Therapeutic ocular surface medium: clinical and in vitro studies

摘要

Therapeutic Ocular Surface Medium (TOSM) is a potential new treatment for patientswith 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 sufferdespite maximal standard therapy, and while efficacious autologous serum therapy isnot routinely available. Like serum, TOSM contains tear components and was expectedto 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 fromTOSM v1 to produce TOSM v2. In pilot studies, conducted over 1 month, TOSM v1improved dry eye signs and symptoms and healed over a quarter of PED. In a 2 monthrandomised double-masked trial, TOSM v2 improved the signs and symptoms of dryeye but was not superior to saline (placebo). No serious or irreversible side-effectsoccurred. The altered composition of TOSM v2 may have reduced its efficacy.However, a significant improvement in blepharitis (eyelid margin disease) andconjunctival impression cytology (an objective measure of ocular surface health) wasfound with TOSM v2. Improvement in blepharitis is an encouraging finding as it hasnot been reported in other dry eye trials.It was hypothesised that TOSM would benefit ocular surface disorders by improvingocular surface health. In vitro, primary and cell line human corneal epithelial cells weresupported by TOSM v1 and TOSM v2. Outgrowth from limbal explants and corneal reepithelialisationfollowing wounding occurred with TOSM v2. This and the impressioncytology findings support our hypothesis. Further, ocular surface damage with dry eyeand 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 onepithelial cells and human corneal fibroblasts. This may translate into a reduction inpotentially vision-threatening corneal scarring in vivo with TOSM. However, ocularsurface disorders are a heterogenous group and wound healing is a complex processsuch that different preparations of TOSM may be needed for use in different disordersand at different stages of the disease process.