Zdrav Vestn Supl | Amblyopia-medical treatment I-37
IZVIrnI člAnek/OrIgInAl ArtIcle
Amblyopia-medical 
treatment Medical treatment of amblyopia:  
Present state and perspectives
Medikamentozno zdravljenje ambliopije
emilio c. campos, Michela Fresina
Abstract
A brief review is provided on the role of experi-
mental modulation of the visual system during 
its plastic period. The importance of several sub-
stances could be demonstrated. Potential clinical 
applications of available studies for amblyopia 
treatment are summarised. The role of the dopa-
minergic system and particularly of dopamine 
in amblyopia are also discussed. Results of the 
use of cytidin-5’-diphosphocoline (citicoline) 
in amblyopia are evaluated in detail. Advantages 
and indications for a combination of citicoline 
with part-time occlusion are discussed in detail. 
Finally, new administration modalities of citico-
line, more detailed evaluation of its efficacy and 
the use of new substances are briefly analysed.
Izvleček
Prikazan je kratek pregled poskusne modulacije 
vidnega sistema v njegovem plastičnem obdobju. 
Dokazati je bilo mogoče pomen mnogih snovi. V 
povzetku so navedene možnosti klinične upora-
be razpoložljivih raziskav zdravljenja ambliopije. 
Prispevek obravnava tudi vlogo dopaminergič-
nega sistema in predvsem dopamina pri ambli-
opiji. Podrobno so ocenjeni rezultati uporabe 
citidin-5’-difosfokolina (citokolina) pri amblio-
piji. Podrobno so tudi obravnavane prednosti in 
indikacije za kombiniranje citokolina s prekriva-
njem očesa za določen čas. Na koncu sledi kratka 
analiza novih načinov aplikacije citokolina, bolj 
podrobna ocena njegove učinkovitosti ter upo-
rabe novih snovi.
Review
With the visual demands of our society, 
amblyopia, and particularly unilateral am-
blyopia, has become a serious socio-econo-
mic problem. It is not easy to evaluate the 
incidence of amblyopia in the entire popu-
lation, but studies in a particular population 
subset have underlined an average prevalen-
ce of amblyopia of between 1 % and 4 %.1,2 
All forms of amblyopia are characterised by 
reduced visual acuity, but they differ from 
one another because of a different progno-
sis. Amblyopia can occur only during the 
critical period of development of the visual 
apparatus. When the same factors that cau-
se amblyopia occur after the visual system 
has matured, they are not capable of indu-
cing the disease. Therefore, these factors are 
effective during the first 7–8 years of life; the 
sooner one of these causes occurs, the more 
difficult the visual recovery. For this reason, 
the earlier the therapy is started, the sooner 
effective results will be obtained.3 The tre-
atment of amblyopia is based on the inter-
ruption of the visual input in the fixing eye, 
in order to stimulate vision development 
in the amblyopic eye. However, sometimes 
this therapeutic approach proves insuffici-
ent, owing either to problems of compliance 
with patching treatment, or to a tendency of 
losing, over time, the benefits obtained.4
For the reasons mentioned above, new 
treatment modalities for amblyopia are con-
stantly proposed. They include bio-feedback 
techniques, perceptual training and medical 
treatment. The latter has been for a long time 
the dream of strabismologists, ever since the 
second half of the 19th century. All efforts 
have been aimed at combining occlusion 
with active pharmacological stimulation 
Ophthalmology Service, 
University of Bologna, 
Bologna, Italy
Korespondenca/
Correspondence:
prof. dr. med. emilio c. 
campos,  
U. O. di Oftalmologia 
Universitaria, Via Palagi 9, 
40138 Bologna, Italy
tel.: +39 051 6362832
fax: +39 051 342821
e-mail: emilio.campos@
unibo.it
Ključne besede:
ambliopija, 
medikamentozno 
zdravljenje, 
nevromodulacija, 
plastičnost, vidni sistem
Key words:
amblyopia, medical 
treatment, neuro-
modulation, plasticity, 
visual system
Citirajte kot/Cite as:
Zdrav Vestn 2012;  
81: I-37–9
Prispelo: 13. feb. 2012, 
Sprejeto: 6. apr. 2012
I-38 Zdrav Vestn Supl | junij 2012 | letnik 81
IZVIrnI člAnek/OrIgInAl ArtIcle
enhances the effects of patching in amblyo-
pic patients of different ages. We have shown 
that this substance improves temporarily 
visual acuity, visual evoked responses and 
contrast sensitivity in both eyes of adult pa-
tients with amblyopia. It enhances the effect 
of part-time occlusion in children. A 30-day 
treatment with 500 mg per day in children 
produced results which would last 6 months. 
