Craniofacial Muscles

304 J. Park et al.
is as high as 50%. It is recommended to inject the toxin into orbicularis oculi
muscles in a super fi cial, subcutaneous plane and spare the central portion of
upper eyelid to prevent blepharoptosis. The tip of the needle should be directed
outwards, not towards the median portion of upper lid. This complication also
can be avoided by using a lower concentration and/or a lower volume, which
reduces the risk of spreading to adjacent areas.
The use of less toxin (<25 units/eye) might be helpful, but there is controversy
about the relationship between volume and dose of each set of injections
and the incidence of blepharoptosis. Dutton and Buckley (Dutton and Buckley
1988 ) reported that the incidence of blepharoptosis will be more than double if
more than 25 units of BoNT are injected per eye. On the other hand, Osako and
Keltner (Osako and Keltner 1991 ) reported no signi fi cant difference in dosage
of BoNT or volume of injections between the patients who developed ptosis
and those who did not.
The blepharoptosis is transient as is the effect of toxin, but if needed, the a 2-
adrenergic agonist Iopidine ® (apraclonidine 0.5%) eye drops can be applied to
correct the ptosis temporarily. This causes Müller’s muscles to contract and
temporarily elevate the upper eyelid up to 2 mm.
(c) Dry eye , Lagophthalmos , Exposure keratopathy : Patients with blepharospasm
often have dry eye. BoNT injection also may induce dry eye secondary to either
exposure keratopathy with lagophthalmos or meibomian gland dysfunction.
This generally lasts several days to weeks and can be treated with lubricants,
taping, and punctal occlusion. Rarely, a temporary tarsorrhaphy may be necessary
in severe patients.
(d) Diplopia : Diplopia secondary to BoNT injections is rare, and the inferior
oblique is the most commonly affected muscle due to the anterior site of its
origin (Wutthiphan et al. 1997 ) . As the toxin may spread deep into the orbit,
thus reaching the inferior oblique muscle, Frueh et al. ( 1988 ) recommended
avoiding injecting into the medial portion of the lower eyelid. Once diplopia
occurs, an eye patch or prism lens can be applied to reduce the discomfort until
the effects of the toxin wear off. In patients with puffy lower eyelids, the dose
injected into the lower lid should be reduced, as the risk of diffusion of BoNT
is greater increasing the risk of diplopia due to inadvertent treatment of the
inferior oblique muscles.
(e) Antibody Formation : One of the main potential long-term side effects of BoNT
use is the development of an immunologic resistance due to the production of
neutralizing antibody to the neurotoxin after repeated injections. This, however,
is still controversial (Jankovic and Schwartz 1993 ; Kalra and Magoon 1990 ) .
Antibody formation is more likely to occur in patients with torticollis than in
those with blepharospasm or hemifacial spasm because the amount of toxin
used is much higher in torticollis patients. The reported incidence of this sensitization
is 3–10% (Greene et al. 1994 ) .
Several risk factors for sensitization to BoNT have been identi fi ed: (Greene
et al. 1994 ; Dressler and Benecke 2007 ) injection of over 100 units of Botox ®