Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum. Among the seven known serotypes (A to G), type A is the most potent and most widely used in clinical practice.
The application of botulinum toxin to treat strabismus began in 1973 when San Francisco ophthalmologist Alan B. Scott injected type A botulinum toxin into the extraocular muscles of rhesus monkeys. He injected the medial and lateral rectus muscles of eight rhesus monkeys via the conjunctiva, observing temporary muscle paralysis and permanent changes in eye position.
The first human report was published in 1981. Injections in 42 patients with horizontal strabismus showed effects lasting up to 411 days after the last injection. On December 29, 1989, type A botulinum exotoxin (BTX-A) was approved by the U.S. FDA for the treatment of strabismus and blepharospasm.
The three main commercially available preparations are as follows:
OnabotulinumtoxinA (Botox®): The first developed preparation. It serves as the standard unit reference in clinical practice.
AbobotulinumtoxinA (Dysport®): 1 unit of Botox is equivalent to 3–5 units of Dysport.
IncobotulinumtoxinA (Xeomin®): Shows equivalent efficacy (1:1) and side effect rates to Botox.
QWhen did botulinum toxin treatment for strabismus begin?
A
It started with animal experiments in 1973, and the first report of efficacy in humans was in 1981. The FDA officially approved it for strabismus treatment in 1989, and it has since become widespread worldwide.
The botulinum toxin molecule consists of a heavy chain (H chain) and a light chain (L chain) linked by a disulfide bond. The H1 subunit binds to the nerve terminal and is taken up into the cell via endocytosis.
The light chain cleaves the SNAP-25/syntaxin complex, inhibiting the release of acetylcholine. As a result, the transmission of motor impulses through the neuromuscular junction is blocked, leading to flaccid paralysis of the extraocular muscles.
The temporal changes in clinical effects are as follows:
Onset of paralysis: 2–4 days after injection
Duration of clinical effect: 5–8 weeks
Recovery of muscle function: 5–14 weeks (depends on injection site, dose, and muscle innervation density)
Botulinum toxin treatment causes pharmacological denervation of the injected muscle. During paralysis, the injected muscle lengthens and the antagonist muscle contracts. The pharmacological effect itself usually disappears within 3 months, but mechanical, proprioceptive, and binocular effects that act during the paralysis period contribute to long-term ocular alignment stability.
4. Diagnosis and Examination Methods (Injection Technique)
There is no unified standard for dosage. The most commonly used dose is 2.5–5 U of Botox. Adjust according to age, deviation angle, and type of strabismus.
Subject
Dose (Botox)
Under 3 years old (<30 PD)
Dominant eye 2.5 U, non-dominant eye 2.5 U
Under 3 years (30 PD or more)
Dominant eye 2.5U, non-dominant eye 5U
3 to 10 years
Dominant eye 2.5U, non-dominant eye 5U
Medial rectus, lateral rectus
3 to 5U
Superior rectus muscle
1.5U
Inferior oblique muscle / Inferior rectus muscle
1.5–2.5U
With fibrosis
10U
When using Disport, apply a correction factor of 3 to 5 times that of Botox.
Dilute 50–100 U of botulinum toxin powder with 2 mL of irrigation fluid (BSS) to achieve a concentration of 5 U per 0.1 mL. Use within 6 hours after reconstitution. The lethal dose in a 70 kg human is 5,000 U (more than 1,000 times the clinical dose), so the clinical dose is well within the safety margin.
A needle (27G or 30G) is inserted tangentially through the conjunctiva to directly approach the target muscle. Electromyography (EMG) is useful for identifying small muscles but is usually unnecessary for injections into the medial or lateral rectus muscles.
QIs general anesthesia required for injection?
A
In adults, the procedure can be performed with topical anesthesia alone. General anesthesia is recommended for children or uncooperative adults, but the duration of general anesthesia is shorter than that for surgery.
5. Standard Treatment (Treatment Outcomes and Efficacy by Indication)
For comitant esotropia with small to moderate preoperative deviation angle (less than 35 PD), BTX injection shows success rates comparable to surgery. A 2017 meta-analysis (9 studies) reported a pooled success rate of 76% for medial rectus BTX injection in infantile esotropia. In Japan, botulinum toxin type A is not approved for pediatric strabismus, but in other countries, early treatment for infantile esotropia has been attempted with good corrective effects reported. Although there are risks of transient overcorrection and ptosis, a major advantage is that orthotropia can be achieved with a single injection without tenotomy of the developing medial rectus muscle.
In large-angle comitant esotropia, combining BTX injection with surgery may improve outcomes. A 2024 retrospective case series of deviations of 55 PD or more reported success in 75% of esotropia patients and 50% of exotropia patients with BTX-A used as a surgical adjunct.
A 2025 review by Al-Dabet et al. presented outcomes of EMG-guided bilateral BTX-A injection (medial rectus) for Duane syndrome type 1. In 8 patients under 3 years of age, mean preoperative esotropia was 32±10 PD. Orthotropia was achieved in half, while 3 cases required additional surgery for persistent esotropia (mean 25 PD)2).
Deviation angles tend to be unstable over time, making outcomes of surgical resection and recession difficult to predict. BTX injection may be advantageous in such cases.
The Cochrane systematic review (4 trials, total 242 participants) concluded that only low-certainty evidence was available to determine the effectiveness of BTX injection as an independent treatment for specific types of strabismus.
QWhich is more effective: botulinum toxin or surgery?
A
For esotropia less than 35PD, both show equivalent success rates. For large-angle strabismus, surgery combined with BTX is considered advantageous. BTX has the advantage of simple injection technique and shorter general anesthesia time. See the “Standard Treatment” section for details.
QWhat is the most common side effect?
A
Transient ptosis is the most common complication, occurring in 12% of adults and 25% of children. It is more frequent with injection into the medial rectus muscle. It usually resolves spontaneously within a few weeks without serious sequelae.
7. Latest Research and Future Prospects (Investigational Reports)
Antibodies against botulinum toxin can form. Non-neutralizing antibodies do not reduce the toxin’s effect at the neuromuscular junction and have no clinical significance. Neutralizing antibodies neutralize BTX at the functional site of the heavy chain and prevent binding to the nerve membrane, but they form only in a very small number of patients. Cross-reactive antibodies between different serotypes have not been identified.