Treatment was therefore prescribed twice a 
year. Yet, till recently, citicoline could be ad-
ministered only intra-muscularly. This made 
it impossible to prescribe the substance in 
very young children. An oral preparation of 
citicoline is now available. Our Group has 
experienced its efficacy and data appear to 
confirm the previous observations made 
with CDP-choline administered via the in-
tramuscular route, which demonstrated that 
the treatment is a useful complement to pat-
ching in order to shorten conventional pat-
ching treatment.20 It is also possible that in 
the near future we shall be able to modulate 
the plasticity of the visual cortex, restored by 
the use of some substances providing phar-
macological stimulation.21,22 It seems alrea-
dy possible to temporarily improve contrast 
sensitivity in the amblyopic visual cortex by 
means of repetitive transcranial magnetic 
stimulation (rTMS), indicating continued 
plasticity of the amblyopic visual system in 
adulthood, and so opening the way for a po-
tential new therapeutic approach to the tre-
atment of amblyopia.23
Acknowledegements
This study was supported in part by the 
Fondazione Cassa di Risparmio in Bologna.
which could make the therapeutic effect of 
patching more effective and enduring. Stri-
chnine was proposed initially;5 in the 50’s of 
the 20th century the use of nicotin acid and 
oxygen was suggested for suppression and 
amblyopia.6 Increasing knowledge has been 
gathered on the role of neuro-transmitters 
in the maturation of the visual system. Am-
blyopic inhibition mechanisms are connec-
ted with synaptic neuro-transmission. Be-
ta-blockers as well as norepinephrine can 
delay the plasticity of the visual system.7,8 
Exogenous nerve growth factor prevents the 
effect of visual deprivation.9 Much more evi-
dence has been gathered on this point and 
brought to a rational use of a neuro-medi-
ator such as dopamine in amblyopia. This 
substance has been shown to improve tem-
porarily suppression scotomas and visual 
function in amblyopia.10 The association of 
carbodopa-levodopa has been demonstra-
ted to induce longer lasting effects.11-13 The 
efficacy of dopamine has been shown objec-
tively by means of functional MRI. Systemic 
side-effects, however, were present with this 
type of treatment.
Our Group has been involved in the use 
of CDP-choline (citicoline) in amblyopia 
since 1992. Citicoline enhances endogeno-
us dopamine activity and does not induce 
systemic side-effects. The stimulation of 
the dopaminergic system with CDP-choli-
ne may be attributable to a mechanism that 
causes an improvement in the retinal and 
post-retinal performance of glaucomatous 
patients when treated with CDP-choline.14 
These considerations have suggested a ratio-
nale for using CDP-choline in patients suffe-
ring from amblyopia,. Inadequate foveal or 
peripheral retinal stimulation and/or abnor-
mal binocular interaction causing different 
visual input from the foveae during the cri-
tical period of visual development induce an 
alteration in genetically programmed pro-
cesses that guide the ganglion axons towards 
the lateral geniculate body and then to the 
visual cortex. As this development process is 
influenced by both endogenous and exoge-
nous stimuli, it could be pharmacologically 
modulated. Previous studies15-19 report that 
intramuscular cytidin-5’ -diphosphocholine 
(also known as CDP-choline or citicoline), 
Zdrav Vestn Supl | Amblyopia-medical treatment I-39
IZVIrnI člAnek/OrIgInAl ArtIcle
13. Leguire LE, Komaromy KL, Nairus TM, Rogers 
GL. Long-term follow-up of L-dopa treatment in 
children with amblyopia. J Ped Ophtalmol Strabi-
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14. Parisi V, Manni G, Colacino G, Bucci MG. Cyti-
dine-5’-diphosphocholine (citicoline) improves 
retinal and cortical responses in patients with gla-
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15. Campos EC, Benedetti P, Schiavi C, Scorolli L. 
Risultati preliminari sull’impiego della citicolina 
nell’ambliopia. Boll. Soc. Med. Chir. Modena 1992; 
4: 357–360.
16. Campos EC, Schiavi C, Benedetti P, Bolzani R, 
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amblyopia: Preliminary results. Graefes Arch Clin 
Exp Ophthalmol 1995; 233:307–312.
17. Campos EC, Bolzani, R, Schiavi C, Baldi A, Porci-
atti V. Cytidine-5’-diphosphocoline enhances the 
effect of part-time occlusion in amblyopia. Doc. 
Ophthalmol. 1997; 93:247–263.
18. Campos EC. Future directions in the treatment of 
amblopia. Lancet 1997; 349:1190–1191.
19. Porciatti V, Schiavi C, Benedetti P, Baldi A, Cam-
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Arch Clin Exp Ophthalmol. 2008; 246:143–150.
21. Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, 
De Pasquale R, O’Leary OF, Castrén E, Maffei L. 
The antidepressant fluoxetine restores plasticity in 
the adult visual cortex. Science. 2008; 320:385–388.
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