Determination Of Intraocular Drug Concentration Of Triamcinolone Acetonide By Different Routes Of Administration And Analysis Of Its Curative Effect On Macular Edema In Uveitis

Part One Subconjunctival injections of triamcinolone acetonide to treat uveitic macular edemaPURPOSE:To evaluate the efficacy and safety of subconjunctival triamcinolone acetonide(TA)injections for treating uveitic macular edema(UME).METHODS:This retrospective case series study included patients with UME who received subconjunctival TA injections with a minimum follow-up period for 6 months.The main outcome measure was central macular thickness(CMT).The secondary outcome measures included best corrected visual acuity(BCVA),recurrence rate and intraocular pressure(IOP).RESULTS:In total,68 patients(83 eyes)were enrolled in this study.The mean CMT decreased from 456.9 ± 171.1 ?m at baseline to 324 ± 175.9 ?m,305.6 ?m 147.7 ?m,331.8± 154.3 ?m and 281.1±147.6 ?m at 1-,2-,3-and 6-months post injection,respectively(all P<0.001).BCVA increased from logMAR 0.5±0.3 at baseline to logMAR 0.4±0.3,logMAR 0.4 ±0.3,logMAR 0.4 ± 0.4 and logMAR 0.4±0.3 at the 1-,2-,3-and 6-months postinjection visits,respectively(all P<0.001).The relapse rate within 6 month was 26.51%.A total of 21/83(25.3%)eyes exhibited elevated IOPs,of which 14 were controlled with topical IOP-lowering agents and 7 eyes underwent surgical removal of subconjunctival TA deposit.CONCLUSION:Subconjunctival TA injections appear to be safe and effective in the treatment of UME.Part Two Section one Concentration of Triamcinolone Acetonide in ocular tissues of rabbits by different site injectionsPURPOSE:To analyze the distribution and concentration of Triamcinolone Acetonide(TA)in rabbit eyes after different site of injections.METHODS:According to the applications of TA in clinic,45 rabbits were randomly divided into 3 groups,with 15 rabbits in each.Three different applications of TA includes:Group A,subconjunctival injection of TA 20mg;Group B,orbital floor injection of TA 20mg;Group C,intravitreal injection of TA 4mg.All of the right eyes were intervened while the left eyes were as the blank controls.On the 1st,3rd,7th,14th and 28th day,three rabbits in each group were sacrificed respectively and eyeballs were dissected at each time point.The concentration of TA was detected by high performance liquid chromatography(HPLC),and the distribution of drug in different tissues were compared.RESULTS:In aqueous humor,the peak concentrations(Cmax)of TA were 0.2344±0.3236 ?g/mL,0.1736±0.1802 ?g/mL,0.3109±0.4964 ?g/ml while the times to peak(Tmax)were 7d,14d,7d in group A,B,C respectively.In vitreous,the Cmax of TA were 0.7321±1.1197 ?g/mL,0.4371±0.2852 ?g/mL,977.7281±854.0102 ?g/ml while Tmax were 7d,14d,1d in group A,B,C respectively.In retinal-choroid,the Cmax of TA were 69.0265±198.4629 ?g/g,40.2925±41.1317 ?g/g,2286.026±1833,1570 ?g/g,and the Tmax were 7d,7d,1d in group A,B,C respectively.CONCLUSION:All of the three applications of TA demonstrated good penetration in aqueous humor,vitreous and retinal-choroid.While the concentration of TA was highest in retinal-choroid than vitreous and aqueous humor.IVTA demonstrated highest drug concentration in rabbits eyes and shortest peak time.Part Two Section Two Comparision of systemic and ocular drug concentration of Triamcinolone Acetonide between subconjunctival injection and orbital floor injectionPURPOSE:To analyze the distribution and concentration of Triamcinolone Acetonide(TA)in rabbit eyes after subconjunctival injection and orbital floor injection.METHODS:50 rabbits were randomly divided into 2 groups,with 25 rabbits in each.The applications of TA includes:Group A,subconjunctival injection of TA 20mg;Group B,orbital floor injection of TA 20mg.All of the right eyes were intervened while the left eyes were as the blank controls.On the 1st,3rd,7th,14th and 28th day,5 rabbits in each group were chosen to have intraocular pressure(IOP)examination and then took 2ml blood from the ear vein.After that the rabbits were sacrificed and eyeballs were dissected.The concentration of TA was detected by high performance liquid chromatography,and the distribution of drug in different tissues were compared.RESULTS:Subconjunctival injections of TA demonstrated higher concentration in rabbit eyes than orbital floor injections.Especially on the 7th day after the intervention,the concentration of TA in the aqueous humor,vitreous and retinal-choroid were significantly higher in the subconjunctival group rather than orbital floor injection group(P=0.023,P=0.014 and P=0.028,respectively,all P<0.05).While the concentration of TA in the plasma was very close(P>0.05).There was no difference between the two groups in IOP before and after the intervention(all P>0.05).CONCLUSION:Both of the applications of TA showed good penetration in ocular tissues in rabbit eyes and it was with highest concentration in retinal-choroid than aqueous humor and vitreous.Subconjunctival injections of TA demonstrated higher concentration in rabbit eyes than orbital floor injectionsPart Three A prospective randomized clinical trial to compare different administrations of triamcinolone acetonide in the treatment of uveitic macular edemaPURPOSE:To compare the efficacy and safety of subconjunctival injections of triamcinolone acetonide(SCTA)and orbital floor injections of TA(OFTA)in the treatment of uveitic macular edema(UME).METHODS:This is a prospective randomized clinical trial which includes patients with noninfectious uveitic macular edema.The patients are randomly divided into two groups:subconjunctival injection of 20mg TA and orbital floor injection of 20mg TA.The central macular thickness(CMT),the best corrected visual acuity(BCVA),intraocular pressure(IOP),effective rate and recurrence rate were observed and compared before and after the treatment.RESULTS:In this study,34 patients(34 eyes)with uveitic macular edema were included,with 18 cases in the SCTA group and 16 cases in the OFTA group.There was no difference in age and gender between the two groups.Both groups demonstrated improved CMT during 6-month follow-up(all P<0.01).The effective rate of SCTA group and OFTA group were 94.44%and 87.5%,respectively,with no significant difference between the two groups(P=0.455,P>0.05).In the first month,the average BCVA of the SCTA group and OFTA group was significantly improved compared with baseline(P=0.001 and P=0.033,respectively).The risk of IOP elevation and recurrence did not differ significantly between the two groups(P>0.05).CONCLUSION:SCTA and OFTA are both effective and safe in the treatment of UME.