The objective of this project is to improve the understanding, diagnosis, and treatment of dry eye disorders, including those associated with decreased tear secretion (eg, lacrimal gland disease and neurotrophic keratitis) and increased tear film evaporation (eg, meibomian gland dysfunction). The proposed protocols specifically will test the following hypotheses in the rabbit models that now exist for these dry eye disorders: 1) In keratoconjunctivitis sicca (KCS), the progression of ocular surface disease can be halted or reversed by treatment with aqueous electrolyte solutions, or by administration of topically active tear secretagogues. 2) In meibomitis, surface disease can be improved by fluid supplementation and treatment of the inflammatory process centered in and around the meibomian glands. 3) In neurotrophic keratitis, surface disease can be improved by fluid supplementation. 4) Rabbits with simultaneous KCS, meibomitis, and neurotrophic keratitis will show epithelial healing abnormalities and perhaps persistent epithelial defects. These defects will heal by using a combination of the separate treatments for these dry eye disorders. 5) Elevated tear osmolarity in dry eye disorders is associated with abnormalities in tear electrolyte composition, and these must be corrected to attain optimum surface haling. In these rabbit models, the natural history of ocular disease over 20 weeks has been or will be mapped, studying tear osmolarity, tear electrolyte composition, ocular surface morphology, corneal epithelial glycogen, and conjunctival goblet-cell density. To determine the effect of treatment on the natural history of disease, rabbits will be treated from 12 to 20 weeks postoperatively. Tear electrolytes will be measured in tear microvolumes using flameless atomic absorption spectrophotometry. To supplement tear fluid in these diseases, electrolyte solutions will be applied by continuous infusion with infusaid pumps, or tear secretion will be stimulated pharmacologically by topically applied secretagogues. To treat inflammation, tetracyclines will be used, as well as other agents that potentially might decrease inflammation or collagenase activity. Based on the data obtained from the rabbit models for KCS, parallel studies will be performed in patients with KCS to test the therapeutic efficacy in humans of agents found to be therapeutic in our rabbit models.
Showing the most recent 10 out of 25 publications
