Application of a PBPK model to elucidate the changes of systemic and liver exposures for rosuvastatin, carotegrast, and bromfenac followed by OATP inhibition in monkeys.

The impact of organic anion-transporting polypeptide (OATP) inhibition on systemic and liver exposures of three OATP substrates was investigated in cynomolgus monkeys. A monkey physiologically-based pharmacokinetic (PBPK) model was constructed to describe the exposure changes followed by OATP functional attenuation. Rosuvastatin, bromfenac, and carotegrast were administered as a single intravenous cassette dose (0.5 mg/kg each) in monkeys with and without predosing with rifampin (RIF; 20 mg/kg) orally. The plasma exposure of rosuvastatin, bromfenac, carotegrast, and OATP biomarkers, coproporphyrin I (CP-I) and CP-III were increased 2.3, 2.1, 9.1, 5.4, and 8.8-fold, respectively, when compared to the vehicle group. The liver to plasma ratios of rosuvastatin and bromfenac were reduced but the liver concentration of the drugs remained unchanged by RIF treatment. The liver concentrations of carotegrast, CP-I, and CP-III were unchanged at 1 h but increased at 6 h in the RIF-treated group. The passive permeability, active uptake, and biliary excretion were characterized in suspended and sandwich-cultured monkey hepatocytes and then incorporated into the monkey PBPK model. As demonstrated by the PBPK model, the plasma exposure is increased through OATP inhibition while liver exposure is maintained by passive permeability driven from an elevated plasma level. Liver exposure is sensitive to the changes of metabolism and biliary clearances. The model further suggested the involvement of additional mechanisms for hepatic uptakes of rosuvastatin and bromfenac, and of the inhibition of biliary excretion for carotegrast, CP-I, and CP-III by RIF. Collectively, impaired OATP function would not reduce the liver exposure of its substrates in monkeys.

Topical bromfenac reduces multiple inflammatory cytokines in the aqueous humour of pseudophakic patients.

Intraocular surgery is associated with increased ocular inflammation. If maintained for a prolonged period after surgery, this inflammation can cause various complications, including subconjunctival fibrosis and bleb scarring. This clinical trial was a prospective, randomised, single-blind, interventional study comparing the efficacy and safety of 0.1% bromfenac sodium ophthalmic solution and 0.02% fluorometholone ophthalmic suspension in the inhibition of multiple inflammatory cytokines in the aqueous humour of 26 patients with pseudophakic eyes who had undergone phacoemulsification and intraocular lens implantation. The patients were randomly assigned to one of the trial drugs, and aqueous humour samples were collected before and after drug administration. Platelet-derived growth factor-AA levels significantly decreased in both drug groups, but they were significantly higher in the fluorometholone group than in the bromfenac group (P = 0.034). Bromfenac also significantly decreased vascular endothelial growth factor level (P = 0.0077), as well as monocyte chemoattractant protein-1 level (P = 0.013), which was elevated for a prolonged period after phacoemulsification. These data suggest that bromfenac is useful to alleviate prolonged microenvironmental alterations in the aqueous humour of pseudophakic eyes.

Efficacy and safety of sodium bromfenac eye drops in the treatment of postoperative inflammation in cataract surgery: A protocol for systematic review and meta-analysis.

BACKGROUND: A cataract is a degenerative change in the optical quality of the lens caused by protein denaturation. Modern medicine is mainly based on surgical treatment. Cataract surgery is often accompanied by severe inflammation, and glucocorticoid therapy has many adverse reactions and side effects. The non-steroidal anti-inflammatory drug sodium bromfenac not only has good anti-inflammatory, analgesic and anti-allergic effects, but also does not produce side effects caused by hormone drugs. Clinical studies have shown that sodium bromfenac eye drops have a good curative effect in treating postoperative inflammation of cataract, with low recurrence rate and certain therapeutic advantages, but lack of evidence-based medicine evidence. The purpose of this study is to systematically evaluate the efficacy and safety of sodium bromfenac eye drops in the treatment of postoperative inflammation of cataracts. METHODS: Use computer to search English and Chinese databases, such as PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, Weipu, China Biomedical Database, and Chinese Clinical Trial Registry for randomized controlled trials on the treatment of postoperative postoperative inflammation in cataract surgery with sodium bromfenac eye drops from the establishment of the database to September 2020, and data extraction and literature quality evaluation were conducted independently by two researchers, and Meta analysis was conducted on the included literature using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of sodium bromfenac eye drops in the treatment of postoperative inflammation of cataract surgery were evaluated by the effective rate, symptom score, adverse reactions, incidence, recurrence rate, etc. CONCLUSION:: This study will provide reliable evidence-based evidence for the clinical application of bromofenac sodium eye drops in the treatment of postoperative inflammation of cataract. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/3KP7R.

