Clinical application of Bromfenac sodium eye drops in ophthalmology / 国际眼科杂志(Guoji Yanke Zazhi)

@#Topical ophthalmic nonsteroidal anti-inflammatory drugs(NSAIDs)are used to treat ocular surface and anterior segment inflammation as well as postoperative management of pain and inflammation. As a new generation of NSAIDs, because of its unique molecule structure, bromfenac is both a kind of potent anti-inflammatory drug and a lipophilic molecule that can penetrate ocular tissues and as a result increase the duration of action. Bromfenac has an extensive global safety record as an anti-inflammatory drug, as well as in the management of ocular pain and inflammation following cataract and refractive surgery. Apart from the functions mentioned above, nowadays researchers have also discovered other ophthalmic applications of bromfenac sodium, and therefore reach a conclusion that bromfenac sodium eye drops are safe, effective and convenient in terms of ophthalmic treatment.This review summarizes recent application progress of bromfenac sodium eye drops in ophthalmology, and then gives prospect about its future application, hoping to provide a new idea for the clinical treatment in ophthalmology in the future.

Inhibitory effect of bromfenac sodium hydrate ophthalmic solution on alkali burn induced-corneal neovascularization in rats / 中华实验眼科杂志

Objective To investigate the inhibitory effect of bromfenac sodium hydrate ophthalmic solution on corneal neovascularization (CNV) induced by alkali burn.Methods A total of 192 specific pathogen free (SPF) degree adult male Sprague-Dawley (SD) rats were used in this study.One hundred and seventy-two rats were chosen to establish CNV model with alkali burn in the right eyes.Following alkali burn,rats were randomly divided into CNV group,model control group,bromfenac sodium group and fluorometholone group,with 43 rats (43 eyes) in each group.Another 20 rats (40 eyes) served as normal control group.One day after modeling,the model control group,bromfenac sodium group and fluorometholone group received phosphate buffer saline (PBS),bromfenac sodium hydrate ophthalmic solution and 0.1％ fluorometholone eye drops,respectively.The state of cornea and anterior chamber and the growth of CNV of rats in each group were observed by slit-lamp microscope every day after modeling.At 1,3,7,14,21 and 28 days after modeling,the anterior segment photos of the experimental eyes were captured,and the percent of cornea areas covered by CNV was calculated.At 7,14 and 28 days after modeling,the eye tissue sections were stained with hematoxylin and eosin staining and immunohistochemistry staining to evaluate the expressions of CD45 and VEGF-A.Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA)were used to detect the expression of COX-2 and VEGF mRNA and protein level.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology(ARVO).Results Each model group showed corneal edema and opacification 1 day after modeling.The corneal edema was aggravated 7 days after modeling.On the 14th day after modeling,the degree of corneal opacity and edema decreased gradually.On the 28th day after modeling,leucoma was observed in CNV group and model control group,and nebula was observed in bromfenac sodium group and fluorometholone group.At 7,14,21 and 28 days after modeling,the percentages of CNV areas in bromfenac sodium group and fluorometholone group were significantly lower than those in CNV group and model control group (all at P＜0.05).No significant difference was found in the percentage of CNV areas between bromfenac sodium group and fluorometholone group at various time points (all at P＞0.05).On the 7th day after modeling,the thinning of corneal epithelial layer,edema and arrangement disorder of stroma layer were observed,and the expression of VEGF-A was positive in all model groups;a small amount of CD45 positive inflammatory cell infiltrations were observed in CNV group and model control group.On the 14th and 28th day after modeling,CNV was seen in the center of cornea in CNV group and model control group;the epithelial keratosis and reduction of corneal edema were seen in each group,and no inflammatory cell infiltration was observed in each group.On the 7th day after modeling,the expressions of COX-2 and VEGF mRNA in CNV group and model control group were significantly higher than those in normal control group,bromfenac sodium group and fluorometholone group (all at P ＜ 0.05),the expressions of COX-2 and VEGF protein in bromfenac sodium group were significantly lower than those in CNV group (all at P＜0.05).The corneal peroration rate in model control group and bromfenac sodium group was 10％ (1 case in 10 rats).The corneal perforation rate in fluorometholone group was 30％ (3 cases in 10 rats).In each model group,10％ to 30％ rats had hyphema.Conclusions Bromfenac sodium hydrate ophthalmic solution can inhibit the formation and growth of CNV after alkali burn in rats.This effect may be mediated by regulating COX-2 expression,reducing inflammation and inhibiting VEGF production.

