Role of microsomal metabolism in bromfenac-induced cytotoxicity.

This study delves into the intricate mechanisms underlying drug-induced liver injury (DILI) with a specific focus on bromfenac, the withdrawn nonsteroidal anti-inflammatory drug. DILI is a pervasive concern in drug development, prompting market withdrawals and posing significant challenges to healthcare. Despite the withdrawal of bromfenac due to DILI, the exact role of its microsomal metabolism in inducing hepatotoxicity remains unclear. Herein, employing HepG2 cells with human liver microsomes and UDP-glucuronic acid (UDPGA), our investigation revealed a substantial increase in bromfenac-induced cytotoxicity in the presence of UDPGA, pointing to the significance of UDP-glucuronosyltransferase (UGT)-dependent metabolism in augmenting toxicity. Notably, among the recombinant UGTs examined, UGT2B7 emerged as a pivotal enzyme in the metabolic activation of bromfenac. Metabolite identification studies disclosed the formation of reactive intermediates, with bromfenac indolinone (lactam) identified as a potential mediator of hepatotoxic effects. Moreover, in cytotoxicity experiments, the toxicity of bromfenac lactam exhibited a 34-fold increase, relative to bromfenac. The toxicity of bromfenac lactam was mitigated by nicotinamide adenine dinucleotide phosphate-dependent metabolism. This finding underscores the role of UGT-dependent metabolism in generating reactive metabolites that contribute to the observed hepatotoxicity associated with bromfenac. Understanding these metabolic pathways and the involvement of specific enzymes, such as UGT2B7, provides crucial insights into the mechanisms of bromfenac-induced liver injury. In conclusion, this research sheds light on the metabolic intricacies leading to cytotoxicity induced by bromfenac, especially emphasizing the role of UGT-dependent metabolism and the formation of reactive intermediates like bromfenac lactam. These findings offer insight into the mechanistic basis of DILI and emphasize the importance of understanding metabolism-mediated toxicity.

Topical bromfenac as adjunctive treatment with intravitreal ranibizumab for diabetic macular edema.

PURPOSE: To determine the safety and efficacy of adding topical bromfenac 0.09% in the treatment of diabetic macular edema. METHODS: Seventy patients (70 eyes) with center involved diabetic macular edema with macular thickness (300-500 µm) were included. Patients were divided randomly into two groups: 35 eyes in each group. Both groups were treated with intravitreal ranibizumab monthly for three consecutive months. Bromfenac 0.09% eye drops twice daily was added to the treatment of study group for six months from commencement of treatment. The efficacy of topical bromfenac was evaluated by comparing both groups through follow-up period as regards to visual acuity, central and average thickness and the need for re-injection. RESULTS: Patients treated with topical bromfenac in addition to intravitreal ranibizumab revealed significant improvement in visual acuity, more reduction in central and average macular thickness and less tendency to need reinjection compared to those treated with ranibizumab alone (p 0.013, p 0.010 and p 0.022, respectively). No side effects was encountered with the use of topical bromfenac. CONCLUSION: Topical bromfenac 0.09% twice a day could enhance and sustain the efficacy of intravitreal ranibizumab in the treatment of diabetic macular edema without increasing the incidence of corneal side effects.

Comparison of the Effect of Bromfenac versus Betamethasone Ophthalmic Solutions in Patients with Diabetic Macular Edema.

