Botulinum toxin therapy of strabismus

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Botulinum toxin therapy of strabismus
Specialty ophthalmologist

Botulinum toxin therapy of strabismus is a medical technique used sometimes in the management of strabismus, in which botulinum toxin is injected into selected extraocular muscles in order to reduce the misalignment of the eyes. The injection of the toxin to treat strabismus, reported upon in 1981, is considered to be the first ever use of botulinum toxin for therapeutic purposes. Today, the injection of botulinum toxin into the muscles that surround the eyes is one of the available options in the management of strabismus. Other options for strabismus management are vision therapy and occlusion therapy, corrective glasses (or contact lenses) and prism glasses, and strabismus surgery.

Contents

The effects that are due only to the toxin itself (including the side effects) generally wear off within 3 to 4 months. In contrast, improvements in alignment may be long-lasting, particularly in two circumstances. First, if the "antagonist" muscle (the muscle pulling in the opposite direction) is active, the injected muscle will be stretched, and may permanently lengthen by adding tissue during the period of toxin paresis.[ citation needed ] Second, if binocular vision has been achieved and stabilized, alignment may "lock in". There are indications that botulinum toxin therapy is as successful as strabismus surgery for patients with binocular vision and that it is less successful than surgery for those who have no binocular vision. [1]

Principle

Botulinum toxin is the most acutely lethal toxin that is known. It is produced by the bacterium clostridium botulinum. It acts inside nerve terminals by decreasing the release of acetylcholine, blocking neuromuscular transmission and thereby causing flaccid muscular paralysis. As a result, the muscle is weakened for about 3 to 4 months.

For treating strabismus, the toxin is used in much diluted form, and the injection is targeted to reach specific muscles that move the eye, thereby temporarily weakening the selected muscles.

Technique

Injection

After local or general anaesthesia has been applied, the botulinum toxin is injected directly into the selected eye muscles using a specially designed needle electrode that is connected to an electromyography (EMG) apparatus as well as to a syringe containing the botulinum toxin solution. [2]

When under local anaesthesia, the patient is asked to move the eyes just before the toxin is injected. This results in an EMG signal which provides instant feedback on the correct placement of the needle. If the patient is a young child, general anaesthesia is always used. [2]

The duration of the intervention is one to two minutes if the person performing the procedure has sufficient experience. [2]

Dosage

The dosage to be used cannot be determined with precision, as no reliable relation between dose and effect could be established so far. [1] The toxicity of botulinum toxin varies from one lot to the next; furthermore, the body may show an immunoreaction by which the efficacy of subsequent treatments is reduced. [2]

Clinical use

Botulinum toxin is considered as an alternative to surgery in certain clinical situations. A study performed in the 1980s found outcomes of surgery to be "more predictable and longer lasting" than those of botulinum toxin therapy. [3] As stated in a review article of 2007, its use for strabismus "varies enormously in different cities and countries for no apparent reason." [4]

In a small-scale study, adults whose reading difficulties due to convergence insufficiency had been unsuccessfully addressed by convergence exercises, base-in prism glasses or strabismus surgery showed improved reading after botulinum toxin therapy, maintaining improved reading remaining also after six months. [5]

Use as primary therapy

Botulinum toxin is considered a useful alternative to surgery in particular cases, for example for persons unfit for general anaesthesia, in evolving or unstable clinical conditions, after unsuccessful surgery, or to provide short-term relief from diplopia. [4]

For patients who have had healthy vision heretofore until a small, horizontal deviation set in suddenly, the injection of botulinum toxin may allow them to maintain the binocular vision skills that had been acquired earlier. [6]

Some consider botulinum injections to be a treatment option for children with small- to moderate-angle infantile esotropia. [7] [8] Studies have provided indications that performing injections into both medial rectus muscles may be more effective than an injection into one medial rectus muscle alone. [2]

