Professional Documents
Culture Documents
2 (April-June 2016)
Efficiency of the occlusion therapy with and without levodopa-carbidopa in amblyopic childrenA tertiary care centre experience
Ishfaq Ahmad Sofi, 1 Satish K Gupta, 2 Anuradha Bharti, 3 Tariq G Tantry 4
1
MBBS, MS. Registrar, Postgraduate Department of Ophthalmology, Government Medical College Srinagar.
MBBS, MS. Professor, Postgraduate Department of Ophthalmology, Government Medical College Jammu.
3
MBBS, MS. Senior resident, Postgraduate Department of Ophthalmology, Government Medical College Jammu.
4
MBBS, Junior resident, Postgraduate Department of Ophthalmology, Government Medical College Srinagar.
2
Abstract:
Objectives: To assess the role, efficacy and tolerability of levodopa-carbidopa in the management of small and older children
with different types of amblyopia.
Methodology: Prospective randomised placebo controlled clinical study, in which 50 amblyopic patients between 5 and 20 years
of age with visual acuity (V/A) < 20/40 were included, was carried on. After having attained the best possible refractive correction,
patients were randomly divided into 2 groups. They were prescribed levodopa-carbidopa (10:1) (4-6mg/kg/day in 2-3 divided
doses) or placebo, plus full-time occlusion of the sound eye, for a period of three months. Assessment of improvement in V/A,
compliance and tolerance was done at follow up visits. Data was analyzed using computer software Ms-Excel and Epi-Info Version
6.0. The statistical significance was assessed by Chi-Square/Fishers Exact Test.
Results: Visual acuity for the amblyopic eye improved significantly in both groups but there was significant improvement in group1
than group 2 (P = 0.0001). In a subgroup of patients older than 12 years, levodopa group showed statistically significant
improvement in baseline V/A (P = 0.0001). In patients with severe amblyopia, each group showed significant improvement in
baseline V/A (p < 0.05), but was significantly more in group1 (P = 0.0001). Compliance rates were similar among the groups and
levodopa-carbidopa at a dose range of 4-6 mg/kg/day was well tolerated.
Conclusion: Levodopa-carbidopa can be used as an adjunct to conventional occlusion therapy in amblyopia particularly in older
children and severe cases of amblyopia, and it is well tolerated.
Keywords: Amblyopia, Levodopa-carbidopa, Occlusion therapy.
Corresponding Author:
250
Efficiency of the occlusion therapy with and without levodopa-carbidopa in amblyopic children
Introduction
Amblyopia affects approximately 2% - 2.5%
of the general population (1) and it is the most
frequent cause of unilateral visual impairment in
childhood and school aged children. (2) Full time
occlusion of the sound eye has been the most
effective therapy of the amblyopia. (1, 3, 4, 50) It
prevents the fixating eye from taking part in the
act of vision, so that the patient is forced to use
his amblyopic eye. There have been reports that
part-time occlusion is as effective as full-time
occlusion. (6) In a randomized trial, the Pediatric
Eye Disease Investigator Group have
compared full-time, or all but one hour per day,
to six hours of patching per day in children with
amblyopia and have found that both treatment
protocols produced similar improvements in
vision. (7) However, many older children and
teenagers with amblyopia fail to achieve near
normal visual acuity. Attempts have been made
to treat amblyopia pharmacologically. Levodopa
administration results in modest degree of
improvement of visual acuity (2.7 lines) and
contrast sensitivity (72%), (8) in older children
and adolescents. (9) Even some studies
concluded that a placebo controlled trial is
necessary to determine whether levodopa can
successfully augment occlusion therapy in the
treatment of amblyopia. (10) The aim of this study
was to assess the role, efficacy and tolerability
of levodopa-carbidopa along with occlusion in
the management of children with different types
of amblyopia.