PURPOSE: To examine the effect of 0.1% bromfenac (BF) ophthalmic solution and 0.1% betamethasone (BM) ophthalmic solution on diabetic macular edema (DME). METHODS: This was a prospective trial. Nineteen patients (mean age of 66.6 ± 10.1 years) with DME and mean retinal thickness within a diameter of 1 mm from the fovea (central subfield thickness: CST) of 250-500 µm were randomized and instilled with BF or BM. CST, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were measured at 4, 8, and 12 weeks after administration. RESULTS: CST at baseline (p = .128) and that at 4, 8, and 12 weeks of administration was not significantly different between the BF (10 patients) and BM groups (9 patients). In patients with glycated hemoglobin (HbA1c) <8.0%, CST, compared with baseline, was significantly decreased in the BF group (seven patients) at 8 (p = .025) and 12 weeks (p = .043) of administration. When compared with the baseline, no significant changes in BCVA were observed at any point in time in either group. Baseline IOP was comparable between the groups. In the BM group, the values of change in IOP from baseline significantly increased at 8 (p = .025) and 12 weeks (p = .044) of administration, with no significant changes in IOP over the 12 weeks of administration in the BF group. CONCLUSIONS: BF did not affect IOP even after 12 weeks of administration, suggesting its effect in reducing CST in DME with good glycemic control. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN-CTR); UMIN000026201, February 18, 2017; Japan Registry of Clinical Trials; jRCTs031180308, March 15, 2019.

Efficacy of Pretreatment with Preservative-Free Topical Bromfenac in Improving Post-Intravitreal-Injection Pain: A Prospective Pilot Study.

(1) Background: To determine the analgesic effect of pretreatment topical bromfenac instillation in patients undergoing intravitreal anti-VEGF treatment. (2) Methods: A prospective, non-randomized pilot study was conducted in patients scheduled to receive repeated intravitreal anti-VEGF injections at a single tertiary hospital. Before the planned second injection, the patients received topical bromfenac eye drops twice a day for 3 days. At 1, 6, and 24 h after the first and second injections, the post-injection pain scores were determined using the numerical rating scale (NRS) telephonically. (3) Results: A total of 28 patients were enrolled in this study. After the first intravitreal injection, the NRS pain scores were 4.04 ± 1.90 at 1 h, 1.57 ± 1.75 at 6 h, and 0.93 ± 1.27 at 24 h. The pain scores after the second intravitreal injection significantly decreased at each measurement time point (p = 0.002, 0.055, and 0.004, respectively) compared to the first injection. (4) Conclusions: The use of topical bromfenac eye drops before intravitreal injection can lead to a significant improvement in injection-related pain scores, which is the basis for a future large-scale randomized comparative study.

Simultaneous determination of ofloxacin and bromfenac in combined dosage form using four different spectrophotometric methods.

Four simple, precise, accurate and validated spectrophotometric methods have been developed for the simultaneous determination of ofloxacin (OFL) and bromfenac sodium (BROM). Firstly, first and second derivative spectrophotometric methods (1D &2D) using a zero-crossing technique utilizing 309.3 and 257.5 nm for OFL and 290.7 and 246.5 nm for BROM as optimum working wavelengths in a binary mixture, respectively. Secondly, the first derivative ratio spectrophotometric method (1DD) in which peak amplitudes at 297.3 nm and 260.7 nm were chosen to simultaneously estimate OFL and BROM, respectively. Thirdly, dual wavelength (DW) method based on two selected wavelengths for each drug in such a way that the difference in absorbance is zero for the second one. At wavelengths 296.4, 348.4 nm BROM has equal absorbance values, therefore, these two wavelengths have been used to determine OFL. Similarly, 271.7 nm and 313.1 nm were selected to determine BROM in the combined formulation. Finally, the fourth method depends on ratio difference spectrophotometry (RDSM), in which the difference between amplitudes at 305.6 nm and 326.5 nm on the ratio spectrum of the mixture was directly proportional to the concentration of OFL; independent of the interfering components. Similarly, the difference between amplitudes at 265.1 nm and 275.4 nm on the ratio spectrum was used for the determination of BROM. The linearity was confirmed in the range of 4 - 18 µg/ml for OFL and BROM for the four methods. The proposed methods were used to determine both drugs in their laboratory prepared mixture and combined formulation with mean percentage recoveries of 99.41 ± 1.35% for OFL and 99.98 ± 1.30 % for BROM in method (A). In method (B), the mean percentage recoveries were 101.70 ± 1.61% for OFL and 101.90 ± 1.45% for BROM. In method (C) OFL was 99.57 ± 1.61% and 100.90 ± 1.62% for BROM. Finally, in method (D) the mean percentage recoveries were 99.37 ± 1.67% for OFL and 100.70 ± 1.59% for BROM. The developed methods were successfully employed for determination of OFL and BROM in laboratory prepared mixtures and combined formulation showing satisfactory recoveries. Methods validation was performed according to the International Conference on Harmonization (ICH) guidelines. The obtained results conformed to the accepted ranges of recovery, precision and repeatability.

