Medical Care
Blepharospasm is a chronic condition that too often progressively worsens. Although no cure exists, patients have excellent treatment options. Since the disease frequently progresses despite treatment, patients may become frustrated and resort to unconventional remedies, sometimes becoming the victims of charlatans. [14]
The most effective of today's conventional treatments include botulinum toxin injections, education, and support provided by the Benign Essential Blepharospasm Research Foundation (BEBRF), pharmacotherapy, and surgical intervention. Unconventional treatments have included faith healing, herbal remedies, hypnosis, and acupuncture.
The first line of treatment for all patients should address the sensory limb of the blepharospasm vicious cycle circuit. Such measures include wearing tinted sunglasses with ultraviolet blocking to decrease the poorly understood cause of painful light sensitivity (photo-oculodynia). [37] Adams et al (2006) showed improved light sensitivity with gray and FL-41 tinted lenses, [38] and Blackburn et al (2009) showed the FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. [39]
Taping up the eyelids and ptosis crutches may be tried but often are not tolerated as a long-term treatment. Lid hygiene to decrease irritation and blepharitis should be encouraged. Frequent applications of artificial tears and punctal occlusion to alleviate dry eyes often improve symptoms.
Benign Essential Blepharospasm Research Foundation, formed in 1981, is a foundation established to undertake, promote, develop, and search for a cure for benign essential blepharospasm (BEB), Meige syndrome, and related disorders. This organization is located in Beaumont, Texas, and promotes awareness of these conditions to both physicians and the general public, organizes support groups throughout the world, and obtains funding for research and education. [40, 41, 42]
Pharmacotherapy
Since the central control center for blepharospasm is unknown, drug therapy directed against this as of yet unidentified center tends to follow a "shotgun approach." Historically, an extensive list of drugs has been used to treat blepharospasm, in part because blepharospasm initially was considered a manifestation of psychiatric illness, and because no one drug was demonstrably more efficacious than another. Recently, these psychoactive medicines have been used not for their psychotropic action but for their motor system action.
Most patients respond incompletely or not at all to pharmacotherapy. At best, pharmacotherapy provides only partial, transient relief. Patients react differently to the various pharmacologic agents, and there is no way to predict which patient may respond to any particular agent. Tricyclic antidepressants do not directly help blepharospasm but are useful if there is depression exacerbating the symptoms. Drugs with the highest percentages of favorable patient responses include lorazepam (67% of patients), clonazepam (42%), and Artane (41%). The relief provided by these agents is variable.
Although drugs from a variety of different classes have demonstrated some effectiveness in blepharospasm, drug therapy for blepharospasm and facial dystonias usually are based upon the following 3 unproven pharmacologic hypotheses: (1) cholinergic excess, (2) GABA hypofunction, and (3) dopamine excess. Pharmacotherapy generally is less effective than botulinum toxin injections and, thus, is reserved as second-line treatment for spasms that poorly respond to botulinum toxin, such as in mid-face and lower-face spasm.
Botulinum toxin
Botulinum A toxin is regarded as the most effective treatment of choice for the rapid but temporary treatment of orbicularis spasm. [43, 44, 45, 46, 47, 48, 49, 50, 51, 52] More than 95% of patients with blepharospasm report significant improvement with use of the toxin. The toxin interferes with acetylcholine (ACh) release from nerve terminals, causing temporary paralysis of the associated muscles. Botulinum A toxin is the product of the bacteria, Clostridium botulinum (a large anaerobic, gram-positive, rod-shaped organism). Two of the commercially available botulinum A preparations include onabotulinumtoxin A (Botox) and incobotulinumtoxin A (Xeomin). Abobotulinumtoxin A (Dysport) also may be effective. [53]
Once injected, the toxin rapidly and firmly binds at receptor sites on cholinergic nerve terminals in a saturable fashion. The toxin is internalized through the synaptic recycling process. Paralysis of muscle is a result of the inhibition of the release of vesicular ACh from the nerve terminal. It is assumed that the toxin attaches to the ACh-containing vesicles in the nerve terminal and prevents calcium-dependent exocytosis.
The paralytic effect is dose related, with a peak of effect at 5-7 days after injection. Patients typically note the onset of relief 2.5 days after injection, with a mean duration of relief from symptoms of 3 months. More than 5% of treated patients have sustained relief for more than 6 months, although some patients require injections as often as monthly. It takes as much as 6-9 months for the injected muscles to recover from the effects of the toxin, and, occasionally, muscles do not fully return to their preinjection level of function. Some have suggested that the development of antitoxin antibodies or the progressive atrophy of muscle may account for variations in the dose response curve, but no studies have supported these findings.
Tear breakup time (TBUT), lissamine green staining, and Ocular Surface Disease Index (OSDI) scores all have been shown to improve after botulinum toxin injection. [54]
Complications of botulinum toxin injections include ptosis (7-11%), corneal exposure/lagophthalmos (5-12%), symptomatic dry eye (7.5%), entropion, ectropion, epiphora, photophobia (2.5%), diplopia (< 1%), ecchymosis, and lower facial weakness. [55, 56] One of the more common adverse effects, ptosis, is due to diffusion of toxin from the upper eyelid injection sites to the exquisitely sensitive levator muscle. The incidence of ptosis has been reported as high as 50% of patients treated more than 4 times. In the hands of experienced injectors, the rate of complications such as ptosis is presumably less. Injection of botulinum toxin into the medial and lateral pretarsal orbicularis is usually sufficient to stop spasms for the duration of effect; avoiding central injections to the preseptal and preorbital orbicularis should help reduce the risk of ptosis.
