Bor-Shyue Hong

Pre-clinical investigation of the efficacy of an artificial tear solution containing hydroxypropyl-guar as a gelling agent

Purpose. Pre-clinical studies of a new artificial tear product (SystaneTM Lubricating Eye Drops Alcon Laboratories, Inc., Fort Worth, TX) containing the novel gelling agent hydroxypropyl-guar (HP-guar) and two demulcents, polyethylene glycol 400 (PEG) and propylene glycol (PG) were conducted to determine the ability of the product to protect ocular surface epithelial cells from desiccation in vivo and in vitro, and to promote recovery of the damaged corneal epithelial barrier in vivo. Other leading artificial tear products were also evaluated as comparators to determine the relative effectiveness of different polymer systems. Methods. Damage due to desiccation was assessed by measuring corneal uptake of methylene blue compared to untreated corneas. Corneas of anesthetized rabbits were treated with the new artificial tear product and subjected to desiccation by holding the eyelids open for 2 hours with a speculum. Control eyes were subjected to desiccation without application of a tear formulation. To measure recovery of the corneal epithelium from damage, corneas of anethesthetized rabbits were exposed to 0.01% benzalkonium chloride (BAC) for 5 minutes to increase epithelial permeability. The corneas were exposed to the new artificial tear for 1.5 hours followed by measurement of uptake of 5,6 carboxyfluorescein (CF). In the desiccation and CF uptake experiments, the new tear product was also compared to a tear product formulation without HP-guar and to a commercially available artificial tear containing carboxymethyl cellulose (CMC) and Purite®. In a third set of experiments, immortalized human corneal epithelial cells and Chang conjunctival cells in culture were exposed to the PEG/PG/HP-guar tear product, the control formulation without HP-guar, a tear formulation preserved with BAC, or the artificial tear containing CMC/Purite® for 15 min. The tear formulation was removed and the cells were exposed to desiccating conditions in a laboratory safety hood for 10 or 30 min. Cell viability was determined using the MTT assay. Results. The in vivo desiccation model, showed that the new tear product, SystaneTM, offered complete protection of the cornea from desiccation (methylene blue uptake not different than naïve control). Following exposure to 0.01% BAC, the new artificial tear product also provided an environment in which the corneal epithelium recovered completely from damage (CF uptake not different than normal, untreated cornea). This level of protection was not observed when corneas were treated with other formulations. Results from the in vitro desiccation procedure indicated that viability of corneal epithelial and Chang cells treated with the PEG/PG/HP-guar product was significantly greater than viability of cells treated with the tear product without HP-guar or the tear products containing BAC or CMC/Purite®. Conclusions. The tear product containing HP-guar, PEG 400 and propylene glycol satisfies several pre-clinical criteria for an appropriate artificial tear formulation. It gives long-term desiccation protection of the intact cornea and also epithelial cells in culture and has no apparent deleterious affects on cells. It also provides conditions in which a damaged corneal epithelium can recover normal barrier function. The combination of ingredients in the formulation appears to provide an effective mucomimetic artificial tear product. These pre-clinical data suggest that the product will be effective in providing superior relief for the dry eye sufferer.