Topical 0.1% Nepafenac versus 0.09% Bromfenac Eye Drops for Inflammation after Laser Peripheral Iridotomy: A Randomized Controlled Trial.

PURPOSE: To assess the safety and efficacy of 0.1% nepafenac versus 0.09% bromfenac eye drops in controlling inflammation after neodymium yttrium-aluminum-garnet (YAG) laser peripheral iridotomy (LPI). DESIGN: Single-masked, single-center, randomized controlled trial. PARTICIPANTS: One hundred and sixty eyes of patients with primary angle-closure suspect (PACS) and primary angle closure (PAC) undergoing bilateral LPI. METHODS: Patients were randomized in a 1:1 ratio to receive 0.1% nepafenac thrice daily or 0.09% bromfenac eye drops twice daily for 2 weeks after neodymium YAG LPI. Assessment was performed by masked investigators at 2 weeks after LPI. A Glaucoma Symptom Scale (GSS) questionnaire was administered both at baseline and 2 weeks after LPI. Subjective comfort scores to the study medications were assessed on the basis of a Likert scale at 2 weeks after LPI. In patients with bilateral PACS or PAC, the right eye was analyzed, and in asymmetrical disease (i.e., when one eye had PACS and the other eye had PAC), the eye with PAC was analyzed. MAIN OUTCOME MEASURES: The primary outcome (end point) was uncontrolled inflammation, defined as symptomatic inflammation within 1 week after LPI, the presence of anterior chamber cells at 2 weeks, or rebound inflammation after medication discontinuation. The secondary outcome was patient-reported comfort levels with study medications based on the GSS and Likert scale. RESULTS: At 2 weeks after LPI, 7 patients (6 with PACS and 1 with PAC) in the nepafenac group and 2 patients with PACS in the bromfenac group achieved the primary end point, without a difference between the medication groups (P = 0.09). Post-LPI burning, smarting, and stinging was more common in the bromfenac group (P = 0.01), which also had a higher comfort score on the Likert scale (P = 0.004). The need for repeat LPI was comparable (10.0% in the nepafenac group vs. 15.4% in the bromfenac group; P = 0.22). A multivariate analysis revealed that a greater number of laser shots was associated with the need for repeat LPI (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; P = 0.04). CONCLUSIONS: Topical 0.09% bromfenac is noninferior to 0.1% nepafenac in controlling inflammation after LPI in eyes with PACS and PAC. Nepafenac may be associated with higher patient-reported comfort.

Development of Bromfenac Sodium Loaded Pluronic Nanomicelles: Characterization and Corneal Permeation Study.

BACKGROUND: The Cataract is the leading cause of visual impairment and preventable blindness worldwide. Cataract removal surgery involves various post-operative complications like pain and inflammation. OBJECTIVES: The objective of this study is to screen the polymer concentration as well as optimize the formulation components to develop the pluronic micelles with nanosized characterization and for enhanced corneal permeation study. METHODOLOGY: For optimization, Central Composite design was employed to study the effect of independent variables, concentration of Pluronic F 127 (X1) and the concentration of Hyaluronic acid (X2) on chosen responses (Y 1 ) Micelle size, (Y 2 ) Entrapment Efficiency, (Y 3 ) Viscosity. The lyophilised powder was used for physical characterisation. RESULTS: The formulation containing 5%w/v Pluronic F127 and 0.2%w/v Hyaluronic acid was the optimised composition with micelle size and zeta potential 38.74±4.12nm and -17.6±0.1 mV respectively. In-vitro drug release was found to be 91.72±1.2 percentage in 8 hours. Surface morphology revealed micelles were spherical in shape. Ocular irritancy study showed that formulation was safe and non-irritant. In vitro corneal permeation studies through excised rabbit cornea indicated 1.5 fold increase in ocular availability without corneal damage compared to an aqueous suspension containing the same amount of drug in nanomicelles. CONCLUSION: In a nutshell, Pluronic Nanomicelles would be a platform for the delivery of Bromfenac Sodium.

