Abstract
Abstract: :
If the ocular surface and tear film are looked at as an integrated system, then the pathology of dry eye becomes more complex. In recognition of this, a variety of components of this system continue to be investigated vis à vis changes in association with dry eye conditions. Evidence of an association of an imbalance in levels of a physiological marker with the presence of disease, however, does not in itself verify that particular imbalance as a target of highest priority for treatment strategies. The lack of parallel systems for looking at potential targets of treatment, combined with the ultimate difficulties of ascertaining therapeutic effect in human dry eye subjects, to date has led to limited validation of these potential targets for treatment of the signs and symptoms of dry eye. Purpose: An approach is described that pursues validation of the ocular surface as a treatment target for signs and symptoms common to dry eye conditions. Methods: Parallel processes utilized include formulating and physical property testing for topical ophthalmic delivery vehicle compatibility, in vitro models of inflammation and cellular tight junctions integrity for investigating toxicity and mechanisms of putative protective effects, animal (safety) studies, and a controlled environment study of clinical efficacy in subjective and objective improvements in human dry eye subjects. Results: Using our approach, physical property results demonstrate vehicle compatibility, in vitro toxicity and inflammation models supply limited information on safety and mechanism of action and animal studies provide only safety data. Conclusions: Due to the lack of parallel systems available for investigation, and the complexity and variable nature of the pathology, a controlled environment study using human subjects provides the most significant information toward validation of the ocular surface as a target for the treatment of signs and symptoms of dry eye.
Keywords: cornea: tears/tear film/dry eye • conjunctiva • clinical research methodology