Botulinum toxin therapy of strabismus is a medical technique used sometimes in the

management of strabismus 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 which

botulinum toxin 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 neuromusc ...

is injected into selected

extraocular muscles The extraocular muscles (extrinsic ocular muscles), are the seven extrinsic muscles of the human eye. Six of the extraocular muscles, the four recti muscles, and the superior and inferior oblique muscles, control movement of the eye and the ot ...

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 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 ...

. Other options for strabismus management are

vision therapy Vision therapy (VT), or behavioral optometry, is an umbrella term for alternative medicine treatments using eye exercises, based around the pseudoscientific claim that vision problems are the true underlying cause of learning disabilities, parti ...

and occlusion therapy, corrective glasses (or

contact lens Contact lenses, or simply contacts, are thin lenses placed directly on the surface of the eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct vision or for cosmetic ...

es) and

prism Prism usually refers to: * Prism (optics), a transparent optical component with flat surfaces that refract light * Prism (geometry), a kind of polyhedron Prism may also refer to: Science and mathematics * Prism (geology), a type of sedimentary ...

glasses, and

strabismus surgery Strabismus surgery (also: ''extraocular muscle surgery'', ''eye muscle surgery'', or ''eye alignment surgery'') is surgery on the extraocular muscles to correct strabismus, the misalignment of the eyes. Strabismus surgery is a one-day procedure ...

. 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. Second, if

binocular vision In biology, binocular vision is a type of vision in which an animal has two eyes capable of facing the same direction to perceive a single three-dimensional image of its surroundings. Binocular vision does not typically refer to vision where an ...

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.

Principle

Botulinum toxin is the most acutely lethal toxin that is known. It is produced by the bacterium

clostridium botulinum ''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans an ...

. It acts inside nerve terminals by decreasing the release of acetylcholine, blocking neuromuscular transmission and thereby causing flaccid muscular

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

. 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 An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or air). Electrodes are essential parts of batteries that can consist of a variety of materials de ...

that is connected to an

electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...

(EMG) apparatus as well as to a

syringe A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside ...

containing the botulinum toxin solution., pages 559–565. In: Gunter K. von Noorden, Emilio C. Campos
''Binocular Vision and Ocular Motility: Theory and Management of Strabismus''
, Sixth Edition. Ophthalmology Books & Manuals (Cyber Sight),

Orbis International Orbis International is an international non-profit non-governmental organization (NGO) dedicated to saving sight worldwide. Its programs focus on the prevention of blindness and the treatment of blinding eye diseases in developing countries throug ...

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

Dosage

The dosage to be used cannot be determined with precision, as no reliable relation between dose and effect could be established so far. 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.

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. As stated in a review article of 2007, its use for strabismus "varies enormously in different cities and countries for no apparent reason." In a small-scale study, adults whose reading difficulties due to

convergence insufficiency Convergence insufficiency is a sensory and neuromuscular anomaly of the binocular vision system, characterized by a reduced ability of the eyes to turn towards each other, or sustain convergence. Symptoms The symptoms and signs associated with con ...

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.

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. 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

skills that had been acquired earlier. Some consider botulinum injections to be a treatment option for children with small- to moderate-angle

infantile esotropia 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 ...

. Studies have provided indications that performing injections into both

medial rectus muscle 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 t ...

s may be more effective than an injection into one medial rectus muscle alone. 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. 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. 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.

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. It is considered particularly useful for patients who have the potential for binocular vision; success rates are higher for treating postoperative

esotropia 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 usual ...

than for treating postoperative

exotropia 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 exotrop ...

. 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.

Side effects

The most common side effects are droopy eyelids ( ptosis) and over- or undercorrections; a further common side effects are

diplopia 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 v ...

and inadvertent vertical deviation (hypo- or

hypertropia 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 fell ...

). The side effects typically resolve in 3–4 months. Vision-threatening complications are rare, and the intervention is generally considered safe, also when performed repeatedly.

Bupivacaine

It is also under investigation whether the injection of

bupivacaine Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease feeling in a specific area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. I ...

into extraocular muscles is of possible therapeutic use for treating some forms of strabismus, be it alone and in combination with botulinum toxin. Bupivacaine is a

local anaesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general ...

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 Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

and by means of

ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

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

History

Alan B. Scott first injected botulinum toxin into extraocular muscles since the early 1970s and published his results 1981, 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 Cataract surgery, also called lens replacement surgery, is the removal of the natural lens of the eye (also called "crystalline lens") that has developed an opacification, which is referred to as a cataract, and its replacement with an intraocu ...

due to the myotoxicity of the

drug bupivaine when inadvertently injected into an extraocular muscle.