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification.

Cataract is the leading cause of visual impairment, and posterior capsular opacification (PCO) is the most common long-term complication of modern cataract surgery, which can cause severe visual impairment after surgery. The proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) stimulated by growth factors and cytokines, are the key pathological mechanisms involved in the development of PCO. This study demonstrated that non-steroidal anti-inflammatory drug (NSAID), bromfenac, was capable of effectively inhibiting cell migration, overexpression of EMT markers, such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α-smooth muscle actin (α-SMA), and transcription factor Snail, and extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3ß (GSK-3ß) signaling induced by transforming growth factor-ß2 (TGF-ß2) in vitro. The inhibitory effect of bromfenac on TGF-ß2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules. Furthermore, based on ultrasonic spray technology, we developed a drug-eluting intraocular lens (IOL) using poly (lactic-co-glycolic acid) (PLGA) with sustained bromfenac release ability for the prevention of PCO development. In the rabbit models of cataract surgery, bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility. In conclusion, bromfenac can inhibit TGF-ß2-induced cell migration and the EMT of LECs via ERK/GSK-3ß/Snail signaling. The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.

Bromfenac 0.09% for the Treatment of Macular Edema Secondary to Noninfectious Uveitis.

PURPOSE: The topical nonsteroidal anti-inflammatory drug bromfenac 0.09% has a potential benefit in uveitic macular edema (UME) with a safe side effect profile. The aim of the study is to assess the efficacy of bromfenac sodium solution in the treatment of UME. METHODS: The charts of 10 patients with macular edema due to noninfectious uveitis treated with bromfenac 0.09% were reviewed retrospectively. The main outcomes studied were the best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) compared 4 months before bromfenac initiation, at the time of its initiation, and 4 months later. RESULTS: Twelve eyes of 10 patients were included. BCVA and CRT were unchanged 4 months befoew bromfenac compared to the time of bromfenac initiation (P = 1.0 and P = 0.2, respectively). There were a significant improvement in BCVA after 4 months of bromfenac treatment (P = 0.043) and a significant decrease in CRT (P = 0.002). Subretinal fluid resolved completely in 8/9 eyes, and 4/9 eyes had a complete resolution of cystoid macular edema at 4 months. CONCLUSION: Bromfenac may be a useful addition to the treatment of UME.

Fixed-Combination Eye Drops Based on Fluorometholone Nanoparticles and Bromfenac/Levofloxacin Solution Improve Drug Corneal Penetration.