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis.

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.

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.

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.

VITREOUS PROSTAGLANDIN E2 CHANGES AFTER TOPICAL ADMINISTRATION OF DICLOFENAC 0.1%, INDOMETHACIN 0.5%, NEPAFENAC 0.3%, AND BROMFENAC 0.09.

PURPOSE: To evaluate the vitreous concentration of different nonsteroidal anti-inflammatory drugs (NSAIDs) after topical administration and the related prostaglandin E2 (PGE2) levels in patients undergoing pars plana vitrectomy. METHODS: A prospective, randomized, investigator-masked study was performed. One hundred four patients scheduled for a pars plana vitrectomy for an epiretinal membrane or a macular hole were randomized to receive topical diclofenac 0.1%, indomethacin 0.5%, nepafenac 0.3%, bromfenac 0.09%, or placebo 3 days before surgery. At the beginning of surgery, a sample of undiluted vitreous was collected in each patient to assess NSAIDs concentration and PGE2 levels. RESULTS: The median vitreous concentrations were 203.35 (interquartile range 146.54-264.18) pg/mL for diclofenac, 243.45 (interquartile range 156.96-365.37) pg/mL for nepafenac, 438.21 pg/mL (interquartile range, 282.52-645.87) for its active metabolite amfenac, 350.14 (interquartile range, 290.88-481.95) pg/mL for indomethacin, and 274.59 (245.43-358.25) pg/mL for bromfenac. Vitreous PGE2 levels were significantly lower for all the NSAIDs groups compared with the control group (P < 0.001). A statistically significant higher vitreous PGE2 level was found in the diclofenac group compared with the other NSAIDs groups (P < 0.05). CONCLUSION: Topical NSAIDs achieve sufficient vitreous concentration to decrease vitreous PGE2 levels compared with the control group. The different efficacy in reducing PGE2 concentration may affect the management of posterior segment inflammation.

Comparison of 2 regimens of loteprednol etabonate and bromfenac for cataract surgery.

OBJECTIVE: We aimed to evaluate the safety and effectiveness of 2 dosing regimens of loteprednol etabonate (LE) ophthalmic gel 0.5% and bromfenac ophthalmic solution 0.07% in patients undergoing routine cataract surgery. DESIGN: Six-week prospective, masked, randomized controlled noninferiority study. PARTICIPANTS: One hundred eyes. METHODS: Patients undergoing uncomplicated cataract surgery were selected in a consecutive manner. Patients were randomized to one of 2 groups: LE QID + qD bromfenac (control group) versus LE BID + qD bromfenac (study group). Primary outcome metrics included summed ocular inflammation score (SOIS) and adverse events. Secondary outcome measures included intraocular pressure, visual acuity, central retinal thickness, and subjective symptomology scores measured at 4 study visits. The final visit included a questionnaire addressing compliance, satisfaction, and comfort with the medications. RESULTS: Both groups demonstrated similar effectiveness and safety between dosing regimens. No statistically significant difference was reported between groups regarding SOIS (visit 1 p = N/A, visit 2 p = 0.66, visit 3 p = 0.60, visit 4 p = 0.08). No adverse events were reported relating to the difference in study regimen. A statistically significant difference was not found regarding secondary outcomes (p > 0.05). Control group patients reported a more difficult time remembering their doses for bromfenac but not LE (bromfenac p < 0.05; LE p = 0.15). CONCLUSIONS: Our data suggest that both groups had similar outcomes with respect to control of ocular inflammation with no differences in adverse outcomes. The compliance questionnaire also suggests a patient preference for the dosing regimen with lower frequency of drop application.

