The Effects And Mechanisms Of Non-steroidal Anti-inflammatory Drugs In Primary Open-angle Glaucoma Patients Treated With Prostaglandin Analogs

Objective: To observe the effects of non-steroidal anti-inflammatory drugs ophthalmic solution on intraocular pressure(IOP)and ocular surface in primary open-angle glaucoma(POAG)patients treated with latanoprost,and to explore its mechanisms of action.So as to provide a new method for drug treatment of patients with glaucoma.Methods: 1.A randomized,controlled clinical trial was conducted.48 cases of patients with POAG at the department of ophthalmology(The West Coast Branch of Affiliated Hospital of Qingdao University)from August 2017 to June 2018 were included.Total 48 patients with POAG were randomized into two study groups(trail and control).The combination of 0.005% latanoprost with 0.1% pranoprofen was used in the trail group for8 weeks.And the only 0.005% latanoprost was used in the control group once a night for8 weeks.The primary evaluated index was IOP,and the secondary outcome measurements were ocular surface symptoms and signs,they were all monitored every 4weeks.2.In order to explore the mechanism of the action,we conducted the following animal experiments.48 C57BL/6 mice were randomized into control group,pranoprofen group,latanoprost group and combination group,with 12 mice in each group.Control group received 0.9% normal saline,pranoprofen group received 0.1% pranoprofen,latanoprost group received 0.005% latanoprost,and combination group received 0.005% latanoprost and 0.1% pranoprofen.IOP was measured at 0,1,2,3,and 6 h after drug administration.The iris and ciliary body were taken out of the mice 3 h after drug administration.The m RNA expression of matrix metalloproteinase-1(MMP-1),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinases-1(TIMP-1)in iris and ciliary body of mice were detected by q RT-PCR.Results: 1.Clinical trial results: 1)there was no statistically significant difference between the two groups in baseline demographic characteristics before treatment(all at P>0.05).At week 4 and 8,the IOP of both trail group and control group was significantly lower than week 0(all at P<0.01),and the IOP of trail group was significantly lower than that of control group(both at P<0.01);2)at week 4 and 8,the ocular symptom scores of the two groups were significantly higher than week 0(all at P<0.01),and the ocular symptom scores of trail group were lower than those of control group(both at P<0.05);3)at week 4 and 8,conjunctival hyperemia scores of trail group and control group were significantly higher than week 0(all at P<0.01),but there was no significant difference in conjunctival hyperemia scores between the two groups(both at P>0.05);4)at week 4 and8,NIBUT in trail group were significantly prolonged compared with week 0(both P<0.01),while NIBUT in control group showed no significant change(P>0.05);5)at week 8,the FLCS score of patients in trail group was significantly lower than week 0(P<0.05),while there was no significant change in the FLCS score of control group(P>0.05).2.Animal experiment results: 1)There was no significant change in the IOP of pranoprofen group and control group during experiment.At 2 h and 3 h after drug administration,the IOP of latanoprost group and combination group was lower than that of control group(all at P<0.05),and the IOP of combination group was lower than that of latanoprost group(both at P<0.01).The difference in IOP between combination group and latanoprost group was the greatest at 3 h after drug administration;2)the results of q RT-PCR: there was little difference of the expressions of MMP-1,MMP-9 and TIMP-1m RNA between pranoprofen group and control group(all at P>0.05).The expressions of MMP-1,MMP-9 and TIMP-1 m RNA in latanoprost group and combination group were significantly higher than those in control group(all at P<0.01).The expression of MMP-1m RNA in combination group was significantly higher than that in the latanoprost group(P<0.05),however,there was no statistically difference in expressions of MMP-9 and TIMP-1 m RNA between the two groups(both at P>0.05).Conclusions: 1.Pranoprofen can enhance the IOP-lowering effect of latanoprost in patients with POAG.2.Pranoprofen can relieve the uncomfortable ocular symptoms caused by latanoprost in patients with POAG.3.It may further increase the expression of MMP-1 in the iris and ciliary body of mice when combined with pranoprofen,so as to enhance the IOP-lowering effect of latanoprost.