Walters T.R.,Texan Eye |
Goldberg D.F.,Wolstan Eye Associates |
Peace J.H.,United Medical Research Institute |
Gow J.A.,Bausch and Lomb Inc.
Ophthalmology | Year: 2014
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. © 2014 by the American Academy of Ophthalmology.
Pavesio C.,Moorfields Eye Hospital |
Zierhut M.,University of Tübingen |
Bairi K.,Bausch and Lomb Inc. |
Comstock T.L.,Bausch and Lomb Inc. |
Usner D.W.,Bausch and Lomb Inc.
Ophthalmology | Year: 2010
Purpose: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). Design: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. Participants: Subjects with unilateral or bilateral NIPU. Methods: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (≥0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (≥0.1 mg/kg daily). Main Outcome Measures: Time to first recurrence of uveitis. Results: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P≤0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. Conclusions: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. © 2010 American Academy of Ophthalmology.
Rajpal R.K.,Clearly Vision Group |
Roel L.,Eastside Westside Research Center |
Siou-Mermet R.,Bausch and Lomb Inc. |
Erb T.,Bausch and Lomb Inc.
Journal of Cataract and Refractive Surgery | Year: 2013
Purpose: To examine the efficacy and safety of a new gel formulation loteprednol etabonate 0.5% in the treatment of inflammation and pain after cataract surgery. Setting: Seventeen United States clinical sites. Design: Prospective double-masked parallel-group study. Methods: Patients with anterior chamber cell (ACC) grade 2 or higher after cataract surgery were randomized to loteprednol etabonate 0.5% gel or vehicle 4 times a day for 14 days. Primary outcome measures included the proportion of patients with complete resolution of ACC and grade 0 (no) pain on postoperative day 8. Safety measures included adverse events, intraocular pressure (IOP), visual acuity, biomicroscopy and funduscopy findings, and tolerability (ocular symptoms and drop comfort). Results: The intent-to-treat population included 406 patients (203 per treatment). On day 8, 30.5% of patients in the loteprednol etabonate group and 16.3% of patients in the vehicle group had complete resolution of ACC, whereas 72.9% and 41.9%, respectively, had grade 0 pain (both P<.001). Significant treatment differences for complete resolution of ACC and grade 0 pain favoring loteprednol etabonate were also found on day 15 and day 18. One patient in each treatment group had a significant increase in IOP (≥10 mm Hg). Analyses of pain, photophobia, and tearing favored loteprednol etabonate at different time points beginning on day 3. More than 85% of patients in each treatment group reported no discomfort on drop instillation. Conclusion: Loteprednol etabonate gel 0.5% was efficacious and safe in treating postoperative inflammation and pain. Financial Disclosure: Dr. Rajpal is a consultant to Bausch & Lomb, Inc., Allergan, Inc., and Alcon Laboratories, Inc. Dr. Siou-Mermet and Ms. Erb are employees of Bausch & Lomb, Inc. Dr. Roel has no financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.
Comstock T.L.,Bausch and Lomb Inc. |
Decory H.H.,Bausch and Lomb Inc.
International Journal of Inflammation | Year: 2012
Topical corticosteroids are effective in reducing anterior segment inflammation but are associated with adverse drug reactions (ADRs) including elevation of intraocular pressure (IOP) and cataract formation. Retrometabolic drug design has advanced the development of new corticosteroids with improved therapeutic indices. Engineered from prednisolone, loteprednol etabonate (LE) has a 17α-chloromethyl ester, in lieu of a ketone group, and a 17β-etabonate group. LE is highly lipophilic and binds with high affinity to the glucocorticoid receptor; any unbound LE is metabolized to inactive metabolites. LE has been studied in several anterior segment inflammatory conditions (giant papillary conjunctivitis, allergic conjunctivitis, anterior uveitis, and keratoconjunctivitis sicca), and in postoperative ocular inflammation and pain. Combined with tobramycin, it is effective in blepharokeratoconjunctivitis. Elevations in IOP are infrequent with LE, and the absence of a C-20 ketone precludes formation of Schiff base intermediates with lens proteins, a common first step implicated in cataract formation with ketone steroids. © 2012 Timothy L. Comstock and Heleen H. DeCory.
Vandermeid K.R.,Bausch and Lomb Inc. |
Su S.P.,Bausch and Lomb Inc. |
Ward K.W.,Bausch and Lomb Inc. |
Zhang J.-Z.,Bausch and Lomb Inc.
