Intraglandular injection of botulinum toxin a reduces tear production in rabbits

Abstract

Purpose: To develop an animal model and investigate the dose-dependent effect of an intraglandular injection of botulinum toxin A (BTX-A) on tear production.

Methods: In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected transconjunctivally in the superolateral lobe of the lacrimal gland of adult New Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9% sodium chloride was injected. Prior to injection and at 1-week postinjection, photographs were taken to evaluate pre- and postoperative eyelid position. Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and Schirmer test was used to assess tear production.

Results: Glands injected with the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a statistically significant decrease in tear production (p = 0.002 and 0.007, respectively) compared with the contralateral saline-injected glands at 1 week. No corneal pathologic factors from excessive dryness were observed following the injection. While postinjection ptosis was observed (p = 0.025), no difference was seen between BTX-A and saline-injected eyes.

Conclusions: In rabbits, intraglandular injection of BTX-A resulted in decreased tear production at 1 week. No additional reduction in tear production was seen with a BTX-A dose greater than 1.25 U, suggesting glandular receptor saturation at this dose. Despite suppression of tear production, no corneal pathologic factors were observed. Further studies are needed to refine this animal model with the ultimate goal of determining optimum delivery route and concentration to reduction in tear production while minimizing side effects in patients.

FIG. 1

A, Intraglandular injection is accomplished by exposing the superolateral lobe of the lacrimal gland with a Desmarres retractor and injecting with a 30-gauge needle. B, Baseline tear production is measured by placing a Schirmer strip in the inferior fornix and leaving in place for 5 minutes. The amount of wetting is measured in millimeter.

FIG. 2

Anterior segment photographs of a rabbit’s eyes 1 week after intraglandular injection of either BTX-A (A, study eye) or saline (B, control eye). Photographs of the same eyes showing an absence of fluorescein staining (C, study eye; D, control eye) and an absence of Rose Bengal staining (E, study eye; F, control eye) 1 week after injection.

FIG. 3

A and B, Normal upper eyelid position in 2 rabbits before injection. Photographs of the same animals, respectively, 1 week after injection (C) with and (D) without ptosis.

FIG. 4

Histology of the lacrimal gland (A) and Harders’ gland (B) 1 week after BTX-A injection (2.5 U). No inflammation or hemorrhage is seen (hematoxylin-eosin, ×10).