Botulinum toxin therapy has been reported to be similarly successful as strabismus surgery for patients with binocular vision and less successful than surgery for those who have no binocular vision. [9] One study found that botulinum toxin therapy had similar long-term success rates for treating infantile esotropia with botulinum toxin A before the age of 12 months as would have been expected from strabismus surgery. [10] Another study reported similar long-term success rates for infantile esotropia treated before 24 months of age by either strabismus surgery or botulinum toxin treatment. [11]

Intra- and postoperational use

Botulinum toxin has also been used postoperatively for improving the alignment in patients with over- or undercorrection after strabismus surgery, leading to rapid elimination of postoperative diplopia but possibly requiring repeated injections or reoperation later on. [12] It is considered particularly useful for patients who have the potential for binocular vision; success rates are higher for treating postoperative esotropia than for treating postoperative exotropia. [6]

It has also been employed in combination with strabismus surgery in cases in which there is a large horizontal eye deviation and eye muscle surgery on both eyes (binocular surgery) is not an option for other reasons. [13]

Side effects

The most common side effects are droopy eyelids (ptosis) and over- or undercorrections; [4] a further common side effects are diplopia and inadvertent vertical deviation (hypo- or hypertropia). [3] The side effects typically resolve in 3–4 months. [1]

Vision-threatening complications are rare, and the intervention is generally considered safe, also when performed repeatedly. [1]

Bupivacaine

It is also under investigation whether the injection of bupivacaine into extraocular muscles is of possible therapeutic use for treating some forms of strabismus, be it alone or in combination with botulinum toxin.

Bupivacaine is a local anaesthetic known to cause considerable myotoxicity and neurotoxicity. Its injection into muscle tissue leads to a dramatic degeneration of muscle fibres accompanied by a moderate inflammatory response. It subsequently leads to a thickening and strengthening of the muscle. The thickening of bupivacaine-injected extraocular muscle has been demonstrated by means of magnetic resonance imaging [14] and by means of ultrasonography. [15]

Bupivacaine injection is therefore being investigated as a further possibility of treating strabismus. In some interventions bupivacaine has been used alone. [16] [17] In others, a botulinum toxin injection into an extraocular muscle is accompanied by a bupivacaine injection into the antagonist muscle. [15] [18]

History

Alan B. Scott first injected botulinum toxin into extraocular muscles since the early 1970s [2] and published his results 1981, [19] giving rise to a wide scope of clinical research on the use of the toxin.

The effect of bupivaine injection on extraocular muscles was first known as causing postsurgical strabismus as a complication of cataract surgery due to the myotoxicity of the local anaesthetic drug bupivaine when inadvertently injected into an extraocular muscle.

Related Research Articles

<span class="mw-page-title-main">Botulinum toxin</span> Neurotoxic protein produced by Clostridium botulinum

Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. The toxin causes the disease botulism. The toxin is also used commercially for medical and cosmetic purposes.

<span class="mw-page-title-main">Esotropia</span> Form of strabismus

Esotropia is a form of strabismus in which one or both eyes turns inward. The condition can be constantly present, or occur intermittently, and can give the affected individual a "cross-eyed" appearance. It is the opposite of exotropia and usually involves more severe axis deviation than esophoria. Esotropia is sometimes erroneously called "lazy eye", which describes the condition of amblyopia; a reduction in vision of one or both eyes that is not the result of any pathology of the eye and cannot be resolved by the use of corrective lenses. Amblyopia can, however, arise as a result of esotropia occurring in childhood: In order to relieve symptoms of diplopia or double vision, the child's brain will ignore or "suppress" the image from the esotropic eye, which when allowed to continue untreated will lead to the development of amblyopia. Treatment options for esotropia include glasses to correct refractive errors, the use of prisms and/or orthoptic exercises and/or eye muscle surgery. The term is from Greek eso meaning "inward" and trope meaning "a turning".

<span class="mw-page-title-main">Strabismus</span> Eyes not aligning when looking at something

Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a large part of childhood, it may result in amblyopia, or lazy eyes, and loss of depth perception. If onset is during adulthood, it is more likely to result in double vision.