Investigative Ophthalmology and Visual Science | Year: 2012
PURPOSE. Tear cytokines and matrix metalloproteinases (MMPs) can be extracted from the Schirmer strip. This study examined the extracted levels of tear cytokines and MMPs from Schirmer strips and potential correlation with Schirmer's test, tear breakup time (TBUT), tear osmolarity, and ocular surface disease index (OSDI). METHODS. Thirty healthy volunteers were clinically evaluated for known methods to diagnose dry eye disease, including Schirmer's test, tear osmolarity, OSDI, and TBUT. Tears were collected by Schirmer strips and proteins were extracted from the Schirmer strip in 0.5 M NaCl with 0.5% Tween 20 and analyzed using multiplex assay kits to examine cytokines or MMPs. Calculated cytokine and MMP concentrations for all samples were sorted into groups according to a positive or negative for each of the above-cited four dry eye diagnostic tests, individually and in combination. RESULTS. Five inflammatory cytokines (IL-1α, -1β, -6, -8, and TNF-_) and five MMPs (MMPs 1, 2, 7, 9, and 10) were extracted from clinical Schirmer strips. Schirmer strip measurement and tear osmolarity correlated well with increased concentrations of the inflammatory cytokines and MMPs, whereas TBUT and OSDI did not. CONCLUSIONS. Both the Schirmer's test and tear osmolarity may be more relevant to the clinician in the diagnosis of ocular surface diseases with an increased level of inflammatory mediators. © 2012 The Association for Research in Vision and Ophthalmology, Inc.
Cavet M.E.,Bausch and Lomb Inc. |
Volhejn S.,Bausch and Lomb Inc. |
Harrington K.L.,Bausch and Lomb Inc. |
Zhang J.-Z.,Bausch and Lomb Inc.
Molecular Vision | Year: 2013
Purpose: To determine the ocular anti-allergic effects of mapracorat, a novel selective glucocorticoid receptor agonist (SEGRA) in primary human conjunctival fbroblasts and epithelial cells. Methods: Two primary human conjunctival cell types, human conjunctival epithelial cells (HConEpiC) and human conjunctival fbroblasts (HConF), were challenged with interleukin-4 (IL-4) or IL-13 plus tumor necrosis factor-alpha (TNF-α). Luminex technology was used to profle the resulting infammatory response. The effects of mapracorat on the release of eotaxin and regulated on activation, normal T cell expressed and secreted (RANTES), two allergy-related che-mokines, as well as proinfammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) were then determined. Small interfering RNA was used to determine whether the effects of mapracorat were mediated via the glucocorticoid receptor (GR). Dexamethasone was used as the control. Results: IL-13 or IL-4 plus TNF-α in the HConF or HConEpiC signifcantly increased eotaxin-1 (HConF only), eo-taxin-3, RANTES, multiple proinfammatory cytokines, and ICAM-1. Synergistic effects of IL-13 or IL-4 plus TNF-α were observed in the HConEpiC for RANTES and monocyte chemoattractant protein-1, and in the HConF for eotaxin-1, eotaxin-3, and RANTES. Mapracorat signifcantly reduced IL-4 or IL-13 plus TNF-α-induced cytokine release and ICAM-1 protein in a dose-dependent manner in both cell types, with comparable effcacy to dexamethasone. These effects were mediated through the glucocorticoid receptor (GR), as demonstrated by the reversal of inhibitory effects after silencing of glucocorticoid receptor expression. Conclusions: Data from these in vitro models indicate that mapracorat is effcacious and potent in reducing IL-4 or IL-13 plus TNF-α-induced release of allergy-related and proinfammatory cytokines from the HConF and the HConEpiC, supporting clinical evaluation of the compound in reducing allergic and infammatory reactions in allergic conjunctivitis. © 2013 Molecular Vision.
Coffey M.J.,Bausch and Lomb Inc. |
Decory H.H.,Bausch and Lomb Inc. |
Lane S.S.,Associated Eye Care
Clinical Ophthalmology | Year: 2013
The eye has protective barriers (ie, the conjunctival and corneal membranes) and defense mechanisms (ie, reflex tearing, blinking, lacrimal drainage) which present challenges to topical drug delivery. Topical ocular corticosteroids are commonly used in the treatment of anterior segment diseases and inflammation associated with ocular surgery, and manufacturers continually strive to improve their characteristics. We describe the development of a novel ophthalmic gel formulation of loteprednol etabonate (LE), a C-20 ester-based corticosteroid with an established safety profile, in the treatment of ocular inflammatory conditions. The new LE gel formulation is non-settling, eliminating the need to shake the product to resuspend the drug, has a pH close to that of tears, and a low preservative concentration. The rheological characteristics of LE gel are such that the formulation is instilled as a drop and transitions to a fluid upon instillation in the eye, yet retains sufficient viscosity to prolong ocular surface retention. The new formulation provides consistent, uniform dosing as evidenced by dose extrusion studies, while pharmacokinetic studies in rabbits demonstrated rapid and sustained exposure to LE in ocular tissues following instillation of LE gel. Finally, results from two clinical studies of LE gel in the treatment of postoperative inflammation and pain following cataract surgery indicate that it was safe and effective. Most patients reported no unpleasant drop sensation upon instillation, and reports of blurred vision were rare. © 2013 Coffey et al, publisher and licensee Dove Medical Press Ltd.
