Transdermal anti-inflammatory therapy for aqueous deficiency.

Abstract

Lacrimal gland inflammation has been identified as an important limitation on aqueous production and associated dry eye disease. Ocular surface inflammation in dry eye disease can be a downstream response to reduced quantities of warmer hyperosmotic aqueous being delivered from an inflamed lacrimal gland with high concentrations of inflammatory mediators. This review examines evidence which shows how topical applications of anti-inflammatory drugs have very limited access to the lacrimal gland and an associated limited capacity to increase aqueous flow by reducing inflammation in the main lacrimal gland. Using cyclosporine as an exemplar immunomodulatory drug, this review examines problems associated with the topical administration of all anti-inflammatory drugs in the treatment of dry eye disease. Limited access to the lacrimal gland for topical applications and their very short on-eye residence times are compared with the therapeutic potential of prolonged therapeutic episodes that could be achieved with transdermal applications of a drug to the skin at the site of the lacrimal gland. Poor access to the lacrimal gland for topically administered drugs is a major barrier to the treatment of aqueous deficiency. While topical inflammatory drug access to the ocular surface is direct, poor access to the lacrimal gland is partly due to drop placement being downstream to the flow of aqueous (Eye Vis 2020;7:1; Eye Vis 2019;6:1). This barrier is much greater according to the degree that reflex tear flow is stimulated by irritation associated with adverse drop temperature, and/or pH and/or tonicity for example.