Overview and Basic Information
Botulinum toxin is produced by the gram-positive anaerobe Clostridium botulinum. The potent neurotoxin acts on the presynaptic terminal of the neuromuscular junction in the peripheral nervous system, inhibiting the release of acetylcholine. This leads to paralysis when injected intramuscularly. There are 7 distinct serotypes of botulinum toxin (A through G), each derived from a different strain of the bacteria. Human tissue is susceptible to 5 of these serotypes (A, B, E, F, and G); however, only types A and B have received FDA approval for injection in the United States.[7,8] The various type A toxin formulations have been approved for both esthetic and functional use, whereas type B toxin is currently only approved to treat cervical dystonia. Our discussion will mainly focus on the type A formulations, as these are the ones most commonly used in oculofacial plastic surgery.
Any of the muscles in the periorbital and facial regions may be targeted with botulinum toxin injection (see Fig. 1 for an anatomic depiction of these muscles). As the toxin acts on the neuromuscular junction, thereby causing paralysis of the injected muscle, it is essential that administering physicians thoroughly understand the anatomy of facial musculature and how the individual muscles behave. This is true when using botulinum toxin for either cosmetic or functional purposes.
Illustration of the various periorbital and facial muscles which may be targeted by botulinum toxin injections.
For instance, when administering esthetic injections to reduce furrows or rhytids, the muscle which causes the wrinkle should be injected (ie, injection of the corrugator supercilii muscle to reduce glabellar furrows; injection of the frontalis muscle to reduce horizontal forehead rhytids). This concept can sometimes be confusing as the targeted muscle is often in a different orientation or located a distance away from the wrinkle of interest. The situation is more straightforward when addressing functional issues as the therapeutic target is the action of the muscle itself (ie, injection of the orbicularis oculi in blepharospasm; injection of the zygomaticus major in hemifacial spasm (HFS), as opposed to the action's byproduct.
It is also important to consider the depth of injection. When injecting the frontalis or corrugator supercilii muscles, both of which are located beneath a thick layer of overlying skin and subcutaneous tissue/muscle, a relatively deeper injection is necessary. Conversely, injection of the orbicularis oculi muscle, which is located just below the skin surface, requires a very superficial injection. Injecting deeply in this area could result in unwanted migration of the toxin to affect extraocular muscles of the orbit, resulting in diplopia.
In general, when botulinum toxin injections are administered properly, serious complications are rare. Periocular ecchymosis and edema is encountered occasionally and is only temporary. With regard to the adverse ophthalmic manifestations, diplopia, ptosis, and dry eyes are the most notable. Given the ubiquity and frequency of its use in modern medicine, all ophthalmologists, even those who do not utilize botulinum toxin in their practice, should be aware of its potential unwanted effects.
Perhaps the most well known and extensively publicized indication of botulinum toxin is the esthetic reduction of facial wrinkles. It should be noted that although the sole FDA-approved cosmetic indication is the treatment of vertical glabellar furrows, the toxin is also very useful in treating other dynamic facial rhytids, including horizontal forehead wrinkles, periocular "crow's feet," and lip rhytids.[2,3] There is widespread off-label use of the toxin for these purposes.
When using botulinum toxin as a cosmetic tool, it is essential to direct the toxin toward the musculature which causes a wrinkle, as opposed to the wrinkle itself. Figure 2 provides basic injection patterns for the treatment of commonly treated facial rhytids. Patients must be aware that the effects of toxin injection are temporary, usually lasting approximately 3 to 6 months. Serial injections are necessary to maintain a good long-term result and may even aid in the prevention of the development of future wrinkles. As with any cosmetic procedure, patient expectations must be thoroughly understood before beginning treatment.
Botulinum toxin for reduction of 3 types of periocular wrinkles. Top row, Photograph of wrinkle. Middle row, Illustration indicating facial muscles responsible for above wrinkle and targeted by injection. Bottom row, Schematic of botulinum toxin injection patterns used to target the above muscles/wrinkles. The arrows indicate which facial muscles are responsible for the wrinkle demonstrated in the photo shown directly above it. The cross marks then indicate botulinum toxin injection locations/patterns used to target those muscles to treat the wrinkles demonstrated above.
Over 30 years ago, Scott[12,13] described the original clinical use of botulinum toxin for the treatment of strabismus by targeting the extraocular muscles. This functional application of the toxin is especially useful in isolated palsies of an extraocular muscle, whereby injecting the antagonizing muscle can help reduce the development of contracture (ie, treating the ipsilateral medial rectus muscle in a case of isolated sixth nerve palsy with lateral muscle paresis). Botulinum toxin can also serve as a noninvasive treatment option in patients with other types of strabismus wishing to avoid surgery.[14–18]
Although botulinum toxin has its therapeutic roots in strabismus, currently its most common functional uses in the periorbital region are the treatment of benign essential blepharospasm (BEB) and HFS.[19,20] Approval of this nonsurgical therapeutic option in 1989 was a huge step forward for patients afflicted with these potentially disabling disorders. Earlier to this, patients were faced with the decision to undergo surgeries with significant levels of morbidity to effectively treat their condition. These surgical procedures included eyelid protractor myectomy for BEB or neurosurgical decompression of the facial nerve for HFS.[21–23] The overactive muscles involved in these conditions are targeted by the toxin. Physicians must individually evaluate patients with BEB and HF to determine which facial muscles are primarily involved, and to what magnitude, in each clinical situation. Figure 3 provides basic injection patterns for these conditions. It must be emphasized that physicians should not adopt a "cookbook" approach as patient-specific dosing is essential to obtain a good result and to avoid complications.
Schematic of botulinum toxin injection sites for the treatment of benign essential blepharospasm (BEB) and hemifacial spasm (HFS).
We also find botulinum toxin injections to be very useful in patients with "secondary" blepharospasm due to ocular surface abnormalities. In this patient population, notably patients with superior limbic keratoconjunctivitis, primary ocular surface inflammation elicits eyelid spasm, which mechanically exacerbates the inflammation, resulting in additional and perhaps more forceful eyelid spasm. Targeting the orbicularis oculi muscles with botulinum toxin can help break this vicious cycle by reducing blepharospasm, the source of additional surface irritation. The ocular surface may then be more susceptible to management with topical medications.
Int Ophthalmol Clin. 2013;53(3):21-31. © 2013 Lippincott Williams & Wilkins