Benign Essential Blepharospasm Treatment & Management
- Author: Robert H Graham, MD; Chief Editor: Edsel Ing, MD, FRCSC more...
Blepharospasm is a chronic condition, which too often progressively worsens. Although no cure currently 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.
The most effective of today's conventional treatments include education and support provided by the Benign Essential Blepharospasm Research Foundation (BEBRF), pharmacotherapy, botulinum toxin injections, 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). Adams et al (2006) showed improved light sensitivity with gray and FL-41 tinted lenses, and Blackburn et al (2009) showed the FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm .
Taping up the eyelids and ptosis crutches may be tried but are often 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.[33, 34, 35]
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 is generally less effective than BOTOX® injections and, thus, is reserved as second-line treatment for spasms that poorly respond to BOTOX®, such as in mid-face and lower-face spasm.
Botulinum A toxin is regarded as the most effective treatment of choice for the rapid but temporary treatment of orbicularis spasm.[36, 37, 38, 39, 40, 41, 42, 43, 44, 45] 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 onabotulinumtoxinA (Botox) and incobotulinumtoxinA (Xeomin). AbobotulinumtoxinA (Dysport) may also be effective.
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 have all been shown to be improved after botulinum toxin injection.
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.[48, 49] 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. 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 incotulinumtoxinA felt that it was more effective, while those who preferred treatment with onabotulinumtoxinA felt that it had a longer duration.
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.
In patients who do not develop sufficient improvement 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.[53, 54, 55, 56, 57, 58] 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.[59, 60] 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.
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. 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.
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.
Dissection begins in a plane between the skin and the pretarsal muscle.
A 1- to 2-mm band of pretarsal muscle is preserved at the eyelid margin, and the rest of the pretarsal muscle is removed.
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.
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.
Karapantzou et al found that, in patients with blepharospasm, frontalis suspension was effective in patients in whom botulinum toxin injections alone were ineffective.
Superior cervical ganglion block
Treatment of BEB focuses heavily on reducing the motor component of the disease. Remember that there is also 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.
Houser M, Waltz T. Meige syndrome and pallidal deep brain stimulation. Mov Disord. 2005 Sep. 20(9):1203-5. [Medline].
Etgen T, Muhlau M, Gaser C. Bilateral putaminal grey-matter increase in primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006 May 11. [Medline].
Fahn S. Blepharospasm: A focal dystonia. In: Bosniak S, ed. Advances in Ophthalmic Plastic and Reconstructive Surgery. Vol 4. Elsevier Science. 1985:87-91.
Jankovic J. Etiology and differential diagnosis of blepharospasm and oromandibular dystonia. Adv Neurol. 1988. 49:103-16. [Medline].
Jankovic JJ. Clinical features, differential diagnosis, and pathogenesis of blepharospasm and cranial-cervical dystonia. In: Bosniak S, ed. Advances in Ophthalmic Plastic and Reconstructive Surgery. Vol 4. Elsevier Science. 1985:67-82.
McCann JD, Gauthier M, Morschbacher R, et al. A novel mechanism for benign essential blepharospasm. Ophthal Plast Reconstr Surg. 1999 Nov. 15(6):384-9. [Medline].
Horie C, Suzuki Y, Kiyosawa M, Mochizuki M, Wakakura M, Oda K, et al. Decreased dopamine D(2) receptor binding in essential blepharospasm. Acta Neurol Scand. 2008 Jun 5. [Medline].
Morrison DA, Mellington FB, Hamada S. Schwartz-Jampel syndrome: surgical management of the myotonia-induced blepharospasm and acquired ptosis after failure with botulinum toxin A injections. Ophthal Plast Reconstr Surg. 2006 Jan-Feb. 22(1):57-9. [Medline].
Quartarone A, Sant'Angelo A, Battaglia F. Enhanced long-term potentiation-like plasticity of the trigeminal blink reflex circuit in blepharospasm. J Neurosci. 2006 Jan 11. 26(2):716-21. [Medline].
Fayers T, Shaw SR, Hau SC, Ezra DG. Changes in corneal aesthesiometry and the sub-basal nerve plexus in benign essential blepharospasm. Br J Ophthalmol. 2015 Apr 22. [Medline].
Hall TA, McGwin G, Searcey K. Health-related quality of life and psychosocial characteristics of patients with benign essential blepharospasm. Arch Ophthalmol. 2006 Jan. 124(1):116-9. [Medline].
Hall TA, McGwin G, Searcey K. Benign essential blepharospasm: risk factors with reference to hemifacial spasm. J Neuroophthalmol. 2005 Dec. 25(4):280-5. [Medline].
Munhoz RP, Teive HA, Della Coletta MV. Frequency of obsessive and compulsive symptoms in patients with blepharospasm and hemifacial spasm. Arq Neuropsiquiatr. 2005 Jun. 63(2A):213-6. [Medline].