<span class="mw-page-title-main">Diplopia</span> Double vision

Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often voluntary. However, when occurring involuntarily, it results in impaired function of the extraocular muscles, where both eyes are still functional, but they cannot turn to target the desired object. Problems with these muscles may be due to mechanical problems, disorders of the neuromuscular junction, disorders of the cranial nerves that innervate the muscles, and occasionally disorders involving the supranuclear oculomotor pathways or ingestion of toxins.

<span class="mw-page-title-main">Duane syndrome</span> Rare congenital disease characterized by external gaze palsy

Duane syndrome is a congenital rare type of strabismus most commonly characterized by the inability of the eye to move outward. The syndrome was first described by ophthalmologists Jakob Stilling (1887) and Siegmund Türk (1896), and subsequently named after Alexander Duane, who discussed the disorder in more detail in 1905.

<span class="mw-page-title-main">Superior rectus muscle</span> Extraocular muscle that elevates the eye

The superior rectus muscle is a muscle in the orbit. It is one of the extraocular muscles. It is innervated by the superior division of the oculomotor nerve (III). In the primary position, its primary function is elevation, although it also contributes to intorsion and adduction. It is associated with a number of medical conditions, and may be weak, paralysed, overreactive, or even congenitally absent in some people.

<span class="mw-page-title-main">Medial rectus muscle</span> Extraocular muscle that rotates the eye medially

The medial rectus muscle is a muscle in the orbit near the eye. It is one of the extraocular muscles. It originates from the common tendinous ring, and inserts into the anteromedial surface of the eye. It is supplied by the inferior division of the oculomotor nerve (III). It rotates the eye medially (adduction).

<span class="mw-page-title-main">Inferior oblique muscle</span> Part of the eye

The inferior oblique muscle or obliquus oculi inferior is a thin, narrow muscle placed near the anterior margin of the floor of the orbit. The inferior oblique is one of the extraocular muscles, and is attached to the maxillary bone (origin) and the posterior, inferior, lateral surface of the eye (insertion). The inferior oblique is innervated by the inferior branch of the oculomotor nerve.

<span class="mw-page-title-main">Exotropia</span> Visual disorder where eyes work independently

Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropia is a fairly common condition. "Sensory exotropia" occurs in the presence of poor vision in one eye. Infantile exotropia is seen during the first year of life, and is less common than "essential exotropia" which usually becomes apparent several years later.

<span class="mw-page-title-main">Sixth nerve palsy</span> Medical condition

Sixth nerve palsy, or abducens nerve palsy, is a disorder associated with dysfunction of cranial nerve VI, which is responsible for causing contraction of the lateral rectus muscle to abduct the eye. The inability of an eye to turn outward, results in a convergent strabismus or esotropia of which the primary symptom is diplopia in which the two images appear side-by-side. Thus, the diplopia is horizontal and worse in the distance. Diplopia is also increased on looking to the affected side and is partly caused by overaction of the medial rectus on the unaffected side as it tries to provide the extra innervation to the affected lateral rectus. These two muscles are synergists or "yoke muscles" as both attempt to move the eye over to the left or right. The condition is commonly unilateral but can also occur bilaterally.

<span class="mw-page-title-main">Hypertropia</span> Condition of misalignment of the eyes

Hypertropia is a condition of misalignment of the eyes (strabismus), whereby the visual axis of one eye is higher than the fellow fixating eye. Hypotropia is the similar condition, focus being on the eye with the visual axis lower than the fellow fixating eye. Dissociated vertical deviation is a special type of hypertropia leading to slow upward drift of one or rarely both eyes, usually when the patient is inattentive.

<span class="mw-page-title-main">Strabismus surgery</span> Surgery to correct strabismus

Strabismus surgery is surgery on the extraocular muscles to correct strabismus, the misalignment of the eyes. Strabismus surgery is a one-day procedure that is usually performed under general anesthesia most commonly by either a neuro- or pediatric ophthalmologist. The patient spends only a few hours in the hospital with minimal preoperative preparation. After surgery, the patient should expect soreness and redness but is generally free to return home.

