Investigating the adverse outcome pathways (AOP) of neurotoxicity induced by DBDPE with a combination of in vitro and in silico approaches.

Current studies have shown an association between DBDPE and neurotoxicity. In this study, the adverse outcome pathway (AOP) and mechanistic analysis of DBDPE-induced neurotoxicity were explored by a combination of in vitro and in silico approaches in SK-N-SH cells. DBDPE-induced oxidative stress caused DNA strand breaks, resulting in the activation of poly (ADP-ribose) (PAR) polymerase-1 (PARP-1). Activation of PARP1 could cause toxic damage in various organ systems, especially in the nervous system. DBDPE-induced apoptosis via the caspase-dependent intrinsic mitochondrial pathway and the PARP1-dependent pathway. Activation of PARP1 by DBDPE was deemed the initiating event, thereby affecting the key downstream biochemical events (e.g., ROS production, DNA damage, membrane potential changes, and ATP reduction), which induced apoptosis. Furthermore, excessive activation of PARP1 was accompanied by the translocation of the apoptosis-inducing factor (AIF), which was associated with PARP1-dependent cell death. The inhibition of PARP1 by PJ34 reduced DBDPE-induced apoptosis and maintained cellular ATP levels. PJ34 also prevented the translocation of AIF from the mitochondria to the nucleus. These findings improve the understanding of the mechanism of DBDPE-induced neurotoxic effects and provide a theoretical basis for the ecological risk of DBDPE.

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery.

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema. Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious. Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

Corneal perforation in undiagnosed Sjögren's syndrome following topical NSAID and steroid drops post routine cataract extraction.

A 74-year-old man presented with a progressive decrease in visual acuity and foreign body sensation in his right eye 8 days post uncomplicated phacoemulsification cataract surgery and intraocular lens insertion. The patient had been placed on a perioperative cataract regimen which consisted of G. Maxitrol (dexamethasone, polymyxin B sulfate, neomycin sulfate) four times a day and G. Yellox twice daily (bromfenac, a non-steroidal anti-inflammatory) for 2 weeks. On examination, he had a corneal ulcer and stromal thinning in his right eye which progressed to a full thickness perforation 12 hours later. The patient required a full thickness tectonic corneal transplant. Direct questioning revealed that this patient had both dry mouth and eyes. Serology revealed that the patient was positive for rheumatoid factor and for anti-Ro and anti-La antibodies. A parotid gland biopsy revealed significant lymphocytic infiltrate consistent with Sjögren's syndrome.

Comparison of topically applied flurbiprofen or bromfenac ophthalmic solution on post-operative ocular hypertension in canine patients following cataract surgery.

OBJECTIVE: To compare the prevalence and kinetics of ocular hypertension after routine cataract extraction when using a predominately COX-2 inhibitor (bromfenac) versus a predominately COX-1 inhibitor (flurbiprofen) in combination with a topical corticosteroid. PROCEDURES: Patients undergoing unilateral or bilateral cataract surgery were randomly assigned to receive flurbiprofen or bromfenac at the day of surgery and continued for 6 weeks postoperatively, along with topical neo poly dexamethasone. No systemic nonsteroidal anti-inflammatory medications were administered before or after surgery. Intraocular pressure was monitored pre and postoperatively. When an IOP of >25 mmHg was detected, therapeutic intervention was performed. RESULTS: Eyes in both treatment groups showed a similar IOP profile with the highest mean IOP occurring two hours postsurgery and slowly declining during the next 6 weeks. However, eyes receiving bromfenac had a higher mean IOP at 2 h post-op (22.1 mmHg) than eyes receiving flurbiprofen (18.8 mmHg) and a slower decrease in IOP in the weeks after surgery. Over the course of the study, a higher percentage of eyes receiving bromfenac had therapy discontinued over concerns of elevated IOP compared to eyes receiving flurbiprofen (bromfenac 23.1% and flurbiprofen 9.8%). On average, the risk of having elevated intraocular pressure with bromfenac is 1.04 times higher than with flurbiprofen. CONCLUSION: Elevated postoperative IOP was observed in both treatment groups; however, bromfenac-treated eyes were more likely to require intervention for elevated IOP.

[Comparison of clinical effects of bromfenac sodium ophthalmic solution 0.1% versus glucocorticoids for post-LASEK usage].