Jankovic J, Orman J. Blepharospasm: demographic and clinical survey of 250 patients. Ann Ophthalmol. 1984 Apr. 16(4):371-6. [Medline].
Bentivoglio AR, Daniele A, Albanese A. Analysis of blink rate in patients with blepharospasm. Mov Disord. 2006 Apr 18. [Medline].
Henderson JW. Essential blepharospasm. Trans Am Ophthalmol Soc. 1956. 54:453-520.
Malinovsky V. Benign essential blepharospasm. J Am Optom Assoc. 1987 Aug. 58(8):646-51. [Medline].
Moon NJ, Lee HI, Kim JC. The changes in corneal astigmatism after botulinum toxin-a injection in patients with blepharospasm. J Korean Med Sci. 2006 Feb. 21(1):131-5. [Medline].
Ronald W. Essential blepharospasm: An often missed diagnosis. In: Bosniak S, ed. Advances in Ophthalmic Plastic and Reconstructive Surgery. Vol 4. Elsevier Science. 1985:93-95.
Martino D, Defazio G, Alessio G. Relationship between eye symptoms and blepharospasm: a multicenter case-control study. Mov Disord. 2005 Dec. 20(12):1564-70. [Medline].
Ben Simon GJ, McCann JD. Benign essential blepharospasm. Int Ophthalmol Clin. 2005. 45(3):49-75. [Medline].
Defazio G, Martino D, Aniello MS. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006 Feb. 77(2):252-4. [Medline].
Srivastava T, Goyal V, Singh S. Pallido-pyramidal syndrome with blepharospasm and good response to levodopa. J Neurol. 2005 Dec. 252(12):1537-8. [Medline].
Weiss EM, Hershey T, Karimi M. Relative risk of spread of symptoms among the focal onset primary dystonias. Mov Disord. 2006 May 3. [Medline].
Defazio G, Abbruzzese G, Aniello MS, et al. Environmental risk factors and clinical phenotype in familial and sporadic primary blepharospasm. Neurology. 2011 Aug 16. 77(7):631-7. [Medline].
Wabbels B. Botulinum toxin therapy in congenital blepharospasm. Case Rep Ophthalmol. 2014 Sep-Dec. 5 (3):435-8. [Medline].
Zhou B, Wang J, Huang Y, Yang Y, Gong Q, Zhou D. A resting state functional magnetic resonance imaging study of patients with benign essential blepharospasm. J Neuroophthalmol. 2013 Sep. 33(3):235-40. [Medline].
Asanuma K, Carbon-Correll M, Eidelberg D. Neuroimaging in human dystonia. J Med Invest. 2005 Nov. 52 Suppl:272-9. [Medline].
Dresel C, Haslinger B, Castrop F. Silent event-related fMRI reveals deficient motor and enhanced somatosensory activation in orofacial dystonia. Brain. 2006 Jan. 129(Pt 1):36-46. [Medline].
Herz NL, Yen MT. Modulation of sensory photophobia in essential blepharospasm with chromatic lenses. Ophthalmology. 2005 Dec. 112(12):2208-11. [Medline].
Adams WH, Digre KB, Patel BC, Anderson RL, Warner JE, Katz BJ. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006 Jul. 142(1):82-87. [Medline].
Blackburn MK, Lamb RD, Digre KB, Smith AG, Warner JE, McClane RW, et al. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology. 2009 May. 116(5):997-1001. [Medline]. [Full Text].
Hallett M, Evinger C, Jankovic J, Stacy M. Update on blepharospasm: report from the BEBRF International Workshop. Neurology. 2008 Oct 14. 71(16):1275-82. [Medline].
Anderson RL, Patel BC, Holds JB, Jordan DR. Blepharospasm: past, present, and future. Ophthal Plast Reconstr Surg. 1998 Sep. 14(5):305-17. [Medline].
Bradley EA, Bradley D, Bartley GB. Evaluating health-related quality of life in ophthalmic disease: practical considerations. Arch Ophthalmol. 2006 Jan. 124(1):121-2. [Medline].
Barnes MP, Best D, Kidd L. The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences. Eur J Neurol. 2005 Dec. 12(12):947-55. [Medline].
Bhidayasiri R, Cardoso F, Truong DD. Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations. Eur J Neurol. 2006 Feb. 13 Suppl 1:21-9. [Medline].
Cheng CM, Chen JS, Patel RP. Unlabeled uses of botulinum toxins: a review, part 2. Am J Health Syst Pharm. 2006 Feb 1. 63(3):225-32. [Medline].
Cheng CM, Chen JS, Patel RP. Unlabeled uses of botulinum toxins: a review, part 1. Am J Health Syst Pharm. 2006 Jan 15. 63(2):145-52. [Medline].
