Neutralization of polyethylene glycol on ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost

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Background Reducing ocular surface toxicity induced by topical antiglaucoma medications,and thus improving the therapeutic compliance of glaucomatous patients to treating drug become an urgent issue in the long-term antiglaucomatous therapies.Whether polyethylene glycol,a new type of artificial tear,can play a protective role from ocular surface toxicity induced by topical antiglaucoma medications remains further study.Objective The present study was to investigate the protective effect of polyethylene glycol on ocular surface toxicity induced by prolonged use of benzalkonium chloride-preserved latanoprost eye drops.Methods Thirty adult female New Zealand rabbits were randomly divided into normal control group,phosphate buffer solution (PBS) group and polyethylene glycol eye drops group.PBS with 0.005％ latanoprost was topically administered for consequent 60 days in the PBS group,and 0.005％ latanoprost with polyethylene glycol eye drops was used at the same way in the polyethylene glycol group.Schirmer Ⅰ test,fluorescein and rose bengal staining of cornea and conjunctiva,conjunctiva impression cytology specimens collecting were performed before experiment as well as 31 and 61 days after administration of drug.Histomorphological and ultrastructural changes of cornea and conjunctiva were observed under the light microscopy,scanning and transmission electron microscopy on day 61.Results The score of corneal fluorescine staining was significantly different among the control group,PBS group and polyethylene glycol group (H =25.265,P＜0.001 ;H=29.426,P＜0.001) on day 31 and day 61.Significant difference also was found in the score of rose bengal staining of cornea and conjunctiva (H=26.167,P＜0.001 ;H =29.212,P＜0.001),Schirmer Ⅰ test value (F=4.746,P＜0.05) and conjunctival goblet cell density (F=18.055,P＜0.001).Compared with the control group,corneal fluorescein scores [0(0,1.0) vs.3 (2.0,3.0)] and rose bengal scores [0(0,1) vs.2(2,3)] were significantly increased (both P＜0.001),and Schirmer Ⅰ test value scores and conjunctival goblet cell density were decreased ((5.18±0.46/)mm vs.(9.43±0.57)mm;(53.04±2.98)/HP vs.(87.73±2.34)/HP) (both P＜0.01)on day 61.Impaired microvilli and organelles of the corneal and conjunctival epithelial cells were observed.Compared with PBS-treated group,PEG-treated group showed decrease in fluorescein [3(2.0,3.0) vs.1 (0.5,1.0)] and rose bengal scores [2 (2,3) vs.1 (0,1)] (both P＜0.001),increase in Schirmer Ⅰ test value scores [(7.00±0.71)mm vs.(5.18±0.46) mm,P＜0.05],increase in goblet cell density ((63.88±3.32)/HP vs.(53.04±2.98)/HP,P＜0.05) and improvement of grading scores of conjunctival epithelium on day 61.In addition,complete mierovilli and cell organelles were found in the corneal and conjunctival epithelial cells in the polyethylene glycol group.Conclusions Topical application of polyethylene glycol can decrease the ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost. Key words: Polyethylene glycol; Latanoprost; Benzalkonium chloride; Ocular surface toxicity