OBJECTIVE: To evaluate the safety, effectiveness and compliance of Bronuck (bromfenac sodium ophthalmic solution 0.1%) following LASEK in comparison with glucocorticoids. METHODS: In this prospective trial, 60 patients (120 eyes) undergoing LASEK were randomized into the bromfenac sodium group (60 eyes) and control group (60 eyes). Patients in both groups initially received dexamethasone 0.1% four times a day after LASEK for 7 days, and then the patients in the bromfenac sodium group were given Bronuck twice a day for the next 11 weeks, while the patients from the control group were given fluorometholone 0.1% with gradually decreased doses during the same period. Results of the routine examinations done before and 3, 10, 30, 90 and 180 days after LASEK were recorded, including uncorrected visual acuity, best corrected visual acuity, intraocular pressure (IOP), corneal topography, ocular symptoms and signs, which were used for comparison between the two groups. All data of right eyes were analyzed for their independence, normality and homogeneity of variance. Independent samples t-test or non-parametric Mann-Whitney test was performed accordingly. RESULTS: There was no statistically significant difference in IOP and corneal topography (K1, K2, SAI, SRI and CY) between the two groups postoperatively. The IOP was (16.33 ± 6.21) mmHg(1 mmHg = 0.133 kPa), (15.67 ± 2.82) mmHg, (15.35 ± 2.22) mmHg and (13.10 ± 3.41) mmHg in the bromfenac sodium group, and (16.87 ± 3.68) mmHg, (14.05 ± 2.23) mmHg, (14.39 ± 2.22) mmHg and (13.18 ± 2.49) mmHg in the control group at 10, 30, 90 and 180 days, respectively. The bromfenac sodium group showed significantly better uncorrected visual acuity (5.16 ± 0.08) than the control group (5.02 ± 0.09) on day 30 (t = 2.32, P < 0.05). In the bromfenac sodium group, four eyes had visual fatigue, and four eyes had dry eye symptoms on day 180. Epithelial flaps were all well positioned with satisfying healing process. Each group had one case (two eyes) of haze on day 30, and the bromfenac sodium group had another case (2 eyes) of new-onset haze on day 60. But all the cases of haze were graded 0.5 according to the Fantes Standard, too mild to compromise their visual acuities, and were resolved after frequent topical medication for 1 month. Four patients from the control group were prescribed antiglaucoma medications due to elevated IOP. The refractive status remained stable for patients from both groups. CONCLUSIONS: Administration of Bronuck can reduce the amount of or partially substitute for corticosteroids. Mild haze early after LASEK may disappear after intensive treatment.

Cytotoxic Effects of a Novel Thialo Benzene Derivative 2,4-Dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) in L929 Cells.

The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of C18H12S2IBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with C18H12S2IBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL C18H12S2IBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of C18H12S2IBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of C18H12S2IBr, this newly synthesized compound may be a good alternative antifungal agent.

Bromfenac ophthalmic solution 0.07% dosed once daily for cataract surgery: results of 2 randomized controlled trials.

PURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.07% (Prolensa) dosed once daily for the treatment of ocular inflammation and pain in subjects who underwent cataract surgery with posterior chamber intraocular lens implantation. DESIGN: Two phase 3, randomized, double-masked, placebo-controlled, multicenter clinical trials. PARTICIPANTS: Four hundred forty subjects (440 study eyes: 222 in the bromfenac group and 218 in the placebo group). METHODS: Two phase 3, prospective, randomized, double-masked, placebo-controlled clinical trials were conducted at 39 ophthalmology clinics in the United States. Subjects 18 years of age or older were randomized to receive either bromfenac 0.07% or placebo dosed once daily beginning 1 day before cataract surgery, on the day of surgery, and continuing for 14 days after surgery (for a total of 16 days). Subjects were evaluated on days 1, 3, 8, 15, and 22 after surgery. The primary efficacy end point was cleared ocular inflammation, as measured by the summed ocular inflammation score of zero (anterior chamber cell count = 0 and absence of flare) by day 15. Secondary end points included cleared ocular inflammation at day 15 and the number of subjects who were pain free at day 1. The data from the 2 clinical trials were integrated for analyses. MAIN OUTCOME MEASURES: Summed ocular inflammation score and ocular pain. RESULTS: A significantly higher proportion of subjects treated with bromfenac 0.07% achieved complete clearance of ocular inflammation by day 15 and at day 15 compared with placebo (P < 0.0001). A statistically significantly higher proportion of subjects in the bromfenac 0.07% group were pain free at all study visits compared with those in the placebo group (P < 0.0001). Fewer subjects in the bromfenac group (3.2%) discontinued investigational product early because of a lack of efficacy than in the placebo group (23.9%; P < 0.0001). The incidence of adverse events was significantly lower in the bromfenac 0.07% group compared with the placebo group (P = 0.0041). CONCLUSIONS: Bromfenac ophthalmic solution 0.07% dosed once daily was clinically safe and effective compared with placebo for the treatment of ocular inflammation and pain in subjects who had undergone cataract surgery and may be a beneficial addition to the current standard of care, which commonly includes ophthalmic antibiotics and corticosteroids.