Materials and methods:
This study was in accordance with the ethical
standards of Declaration of Helsinki and was
approved by the Ethical committee of the
institution. A written informed consent was
taken from all the participants. Fifty cases that
attended our institution were studied over a
period of one year from November 2011 to
October 2012. Patients between 5 and 20 years
of age of either sex with different types of
amblyopia
(Anisometropic,
Strabismic,
Ametropic and Mixed anisometropic +
strabismic), with best corrected visual acuity
(BCVA) in the amblopic eye <20/40 were
included in the study. Cases having any ocular
cause for reduced visual acuity visible on
examination, history of narrow-angle glaucoma,
paralytic or restrictive strabismus, with history of
dystonic reactions were excluded. All patients
included were examined in our squint clinic after
251
252
Efficiency of the occlusion therapy with and without levodopa-carbidopa in amblyopic children
Syndopa 110 mg
(tablets/day)
Levodopa Dose
(mg/kg)
15-20
1 tablet
6.66 - 5.00
21-24
1 tablet
4.70 - 4.10
25 - 30
1.5 tablets
6.00 - 5.00
31 - 40
2 tablets
6.45 - 5.00
41 - 50
2.5 tablets
6.09 - 5.00
51 - 60
3 tablets
5.88 - 5.00
Group2
p value
<8
9(36%)
7(28%)
1.34
0.51
08- 12
8(32%)
12(48%)
>12
8(32%)
6(24%)
Male
14(56%)
13(52%)
0.08
0.77
Female
11(44%)
12(48%)
Age (years):
Gender:
"yates
corrected"
Severity:
Moderate (0.5 log
MAR)
7(28%)
14(56%)
18(72%)
11(44%)
Unilateral
19(76%)
19(76%)
Bilateral
6(24%)
6(24%)
Strabismic
5(20%)
4(16%)
Anisometropic
12(48%)
13(52%)
Mixed (strabismic
+ anisometropic)
5(20%)
4(16%)
Ametropic
3(12%)
4(16%)
2.96
0.08
0.41
0.3
Laterality:
Causes/Types:
253
Table 3. Comparison between the two study groups at baseline and at 1st, 2nd & 3rd FU visits
Effect of treatment on the mean logMAR in both dominant and amblyopic eyes at baseline
and at 1st, 2nd & 3rd FU visits
Group 1,
Levodopa /
carbidopa +
occlusion, n=25,
mean (SD)
Group 2,
Occlusion +
placebo, n=25,
mean (SD)
t-test
P value
Dominant
0.138 (0.216)
0.142 (0.186)
-0.063
0.95
Amblyopic
0.728 (0.270)
0.606 (0.262)
1.614
0.113
Dominant
0.100 (0.173)
0.128 (0.170)
-0.592
0.557
Amblyopic
0.338 (0.181)
0.503 (0.240)
-2.732
0.009
Dominant
0.079 (0.136)
0.116 (0.147)
-0.935
0.355
Amblyopic
0.210 (0.157)
0.430 (0.239)
-3.836
0.0001
Dominant
0.049 (0.092)
0.108 (0.139)
-1.767
0.84
Amblyopic
0.106 (0.135)
0.398 (0.254)
-5.06
0.0001
follow-up visit
Baseline
1st FU visit
(month 1)
2nd FU visit
(month 2)
3rd FU visit
(month 3)
LogMAR
Final (3month)
FU visit
t-test
P value
0.728 0.27
0.106 0.14
11.89
0.0001
0.606 0.26
0.398 0.25
6.981
0.001
Group 1,
n=25
Group 2,
n=25
Baseline,
(mean SD)
Final visit,
(Mean SD)
t test
P value
Group 1, n=8
0.845 0.30
0.164 0.11
7.25
0.0001
Group 2, n=6
0.733 0.30
0.667 0.32
1.58
0.17
Efficiency of the occlusion therapy with and without levodopa-carbidopa in amblyopic children
Baseline,
(mean SD)
Final visit,
(Mean SD)
Paired ttest
p value
Group 1, n=18
0.839 0.23
0.114 0.11
14.52
0.0001
Group 2, n=11
0.851 0.18
0.609 0.23
4.32
0.001
Table 7. Difference between the two study groups regarding improvement of BCVA in patients
with severe amblyopia
Effect of treatment on the mean logMAR for amblyopic eyes at baseline and at final (3
month) FU visits in the subgroup of patients with severe ( > 0.5) amblyopia
LogMAR
Baseline,
(mean SD)
Final visit,
(mean SD)
Group 1,
Levodopa/carbidopa +
occlusion, n=18
Group 2,
occlusion +
placebo, n=11
MannWhitney test
P value
0.839 0.23
0.851 0.18
91
0.74
0.114 0.11
0.609 0.23
0.0001
Figure1. Line diagram showing Improvement for the amblyopic eyes in the two study groups
regarding mean logMAR at baseline, and at 1st, 2nd and 3rd FU visits
0.8
Group 1
Group 2
0.7
0.6
Log MAR
254
0.5