PURPOSE: The multi-instillation of three commercially available (CA) eye drops [fluorometholone (FL)-, bromfenac (BF)- and levofloxacin (LV)-eye drops] has been used to manage pain and inflammation post-intraocular surgery. However, the multi-instillation of these three eye drops causes corneal damage, and the FL drops have the disadvantage of low ocular bioavailability. To overcome these problems, we prepared fixed-combination eye drops based on FL nanoparticles (FL-NPs) and BF/LV solution (nFBL-FC), and evaluated the corneal toxicity and transcorneal penetration of the nFBL-FC eye drops. METHODS: FL powder was mixed in 2-hydroxypropyl-ß-cyclodextrin solution containing benzalkonium chloride, mannitol and methylcellulose, and milled with a Bead Smash 12 (5500 rpm for 30 s×30 times). The BF/LV solution was then added to the milled-dispersions to be used as nFBL-FC. The FL, BF and LV concentrations were measured by HPLC methods, and transcorneal penetration was evaluated in rabbits. RESULTS: The FL particle size in nFBL-FC was 40-150 nm, with only 0.0018% in liquid form. No aggregation of FL particles in the nFBL-FC was observed for 1 month. The viability of human corneal epithelial cells treated with nFBL-FC was remarkably higher than that of cells subjected to the multi-instillation of the corresponding three CA-eye drops. In addition, the corneal penetrations (AUC) of the FL, BF and LV in nFBL-FC were 4.9-, 1.8-, and 7.1-fold those of the corresponding CA-eye drops, respectively. Moreover, the caveolae-dependent endocytosis (CavME) inhibitor (nystatin) significantly prevented the transcorneal penetration of these drugs. CONCLUSION: We prepared fixed-combination eye drops based on FL-NPs and BF/LV solution (nFBL-FC), and show that high levels of FL-NPs and dissolved BF/LV (liquid drugs) can be delivered into the aqueous humor by the instillation of nFBL-FC. Further, we show that CavME is mainly related to the enhancement of transcorneal penetration of both the solid (NPs) and liquid drugs.

Asymmetry in Drug Permeability through the Cornea.

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.

Effects of Topical Prostaglandin Analog on Macular Thickness Following Cataract Surgery with Postoperative Topical Bromfenac Treatment.

PURPOSE: To evaluate changes in macular thickness in patients continuing prostaglandin analog (PGA) treatment during the perioperative period involving bromfenac treatment. METHODS: Patients with glaucoma who were using a topical PGA were randomly assigned to two groups in this randomized controlled trial: PGA continuing study group and PGA discontinued glaucoma control group. Patients without ocular diseases other than cataract were enrolled into the non-glaucomatous group. After the cataract surgery, the patients used bromfenac twice per day for 4 weeks. Optical coherence tomography was performed in all patients preoperatively and at 1 month postoperatively. Changes in macular thickness were compared among the three groups. RESULTS: There were 32 eyes in the study group, 33 eyes in the glaucoma control group, and 58 eyes in the non-glaucomatous group. We found statistically significant postoperative changes in central macular thickness in all groups (4.30 ± 8.01 µm in the PGA continuing group, 9.20 ± 13.88 µm in the PGA discontinued group, and 7.06 ± 7.02 µm in the non-glaucomatous group, all p < 0.008), but no significant difference among the three groups (p = 0.161). Cystoid macular edema occurred in only one patient in the non-glaucomatous group (p = 0.568). CONCLUSIONS: Continuous use of PGAs during the perioperative period was not significantly associated with increased macular thickness after uncomplicated cataract surgery. In the absence of other risk factors (e.g., capsular rupture, uveitis, or diabetic retinopathy), discontinuing PGAs for the prevention of macular edema after cataract surgery with postoperative bromfenac treatment is unnecessary in patients with glaucoma.

Comparing Combination Drop Therapy to a Standard Drop Regimen After Routine Cataract Surgery.

PURPOSE: To evaluate the efficacy of a combined steroid/antibiotic/non-steroidal anti-inflammatory drop relative to a regimen of multiple drops after cataract surgery. SETTING: Single clinical practice in the USA. DESIGN: Prospective randomized contralateral eye study. METHODS: Subjects presenting for bilateral cataract surgery were enrolled with contralateral eyes randomly assigned to one of the two groups. Test eyes received a combination therapy (prednisolone acetate 1%, gatifloxacin 0.5%, and bromfenac sodium 0.075%) while control eyes received the same medications in separate drops (bromfenac sodium was 0.07%). Subjects were examined 1, 15 and 30 days after surgery. Visual acuities were measured, along with the refraction, intraocular pressure, patient pain and satisfaction, macular thickness and corneal pachymetry. The primary measure of interest was the change in macular thickness from baseline to the 15- and 30-day visits. The frequency and severity of reported ocular adverse events were tabulated for each group and compared. RESULTS: Thirty-three subjects completed the study. Changes in central macular thickness were similar between groups, with only one control eye exhibiting significant macular edema. No differences in visual acuity, corneal edema, cells or flare were observed between groups. There were eight mild adverse events reported for all eyes of all subjects; the difference in the number of eyes experiencing adverse events was not statistically significantly different between groups (p ≥ 0.05 for all comparisons). While subjective symptoms were similar, all subjects indicated that they preferred the combination drop. CONCLUSION: A combination drop showed similar efficacy to multiple drops and was overwhelmingly preferred by subjects.

