Pharmacologic Management of Strabismus
Jeffrey S. Hunter, MD
Pharmacologic treatments may offer nonsurgical alternatives to surgery for pediatric and adult strabismus/motility disorders.1
MIOTICS / PARASYMPATHOMIMETICS (ECHOTHIOPHATE IODIDE [0.125%])
These drugs have traditionally been used for glaucoma treatment but also have been used to treat esotropia since the 1940s. These agents uncouple the mechanism that facilitates the accommodative convergence response, thus allowing the eyes to focus without stimulating convergence. Miotics work best in patients with some fusional potential and small angle deviations (<20 prism diopters [PD]). They may work particularly well in patients with high accommodative convergence to accommodation (AC/A) ratios.2
Echothiophate iodide has a shelf life of 3-4 weeks and may lose efficacy at the end of that time. It is currently only manufactured by Pfizer, Inc. as phospholine iodide and requires special order to the pharmacy as a “drop shipment.”
Mechanism of action:
Binds cholinesterase in the erythrocytes and plasma irreversibly, causing acetylcholine levels to increase, which potentiates accommodation.
Increases uveal outflow.
Indications:
Treating accommodative esotropia (both high and normal AC/A ratio types):
As an alternative to single vision glasses for a child who will not wear spectacles.
As an alternative to bifocal in a child with high AC/A ratio.
Treating postoperative esotropia:
Consecutive esotropia after exodeviation surgery.
Residual esotropia after eso-surgery (small angle <15-20 prism diopters).
Accommodative component esotropia after surgery for infantile esotropia
Testing for accommodative component in esotropia—useful in distinguishing accommodative from nonaccommodative esotropia, especially in infants who resist wearing spectacles.
Dosage—Start with 1 drop of echothiophate 0.125% bilaterally every morning. If effective, the dosage can be reduced to every other day, or even every 3rd day. The dose can be titrated up or down depending on clinical response and side effect profile.1 The drug may be more effective for controlling esotropia when dosed in the morning, but dosing in the evening may reduce side effects.
If no response is measurable in 2-3 weeks, increase dosing to twice a day. Cease treatment if there is no improvement after a few more weeks at this dosage.
Side effects:
Iris cysts—occurs in 20%-50% of children, usually within 2-40 weeks. Clinicians should monitor for iris cysts at the slit lamp or in the retinoscopy streak at each follow-up appointment when children are using echothiophate. The cysts are not typically visually significant and usually resolve with discontinuation of the echothiophate. The addition of phenylephrine 2.5% daily reduces the incidence of iris cysts.
Brow ache—usually subsides after a few days or if dosed at bedtime.
Lens opacities.
Angle closure glaucoma (very rare).
Impaired dark adaptation.
Induced myopia.
Gastrointestinal hypermotility symptoms.
Contraindications—uveitis.
Echothiophate iodide depletes cholinesterase from the blood, increasing the patient’s susceptibility to the effects of depolarizing muscle relaxants, such as succinylcholine. Advise anesthesia team of usage, consider non-depolarizing agents or discontinue echothiophate 6 weeks prior to general anesthesia.
CYCLOPLEGICS (ATROPINE SULFATE [0.5-1%] AND HOMATROPINE [5%])
These medications can be used to treat accommodative spasm (spasm of the near synkinetic reflex). The diagnosis of accommodative spasm/induced overconvergence is usually made clinically. Signs of accommodative spasm include acute esotropia with or without diplopia, accompanied by miosis of the pupils, and a myopic shift in refractive error.
The two most common etiologies of accommodative spasm are functional, often in association with anxiety and emotional distress, or organic, with underlying head trauma or neurologic disease.
Mechanism of action—Atropine and homatropine are anticholinergic/antimuscarinic agents that block the effects of acetylcholine leading to relaxation of the ciliary muscle (accommodation), and inhibition of the pupillary sphincter fibers (mydriasis).
Indications:
Blocking or relaxing accommodation in treating accommodative spasm.
Inhibiting accommodation (cycloplegia) to allow accurate measurement of refractive error or for amblyopia treatment.
Dosage:
Accommodative spasm—Instill 1 drop of atropine 1% to both eyes twice a day (with plus lenses) until symptoms resolve.
Atropine refraction—Instill 1 drop of atropine 1% to both eyes twice daily for 3 days before and on the day of refraction.
Side effects:
Eyelid edema or dermatitis.
Blurred vision.
Prolonged mydriasis/photophobia.
Confusion/delirium.
Dry mouth.
Tachycardia and ventricular or supraventricular fibrillation—rare.
Anaphylaxis—rare.
If a severe adverse reaction is encountered, use physostigmine (0.02 mg/kg IM or IV).
ONABOTULINUM TOXIN A (BOTOX/BTX)
In the early 1980’s, Alan Scott, MD, isolated, purified, and demonstrated effective, safe usage of botulinum toxin A (Botox) to treat strabismus.5,6
Mechanism of action—Botulinum toxin acts by binding presynaptically to high-affinity sites on the cholinergic nerve terminals, blocking the release of acetylcholine, causing a neuromuscular blocking effect that causes a weakening of the muscle.
Botox has a temporary effect that usually lasts 3-4 months. It takes 24-48 hours to see clinically evident paresis. Half of the patients treated with Botox for strabismus will require repeat injections.6,7,8
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