Comparison of clinical effects between bromfenac sodium versus loteprednol etabonate following FS-LASIK / 中华实验眼科杂志

Objective To compare the efficacy,safety and tolerability between bromfenac sodium ophthalmic solution 0.1％ eye drop and loteprednol etabonate 0.5％ eye drop after femtosecond laser in situ keratomileusis (FS-LASIK).Methods A prospective randomized controlled trail was performed.Seventy-six patients who had been undergone FS-LASIK in Daping Hospital were enrolled from December 2013 to December 2014.They were divided into two groups randomly by using the random number table method.The bromfenac sodium group included 38 patients administered 0.1％ bromfenac sodium ophthalmic solution,and the loteprednol etabonate group comprised 38 patients treated with 0.5％ loteprednol etabonate.Patients in both groups initially administered tobramycin-dexamethasone four times a day after FS-LASIK for 1 week.Then the patients in the bromfenac sodium group were treated with bromfenac sodium twice a day until 1 month postoperatively.While the patients from the loteprednol etabonate group were treated with loteprednol etabonate twice a day until 1 month after surgery.Visual acuity,refraction,intraocular pressure and ocular manifestation were examined preoperative and 1 day,1 week,1 month,3 months,6 months after FS-LASIK.This study was approved by the medical ethics Committee of Daping Hospital.Results No significant difference was found in the rate of uncorrected visual acuity (UCVA) which achieved to preoperative best corrected visual acuity (BCVA) between the two groups at each time point after operation (x2 =8.000,P =0.613).There was no difference in spherical equivalent (SE) between the two groups postoperatively (Fgroup =1.137,P =0.288),but a significant difference was found between the different time points (Ftime =29.771,P =0.000).Postoperative SE in the two groups tended to have mild hyperopia in the early days,and then gradually tended to " zero" or mild myopia.There was a significant difference with intraocular pressure among different time points (Ftime =87.519,P =0.000),but no significant difference of intraocular pressure was found between the groups (Fgroup =1.989,P =0.161).One month after surgery,the intraocular pressure were higher than 20 mmHg in two eyes in the loteprednol etabonate group,and two eyes were 5 mmHg higher than preoperative intraocular pressure.In bromfenac group,no one was higher than 5 mmHg compared with the preoperative intraocular pressure,and the pressures of all the eyes were lower than 18 mmHg.All the patients in bromfenac group were no drug withdrawal.But three patients were forced to guide drug withdrawal due to high intraocular pressure in loteprednol group.Conclusions Bromfenac sodium is safe,effective and well tolerated after FS-LASIK.

Clinical analysis of 1g/L bromfenac sodium eye drops in patients with high myopia astigmatism after sub-Bowman keratomileusis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the curative effect of 1 g/L bromfenac sodium eye drops on high myopia astigmatism in patients after sub-Bowman keratomileusis.· METHODS:Totally 48 cases (96 eys) of High myopic astigmatism (-6.00D＜ equivalent sphere＜-11.00D) from our hospital were selected and randomly divided into 2 groups,24 cases(48 eyes) each.The control group was treated with fluorometholone eye drops,the experimental group was treated with 1g/L bromfenac sodium eye drops,and 2 groups were treated for 2wk.Uncorrected visual acuity,intraocular pressure and corneal topography (K1,K2,the degree of astigmatism) were recorded,at the same time visual symptoms and signs score,corneal haze and DLK were compared at preoperative and postoperative 1d,1wk,1 and 3mo.RESULTS:At different time points,uncorrected visual acuity,intraocular pressure,K1 value,K2 value,the degree of astigmatism of the two groups were statistically significant (P ＜ 0.05).Compared with preoperative,distance visual acuity increased at postoperative 1d,1wk,1 and 3mo;at postoperative 1 and 3mo intraocular pressure decreased(P＜0.05).Compared with the control group,the patients in the experimental group had better uncorrected visual acuity at postoperative 3mo and lower intraocular pressure at postoperative 1 and 3mo(P＜0.05).Compared with preoperative,K1,K2 value of two groups decreased at postoperative 1 and 3mo,the degree of astigmatism increased(P＜0.05).There was no significant difference in K1,K2 and astigmatism between the two groups at postoperative 1 and 3mo (P＞ 0.05).The symptoms and signs of the two groups were similar,and there was no haze phenomenon after operation.The DLK evaluation of the experimental group was better than that of the control group (P＜0.05).CONCLUSION:The 1 g/L bromfenac sodium eye drops and fluorometholone eye drops have similar efficacy in the treatment of SBK after operation,but it can effectively reduce the risk of DLK and intraocular pressure,avoid the adverse reactions caused by glucocorticoid,and is an effective treatment plan.

