Increasing Muscle Strength as a Treatment for Strabismus: Sustained Release of Insulin-like Growth Factor-1 in Rabbit Extraocular Muscle

Purpose: Currently, no drug treatment is available for strengthening underacting extraocular muscles (EOM) in strabismus. We showed previously that single injections of insulin-like growth factor (IGF-1) result in significant but short-term increases in muscle force generation. This study examined the effects of sustained release of IGF-1 on force generation in rabbit superior rectus muscles. Methods: In adult rabbits, slow-release pellets containing IGF-1 were implanted on the global side of one superior rectus muscle. After 1 week, or 1, 2, 3, or 6 months, treated and control muscles were examined for force generation using an in vitro physiology apparatus. All muscles were prepared for histology and mean myofiber cross-sectional areas were determined. Results: One and 3 months after pellet implantation, treated muscles generated significantly greater force than contralateral control muscles, whereas at 2 months, no significant difference was found. Force per cross-sectional area (mN/cm²) at 3 months also increased significantly in the treated muscles. Mean muscle cross-sectional area increased significantly after 1, 2, and 3 months of sustained exposure to IGF-1 compared with controls. After an additional 3 months without IGF-1 exposure, mean cross-sectional areas were significantly greater than controls but significantly reduced compared with areas at 1, 2, and 3 months. Conclusions: IGF-1 appears to be highly effective in increasing muscle force generation. Because slow release of IGF-1 results in sustained increases in EOM force generation, it may be a potentially useful alternative to surgical resection procedures because it avoids many of the potential long-term biomechanical hazards of resection surgery.