The Effect of Topical Bromfenac on Intraretinal and Subretinal Fluid in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the effect of topical bromfenac, a non-steroidal anti-inflammatory drug (NSAID), in a case of neovascular age-related macular degeneration (AMD). METHODS: An 85-year-old woman presented with a complaint of visual acuity reduction in the right eye. Comprehensive ophthalmological examination and retinal imaging were performed. RESULTS: Best corrected visual acuity was 2/100. Fundus examination showed reticular pseudodrusen and a small hemorrhage in the fovea. Fluorescein angiography showed an active neovascular membrane. Spectral-domain optical coherence tomography (SD-OCT) confirmed diagnosis and revealed subretinal and intraretinal fluid. The patient refused recommended intravitreal anti-vascular endothelial growth factor treatment and received topical bromfenac 0.09% twice daily. Follow-up with SD-OCT showed subretinal followed by intraretinal fluid reduction at 16 weeks after treatment. CONCLUSION: Short-term reduction of subretinal and intraretinal fluid was observed with topical bromfenac monotherapy in neovascular AMD.

Protective effect of bromfenac sodium on femtosecond laser­assisted cataract surgery via modulating cyclooxygenase­2 expression.

Cataract is a blinding­caused disease and affects millions of individuals worldwide. Although conventional phacoemulsification (CPCS) has been widely used for treatment of cataract, the incidence of cataract­caused blindness still increased year by year. Recently, femtosecond laser technology has been expanded to variety of clinical applications, including cataract surgery. The present study evaluated the curative effect of bromfenac sodium (BS) after femtosecond laser­assisted cataract surgery (FLACS) and analyzed the mechanism of action. A total of 90 patients were randomly divided into five groups: Group I, conventional phacoemulsification treatment (CPCS) + dexamethasone (DEX)/tobramycin (TOB); group II, CPCS + bromfenac sodium (BS); group III, Femtosecond laser­assisted cataract surgery (FLACS) + DEX/TOB; group IV, FLACS + BS; and group V, FLACS + pranoprofen. Aqueous humor was collected from these patients post­surgery. For in vitro studies, SRA01/04 cells were irradiated using UV, followed by the collection of culture media and cell lysate. Prostaglandin E2 (PGE2) levels, an indicator of inflammation, were measured using ELISA both in vivo and in vitro. In addition, cyclooxygenase (COX) and cleaved caspase­1 p20 expression levels were analyzed using western blotting. The findings suggested that BS was more effective and safer compared with glucocorticoids (GCs) after cataract surgery. BS can protect against post­operative inflammation by inhibiting PGE2 production. Under in vitro conditions BS prevented the SRA01/04 cells from undergoing apoptosis after UV treatment and also suppressed PGE2 release from UV­irradiated SRA01/04 cells by modulating COX­2 expression. Furthermore, BS may have an inhibitory effect on the inflammatory form of cell death. Overall, these results indicated that BS could replace existing GCs as a reliable drug for a perioperative period of cataract surgery. It was also identified that the inhibitory effect of BS on PGE2 production was mediated via the regulation of COX­2.