Acute corneal melt associated with topical bromfenac use.

PURPOSE: To report a case of acute corneal melt associated with use of bromfenac ophthalmic solution. METHODS: Case report. RESULTS: A 61-year-old man developed acute corneal melt 5 days after having combined cataract and pterygium surgery in his left eye. Postoperatively, he had been using bromfenac eyedrops four times daily along with the combination of ofloxacin and dexamethasone six times and timolol eyedrops twice daily. Ocular examination revealed the presence of asymptomatic dry eyes. He was managed conservatively with topical antibiotics, lubricants, and bandage contact lens application. The corneal melt healed completely with best-corrected visual acuity of 20/30 at 4 weeks postoperatively. CONCLUSIONS: The current case suggests that corneal melt can occur as a complication of inadvertent excessive use of topical bromfenac in the presence of preexisting ocular surface disorders. However, good visual outcome can be achieved by prompt conservative treatment if accurate diagnosis is made at an early stage.

Once daily dosing of bromfenac ophthalmic solution 0.09% for postoperative ocular inflammation and pain.

OBJECTIVE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% dosed once daily for the treatment of ocular inflammation and pain following cataract extraction with posterior chamber intraocular lens implantation. METHODS: A total of 455 subjects (455 study eyes: 230 bromfenac, 225 placebo) were enrolled in two randomized double-masked, placebo-controlled, clinical trials at 64 ophthalmology clinics in the United States. Subjects were randomized to receive either bromfenac 0.09% or placebo dosed once daily. Dosing began 1 day before cataract surgery (Day -1), continued on day of surgery (Day 0), and for 14 days following surgery. Evaluations were completed on Days 1, 3, 8, 15 and 22. The primary efficacy endpoint was cleared summed ocular inflammation score (SOIS) by Day 15. The secondary efficacy endpoint was the number of subjects who were pain-free at Day 1. RESULTS: The bromfenac 0.09% group was significantly higher compared to the placebo group in the primary endpoint of the proportion of subjects who had cleared ocular inflammation by Day 15 (P < 0.0001). The mean SOIS for the bromfenac 0.09% group was lower than the placebo group at Days 3, 8, 15, and 22 (P < 0.0001). More bromfenac 0.09% subjects were pain free at Days 1, 3, 8, and 15 (P < 0.0001). Fewer subjects in the bromfenac 0.09% group withdrew from the clinical trials due to lack of efficacy at Day 15 (P < 0.0001). Fewer adverse events were reported in the bromfenac 0.09% group than the placebo group. Limitations included advanced age, female predominance, and surgical nuances among cataract surgeons, making cross-trial comparisons difficult. CONCLUSIONS: Bromfenac ophthalmic solution 0.09% dosed once daily is clinically safe and effective for the treatment of ocular inflammation and the reduction of ocular pain associated with cataract surgery.

Safety and efficacy of bromfenac ophthalmic solution (Bromday) dosed once daily for postoperative ocular inflammation and pain.

PURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution (bromfenac) 0.09% dosed once daily for the treatment of ocular inflammation and pain after cataract surgery with posterior chamber intraocular lens implantation. DESIGN: Randomized, double-masked, vehicle-controlled or active-controlled, multicenter, clinical trials. PARTICIPANTS AND CONTROLS: A total of 872 subjects (872 study eyes: bromfenac in 584, placebo in 288). METHODS: Four randomized, double-masked, vehicle or active-controlled, clinical trials were conducted at 134 ophthalmology clinics in the United States. Subjects aged ≥ 18 years were randomized to receive either bromfenac 0.09% or placebo dosed once daily beginning 1 day before cataract surgery (day -1), continuing on the day of surgery (day 0), and continuing for an additional postoperative 14 days. Subjects were evaluated for efficacy and safety on days 1, 3, 8, 15, and 22. The primary efficacy end point was cleared ocular inflammation, measured by the summed ocular inflammation score (SOIS; anterior chamber cells and flare) by day 15. The secondary efficacy end point was the number of subjects who were pain-free at day 1. The data from the 4 trials were pooled for analyses. MAIN OUTCOME MEASURES: The SOIS and ocular pain. RESULTS: The proportion of subjects who had cleared ocular inflammation by day 15 was significantly higher in the bromfenac 0.09% group than in the placebo group (P < 0.0001). The mean SOIS in the bromfenac 0.09% group was significantly lower than in the placebo group at days 3, 8, 15, and 22 (P < 0.0001). The proportion of subjects who were pain-free at days 1, 3, 8, and 15 was significantly higher in the bromfenac 0.09% group than in the placebo group (P < 0.0001). The incidence of adverse events reported in the bromfenac 0.09% group was significantly lower than in the placebo group (P < 0.0001). On day 15, 84.0% of the bromfenac subjects had ≥ 1-line improvement in visual acuity compared with 66.1% of placebo subjects (P < 0.0001). CONCLUSIONS: Bromfenac 0.09% dosed once daily was clinically safe and effective for reducing and treating ocular inflammation and pain associated with cataract surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Efficacy and safety of bromfenac for the treatment of corneal ulcer pain.

PURPOSE: To evaluate the efficacy and safety of bromfenac ophthalmic solution 0.09% (Xibrom™, ISTA Pharmaceuticals Inc., Irvine, CA, USA) for treating pain associated with corneal ulcers. METHODS: Twenty-five eyes of 24 patients with corneal infiltrates (bacterial or fungal) were treated with appropriate anti-infective agents along with bromfenac twice daily for up to 102 days to treat the pain caused by the infection. Follow-up visits were frequent in the first 2 weeks upon initiation of treatment, then at least weekly until infections were resolved. The best corrected visual acuity, location, size, and density of corneal infiltrates, the size and presence of a corneal epithelial defect, subjective eye pain (scale of 0-4) and time to pain resolution, the ability to conduct daily activities, and adverse events were recorded at each follow-up visit. The results of these treated patients were compared with those of 10 control eyes with corneal infiltrates (bacterial or fungal) where appropriate anti-infectives were used without adjunct medications. RESULTS: Fifty-two percent of bromfenac-treated patients reported no pain by day 3, compared with 0% of untreated controls (P=0.023). Most of the treated patients' epithelium healed by day 20 (68%) compared with only 10% of controls (P=0.040). Most bromfenac-treated patients (71%) returned to normal activities within 2 days of starting treatment with bromfenac, compared with 0% of controls (P=0.018). No adverse events were recorded. CONCLUSION: Bromfenac was effective in treating pain associated with infectious keratitis and did not delay corneal epithelialization nor cause any corneal adverse events in this group of 25 eyes.

Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes.

PURPOSE: To compare the efficacy of bromfenac sodium ophthalmic solution (BF) and a steroidal solution (ST) administered prophylactically against cystoid macular oedema and anterior-chamber inflammation after phacoemulsification and intraocular lens implantation and to assess macular thickness changes using optical coherence tomography (OCT). METHODS: In this prospective study, 62 eyes of 62 patients were randomized to either the BF group (n=31) or the ST group (n =31). The average perifoveal thickness (AFT) was measured by OCT preoperatively, and 1 day and 1, 2, 4 and 6 weeks postoperatively. The best-corrected visual acuity, intraocular pressure and flare in the anterior chamber were recorded at each visit. The same method was used to compare patients with non-proliferative diabetic retinopathy (NPDR) in the BF (n = 16) and ST (n =11) groups. RESULTS: In the analysis of all patients, flare in the anterior chamber was significantly (p = 0.007) lower in the BF group 2 weeks postoperatively. In patients with NPDR, the anterior chamber flare values were significantly lower in the BF group at 4 weeks (p = 0.0009) and 6 weeks (p = 0.005). The AFT values were significantly lower in the BF group at 4 weeks (p < 0.0001) and 6 weeks (p < 0.0001). No adverse events occurred in either group. CONCLUSION: BF suppressed anterior chamber inflammation and increasing retinal thickening after cataract surgery in patients with NPDR.