Haas W.,Bausch and Lomb Inc. |
Pillar C.M.,Eurofins |
Torres M.,Eurofins |
Morris T.W.,Bausch and Lomb Inc. |
American Journal of Ophthalmology | Year: 2011
Purpose: To determine the antibacterial susceptibility profile of bacterial pathogens from ocular infections against relevant aminoglycoside, β-lactam, cephalosporin, chloramphenicol, fluoroquinolone, glycopeptide, lincosamide, and macrolide antibacterial agents. Design: Laboratory investigation. Methods: Isolates from patients with bacterial eye infections were collected prospectively by 34 institutions across the United States and were submitted to a central laboratory for inclusion in the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) study. Minimum inhibitory concentrations were determined by microbroth dilution for 200 Staphylococcus aureus (S. aureus), 144 coagulase-negative staphylococci, 75 Streptococcus pneumoniae (S. pneumoniae), 73 Haemophilus influenzae (H. influenzae), and 100 Pseudomonas aeruginosa (P. aeruginosa) isolates. Results: A large proportion of S. aureus and coagulase-negative staphylococci isolates were resistant to oxacillin/methicillin, azithromycin, or fluoroquinolones; 46.5% of S. aureus, 58.3% of coagulase-negative staphylococci, 9.0% of P. aeruginosa, and 9.3% of pneumococcal isolates were nonsusceptible to 2 or more antibacterial drug classes. Only 2.7% of H. influenzae isolates were nonsusceptible to 1 of the agents tested. Methicillin-resistant staphylococci were statistically more likely (all P <.0038) also to be resistant to fluoroquinolones, aminoglycosides, and macrolides. Conclusions: Resistance to 1 or more antibiotics is prevalent among ocular bacterial pathogens. Current resistance trends should be considered before initiating empiric treatment of common eye infections. © 2011 Elsevier Inc.
Cavet M.E.,Bausch and Lomb Inc. |
Vittitow J.L.,Bausch and Lomb Inc. |
Impagnatiello F.,NicOx |
Ongini E.,NicOx |
Investigative Ophthalmology and Visual Science | Year: 2014
The predominant risk factor for the progression of glaucoma is an increase in IOP, mediated via a reduction in aqueous outflow through the conventional (trabecular meshwork and Schlemm's canal) outflow pathway. Current IOP lowering pharmacological strategies target the uveoscleral (nonconventional) outflow pathway or aqueous humor production; however, to date no therapy that primarily targets the conventional pathway exists. Nitric oxide (NO) is an intracellular signaling molecule produced by endogenous NO synthases, well-known for its key role in vasodilation, through its action on smooth muscle cells. Under physiological conditions, NO mediates a multitude of diverse ocular effects, including maintenance of IOP. Nitric oxide donors have been shown to mediate IOP-lowering effects in both preclinical models and clinical studies, primarily through cell volume and contractility changes in the conventional outflow tissues. This review is focused on evaluating the current knowledge of the role and mechanism of action of endogenous NO and NO donors in IOP regulation. Data on key additional functions of NO in glaucoma pathology (i.e., ocular blood flow and effects on optic neuropathy) are also summarized. The potential for future therapeutic application of NO in the treatment of glaucoma is then discussed. © The Association for Research in Vision and Ophthalmology, Inc.
Donnenfeld E.D.,Bausch and Lomb Inc. |
Comstock T.L.,Bausch and Lomb Inc. |
Proksch J.W.,Bausch and Lomb Inc.
Journal of Cataract and Refractive Surgery | Year: 2011
Purpose: To determine the concentrations of besifloxacin, moxifloxacin, and gatifloxacin in human aqueous humor after topical instillation of commercially available besifloxacin ophthalmic suspension 0.6%, moxifloxacin ophthalmic solution 0.5%, and gatifloxacin ophthalmic solution 0.3%, and to assess these concentrations relative to the minimum inhibitory concentration for 90% of strains (MIC 90) for each drug against bacterial pathogens identified in recent cases of postoperative endophthalmitis. Setting: Six clinical sites, United States. Design: Randomized open-label controlled clinical trial. Methods: The aqueous humor drug concentrations were compared 60 minutes ± 5 minutes after instillation of 1 topical drop to patients aged 18 years or older having uncomplicated cataract surgery. Concentrations of besifloxacin, moxifloxacin, and gatifloxacin were determined using a validated liquid chromatography with tandem mass spectrometry method. Results: A total of 105 patients were randomized, and aqueous humor samples were analyzed for 103 patients. Mean aqueous humor concentrations were 0.13 μg/mL ± 0.58 (SD), 0.67 ± 0.50 μg/mL, and 0.13 ± 0.08 μg/mL for besifloxacin, moxifloxacin, and gatifloxacin, respectively. Both besifloxacin and moxifloxacin achieved aqueous humor concentrations equal to or slightly higher than their respective MIC 90 for methicillin-resistant and methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis; none of the fluoroquinolones achieved concentrations above their MIC 90 for ciprofloxacin-resistant strains of S aureus and S epidermidis. Conclusions: Based on the aqueous humor drug concentrations measured in this study, it is unlikely that any of the fluoroquinolones tested would be therapeutically effective in the aqueous humor against the most frequently identified drug-resistant staphylococcal isolates from recent cases of postoperative endophthalmitis. Financial disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. © 2011 ASCRS and ESCRS.