Topical Bromfenac Sodium in Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the effect of preoperative 0.09% bromfenac ophthalmic solution for the reduction of intraoperative miosis and pain in patients who have undergone femtosecond laser-assisted cataract surgery. METHODS: This prospective randomized clinical study included 65 patients with senile cataracts in the absence of significant ocular comorbidity. The patients received 0.09% bromfenac ophthalmic solution or control placebo twice a day for 3 days before surgery. Pupil diameter was measured at the initiation and finalization of femtosecond laser-assisted cataract surgery, and pain quantification was assessed by an analogous pain scale after one day of follow-up. RESULTS: A total of 65 patients were randomly divided into two groups. Five patients were excluded due to defective coupling with the laser interface. Each of the 60 patients was randomized to receive preoperative topical treatment with either 0.09% bromfenac or 0.1% sodium hyaluronate. Baseline characteristics were similar between groups for age and gender. The mean change in horizontal and vertical pupil diameter from the preoperative to post-femtosecond laser measurements were significantly less in the bromfenac group than in the placebo group (0.43 ± 0.6 vs. 1.71 ± 0.9, P < 0.001 and 0.40 ± 0.6 vs. 1.78 ± 0.9, P < 0.001, respectively). Compared with untreated patients, the quantification of pain one day after the procedure was significantly lower in the 0.09% bromfenac group (46.7% with a score of 3 vs. 50% with a score of 1, P < 0.001, respectively). CONCLUSIONS: The maintenance of pupil dilation and the prevention of miosis were more effective in the 0.09% bromfenac group than in the control group. Likewise, the greater control of postoperative pain represented an additional significant benefit.

Intravitreal bromfenac liposomal suspension (100 µg / 0.1 ml). A safety study in rabbit eyes.

INTRODUCTION: There is a need to find alternative treatments for MEe. Bromfenac has shown promise in inhibiting the COX-2 enzymatic pathway that partially causes the inflammatory cascade which contributes to the precipitation of ME. However, like other NSAID's, its intraocular half-life is limited. We hypothesize that a delayed-release liposome formulation containing bromfenac might provide a similar anti-inflammatory effect as long-lasting steroid release systems without the well-known steroidal side-effects. We introduced a novel formulation with these characteristics into the vitreous cavity of rabbit eyes in order to evaluate its safety profile. MATERIAL AND METHODS: 10 left eyes of rabbits were injected with the liposome-encapsulated bromfenac suspension (100 µg/0.1 ml). Basal ERG's were recorded. Total follow-up time was 3 months, at which point ERG's were repeated and eyes were enucleated for histopathological study. Total amplitude and implicit times were recorded. A difference of 25% in either recording was considered significant. Significance was assessed using the paired-t test and Wilcoxon matched-pairs signed-rank test. A p-value of <0.05 was considered significant. RESULTS: No significant changes were recorded in ERG measurements after 3 months when compared to basal measurements. Histopathological analysis of retinal specimens found no traces of liposome-induced toxicity. CONCLUSION: The liposome-encapsulated bromfenac suspension (100 µg/0.1 ml) is not toxic and has been proven safe to use in an animal model. Therefore, this formulation shows promise as a possible future alternative treatment for ME and should be further studied to show its biological effect and efficacy.

Effect of 0.1% Bromfenac for Preventing Macular Edema after Cataract Surgery in Patients with Diabetes.

PURPOSE: To investigate the effect of 0.1% bromfenac sodium hydrate ophthalmic solution for prevention of macular edema after cataract surgery in patients with diabetes. METHODS: A retrospective analysis of 75 patients with diabetes who underwent cataract surgery was performed. Thirty-eight patients (52 eyes) were instilled with 0.1% bromfenac solution (bromfenac group) and 37 patients (46 eyes) were not (control group). RESULTS: There were no significant preoperative between-group differences. Compared to the control group, at 1 month after surgery, the bromfenac group showed slightly better best-corrected visual acuity (0.12 ± 0.12 vs. 0.32 ± 0.42, p = 0.142), lower central macular thickness (265.58 ± 31.28 vs. 314.15 ± 76.11 µm, p < 0.001), and lower macular volume (8.46 ± 0.60 vs. 9.14 ± 1.53 mm³, p = 0.022). There were no significant differences between the two groups at 4 and 6 months postoperatively (p > 0.05). Mean changes in central macular thickness showed significant differences at 1 and 4 months postoperatively (-1.44 ± 11.72 and 10.44 ± 22.48 µm in bromfenac group vs. 47.19 ± 70.24 and 31.69 ± 48.04 µm in control group, p < 0.001 and p = 0.016) and mean changes in macular volume showed a significant difference at 1 month postoperatively (-0.08 ± 0.47 mm³ in bromfenac group vs. 0.58 ± 1.28 mm³ in control group, p < 0.001). There were no significant differences thereafter (p > 0.05). CONCLUSIONS: Treatment with 0.1% bromfenac sodium hydrate ophthalmic solution showed good efficacy for preventing cystoid macular edema early after cataract surgery in patients with diabetes.

