A Novel Rabbit Model of Meibomian Gland Dysfunction-Induced Dry Eye.

Abstract

PURPOSE: The objective of this three-phase study was to develop a model of mild to moderate evaporative dry eye to be used to evaluate tear film stability endpoints during product development. METHODS: Rabbits were sedated prior to ophthalmic cautery of meibomian gland orifices. The orifices of eyelid meibomian glands were half-cauterized (to yield obstruction of every other meibomian gland orifices), fully cauterized (to yield obstruction of all meibomian gland orifices), or untreated. The primary outcome measures were model repeatability, tear film break-up time (TBUT), non-invasive tear break-up time (NIBUT), and model confirmation with daily artificial tears. Other examinations included Draize score, tear production, fluorescein staining, eschar, and histopathology. RESULTS: Cauterization was well tolerated in all phases. In phase I, TBUT was significantly decreased compared to baseline on days 14, 21, 28, and 35 in fully cauterized meibomian gland orifices but not in half-cauterized meibomian gland orifices. In phase II, both NIBUT and TBUT were similarly and significantly reduced in the fully cauterized meibomian gland orifices compared to the control eyes on days 7, 9, 14, and 28. In the confirmation phase, the administration of eye drops significantly improved NIBUT over the course of the study. CONCLUSIONS: A rabbit model of dry eye was successfully and safely created through the obstruction of meibomian gland orifices by cautery, which yielded a significant reduction in tear film stability. A quantifiable benefit of artificial tears relative to untreated control was demonstrated within the model. TRANSLATIONAL RELEVANCE: When the model is deployed, the utility and efficacy of therapeutic formulations can be evaluated.