Folie 1

1
During her residency in Mannheim, Daniela
Claessens concentrated on multifocal intraocular
lenses. During a fellowship at Massachusetts Eye
and Ear Hospital she examined the effect of
alpha interferon on experimentally induced
subretinal neovascularisations in an animal
model. She completed her ophthalmological
training at Heinrich Heine University Düsseldorf
with a focus on cornea and immunology.
2
Purpose If spastic entropion leads to discomfort
by trichiasis, conjunctivitis or keratitis,
eversion of the lower lid can be achieved by
intramuscular injection of botulinum toxin A (for
example Dysport, Ipsen Pharma or Botox,
Allergan). Historical background The german
physician and poet Justinus Kerner (1786 1862)
described the effect and conceived a possible
therapeutic use of botulinum toxin A (BTX-A) and
called it sausage poison as BTX can cause
poisoning by growing in badly handled or prepared
meat products. In 1895 Emile van Ermengen
isolated the bacterium clostridium botulinum.
Edward isolated the toxin from cultured
clostridium botulinum in 1944 and Bergen
discovered in 1949 that it blocks neuromuscular
transmission. By 1973 Alan B.Scott used BTX-A
experimentally and in 1980 he officially used it
for the first time to treat strabism in humans.
In 1989 BTX-A was approved by the US food and
drug administration (FDA) for the treatment of
strabism, blepharospasm and hemifacial spasmus
approval for cervical dystonie followed in
2000 and for temporary treatment of frown lines
in 2002.
3
Chemical mechanism Botulinum toxin is a protein
produced by clostridium botulinum. There exist
seven serologically distinct toxin types of
botulinum toxin. The toxin is a
two-chain polypeptide. The light chain is an
enzyme that attacks one of the fusion proteins at
the neuromuscular junction, thus preventing
vesicles from anchoring to the membrane and
releasing acetylcholine. By inhibiting
acetylcholine release, the toxin interferes with
nerve impulses and causes paralysis of the
muscle. This effect lasts 3-6 months. Side
effects Allergic reaction, haematoma, infection,
headache paralysis of the wrong muscle (leading
to ptosis, ectropion or diplopia) is temporary as
well as the therapeutical effect. Contraindicatio
ns Respiratory disorders, disturbances of the
motor endplate (myasthenia gravis),
hypersensitivity to one of the components of the
drug, infection at injection site, simultaneous
treatment with aminoglycosid antibiotics,
pregnancy or nursing.
4
Methods To prepare the injected solution, 2.5 ml
of sterile sodium chloride were carefully
injected in a bottle with 500 IU of botulinum
toxin A which produced a clear solution of 20 IU
per 0.1 ml. Since 2003 10 eyes of 10 patients
with spastic entropion were treated with BTX-A.
Follow up was 24 36 months. Patients with
spastic entropion who had contraindications for
entropion operation or who did not want surgical
therapy signed informed consent after
information about off label use, risks and side
effects, duration of the therapeutical effect and
therapeutical alternatives. If desired, al local
anaesthetic ointment was used 15-20 minutes prior
to treatment. The lower lid was disinfected with
alcohol free disinfectant to avoid denaturation
of protein components of BTX. Using a 20-gauge
needle a total of 60 IU BTX-A was injected at
two different sites of the lateral lower lid into
the orbicularis muscle (as shown above). The
dosage was monitored using a 1.0 syringe with a
0.01 scale. Following injection an ice pack was
used to diminish pain and to counteract diffusion
by vasoconstriction. The patients were advised to
stay in a supine position for the following 4
hours to prevent diffusion of BTX.
5
Results In all cases normal position of the
lower lid could be achieved 2-7 days after
injection and persisted for 3 6 months. 9
patients decided to have retreatments when the
therapeutical effect vanished, 1 patient
underwent surgery after recurrence.1 patient
developed mild haematoma after injection, 3
patients described flue like symptoms and
headache after the initial treatment.
Complications like infection, overcorrection
leading to ectropion or diplopia occurred in none
of the described cases.
6
Spastic entropion of left lower lid
before treatment
Position of left lower lid 7 days after injection
7
Spastic entropion of right lower lid
before treatment
Position of left lower lid 10 days after injection
8
Conclusion As an office procedure injection of
botulinum toxin A is an alternative to surgery
of spastic entropion. The therapeutical effect is
not permanent, therefore the costs of the drug
have to be considered. However, the majority of
the described patients preferred to have
retreatments in order to avoid an
operation. Literature Botox History and
development (http//www.botox.com/site/professiona
ls/product_info/history_and_development.asp) Botul
inum Toxins Pharmacology and its current
therapeutic evidence for use (http//www.ncbi.nlm.
nih.gov/entez/query.fcgi) Wieder, JM, Moy RL,
Understanding Botulinum Toxin,Dermatol.Surg.
1998, 24 1168 1170 Kraft SP and Land AE,
Botulinum toxin injections in the treatment of
blepharospasm, hemifacial spasm and eyelid
fasciculations. Can J Neurol Sci 19(( 15 ( 3)
276-80S