Retrospective review of the efficacy of topical bromfenac (0.09%) as an adjunctive therapy for patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to assess the efficacy of topical bromfenac (0.09%) as an adjunctive therapy for patients with neovascular age-related macular degeneration demonstrating persistent exudation despite monthly intravitreal antivascular endothelial growth factor therapy. METHODS: Twenty-one patients (22 eyes) who manifested persistent subretinal and/or intraretinal fluid after at least 3 monthly intravitreal injections of ranibizumab or bevacizumab were prescribed topical bromfenac (0.09%) ophthalmic solution twice daily for 2 months. The efficacy of topical bromfenac was evaluated by comparing visual acuity (logarithm of the minimal angle of resolution and Snellen equivalent), masked readings of spectral domain optical coherence tomography center-point retinal thickness, and the height of pigment epithelial detachment (when present) at baseline and at 1 month and 2 months after the initiation of combined treatment. RESULTS: The mean visual acuity logarithm of the minimal angle of resolution (Snellen equivalent) at baseline was 0.55 +/- 0.35 (20/70), and it did not change significantly after 1 month (0.53 +/- 0.35; P = 0.41, paired Student's t-test) or 2 months (0.52 +/- 0.34; P = 0.26) after the initiation of combined treatment. The mean central retinal thickness was 311 microm at baseline, 308 microm (P = 0.73, paired Student's t-test) after 1 month, and 299 microm (P = 0.34) after 2 months. In 20 eyes of 19 patients manifesting a pigment epithelial detachment, the mean pigment epithelial detachment height was 275 microm at baseline, 271 microm (P = 0.33, paired Student's t-test) at 1 month, and 274 microm (P = 0.76) at 2 months. There were no adverse events associated with the extended administration of topical bromfenac. CONCLUSION: In patients with neovascular age-related macular degeneration manifesting persistent exudation despite monthly intravitreal antivascular endothelial growth factor therapy, we could not detect a beneficial effect of adding topical bromfenac (0.09%) twice daily over 2 months.

Comparison of efficacy of bromfenac sodium 0.1% ophthalmic solution and fluorometholone 0.02% ophthalmic suspension for the treatment of allergic conjunctivitis.

AIMS: Bromfenac sodium (BF) 0.1% was compared with fluorometholone (FML) 0.02% for the treatment of seasonal allergic conjunctivitis when concomitantly used with disodium cromoglycate (DSCG) 2.0%. METHODS: Eighty-six patients with seasonal allergic conjunctivitis were treated with DSCG four times a day, and BF was concomitantly administered twice a day in one eye and FML was administered four times a day in the contralateral eye for 1 week. Ocular signs were scored on a four-graded severity. Patients recorded symptoms using visual analog scale. Patients were asked which concomitant treatment was more suitable for them and scored global evaluation. RESULTS: All subjective symptom scores were decreased in both concomitant treatment groups compared with baseline (P < 0.05). Objective signs were significantly improved with the concomitant use of BF or FML with DSCG (P < 0.05). Neither symptoms nor signs differed significantly between the concomitant use of BF and FML. Fifteen patients selected BF and 29 patients selected FML as the more preferred concomitant eye drops, 42 patients judged no difference in efficacy between the groups. No significant difference was observed in patient's global evaluation between the groups. CONCLUSIONS: Bromfenac sodium for allergic conjunctivitis was effective, with efficacy equivalent to that of FML when used with DSCG.

Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery.

PURPOSE: This study compared the post-cataract surgery anti-inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling. METHODS: Seventy-two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time-points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery. RESULTS: There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone. CONCLUSIONS: There were no significant differences in anti-inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery.

The systemic safety of bromfenac ophthalmic solution 0.09%.

