MS (RRMS), two were secondary
schedule. Uveitis was anatomically classified according to progressive MS (SPMS). The mean annual number of MS
the International Uveitis Study Group criteria [6] as anterior relapses was 0.610.38 (0.15-1.4). The mean duration of MS
(iridocyclitis), posterior (the primary site of inflammation is was 10.8 10.3y (range 2-32), and the mean duration of
in the retina or in the choroid), intermediate uveitis (pars uveitis 10.3 9.9y (range 1-30). The mean age at onset of
planitis) or panuveitis. Medical records were documented and uveitis was 31.7 9.2y (range 17-45), and the mean age at
summarized about treatment of uveitis as follows: 1) anterior onset of MS 31.2 7.5y (range 20-42). Four patients had a
uveitis was treated with topical corticosteroids and history of uveitis prior to the onset of MS. The onset of
mydriatics; 2) bilateral active posterior uveitis with VA uveitis preceded that of MS by an interval of 1-11y (mean
poorer than 20/40 in the better eye, was managed with 5.04.3y). MS was diagnosed prior to the onset of uveitis in
systemic corticosteroids; 3) intermediate uveitis was treated our five patients by an interval of 0.75-16y (mean 4.956.24y).
with systemic and local steoroids in patients with VA poorer Median follow-up was 5y (range 2-32). No correlation was
than 20/40, however patients with VA better than 20/40 were found between the type of MS and type of uveitis. The
monthly followed-up. Panuveitis was treated with systemic detailed clinical data of the 16 eyes of 9 MS patients with
and local steroids. Patients treated with immunosupressive uveitis are summarized in Table 1.
agents when there was reactivation of uveitis following Anterior uveitis (iridocyclitis) was present in two eyes,
withdrawal or tapering of steroids, no response or tolerance intermediate uveitis (pars planitis) in five, posterior uveitis in
to steroid treatment, or when there was a need for more four and panuveitis in five eyes. Only one patient had acute
intensive treatment due to high risk of blindness. course of uveitis, and the remaining eight suffered from
The complications of the uveitis were divided into three chronic course. Uveitis was bilateral in most patients
groups: cataract, glaucoma, and retinal neovascularization. (77.8%). Granulomatous uveitis was present in four eyes of
Cataract surgery was performed when visually significant two patients. Three eyes were treated with topical steroids,

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Uveitis associated with multiple sclerosis

Table 2 The ophthalmologic findings and outcome of uveitis in our patients

Type of VA before VA after Causes of decreased
Patient Laterality Surgery
uveitis treatment treatment final VA
R Panuveitis 20/100 20/60 CAT ECCE+PCIOL
P1
L Panuveitis 20/250 20/200 CAT+ERM ECCE+PCIOL
P2 R Intermediate 20/30 20/25 CAT ECCE+PCIOL
P3 R Panuveitis 20/60 20/30 - None
R Intermediate 20/25 20/22 - None
P4
L Intermediate 20/25 20/22 - None
R Posterior 20/60 20/40 CAT+Glaucoma ECCE+PCIOL+trab
P5
L Posterior 20/100 20/40 CAT+Glaucoma ECCE+PCIOL+trab
R Posterior 20/800 20/400 CAT+Glaucoma+ERM Vitrectomy+trab+5FU
P6
L Posterior 20/40 20/25 CAT ECCE+PCIOL
R Panuveitis 20/100 20/35 CAT ECCE+PCIOL
P7
L Panuveitis 20/200 20/50 Vitreous haemorrhage Vitrectomy+laser PRP
R Intermediate 20/100 20/60 CAT+RD+CME ECCE+PCIOL+vitrectomy
P8
L Intermediate 20/100 20/40 CME None
R Anterior 20/25 20/20 - None
P9
L Anterior 20/22 20/20 - None
CAT: Cataract; ECCE+PCIOL: Extracapsular cataract extraction with posterior chamber intraocular lens implant; trab:
Trabeculectomy; RD: Retinal detachment; CME: Cystoid macular edema; PRP: Pan-retinal photocoagulation; ERM: Epiretinal
membrane; 5FU: 5-fluorouracil; VA: Visual acuity.

two eyes were treated with intravitreal steroids, eight with The most common types of uveitis were intermediate (pars
systemic steroids, and 4 out of these 8 patients were treated planitis) and panuveitis. These findings are in line with
with additional immnosupressive agents. Three eyes were Markomichelakis's and Biousse 's findings [4,9], but are
followed-up without any medication for uveitis. The most not consistent with Le Scanff [15]
who reported the most
common complication was cataract (9/16 eyes; 56% ) and common type of uveitis as posterior uveitis, Schmidt [18]

cataract surgery was performed in 8 eyes, because one patient and Towler and Lightman as anterior uveitis. It was shown
[11]