Treatment of central serous chorioretinopathy with topical NSAIDs.

PURPOSE: Central serous chorioretinopathy (CSCR) is a common retinopathy that is often observed until resolution. The purpose of this study is to evaluate the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on timing of CSCR recovery. METHODS: An IRB-approved retrospective review was conducted on patients that had been diagnosed with a new-onset, symptomatic case of CSCR. Patients were either observed only (13 untreated eyes) or treated with topical bromfenac or nepafenac (14 eyes) over an average of about a 4-5 week follow-up period. RESULTS: There was no statistical significance between central macular thickness (CMT) and visual acuity of treatment and control groups at the initial presentation. However, at the follow-up visit, CMT reductions in the treatment group were significantly higher than in the control group (p<0.006). CONCLUSION: Use of topical NSAIDs in the treatment of acute CSCR leads to a faster rate of reduction in the subretinal fluid volume over a follow-up period of a few weeks.

Bromfenac Ophthalmic Solution 0.07% Versus Nepafenac Ophthalmic Suspension 0.3% for Post-Cataract Surgery Inflammation: A Pilot Study of Identical Dosing Regimens with Pre-Surgical "Pulse" Dose.

INTRODUCTION: This small pilot study is the first direct comparison of the currently marketed formulations of bromfenac (0.07% solution) and nepafenac (0.3% suspension) using identical dosing regimens and including an extra pre-surgical "pulse" dose in patients undergoing cataract surgery. METHODS: Adults scheduled for unilateral phacoemulsification with intraocular lens implantation were randomly assigned to bromfenac 0.07% or nepafenac 0.3%, each given once-daily 1 day prior to surgery, on the day of surgery plus an extra dose 1 h before surgery, and for 14 days after surgery. Assessments included summed ocular inflammation score (SOIS), visual acuity (VA), and retinal thickness measured via optical coherence tomography. RESULTS: The study population included 49 patients (bromfenac, n = 24; nepafenac, n = 25). The percentage of patients with a SOIS = 0 (no cells or flare) at post-surgical day 15 (primary efficacy endpoint) was statistically similar between the bromfenac (57.1%) and nepafenac (50.0%) treatment groups (intent-to-treat with last observation carried forward) (P = 0.6318). The proportions of patients with an SOIS of 0 at days 3 and 8 were significantly (P < 0.05) higher in the bromfenac group (23.8 and 52.4%, respectively) versus the nepafenac group (0.0 and 20.8%, respectively). Visual acuity was similar between groups at each study visit, as were mean retinal thickness and change from baseline in retinal thickness. Rescue medication (typically difluprednate) was given on or before day 15 to 13 patients in each treatment group (bromfenac, 54.2%; nepafenac, 52.0%). There were no adverse events considered to be related to either treatment. CONCLUSIONS: The results of this small pilot study suggest that once-daily bromfenac 0.07% produces similar benefits with regard to postsurgical inflammation, VA, and retinal thickness as once-daily nepafenac 0.3%, and possibly has a faster onset of anti-inflammatory action, when compared using identical dosing regimens. FUNDING: Bausch & Lomb Incorporated. TRIAL REGISTRATION: NCT03886779.