Topical bromfenac transiently delays axotomy-induced retinal ganglion cell loss.

Optic nerve axotomy in rodents allows detailed studies of the effect of different treatments on the survival of central nervous system neurons, the retinal ganglion cells (RGCs). Here we have analyzed the neuroprotective effect of topical bromfenac treatment, a nonsteroidal anti-inflammatory drug (NSAID) used in clinic to ameliorate post-operative inflammation, on axotomized rat RGCs. The left optic nerve of adult rats was subjected to optic nerve crush (ONC). Half of the rats were treated with a topical instillation of saline. On the other half, immediately after the surgery, 2 drops of bromfenac (0.09% Yellox; Bausch & Lomb) were instilled, and then every 12 h until analysis. Retinas in both groups were dissected 3, 5, 7, 9 and 14 days after ONC (n = 4-8/time point/group). Toxicity of bromfenac was assessed in intact retinas treated during 14 days (n = 6). Intact untreated retinas were used as control of the RGC population. RGCs were identified by Brn3a immunodetection and automatically quantified. Our results show that bromfenac does not cause RGC loss in intact retinas. In the injured groups, the number of RGCs at 7, 9 and 14 days after the lesion was significantly higher in treated vs. untreated retinas. To our knowledge this is the first report showing that a topical treatment with a NSAIDs delays axotomy-induced RGC loss and indicates that treatment with NSAIDs could be used as conjunctive therapy in diseases that proceed with optic nerve damage.

Effect of NSAIDs on Pupil Diameter and Expression of Aqueous Humor Cytokines in FLACS Versus Conventional Phacoemulsification.

PURPOSE: To compare the concentrations of interleukin (IL) (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and TNF-ß in the aqueous humor of patients undergoing femtosecond laser-assisted cataract surgery (FLACS) and corneal mechanical paracentesis treated with two different topical nonsteroidal anti-inflammatory drugs (NSAIDs): bromfenac and indomethacin. METHODS: In this prospective, randomized controlled, single-center study, aqueous humor samples were obtained immediately after performing the femtosecond laser procedure or at the start of conventional phacoemulsification. Preoperatively, the FLACS groups were administered (once daily and four times daily, respectively) either topical bromfenac 0.09% (12 eyes) or indomethacin 0.1% (12 eyes). The corneal paracentesis bromfenac and indomethacin groups received the same regimen of instillation of NSAIDs, respectively. Quantitative analysis of the expressed cytokines in the aqueous humor was performed using FlowCytomix FC 500 Pro 3.0 Software (Bender MedSystems GmbH, Vienna, Austria). RESULTS: The intraoperative pupil diameter was correlated with the expression of IL-6 after the femtosecond laser procedure in the FLACS indomethacin group (r = -0.53; P = .07). A significant difference in mean pupillary size was detected between the FLACS bromfenac and indomethacin groups at the aspiration/irrigation time point (0.53 ± 0.26 mm) and at the end of surgery (0.68 ± 0.37 mm). Progressive pupillary constriction was observed in the indomethacin and bromfenac groups. CONCLUSIONS: A smaller expression of IL-6 to the overall cytokine network value was observed in cases receiving preoperative bromfenac 0.09%, explaining improved maintenance of intraoperative mydriasis. [J Refract Surg. 2018;34(10):646-652.].

Topical non-steroidal anti-inflammatory drugs for the treatment of cystoid macular edema post Descemet's stripping automated endothelial keratoplasty.

PURPOSE: To investigate the effectiveness of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular edema (CME) post Descemet's stripping automated endothelial keratoplasty (DSAEK). STUDY DESIGN: Retrospective observational study METHODS: In this study of 334 patients who underwent DSAEK at the Baptist Eye Institute, Kyoto, Japan between July 2011 and December 2015, 18 patients with postoperative CME (determined by optical coherence tomography) treated with topical NSAIDs after the onset of CME were included. RESULTS: At CME onset, 17 of the 18 patients were treated with bromfenac eye drops and 1 was treated with nepafenac eye drops. Post initiation of treatment with topical NSAIDs, CME in 17 (94.4%) of the 18 patients improved at 1 month and all cases completely recovered within 3 months. At 12-months post initiation of treatment, 61.1% (n = 11) of patients achieved a visual acuity (VA) of 20/40 or better, and there was no significant difference of VA between the patients with or without an episode of postoperative CME (P = 0.55). CONCLUSION: The administration of topical NSAID eye drops was found to be effective in treating patients with CME post DSAEK.