STUDY OBJECTIVE: The aim of this study was to evaluate the systemic safety of a commercially available bromfenac ophthalmic solution 0.09% for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction. DESIGN: Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled, clinical trials were conducted under a common protocol. These data were pooled for analysis. SETTING: The setting for this study was a series of multicentered, private, and university-affiliated ophthalmology clinics in the United States. SUBJECTS: A total of 527 subjects were sequentially assigned, according to a computer-generated randomization list (2:1) to either bromfenac (n = 356) or placebo (n = 171). Potential subjects were excluded if using nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, anticoagulants, or with uncontrolled ocular or systemic disease, preexisting ocular inflammation, surgical complications, or liver chemistry values of > or =Grade 1 according to World Health Organization Common Toxicity Criteria scoring. INTERVENTION: Subjects who underwent cataract surgery without prior anti-inflammatory treatment and had a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or placebo. Subjects self-instilled 1 drop of the assigned test agent twice-daily for 14 days and were followed for an additional 14 days for safety evaluation. MAIN OUTCOME MEASURES: Safety data were collected and the results for systemic safety are reported in this paper. RESULTS: Five hundred and twenty-seven (527) subjects comprised the safety population. A total of 290 of 356 bromfenac and 93 of 171 placebo subjects received 28 doses of test agent. No clinically significant treatment-related systemic adverse effects or changes in liver chemistries were observed. CONCLUSIONS: Bromfenac ophthalmic solution 0.09% demonstrated neither treatment-related systemic adverse events nor evidence of hepatic toxicity.

Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use.

We report a case of a 20-year-old woman with tear deficiency secondary to Stevens Johnson syndrome who developed bilateral corneal melting following use of bromfenac (Xibrom), a nonsteroidal antiinflammatory drug (NSAID), for 2 weeks. The patient presented with complaints of light sensitivity and pain in the right eye. The slitlamp examination revealed a corneal perforation with iris plug in the right eye and an 85% thinned cornea in the left eye. She was admitted to the hospital, where Xibrom was discontinued, therapeutic contact lenses were placed, and a regimen of topical antibiotic agents was instituted. One day after admission, penetrating keratoplasty was performed in the right eye, an amniotic membrane was placed in the left eye, and tarsorrhaphy was performed bilaterally. The clinical features of this case highlight the importance of being selective when administering NSAIDs in patients with a compromised ocular surface.

Bromfenac ophthalmic solution 0.09% (Xibrom) for postoperative ocular pain and inflammation.

OBJECTIVE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% (Xibrom) for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction (CE). DESIGN: Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled clinical trials were conducted under a common protocol. Data were pooled for analyses. PARTICIPANTS: Five hundred twenty-seven subjects were sequentially assigned, according to a computer-generated randomization list (2:1), to bromfenac (n = 356) or a placebo (n = 171). INTERVENTION: Subjects who underwent cataract surgery without prior antiinflammatory treatment with a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or the placebo, instilled twice daily for 14 days in the study eye, and observed for an additional 14 days for safety evaluation. MAIN OUTCOME MEASURE: Cleared ocular inflammation with a SOIS of 0 (cells< or =5 and absence of flare after 14 days of treatment). Secondary outcomes included time to resolution of ocular inflammation, time to resolution of ocular pain, proportion of subjects with photophobia, and ocular adverse events. RESULTS: Baseline characteristics were comparable between groups for age, gender, and race. The baseline mean SOIS was 3.7 in both groups. A greater proportion of bromfenac (64.0%) than placebo subjects (43.3%) achieved complete clearance of ocular inflammation at study day 15 (P<0.0001). The effect of bromfenac on clearance of ocular inflammation was as early as study day 3 after initiation of treatment, compared with the placebo (8.4% vs. 1.2%, P = 0.0012). The median time to resolution of ocular pain was 2 days (bromfenac) versus 5 days (placebo) (P<0.0001). Numbers of most ocular adverse events were lower for the bromfenac group than for the placebo group. Eye irritation was reported in a lower percentage of subjects for bromfenac (2.5%) versus placebo (4.7%), as were burning and stinging (1.4% vs. 2.5%), and photophobia (2.0% vs. 11.1%). CONCLUSIONS: Bromfenac ophthalmic solution 0.09% effectively and rapidly cleared ocular inflammation and reduced ocular pain after CE. There were no serious ocular adverse events, and fewer adverse events were reported for the bromfenac group.