Treatment of strabismus and blepharospasm with Botox (onabotulinumtoxinA): Development, insights, and impact

Abstract

Strabismus, deviation of the ocular alignment, can adversely affect quality of life and activities of daily living. Surgery was the prior standard of care for strabismus, but up to 40% of patients required additional surgeries. This need for more effective and less invasive treatment, along with the convergence of other events such as the development of electromyography, purification of botulinum toxin A, and the finding that injection of botulinum toxin type A could paralyze the hind limbs of chicks, led Dr. Alan Scott to investigate injection of his formulation for strabismus. The positive results of initial trials in monkeys segued to human trials with observations of alignment improvements and few adverse events. The success of botulinum toxin type A in the treatment of strabismus led to interest in its use to treat other skeletal muscles, particularly in blepharospasm, a type of focal dystonia involving eyelid spasms and involuntary eye closure that lacked an effective pharmacological treatment. Patient groups helped to increase awareness of this novel treatment, and results from clinical trials confirmed its effectiveness. Dr. Scott's formulation, then known as Oculinum, received its first Food and Drug Administration approvals in 1989 for strabismus and blepharospasm. Allergan acquired Oculinum in 1991, renaming it Botox. These initial uses led to its application in a myriad of other indications as outlined in other articles of this supplement.

Figure 1

. Drs. Alan Scott and Joseph Jankovic. Photo provided by Dr. Joseph Jankovic.

Figure 2.

Lid lifters designed for blepharospasm patients. (A) Photograph showing wire lifters fashioned on eyeglasses by the patient’s husband, who was a dentist. (B) Blepharospasm patient wearing lid lifters. Photos provided by Dr. Mitchell Brin.

Figure 3

. Before and after photos of botulinum toxin A treatment for strabismus. (A) Prior to injection with botulinum toxin A. (B) Primary position gaze 2 days after injection with 1.56 × 10-3 μg botulinum toxin A. (C) Left gaze 2 days after injection, with absence of abduction due to lateral rectus paralysis. (D) Primary position gaze at 3 months after injection, with reduction of exotropia. (E) Left gaze 3 months after injection, with full return of abduction. Reprinted from Ophthalmology, Vol 87, Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Pages 1044–9, Copyright 1980, with permission from Elsevier.

Figure 4.

Decreases in deviation of ocular alignment by patients following injection of botulinum toxin A for the treatment of strabismus. Data are included for patients (numbered) who received at least the therapeutic dose threshold of 3.12 x 10-4 μg botulinum toxin A, did not receive eyelid injections, and were followed for at least 100 days after injection. Patients with paralytic strabismus or neuromyotonia were excluded. Reprinted with permission of the American Ophthalmological Society from Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc. 1981;79:734–70.

Figure 5

. Eyelid closure force before and after botulinum toxin A treatment for blepharospasm (A) measured with a modified calibrated spring-loaded speculum in four patients, and (B) mean eyelid closure force and eyelid spasm scores from 27 patients, each measured on scales ranging from 0 to 4. For force, 0 indicated minimal effort for eyelid separation and 4 an inability to separate the eyelids with the thumbs. For spasm, 0 indicated no spasm, with 4 indicating severe, incapacitating spasm. Panel A: Reproduced with permission from Arch Ophthalmol. 1985;103(3):347–50. Copyright (1985) American Medical Association. All rights reserved. Panel B: Figure 2 from "Treatment of blepharospasm with medication, surgery and type A botulinum toxin" by Arthurs B, Flanders M, Codere F, et al published in the Canadian Journal of Ophthalmology. 1987;22(1):24–8 is used under a CC BY-ND 4.0 license.