The Comparative Efficacy and Tolerability of Diclofenac 0.1% and Bromfenac 0.09% Ophthalmic Solutions after Cataract Surgery.

PURPOSE: To compare the efficacy and tolerability of diclofenac and bromfenac ophthalmic solutions as adjunctive therapy after cataract surgery. MATERIALS AND METHODS: This prospective randomized controlled study included 130 patients who underwent cataract surgery. One hundred patients were randomized to receive postoperatively diclofenac 0.1% (four times daily for 28 days, Group 1) or bromfenac 0.09% (twice daily for 14 days, Group 2) ophthalmic solutions in addition to steroid-antibiotic combination. Thirty patients instilled only steroid-antibiotic combination (Control Group 3). Laser flare-cell photometry and optical coherence tomography scans with central foveal thickness (CFT) measurement were performed before (V0) and 7 (V1), 14 (V2) and 28 days (V3) after surgery. Treatment tolerability was scored using the Ocular Comfort Grading Assessment. RESULTS: Laser flare-cell photometry values were significantly higher at V1, V2 and V3 compared to V0 in all the groups (respectively 13.3 ± 1.0, 12.7 ± 0.9 and 9.6 ± 0.9 vs 8.4 ± 0.6 ph/ms for Group 1; 13.4 ± 1.0, 12.7 ± 0.9 and 12.7 ± 1.0 vs 8.1 ± 0.6 for Group 2; 15.9 ± 0.8, 15.4 ± 0.7 and 14.5 ± 0.7 vs 7.5 ± 0.5 for Group 3) (p < 0.001); flare increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.001). CFT values were higher after surgery in all the three groups; the increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.0002). The percentage of symptoms-free patients after study treatment was significantly higher in Group 2 compared to Group 1 (respectively 74% vs 14% of the total; p < 0.001). CONCLUSION: The addition of diclofenac or bromfenac ophthalmic solutions contributed to further reduce both inflammation and cystoid macular edema after cataract surgery compared to steroid-antibiotic combination alone. Diclofenac appeared to be more effective in reducing postoperative intraocular inflammation with a more intense and prolonged regimen, while bromfenac more tolerated with lower daily dose and treatment duration.

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.

Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.

PURPOSE: To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING: Twelve European study centers. DESIGN: Randomized clinical trial. METHODS: Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS: The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 µm and 9.7 µm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS: Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.

European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 1.

PURPOSE: To compare the efficacy of a topical nonsteroidal antiinflammatory drug, topical corticosteroid, and a combination of both drugs to prevent the occurrence of cystoid macular edema (CME) after cataract surgery in nondiabetic patients. SETTING: Twelve European study centers. DESIGN: Randomized clinical trial. METHODS: Nondiabetic patients having uneventful cataract surgery were included in this study. Patients were randomized to receive topical bromfenac 0.09% twice daily for 2 weeks or dexamethasone 0.1% 4 times daily with 1 drop less per day every following week, or a combination of both. The primary outcome was the difference in central subfield mean macular thickness 6 weeks postoperatively. Secondary outcome measures included corrected distance visual acuity as well as the incidence of CME and clinically significant macular edema (CSME) within 6 weeks and 12 weeks postoperatively. RESULTS: This study comprised 914 patients. Six weeks postoperatively, the central subfield mean macular thickness was 288.3 µm, 296.0 µm, and 284.5 µm in the bromfenac group, dexamethasone group, and combination treatment group, respectively (overall P = .006). The incidence of clinically significant macular edema within 12 weeks postoperatively was 3.6%, 5.1%, and 1.5%, respectively (overall P = .043). CONCLUSION: Patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% had a lower risk for developing CSME after cataract surgery than patients treated with a single drug.

Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse.

