Prevalence of visual field defects following exposure to
vigabatrin therapy: A systematic review
M.J. Maguire1, K. Hemming2 , J.L. Hutton2, A.G. Marson1
(1) University of Liverpool, Dept of Neuroscience, UK (2) University
University of Warwick, Dept of Statistics, Coventry, UK
CUMULATIVE ESTIMATES
BACKGROUND
 Vigabatrin is an efficacious antiepileptic drug licensed as add-on therapy in refractory
epilepsy and used in infantile spasms.
Daneshva r H,1 999
Kal vi ainen R,1999
Lawden MC, 1 999
Mi l le r NR, 199 9
 Post-marketing surveillance identified strong and probably causative associations
Wi l d JM,1999
Wo hl rab G, 19 99
Gross-Tsur V, 2000
Ian netti P, 2000
with bilateral visual field defects (VFD).
Ma nuchehri K, 2000
Mi de lfart A, 2000
Nousi ainen I, 2001
Paul SR, 2001
Pel osse B, 2001
Roccel la M, 2 001
Toggweil er S, 200 1
 Factors associated with an increased risk of a VFD in vigabatrin exposed
Jensen H, 2002
Newman WD, 2002
Ni col son A, 20 02
patients have not been clearly identified.
Schmi tz B, 2002
Van Der T orren, 200 2
Vanhatal o S, 2002
Ascaso FJ, 2003
McDonagh J, 2003
AIMS
Ri ise P, 2003
Mo re no MC, 2005
Poj da-Wi l czek D, 2005
Ki nirons P, 2006
Ki nirons P, 2006
Tseng YL, 2006
We rth R, 2006
You SJ, 2 006
Wi l d JM, 2007
 We report a systematic review ascertaining the magnitude of risk of VFDs and any
.15
.61
Proportion with VFD
clinical predictors of risk in epilepsy patients treated with vigabatrin.
PREDICTORS OF RISK FOR VFD
METHODS
•
Electronic searches of MEDLINE (1950-2007), SCOPUS (1960-2007), CINAHL (1982-
Meta-regression of pooled random effects analysis of study and patient covariates for vigabatrin visual field studies (on a logi t-scale)
2007), Cochrane Epilepsy Group's Specialized Register (1993-2007), Cochrane
Covariate
Central Register of Controlled Trials (CENTRAL) and DARE database were conducted.
•
No of studies
Fully published reports of controlled or uncontrolled longitudinal or cross-sectional
studies investigating the prevalence of VFDs by static or dynamic perimetry in
partial epilepsy patients of any age treated with vigabatrin were included.
•
Outcomes were a) proportion with an overall VFD b) vigabatrin-attributed VFD, c)
relative risk of a VFD .
•
% Visual field defect (all)
Coefficient
P value
Study design (1: Longitudinal)
32
-0.23
0.37
Assessment method (1:H;2:G;3:Both)*
32
0.11
0.54
Assessor blinding (1: blind)
11
-0.48
0.44
Mean age (years)
21
0.29
0.07
Gender (1:male)
24
-0.29
0.89
Cumulative dose VGB (gm)
18
0.36
0.02
Mean length of treatment (days)
20
0.29
0.04
Mean Co-AEDs
15
-0.09
0.69
6
0.31
0.31
Mean epilepsy duration
Study estimates were synthesised using inverse variance random effects models
RESULTS
RELATIVE RISK ESTIMATE
Relative risk of a vigabatrin-attributed visual field defect for controlled studies (n=18)
•
Thirty-two studies were identified and published in full between 1999 and 2007
(10 child studies, 22 adult studies)
Study
ID
•
Four were non-English, 8 were funded and 7 were multi-centre studies.
•
Sixteen were cross-sectional studies and 16 were longitudinal studies investigating
adult
Nousiainen I (2001)
Wild JM (2007)
Jensen H (2002)
Lawden MC (1999)
Wild JM (1999)
Kinirons P (2006)
Newman WD (2002)
Kalviainen R (1999)
Schmitz B (2002)
McDonagh J (2003)
Miller NR (1999)
Midelfart A (2000)
Manuchehri K (2000)
Daneshvar H (1999)
Toggweiler S (2001)
Moreno MC (2005)
Subtotal (I-squared = 8.3%, p = 0.358)
.
child
Wohlrab G (1999)
Werth R (2006)
Subtotal (I-squared = 0.0%, p = 0.412)
.
Overall (I-squared = 1.9%, p = 0.432)
between 10 and 325 exposed vigabatrin patients .
•
Eighteen studies included control groups, with between 5 and 134 patients,
equivalent to between 6% and 125% of the vigabatrin sample.
RR (95% CI)
%
Weight
15.78 (1.01, 247.28)
80.75 (5.05, 1290.82)
7.00 (0.41, 120.16)
18.70 (1.20, 292.48)
1.94 (0.93, 4.04)
19.59 (1.26, 304.04)
8.06 (0.53, 122.00)
16.03 (1.01, 254.56)
4.63 (1.47, 14.61)
26.00 (1.65, 408.66)
13.14 (0.86, 199.72)
9.79 (0.68, 140.29)
6.05 (0.90, 40.87)
5.95 (0.38, 92.30)
7.76 (1.15, 52.39)
11.63 (0.73, 184.43)
6.00 (3.58, 10.07)
2.71
2.67
2.54
2.72
33.63
2.73
2.78
2.69
14.84
2.71
2.77
2.90
5.57
2.73
5.57
2.69
92.26
5.00 (0.68, 36.66)
21.08 (1.28, 347.72)
8.10 (1.60, 41.11)
5.13
2.62
7.74
5.49 (3.48, 8.65)
100.00
NOTE: Weights are from random effects analysis
.00077
SUMMARY ESTIMATES
PROPORTION VISUAL FIELD DEFECT
(ALL CAUSES)
(VIGABATRIN-ATTRIBUTED)
Median
studies
25th and 75 th
Number of
percentiles
studies
Median
VFDs occur on average in half of adult epilepsy patients, and in one third of
children, exposed to vigabatrin therapy.
•
Longer treatment duration, higher cumulative dose, and older age were all found
to be significantly associated with increases in the likelihood of VFDs
•
Prescribing of vigabatrin should be reserved for those patients where there is no
other safe alternative or where the patient has considered the benefit of ongoing
treatment to outweigh the risk of visual field problems.
percentiles
32
44
33, 60
7
29
17, 51
PROSPECTIVE COHORT
16
44
29,57
3
18
13,51
CROSS-SECTIONAL STUDY
16
43
35, 62
4
35
27,47
HUMPRHEY FIELD STUDIES
9
37
29,53
1
24
-
14
43
33,54
3
18
13,53
29,51
BOTH ASSESSMENT METHODS
•
25th and 75 th
ALL STUDIES
GOLDMANN PERIMETRY STUDIES
1291
CONCLUSIONS
PROPORTION VISUAL FIELD DEFECT
Number of
1
9
55
41,61
3
41
CHILD STUDIES
10
33
22,53
1
18
-
ADULT STUDIES
22
48
40,61
6
29
17,51