Meticulous technique in the administration of botulinum toxin helps ensure reliable and consistent results. BOTOX® should be hydrated with 0.9% nonpreserved saline, which should be introduced slowly into the vacuum-sealed vial to prevent frothing. If there is no vacuum in the BOTOX® bottle, it should not be used. Once reconstituted, the solution should be used immediately or kept refrigerated.
At the first treatment, use of a total dose of no more than 25 units per eye, divided among 4-6 periocular injection sites is recommended to avoid adverse effects. Subsequent treatments should be adjusted depending on patient response to the initial doses. [57] At each site, inject 2.5-10 units of BOTOX®. Use of lower volumes (higher concentrations) is suggested to avoid the risk of spread to adjacent areas. The solution should be injected subcutaneously over the orbicularis oculi and intramuscularly over the thicker corrugator and procerus muscles. Patients may return home without restrictions of activity. Most patients require repeated treatment every 3 months, but this ranges from 1-5 months.
Chundury et al found that patients who preferred treatment with incobotulinumtoxin A felt that it was more effective, whereas those who preferred treatment with onabotulinumtoxin A felt that it had a longer duration. [58]
However, Saad and Gourdeau found in a “split-face” technique study that no difference was noted in either subjective or objective measures between the two toxins. [59]
Long term use (up to 30 years) of botulinum toxins have been found to be safe and effective. [60]
In patients with blepharospasm, transcranial magnetic stimulation has been shown to improve the effectiveness of botulinum toxin A, with a corresponding reduction in anxiety and depression. [61, 62]
Surgical Care
In patients with blepharospasm who do not improve sufficiently with an adequate trial of botulinum toxin injections, surgical intervention may be considered. The mainstay of surgical treatment of spasm of the orbicularis oculi is myectomy. [63, 64, 65, 66, 67, 68] An older procedure, neurectomy, has almost completely been abandoned because of a higher complication rate than seen with myectomy. Many patients with BEB have a component of apraxia of eyelid opening. [69, 70] It is estimated that almost 50% of patients who are considered failures of BOTOX® treatment have apraxia of eyelid opening. Frontalis suspension and limited myectomy with complete removal of the pretarsal orbicularis should be considered for patients who are visually disabled by apraxia of eyelid opening.
Patients may fail botulinum toxin therapy because they have eyelid malposition, aesthetic concerns, apraxia of eyelid opening, or photo-oculodynia. These conditions require surgeries in addition to or in place of myectomy.
Myectomy/Myotomy
Limited myectomy involves surgical extirpation of protractors of the eyelids, including the pretarsal, preseptal, and orbital portions of the upper and lower eyelid orbicularis oculi muscle. Myotomy of residual orbicularis, as described by Lai, has been shown to offer improvements similar to an extended myectomy, but with improved cosmetic outcomes. [60, 71]
Extended myectomy includes removal of the procerus and corrugator muscles. Myectomy is a staged procedure with upper eyelid surgery typically performed first, followed by lower eyelid surgery if symptoms persist. Simultaneous upper and lower eyelid myectomy is avoided because it typically leads to chronic lymphedema.
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Adequate access to the orbicularis oculi, corrugator, and lateral procerus muscle can be gained through an upper eyelid crease incision. Muscle is removed in 3 en block sections.
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Dissection begins in a plane between the skin and the pretarsal muscle.
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A 1- to 2-mm band of pretarsal muscle is preserved at the eyelid margin, and the rest of the pretarsal muscle is removed.
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Dissection proceeds superior in a plane between the skin and the muscle to above the eyebrow. The orbital septum is left intact, and the preaponeurotic fat pad is not sculpted. The remaining preseptal and orbital orbicularis is removed. A thin band of muscle is left beneath the eyebrow to prevent alopecia.
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Finally, the lateral orbicularis is removed over the lateral raphe and extending into the lateral portion of the inferior orbicular. The lateral dissection is aided by retroilluminating the skin muscle flap. When lower lid myectomy is required, adequate access can be obtained via a lower eyelid crease incision.
Many patients with BEB have aesthetic concerns about eyebrow ptosis or forehead rhytids, which can be addressed safely at the time of myectomy by sculpting or repositioning of the retro-orbicularis oculi fat pad or by endoscopic forehead lift surgery.
Frontalis suspension
Karapantzou et al found that, in patients with blepharospasm, frontalis suspension was effective in patients in whom botulinum toxin injections alone were ineffective. [72]
Superior cervical ganglion block
Treatment of BEB focuses heavily on reducing the motor component of the disease. Remember that there also is a sensory loop of the disease, which is harder to quantify because it involves the patient's subjective complaints of ocular surface irritation and photosensitivity. In some patients in which BOTOX® treatment fails, a careful history and examination reveals that BOTOX® does reduce spasm and weaken the orbicularis muscle but does not relieve the sensory symptoms of the disease. For patients who complain of debilitating light sensitivity (photo-oculodynia) intervention by a pain clinic may benefit the patient.
Two reports have demonstrated reduction of photo-oculodynia after superior cervical ganglion blocks to chemodenervate the orbital sympathetics. These preliminary studies suggest that the sympathetic nervous system may play a role in maintaining the afferent loop of the disease. [73]
Interventions involving the globus pallidus
Deep brain stimulation of the globus pallidus internus and pallidotomy have been described for Meige syndrome. [74]
Long-Term Monitoring
Treatments such as botulinum toxin injections usually provide temporary relief from blepharospasm, and long-term follow-up care is needed.