OBJECTIVE: This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane (DBDPE). METHODS: In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 (CYP) levels and activities and uridinediphosphate-glucuronosyltransferase (UDPGT) activities were investigated. Liver and thyroid glands were observed. RESULTS: There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and fT3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency. CONCLUSION: DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by AhR and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.

Comparison of the Efficacy of Dexamethasone, Nepafenac, and Bromfenac for Preventing Pseudophakic Cystoid Macular Edema: an Open-label, Prospective, Randomized Controlled Trial.

PURPOSE: To evaluate the incidence of pseudophakic cystoid macular edema (PCMO) in patients treated with corticosteroids alone or in combination with bromfenac or nepafenac eyedrops after uneventful cataract surgery. MATERIALS AND METHODS: Prospective, randomized, open-label, placebo-controlled clinical trial. Patients who underwent routine cataract surgery with intraocular lens (IOL) implant were randomly divided into three groups receiving either bromfenac or nepafenac in association with dexamethasone or dexamethasone alone (control group) postoperatively. Best-corrected visual acuity (BCVA) measurement, slit lamp and fundus examination and optical coherence tomography (OCT) were performed preoperatively, 1 and 5 weeks after surgery. Primary outcome was defined as patients (%) in whom macular edema developed within 5 weeks after cataract surgery; secondary end points were patients (%) with BCVA improvement from pre-op through 5 weeks after surgery and corneal toxicity. RESULTS: A total of 144 patients completed the study, 48 for each group. In all groups, mean central subfield thickness at OCT increased significantly 5 weeks after surgery (p < 0.01). However, at this time point, four patients (8.3%) of the control group and none in nepafenac and bromfenac groups developed PCMO (p = 0.016). Compared with baseline, mean BCVA significantly improved both at 1 and 5 weeks in all groups (p < 0.01). At 1 week, the nepafenac group showed a mean BCVA significantly lower compared with both the control (p = 0.038) and bromfenac group (p = 0.002). CONCLUSIONS: Co-administration of nepafenac or bromfenac and steroids in patients who underwent routine cataract surgery is associated with a lower incidence of PCMO compared with steroid monotherapy.

[Effect of medicinal treatment on epithelial wound healing after phacoemulsification]. / . Vliianie medikamentoznoi terapii na épitelizatsiiu rogovichnogo razreza posle fakoémul'sifikatsii.

AIM: to compare the dynamics of epithelial wound healing under two different post-op treatments in patients after uncomplicated phacoemulsification. MATERIAL AND METHODS: This prospective randomized clinical trial included 40 eyes of 40 patients aged 66.4±8.2 years who underwent uncomplicated phacoemulsification with flexible intraocular lens implantation through a 2.2-mm corneal incision. Patients were randomized to receive either dexamethasone 0.1% and diclofenac 0.1% (n=20 eyes, Group I), or bromfenac 0.09% (n=20 eyes, Group II). Also, all patients instilled levofloxacin 0.5%. The dynamics of epithelial wound healing was assessed with the RTVue-100 spectral domain optical coherence tomograph with CAM-L corneal module in the 3D CORNEA mode 2 hours after surgery and on days 1, 3, 5, and 10. RESULTS: The postoperative period was uneventful in all cases. Two hours after surgery, epithelial defects were found in all eyes and their length did not differ statistically p=0.47. On the first day after surgery, complete epithelization was observed in 30% of cases from Group I and 60% of cases from Group II. The average length of epithelial defects was reliably smaller in Group II than in Group I (p=0.04 respectively). On postoperative day 3, 20% eyes from Group I still had epithelial defects with the average length of 0.45±0.13 mm, while there was only one eye with a 0.2-mm epithelial defect in Group II. Finally, on postoperative day 5, there was a single 0.3-mm epithelial defect in one eye from Group I. On day 10, none of the patients had epithelial defects in either group. CONCLUSION: Epithelial wound healing at the site of corneal incision after non-complicated phacoemulsification was found to be faster in patients instilled with bromfenac twice daily than in patients receiving dexamethasone and diclofenac four times daily as anti-inflammatory therapy and given topical fluoroquinolones for antibacterial purpose.