Dutton JJ, White JJ, Richard MJ. Myobloc for the treatment of benign essential blepharospasm in patients refractory to botox. Ophthal Plast Reconstr Surg. 2006 May-Jun. 22(3):173-7. [Medline].
Seiff SR, Zwick OM. Botulinum toxin management of upper facial rhytidosis and blepharospasm. Otolaryngol Clin North Am. 2005 Oct. 38(5):887-902. [Medline].
Silveira-Moriyama L, Goncalves LR, Chien HF. Botulinum toxin a in the treatment of blepharospasm: a 10-year experience. Arq Neuropsiquiatr. 2005 Jun. 63(2A):221-4. [Medline].
Truong D, Comella C, Fernandez HH, Ondo WG. Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential blepharospasm: a randomized, placebo-controlled, phase II trial. Parkinsonism Relat Disord. 2008. 14(5):407-14. [Medline].
Kenney C, Jankovic J. Botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J Neural Transm. 2008. 115(4):585-91. [Medline].
Roggenkamper P, Jost WH, Bihari K. Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm. 2006 Mar. 113(3):303-12. [Medline].
Simpson DM, Hallett M, Ashman EJ, Comella CL, Green MW, Gronseth GS, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10. 86 (19):1818-26. [Medline].
Kocabeyoglu S, Sekeroglu HT, Mocan MC, Muz E, Irkec M, Sanac AS. Ocular surface alterations in blepharospasm patients treated with botulinum toxin A injection. Eur J Ophthalmol. 2014 Nov-Dec. 24 (6):830-4. [Medline].
Cote TR, Mohan AK, Polder JA. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol. 2005 Sep. 53(3):407-15. [Medline].
Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988 Jun. 51(6):767-72. [Medline].
Ortisi E, Henderson HW, Bunce C. Blepharospasm and hemifacial spasm: a protocol for titration of botulinum toxin dose to the individual patient and for the management of refractory cases. Eye. 2006 Mar 10. [Medline].
Chundury RV, Couch SM, Holds JB. Comparison of preferences between onabotulinumtoxinA (Botox) and incobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm. Ophthal Plast Reconstr Surg. 2013 May-Jun. 29(3):205-7. [Medline].
Saad J, Gourdeau A. A direct comparison of onabotulinumtoxina (Botox) and IncobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm: a split-face technique. J Neuroophthalmol. 2014 Sep. 34(3):233-6. [Medline].
Garland PE, Patrinely JR, Anderson RL. Hemifacial spasm. Results of unilateral myectomy. Ophthalmology. 1987 Mar. 94(3):288-94. [Medline].
Gillum WN, Anderson RL. Blepharospasm surgery. An anatomical approach. Arch Ophthalmol. 1981 Jun. 99(6):1056-62. [Medline].
Grivet D, Robert PY, Thuret G. Assessment of blepharospasm surgery using an improved disability scale: study of 138 patients. Ophthal Plast Reconstr Surg. 2005 May. 21(3):230-4. [Medline].
Patel BC. Surgical management of essential blepharospasm. Otolaryngol Clin North Am. 2005 Oct. 38(5):1075-98. [Medline].
Patil B, Foss AJ. Upper lid orbicularis oculi muscle strip and sequential brow suspension with autologous fascia lata is beneficial for selected patients with essential blepharospasm. Eye. 2008 Oct 17. [Medline].
Georgescu D, Vagefi MR, McMullan TF, McCann JD, Anderson RL. Upper eyelid myectomy in blepharospasm with associated apraxia of lid opening. Am J Ophthalmol. 2008 Mar. 145(3):541-547. [Medline].
Kerty E, Eidal K. Apraxia of eyelid opening: Clinical features and therapy. Eur J Ophthalmol. 2006 Mar-Apr. 16(2):204-8. [Medline].
Lopez Valdes E, Posada Rodriguez IJ, Bilbao-Calabuig R. Botulinum toxin A injections improve apraxia of eyelid opening without overt blepharospasm associated with neurodegenerative diseases. Mov Disord. 2008 Apr 15. 23(5):773; author reply 773. [Medline].
Karapantzou C, Dressler D, Rohrbach S, Laskawi R. Frontalis suspension surgery to treat patients with essential blepharospasm and apraxia of eyelid opening-technique and results. Head Face Med. 2014 Oct 22. 10:44. [Medline].
Fine PG, Digre KB. A controlled trial of regional sympatholysis in the treatment of photo- oculodynia syndrome. J Neuroophthalmol. 1995 Jun. 15(2):90-4. [Medline].
Ababneh OH, Cetinkaya A, Kulwin DR. Long-term efficacy and safety of botulinum toxin A injections to treat blepharospasm and hemifacial spasm. Clin Experiment Ophthalmol. 2014 Apr. 42 (3):254-61. [Medline].