0.4
0.3
**
0.2
**
0.1
0
Baseline
1st FU
2nd FU
3rd FU
255
Figure 2. Line diagram showing Effect of treatment on the mean logMAR at baseline and at final
FU visit for amblyopic eyes in the subgroup of patients older than 12 years in each study group
Group 2, n=6
Group 1, n=8
**
Final visit
Baseline
0.2
0.4
0.6
0.8
Log MAR
*P-value <0.001, **P-value >0.05
Discussion
Occlusion therapy of the sound eye is
considered as the standard treatment of
amblyopia (1) so this study used occlusion
therapy in all the cases. Visual evoked potential
(VEP) abnormalities (phase-misalignment and
reduced signal-to-noise ratios) associated with
amblyopia improved after occlusion therapy of
the sound eye. (11) Several studies have used
levodopa as a pharmacological agent alone (1214)
or in combination (15-19) with standard
occlusion therapy. These studies have used this
agent for a period varying from 1 day to 7 weeks
(12, 13, 23, 24)
with doses varying from 0.5 mg/kg to
8.3mg/kg per day (8, 10, 16, 21-23) in different age
groups. The present study used levodopacarbidopa (ratio 10:1) in a dose range of 4.1 to
6.6 mg/kg/day for 12 weeks. The purpose of this
study was to assess the role, efficacy and
tolerability of this drug in addition to the occlusion
therapy in the management of amblyopia in
children. The baseline characteristics including
demographic data, severity of amblyopia,
laterality and mean baseline logMAR were
insignificantly different in two groups. There was
a significant improvement of mean logMAR at
1st, 2nd and 3rd / final FU visit in both the groups
but showing significantly more improvement in
256
Efficiency of the occlusion therapy with and without levodopa-carbidopa in amblyopic children
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
amblyopia.
J
Pediatr
Ophthalmol
Strabismus, 1993; 30:354-60.
Pediatric Eye Disease Investigator Group.
A prospective, pilot study of treatment of
amblyopia in children 10 to <18 years old.
Am J Ophthalmol, 2004; 137:581-3.
Repka MX, Kraker TR, Beck RW, Atkinson
SC, Bacal DA, Bremer DL, et al. A pilot
study of levodopa dosage as treatment for
residual amblyopia in children 8 to <18
Years old. Arch Ophthalmol, 2010;
128:1215-7.
Kelly JP, Tarczy-Hornoch K, Herlihy
E, Weiss AH. Occlusion therapy improves
phase-alignment of the cortical response in
amblyopia. Vision Res, 2015; 114:142-50.
Gottlob I, Charlier J, Reinecke RD.Visual
acuities and scotomas after one week
levodopa
administration
in
human
amblyopia. Invest Ophthalmol Vis Sci,
1992; 33:2722-8.
Gottlob I, Wizov SS, Reinecke RD. Visual
acuities and scotomas after 3 weeks'
levodopa administration in adult amblyopia.
Graefes Arch Clin Exp Ophthalmol, 1995;
233:407-13.
Wu X, Liu S, Xu H, Huang P, Xu H, Ming X,
et al. A preliminary report of the effect of
levodopa and carbidopa for childhood
amblyopia. Yan Ke Xue Bao, 1998; 14:23841.
Leguire LE, Rogers GL, Walson PD,
Bermer DL, McGregor ML. Occlusion and
levodopa-carbidopa treatment for childhood
amblyopia. J AAPOS, 1998; 2:257-64.
LeguireLE, Walson PD, Rogers GL, Bermer
DL, McGergor ML. Levodopa/carbidopa
treatment for amblyopia in older children. J
Pediatr Ophthalmol Strabismus, 1995;
32:143-51.
Procianoy E, Fuchs FD, Procianoy L,
Procianoy F. The effect of increasing doses
of levodopa on children with strabismic
amblyopia. J AAPOS, 1999; 3:337-40.
Mohan K, Dhankar V, Sharma A. Visual
acuities after levodopa administration in
amblyopia.
J
Pediatr
Ophthalmol
Strabismus, 2001; 38:62-7.
Bhartiya P, Sharma P, Biswas NR, Tandon
R, Khokhar SK. Levodopa-carbidopa with
occlusion in older children with amblyopia.
J AAPOS, 2002; 6:368-72.
Leguire LE, Komaromy KL, Nairus TM,
Rogers GL. Long-term follow-up of L-dopa
21.
22.
23.
24.
25.
26.
27.
28.
257