Clinical observation on 1g/L bromfenac sodium hydrate ophthalmic solution associated with glucocorticoid in high myopia after LASEK / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the efficacy and safety of 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis (LASEK).METHODS: Totally 104 cases (208 eyes) were received LASEK, which were selected and divided into study group and control group.The study group were adopted 1g/L bromfenac sodium hydrate ophthalmic solution combined with tobramycin dexamethasone eye drops and fluorometholone eye drops, the control group were adopted tobramycin dexamethasone eye drops and fluorometholone eye drops.The changes of visual acuity and intraocular pressure of two groups were recorded before and after surgery, and the score of painness and the occurrence of haze were observed after surgery.RESULTS: At postoperative 1, 2, 3d, respectively, the pain score of the study group were 1.70±0.35, 1.25±0.34, 0.82±0.32, the pain score of the control group were 2.30±0.43, 1.68±0.44, 1.12±0.33, the differences were significant (P0.05), and the differences were not significant(P>0.05).At preoperative and postoperative 1, 2wk, 1 and 3mo of surgery, respectively, the intraocular pressure of study group were 17.33±1.58, 7.54±1.28, 7.23±1.58, 7.26±1.47, and 7.30±1.36 mmHg;the intraocular pressure of control group were 17.53±1.43,7.57±1.32,7.73±1.55,7.80±1.38,7.86±1.43 mmHg,the differences were not significant between before and at 2wk after surgery(P>0.05), the differences were significant between the two groups at 2wk, 1mo and 3mo (P0.05).CONCLUSION: It is safe and effective that 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis.The patient has a lower intraocular pressure, has similar therapeutic effect as glucocorticoid in vision and antiinflammatory.

Clinical Efficacy Observation of Bromfenac Sodium Eye Drops in the Treatment of Xerophthalmia / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of Bromfenac sodium eyed drops in the treatment of xe-rophthalmia. METHODS:80 patients with xerophthalmia were randomly divided into observation group and control group,with 40 cases in each group. Control group was given 0.1% Sodium hyaluronate,one drop,qd;observation group was given 0.1% Sodi-um hyaluronate eye drops,one drop,bid. Both groups received 14 d of treatment. The subjective symptom and sign,the time of lacrimal film break-up,fluorescent staining score and schemer test were observed in 2 groups before treatment,3,7,14 d after treatment. Clinical efficacy and the occurrence of ADR were observed in 2 groups. RESULTS:There was no statistical significance in subjective symptom and sign,the time of lacrimal film break-up,fluorescent staining score and tear between 2 groups before treatment,3,7 d after treatment(P>0.05). 14 d after treatment,subjective symptom and sign and fluorescent staining score of 2 groups were decreased significantly,and the time of lacrimal film break-up was prolonged and secretion was increased significant-ly;the observation group was significantly better than the control group,with statistical significance (P0.05). CONCLUSIONS:Sodium hyaluronate eye drops is effective for xerophthalmia,and can relieve the symptoms with good safety.

Determination of Residual Organic Solvents in Bromfenac Sodium by Headspace Gas Chromatography / 中国药师

Objective:To establish a headspace capillary GC method for the determination of residual solvents in bromfenac sodi-um. Methods:A headspace GC was used to separate the residual solvents on an HP-5 capillary column with an FID detector. The car-rier gas was nitrogen at the flow rate of 0. 8 ml·min-1 . The temperature of the injector was 200 ℃ and that of the FID was 250 ℃. The programmed column temperature was set as follows:maintained at 40℃ for 10 min, and then raised to 150℃ at the rate of 30℃·min-1 and maintained for 5 min. The containers of headspace injector were in equilibrium at 100 ℃ for 20 min. Dimethyl sulfoxide was used as the solvent. The amount of the residual solvents, such as methylbenzene, isopropanol, dichloromethane, methanol and iso-propyl ether was calculated by an external standard method. Results:All the solvents could be completely separated with good linear relationship. The average recovery of the five solvents was 98. 9%( RSD =2. 01%),99. 2% ( RSD =1. 95%),99. 6% ( RSD =1. 65%),100. 5%(RSD=1. 38%)and 100. 8%(RSD=1. 36%)(n=9),respectively. Conclusion:The method is simple and accu-rate in the determination of the five residual solvents in bromfenac sodium.

