difluprednate and Inflammation

To establish whether difluprednate 0.05% nanoemulsion (DIFL) twice a day is as effective as prednisolone acetate 1% + phenylephrine hydrochloride 0.12% suspension (PRED) 4 times a day for postsurgical inflammation treatment.. 4 private Argentine ophthalmological centers.. Noninferiority, prospective, multicenter, double-blind, randomized, parallel-group, comparative trial.. A total of 259 patients who underwent phacoemulsification randomly received DIFL or PRED, starting the day before surgery and continuing for 28 days. The primary endpoint was central corneal thickness. Noninferior anti-inflammatory efficacy was considered if the difference of corneal thickness between baseline and day 4 did not differ beyond 17 μm between treatments. Secondary endpoints were cell and flare, corrected distance visual acuity (CDVA), endothelial cell count, optical coherence tomography (OCT) central macular thickness, and intraocular pressure. All outcomes were evaluated at baseline and day 1, 4, and 28 postoperatively.. 225 patients finished the study. The difference in corneal thickness at baseline and day 4 did not differ beyond 17 μm between treatments (95% CI -2.78 μm to 14.84 μm), with no statistically significant difference ( P = .523). No statistically significant differences were found between groups in total anterior chamber clearance at any study timepoint ( P > .05). Moreover, no statistically significant differences were reported between treatments in CDVA ( P = .455), endothelial cell count ( P = .811), OCT central macular thickness ( P = .869), and intraocular pressure outcome ( P = .316).. Difluprednate administered twice a day was at least as effective as prednisolone acetate administered 4 times a day for inflammatory treatment after cataract surgery.

Topics: Cataract; Eye Diseases; Fluprednisolone; Humans; Inflammation; Phacoemulsification; Postoperative Complications; Prednisolone; Prospective Studies

We investigated the early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on blood-aqueous barrier (BAB) breakdown by paracentesis in dogs.. We studied 21 healthy beagles with normal eyes.. Controlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti-inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E. Aqueous protein and PGE. Early postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE

Topics: Animals; Anti-Inflammatory Agents; Aqueous Humor; Betamethasone; Blood-Aqueous Barrier; Dinoprostone; Dog Diseases; Dogs; Eye; Eye Diseases; Eye Proteins; Female; Fluprednisolone; Glucocorticoids; Inflammation; Male; Ophthalmic Solutions; Paracentesis

PurposeTo evaluate safety and efficacy of difluprednate 0.05% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05% four times daily or prednisolone acetate 1% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5%, n=1; prednisolone acetate 1%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05% compared with prednisolone acetate 1%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05%, n=30 (78.9%); prednisolone acetate 1%, n=31 (77.5%). Compared with prednisolone acetate 1%, approximately twice as many difluprednate 0.05%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8%) vs n=7 (17.5%) and day 8 (n=18 (48.7%) vs n=10 (25.0%).ConclusionsDifluprednate 0.05% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1% four times daily in children 0-3 years undergoing cataract surgery.

Topics: Administration, Topical; Aphakia, Postcataract; Cataract; Cataract Extraction; Child, Preschool; Double-Blind Method; Female; Fluprednisolone; Glucocorticoids; Humans; Infant; Infant, Newborn; Inflammation; Intraocular Pressure; Lens Implantation, Intraocular; Male; Ophthalmic Solutions; Prednisolone; Uveitis, Anterior

To compare the effects of 2 corticosteroids on corneal thickness and visual acuity after cataract surgery.. Multicenter, randomized, contralateral-eye, double-masked trial.. Fifty-two patients (104 eyes) underwent bilateral phacoemulsification. The first eye randomly received difluprednate 0.05% or prednisolone acetate 1%; the fellow eye received the alternative. Before surgery, 7 doses were administered over 2 hours; 3 additional doses were given after surgery, before discharge. For the remainder of the day, corticosteroids were administered every 2 hours, then 4 times daily during week 1 and twice daily during week 2. Corneal pachymetry, visual acuity, and corneal edema were evaluated before surgery and at days 1, 15, and 30 after surgery. Endothelial cell counts were evaluated before surgery and at 30 days after surgery. Retinal thickness was evaluated before surgery and at 15 and 30 days after surgery.. Corneal thickness at day 1 was 33 μm less in difluprednate-treated eyes (P = .026). More eyes were without corneal edema in the difluprednate group than in the prednisolone group at day 1 (62% vs 38%, respectively; P = .019). Uncorrected and best-corrected visual acuity at day 1 were significantly better with difluprednate than prednisolone by 0.093 logMAR lines (P = .041) and 0.134 logMAR lines (P < .001), respectively. Endothelial cell density was 195.52 cells/mm(2) higher in difluprednate-treated eyes at day 30 (P < .001). Retinal thickness at day 15 was 7.74 μm less in difluprednate-treated eyes (P = .011).. In this high-dose pulsed-therapy regimen, difluprednate reduced inflammation more effectively than prednisolone acetate, resulting in more rapid return of vision. Difluprednate was superior at protecting the cornea and reducing macular thickening after cataract surgery.