Synkinesis is a neurological symptom in which a voluntary muscle movement causes the simultaneous involuntary contraction of other muscles. An example might be smiling inducing an involuntary contraction of the eye muscles, causing a person to squint when smiling. Facial and extraocular muscles are affected most often; in rare cases, a person's hands might perform mirror movements.

Chronic progressive external ophthalmoplegia (CPEO) is a type of eye disorder characterized by slowly progressive inability to move the eyes and eyebrows. It is often the only feature of mitochondrial disease, in which case the term CPEO may be given as the diagnosis. In other people suffering from mitochondrial disease, CPEO occurs as part of a syndrome involving more than one part of the body, such as Kearns–Sayre syndrome. Occasionally CPEO may be caused by conditions other than mitochondrial diseases.

Infantile esotropia is an ocular condition of early onset in which one or either eye turns inward. It is a specific sub-type of esotropia and has been a subject of much debate amongst ophthalmologists with regard to its naming, diagnostic features, and treatment.

Dissociated vertical deviation (DVD) is an eye condition which occurs in association with a squint, typically infantile esotropia. The exact cause is unknown, although it is logical to assume it is from faulty innervation of eye muscles.

Ocular surgery may be performed under topical, local or general anesthesia. Local anaesthesia is more preferred because it is economical, easy to perform and the risk involved is less. Local anaesthesia has a rapid onset of action and provides a dilated pupil with low intraocular pressure.

<span class="mw-page-title-main">Stereopsis recovery</span>

Stereopsis recovery, also recovery from stereoblindness, is the phenomenon of a stereoblind person gaining partial or full ability of stereo vision (stereopsis).

The management of strabismus may include the use of drugs or surgery to correct the strabismus. Agents used include paralytic agents such as botox used on extraocular muscles, topical autonomic nervous system agents to alter the refractive index in the eyes, and agents that act in the central nervous system to correct amblyopia.

Alan Brown Scott was an American ophthalmologist specializing in eye muscles and their disorders, such as strabismus. He is best known for his work in developing and manufacturing the drug that became known as Botox, research described as "groundbreaking" by the ASCRS.

References

  1. 1 2 3 4 Rowe, Fiona J.; Noonan, Carmel P. (2 March 2017). "Botulinum toxin for the treatment of strabismus". The Cochrane Database of Systematic Reviews. 2017 (3): CD006499. doi:10.1002/14651858.CD006499.pub4. ISSN   1469-493X. PMC   6464099 . PMID   28253424.
  2. 1 2 3 4 5 6 "Chapter 25: Chemodenervation of Extraocular Muscles – Botulinum Toxin" (PDF). Archived from the original (PDF) on 2014-04-13. Retrieved 2014-04-12., pages 559–565. In: Gunter K. von Noorden, Emilio C. Campos: Binocular Vision and Ocular Motility: Theory and Management of Strabismus Archived 2014-04-13 at the Wayback Machine , Sixth Edition. Ophthalmology Books & Manuals (Cyber Sight), Orbis International
  3. 1 2 Flanders M; et al. (June 1987). "Injection of type A botulinum toxin into extraocular muscles for correction of strabismus". Can. J. Ophthalmol. 22 (4): 212–217. PMID   3607594.
  4. 1 2 3 Kowal L, Wong E, Yahalom C (Dec 15, 2007). "Botulinum toxin in the treatment of strabismus. A review of its use and effects". Disabil Rehabil. 29 (23): 1823–1831. doi:10.1080/09638280701568189. PMID   18033607. S2CID   19053824.
  5. ↑ Peiter Saunte, Jon; Holmes, Jonathan M. (2014). "Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency". Strabismus. 22 (3): 95–99. doi:10.3109/09273972.2014.907815. PMC   4324975 . PMID   24786379.
  6. 1 2 Ripley L, Rowe FJ (July–September 2007). "Use of botulinum toxin in small-angle heterotropia and decompensating heterophoria: a review of the literature". Strabismus. 15 (3): 165–171. doi:10.1080/09273970701506094. PMID   17763254. S2CID   21369595.
  7. ↑ Thouvenin D, Lesage-Beaudon C, Arné JL (January 2008). "(translated from French) Botulinum injection in infantile strabismus. Results and incidence on secondary surgery in a long-term survey of 74 cases treated before 36 months of age". J Fr Ophtalmol. 31 (1): 42–50. doi:10.1016/S0181-5512(08)70329-2. PMID   18401298.
  8. ↑ de Alba Campomanes AG, Binenbaum G, Campomanes Eguiarte G (April 2010). "Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia". J AAPOS. 14 (2): 111–116. doi:10.1016/j.jaapos.2009.12.162. PMID   20451851.
  9. ↑ Rowe FJ, Noonan CP (2017). "Botulinum toxin for the treatment of strabismus". Cochrane Database Syst Rev. 2017 (3): CD006499. doi:10.1002/14651858.CD006499.pub4. PMC   6464099 . PMID   28253424.
  10. ↑ McNeer KW, Tucker MG, Guerry CH, Spencer RF (2003). "Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A". Journal of Pediatric Ophthalmology and Strabismus. 40 (5): 288–92. doi:10.3928/0191-3913-20030901-10. PMID   14560837.
  11. ↑ Gursoy, Huseyin; Basmak, Hikmet; Sahin, Afsun; Yildirim, Nilgun; Aydin, Yasemin; Colak, Ertugrul (2012). "Long-term follow-up of bilateral botulinum toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile esotropia". Journal of American Association for Pediatric Ophthalmology and Strabismus. 16 (3): 269–273. doi:10.1016/j.jaapos.2012.01.010. ISSN   1091-8531. PMID   22681945.
  12. ↑ Wutthiphan S. (2008). "Botulinum toxin A in surgically overcorrected and undercorrected strabismus". J. Med. Assoc. Thai. 91 (Suppl. 1): 86–91. PMID   18672599.
  13. ↑ Nilza Minguini; et al. (March 2012). "Surgery with intraoperative botulinum toxin-A injection for the treatment of large-angle horizontal strabismus: a pilot study". Clinics (Sao Paulo). 67 (3): 279–282. doi:10.6061/clinics/2012(03)13. PMC   3297039 . PMID   22473411.
  14. ↑ Creig S Hoyt (February 2007). "A problem! Now a solution?". British Journal of Ophthalmology. 91 (2): 127–128. doi:10.1136/bjo.2006.111096. PMC   1857604 . PMID   17244653.
  15. 1 2 Hopker, LM; Zaupa, PF; Lima Filho, AA; Cronemberger, MF; Tabuse, MK; Nakanami, CR; Allemann, N.; Mendonça, TS (March–April 2012). "Bupivacaine and botulinum toxin to treat comitant strabismus". Arquivos Brasileiros de Oftalmologia. 75 (2): 111–115. doi: 10.1590/s0004-27492012000200008 . PMID   22760802.
  16. ↑ Scott, AB; Miller, JM; Shieh, KR (April 2009). "Bupivacaine injection of the lateral rectus muscle to treat esotropia". J AAPOS. 13 (2): 119–122. doi:10.1016/j.jaapos.2008.10.016. PMID   19393509.
  17. ↑ Miller, JM; Scott, AB; Danh, KK; Strasser, D; Sane, M (December 2013). "Bupivacaine injection remodels extraocular muscles and corrects comitant strabismus". Ophthalmology. 120 (12): 2733–2740. doi:10.1016/j.ophtha.2013.06.003. PMID   23916485.
  18. ↑ Scott, AB; Miller, JM; Shieh, KR (December 2009). "Treating strabismus by injecting the agonist muscle with bupivacaine and the antagonist with botulinum toxin". Transactions of the American Ophthalmological Society. 107: 104–109. PMC   2814569 . PMID   20126486.
  19. ↑ Scott AB (1981). "Botulinum toxin injection of eye muscles to correct strabismus". Trans Am Ophthalmol Soc. 79 (79): 734–770. PMC   1312202 . PMID   7043872.

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