The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

Comparison of clinical effects between bromfenac sodium versus glucocorticoid following LASIK / 中华实验眼科杂志

Background Laser in-situ keratomileusis (LASIK) has been widely used to correct myopia,and the glucocorticoid-induced complication is increased.Bromfenac sodium 0.1％ is a non-steroidal anti-inflammatory drug used post-LASIK,but if it is better in clinical effects,safety and tolerance than glucocorticoid is unclear.Objective This study was to evaluate the safety,effectiveness,compliance of bromfenac sodium ophthalmic solution compared with glucocortieoid following LASIK.Methods A prospective randomized controlled trail were performed.Two hundred thirty-eight myopic eyes of 119 patients for LASIK were included in Peking Union Medical College Hospital from January 2011 to May 2012.The myopic eyes were firstly assigned to moderate and low spherical equivalent (SE) group (≤-6.0 D) or high SE group(＞-6.0 D) and then were further randomized into a NSAIDs subgroup and a glucocorticoid subgroup.Bromfenac sodium ophthalmic solution 0.1％ was topically administered 4 times per day for 10 days in the NSAIDs subgroup,and 0.1％ dexamethasone eye drops was used in the same way in the glucocorticoid subgroup after the LASIK.Uncorrected visual acuity (UCVA),best corrected visual acuity (BCVA),intraocular pressure (IOP),corneal topography,clinical symptom were examined and compared between the groups 1 day,10 days,1 month,3 months and 6 months after LASIK.Results There was no statistically significant postoperative difference in visual acuity and corneal topography (K1,K2,surface asymmetry index [SAI],surface regular index [SRI] and cylinder) between the NSAIDs and control group (P＞0.05).Postoperative IOP was significantly lower than that in preoperation,and lower IOP was found in the NSAIDs group than that of the glucocorticoid group.The IOP values in the moderate and low SE subjects of the NSAIDs group and glucocorticoid group were (13.31±2.44) mmHg and (16.62±4.74) mmHg on postoperative 10 days,(12.93±2.25) mmHg and (12.82± 1.72) mmHg in 1 month,(13.83±3.08) mmHg and (13.33 ±2.10) mmHg in 3 months,(11.67 ±2.48) mmHg and (13.64± 1.37)mmHg in 6 months after operation,respectively,showing significant differences among the groups and various timepoints (Fgroup =4.067,P =0.045 ; Ftime =10.689,P =0.000 ; Finteraction =2.897,P =0.023).In the high SE subjects of the NSAIDs and glucocorticoid group,the IOP values were (12.36± 1.30) mmHg and (17.32±4.74) mmHg in postoperative 10 days,(12.10t2.12)mmHg and (14.81 ±2.26)mmHg in postoperative I month,with a significant difference among the groups and timepoints (Fgroup =2.188,P =0.121 ;Ftime =14.025,P =0.000 ;Fi tion =15.805,P=0.000).No haze or diffuse lamellar keratitis (DLK) appeared in both groups,and the epithelial flaps were wellpositioned with satisfying healing process except for one eye in the moderate and low SE eyes of the NSAIDs group.Bromfenac sodium ophthalmic solution 0.1％ was well tolerated by all patients in the NSAIDs group,but discontinuation sensation occurred in 8 eyes of 6 patients and the antiglaucoma drugs were administered due to elevated IOP in the glucocorticoid group.The refractive status remained stable for patients of the moderate and low SE group.Conclusions Bromfenac sodium ophthalmic solution 0.1％ is safe,effective and well tolerated after topically administered following LASIK,and its outcomes in recovery of visual acuity,anti-inflammation and stabilizing refractive status and IOP are satisfying.But long-term attention should be payed to the high-myopic eyes.

Application and notice of a new generation of non-steroidal eye drops in refractive surgery / 中华实验眼科杂志

The efficacy and safety of excimer laser corneal refractive surgery for refractive error correction have been widely recognized,and effective and appropriate application of perioperative medication also greatly improved patients' satisfaction with surgery.Topical application of glucocorticoid is indispensable for the excimer laser corneal refractive surgery,and it can not be replaced by any other medication for more than 20 years.However,adverse reactions and complications after the application of glucocorticoid are not rare,especially in patients who are long-term users.Therefore,in recent years,non-steroidal anti-inflammatory drugs are becoming more widely used in ophthalmology.Bromfenac sodium,an inhibitor of cyclooxygenase-2,could assume the role as low-concentration glucocorticoids with good medical effects and less adverse effects.But whether it could attain the same therapeutic effects as glucocorticoids in corneal refractive surgery is a subject worth studying.