Therapeutic ocular surface medium: clinical and in vitro studies

Abstract

Therapeutic Ocular Surface Medium (TOSM) is a potential new treatment for patients with ocular surface disorders such as dry eye and persistent epithelial defect (PED). New therapies are needed as many patients with dry eye and PED continue to suffer despite maximal standard therapy, and while efficacious autologous serum therapy is not routinely available. Like serum, TOSM contains tear components and was expected to have some of the physiological effects of tears. Clinical and in vitro studies were used to evaluate two similar formulations of TOSM. To comply with local pharmacy manufacturing policies, components were omitted from TOSM v1 to produce TOSM v2. In pilot studies, conducted over 1 month, TOSM v1 improved dry eye signs and symptoms and healed over a quarter of PED. In a 2 month randomised double-masked trial, TOSM v2 improved the signs and symptoms of dry eye but was not superior to saline (placebo). No serious or irreversible side-effects occurred. The altered composition of TOSM v2 may have reduced its efficacy. However, a significant improvement in blepharitis (eyelid margin disease) and conjunctival impression cytology (an objective measure of ocular surface health) was found with TOSM v2. Improvement in blepharitis is an encouraging finding as it has not been reported in other dry eye trials. It was hypothesised that TOSM would benefit ocular surface disorders by improving ocular surface health. In vitro, primary and cell line human corneal epithelial cells were supported by TOSM v1 and TOSM v2. Outgrowth from limbal explants and corneal reepithelialisation following wounding occurred with TOSM v2. This and the impression cytology findings support our hypothesis. Further, ocular surface damage with dry eye and PED may activate the corneal wound healing response. For wound healing, compared to human serum, TOSM v1 and TOSM v2 had beneficial effects in vitro on epithelial cells and human corneal fibroblasts. This may translate into a reduction in potentially vision-threatening corneal scarring in vivo with TOSM. However, ocular surface disorders are a heterogenous group and wound healing is a complex process such that different preparations of TOSM may be needed for use in different disorders and at different stages of the disease process.