(P6) did not want to have surgery. The visual outcome that all types of uveitis could be seen in MS, however the
following surgery was satisfactory in all eyes except the left HLA-DR15 allele was shown to cause a predisposition to MS
eye of P1. The second most common complication was and pars planitis [19-23]. Thus, diagnosis of multiple sclerosis
glaucoma (3/16 eyes; 19%) and trabeculectomy was performed should be considered preferably if there is bilateral pars
in all eyes as medical treatment was not able to lower IOP planitis, particularly in females [24]. The majority of our
(Table 2). patients with uveitis had bilateral involvement which is
The range of visual acuity of affected eyes was 20/800 to similar to other studies[9,17,25,26].
20/22, with six of 16 affected eyes better than 20/40 before
Most previous reports on MS-associated uveitis give
treatment. The visual acuity of the affected eyes after
relatively little information on visual prognosis. The present
treatment was better than 20/40 in 11 of 16 eyes.
study is important for detecting complications associated with
DISCUSSION
the type of uveitis and visual outcome that were seen in MS
In this study we identified that 0.52% of 1702 definite MS
patients. In our patients, the VA was 20/200 or worse in 19%
patients were associated with uveitis. This finding is
of affected eyes before treatment, whereas it was 13% of
consistent with several previous studies performed by Le
affected eyes after treatment. The VA was 20/40 or better in
Scanff [15]
who found 0.65% of 4300 MS patients had
uveitis, Thouvenot [16]
who found 0.7% of 700 had 37% of affected eyes before treatment and in 68% of affected
uveitis, and Biousse [9]
who found that approximately eyes after treatment. It was observed that the poor visual
1% of 1098 MS patients had uveitis, but seems to be little prognosis was associated with the complications seen in the
lower than Zein [17]
who reported uveitis 1.3% in 1254 retina. There were epiretinal membrane in two eyes and
MS patients and Schmidt [18]
1.8% in 450 MS patients. vitreous haemorrhage in one eye of the patients who had a
This might be due to the difference in the diagnostic criteria VA of 20/200 or worse. These findings reinforced that
of the diseases in the studies. There was a female panuveitis and intermediate uveitis could give rise to
preponderance (89% ) which was also reported previously permanent complications despite appropriate treatment.
[9,11,17]
. There were four patients with uveitis diagnosed before Nevertheless, the visual outcome following vitrectomy and
the onset of MS, and five patients vice versa. There was no panretinal photocoagulation for vitreous haemorrhage in our
patient that had both concurrently. patient was very satisfactory as VA improved from 20/200 to
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20/50. The VA improved to a higher level in the patients who 5 Smith JR, Rosenbaum JT. Neurological concomitants of uveitis.
had also relatively good VA before treatment. 2004;88(12):1498-1499
6 Bloch-Michel E, Nussenblatt RB. International uveitis study group
The most common complication of uveitis was cataract. VA
recommendations for the evaluation of intraocular inflammatory disease.
was considerably improved after surgery in patients with 1987;103(2):234-235
isolated cataract secondary to uveitis. On the other hand, 7 Capone A, Aaberg TM. Intermediate uveitis. In Albert DM and Jakobiec
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Our study has several limitations. First, our data were
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subclinical deficits could not be accounted for. Third, we did Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW. New diagnostic
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Uveitis associated with multiple sclerosis. 2008;14(3):415-417
was reported that MRI features in patients with
16 Thouvenot E, Mura F, De Verdal M, Carlander B, Charif M, Schneider
MS-associated uveitis had no convincing evidence of a C, Navarre S, Camu W. Ipsilateral uveitis and optic neuritis in multiple
special lesional distrubution[18]. sclerosis. 2012; 2012:372361
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18 Schmidt S, Wessels L, Augustin A, Klockgether T Patients with
possibility of uveitis, may develope. On the other hand,
multiple sclerosis and concomitant uveitis/periphlebitis retinae are not
uveitis could be a manisfestation of an underlying disease
distinct from those without intraocular inflammation. 2001;187
like MS. Therefore patients with uveitis should undergo a (1-2):49-53
detailed neurological examination, and also presence of 19 Birnbaum AD, Little DM, Tessler HH, Goldstein DA. Etiologies of
interval between uveitis and MS onset should be kept in mind chronic anterior uveitis at a tertiary referral center over 35 years.
for further follow-up. The patients with MS-associated uveitis 2011;19(1):19-25
20 Stamenkovic M, Obradovic D. Retinal periphlebitis in patients with
may need to be treated as early as possible with appropriate
multiple sclerosis. 2011;68(7):544-549
surgical interventions for protecting their optimum vision and
21 Paroli MP, Abicca I, Sapia A, Bruschi S, Pivetti Pezzi P. Intermediate
for improving the quality of life. uveitis: comparison between childhood-onset and adult-onset disease.
ACKNOWLEDGEMENTS 2013; 24(1): 94-100
Conflicts of Interest: Kaya D, None; Kaya M, None; 22 Karara AM, Macky TA, Sharawy MH. Pattern of uveitis in an Egyptian
zakba S, None; Idiman E, None. population with multiple sclerosis: a hospital-based study.
2013;49(1):25-29
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