Topics: Aged; Aged, 80 and over; Cell Count; Cornea; Corneal Edema; Double-Blind Method; Endothelium, Corneal; Female; Fluprednisolone; Glucocorticoids; Humans; Inflammation; Intraocular Pressure; Lens Implantation, Intraocular; Male; Middle Aged; Phacoemulsification; Prednisolone; Prospective Studies; Pulse Therapy, Drug; Refraction, Ocular; Uveitis, Anterior; Visual Acuity

To assess the efficacy and safety of difluprednate ophthalmic emulsion 0.05% (Durezol) 2 or 4 times a day compared with those of a placebo in the treatment of inflammation and pain associated with ocular surgery.. Twenty-six clinics in the United States.. One day after unilateral ocular surgery, patients who had an anterior chamber cell grade of 2 or higher (>10 cells) were treated with 1 drop of difluprednate 2 times or 4 times a day or with a placebo (vehicle) 2 times or 4 times a day in the study eye for 14 days. This was followed by a 14-day tapering period and a 7-day safety evaluation. Outcome measures included cleared anterior chamber inflammation (grade 0, or=10 mm Hg and >or=21 mm Hg from baseline, respectively) versus 1% in the placebo group.. Difluprednate given 2 or 4 times a day cleared postoperative inflammation and reduced pain rapidly and effectively. There were no serious ocular adverse events. Fewer adverse events were reported in the difluprednate-treated groups than in the placebo group.

Topics: Adult; Aged; Aged, 80 and over; Anterior Chamber; Cell Count; Double-Blind Method; Emulsions; Female; Fluprednisolone; Glucocorticoids; Humans; Inflammation; Male; Middle Aged; Ophthalmic Solutions; Ophthalmologic Surgical Procedures; Pain; Postoperative Complications; Uveitis, Anterior

Uveitis is a sight-threatening disease that causes inflammation in the uvea; difluprednate (DFB) is the first approved drug molecule for postoperative pain, inflammation, and endogenous uveitis. Complex ocular physiology and structure make it difficult to deliver drugs to the eye. Increased permeation and retention in the layer of the eye are required to improve the bioavailability of ocular drugs. In the current research investigation, DFB-loaded lipid polymer hybrid nanoparticles (LPHNPs) were designed and fabricated to enhance the corneal permeation and sustained release of DFB. A well-established two-step approach was used to fabricate the DFB-LPHNPs, comprising of Poly-Lactic-co-Glycolic Acid (PLGA) core that entrapped the DFB and DFB loaded PLGA NPs covered by lipid shell. The manufacturing parameters were optimized for the preparation of DFB-LPHNPs; the optimal DFB-LPHNPs showed a mean particle size of 117.3 ± 2.9 nm, suitable for ocular administration and high entrapment efficiency of 92.45 ± 2.17 % with neutral pH (7.18 ± 0.02) and isotonic Osmolality (301 ± 3 mOsm/kg). Microscopic examination confirms the core-shell morphological structure of DFB-LPHNPs. The prepared DFB-LPHNPs were extensively characterized using spectroscopic techniques and physicochemical characterization, which confirms the entrapment of the drug and the formation of the DFB-LPHNPs. The confocal laser scanning microscopy studies revealed that Rhodamine B-loaded LPHNPs were penetrated into stromal layers of the cornea in ex-vivo conditions. The DFB-LPHNPs showed a sustained release pattern in simulated tear fluid and 4- folds enhanced permeation of DFB as compared to pure DFB solution. The ex-vivo histopathological studies revealed that DFB-LPHNPs didn't cause any damage or no alteration in the cellular structure of the cornea. Additionally, the results of the HET-CAM assay confirmed that the DFB-LPHNPs were not toxic for ophthalmic administration.

Topics: Delayed-Action Preparations; Humans; Inflammation; Lipids; Nanoparticles; Particle Size; Polymers

To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery.. Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively.. Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P>0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P<0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P>0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit.. The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.

Topics: Aged; Aged, 80 and over; Anterior Chamber; Anti-Inflammatory Agents; Cataract Extraction; Cornea; Corneal Edema; Eye Diseases; Female; Fluprednisolone; Gels; Glucocorticoids; Humans; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Male; Middle Aged; Postoperative Complications; Visual Acuity

Topics: Anti-Inflammatory Agents; Cataract; Cataract Extraction; Child; Double-Blind Method; Fluprednisolone; Humans; Inflammation; Ophthalmic Solutions; Postoperative Complications; Prednisolone

Topics: Anti-Inflammatory Agents; Cataract; Cataract Extraction; Child; Double-Blind Method; Fluprednisolone; Humans; Inflammation; Ophthalmic Solutions; Postoperative Complications; Prednisolone

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature