Dry eye disease immune responses and topical therapy

Abstract

There is accumulating evidence that inflammation is one of the key components of dry eye because chronic ocular surface inflammation can be both a result as well as an initiator of dry eye. The need for continuing anti-inflammatory therapy may be determined in part by the extent that non-modifiable factors such as gender and age-related aqueous or lipid or mucus production deficiencies contribute to its chronicity. This perspective examines how the need for increased dosage of a topical anti-inflammatory drug may be determined by the degree of difficulty that a topically administered drug has in accessing different sites of tear deficiency and associated inflammation.

Aqueous deficiency is a contributor to evaporation-related dry eye disease

“…While topical-inflammatory drug access to the ocular surface is direct, access to the lacrimal gland is problematic [40]. More frequent dosing may be beneficial in topical treatment for lacrimal gland inflammation in ADDE [40].…”

“…While topical-inflammatory drug access to the ocular surface is direct, access to the lacrimal gland is problematic [40]. More frequent dosing may be beneficial in topical treatment for lacrimal gland inflammation in ADDE [40]. Apart from the risk of difficulties associated with topical administration however, more frequent topical instillation to achieve better access to the lacrimal gland [40] raises the possibility of over-correcting an ocular surface imbalance of pro-inflammatory over antiinflammatory cytokines.…”

“…More frequent dosing may be beneficial in topical treatment for lacrimal gland inflammation in ADDE [40]. Apart from the risk of difficulties associated with topical administration however, more frequent topical instillation to achieve better access to the lacrimal gland [40] raises the possibility of over-correcting an ocular surface imbalance of pro-inflammatory over antiinflammatory cytokines. The problems associated with accessing the lacrimal gland with topical therapy [40] are illustrated by a study involving New Zealand white rabbits and treatment with an aqueous nanomicellar Cyclosporine solution (OTX 101 0.05%) [41].…”

“…Apart from the risk of difficulties associated with topical administration however, more frequent topical instillation to achieve better access to the lacrimal gland [40] raises the possibility of over-correcting an ocular surface imbalance of pro-inflammatory over antiinflammatory cytokines. The problems associated with accessing the lacrimal gland with topical therapy [40] are illustrated by a study involving New Zealand white rabbits and treatment with an aqueous nanomicellar Cyclosporine solution (OTX 101 0.05%) [41]. That study found that after instillation of a single topical drop, the maximum lacrimal gland concentration of Cyclosporine was only 2.7, 2.5 and 1.8% of the corneal, superior bulbar conjunctival and third eyelid concentrations, respectively [41].…”

A Novel Selective 11β-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye Syndrome

“…Either the tear film component that protects the surface of the eye is excessively evaporated or there is a lack of secretion in the eyes, causing discomfort, redness, and burning sensation, thus resulting in DES [2]. Continued progression of DES can cause inflammation, which can cause problems with cornea or conjunctiva and finally could have a bad effect on the vision [3].…”