Kirk Bateman

Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis.

ABSTRACT Objective: This study compared the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet*) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; Tobradex†) in the treatment of ocular inflammation associated with blepharokeratoconjunctivitis. Research design and methods: This was a multicenter, randomized, investigator-masked, parallel-group study. Subjects with clinically diagnosed blepharokeratoconjunctivitis in at least one eye were randomized to LE/T (n = 138) or DM/T (n = 138) administered four times per day, for 14 days. The primary efficacy endpoint was the change from baseline to Day 15 (± 1 day) in the signs and symptoms composite score using a non-inferiority metric to compare LE/T to DM/T. Safety endpoints included visual acuity (VA), biomicroscopy, intraocular pressure (IOP) assessments, and adverse events. Results: At Day 15, the mean (SD) change from baseline in the signs and symptoms composite score was −15.2 (7.3) for LE/T-treated subjects and −15.6 (7.7) for DM/T-treated subjects. The upper bound of the 90% confidence interval for the difference in change from baseline was less than the non-inferiority margin not only at Day 15 but also at Day 7 and Day 3 for both the intent-to-treat and per protocol populations. Subjects treated with DM/T experienced a significant increase in IOP versus those treated with LE/T at Day 7, Day 15, and overall (mean [SD] of 0.6 [2.3] vs, −0.1 [2.2], p = 0.03, 1.0 [3.0] vs. −0.1 [2.4], p = 0.01, and 2.3 [2.3] vs. 1.6 [1.7], p = 0.02, respectively). Conclusions: LE/T satisfied the condition of non-inferiority to DM/T in decreasing the signs and symptoms of ocular inflammation associated with blepharokeratoconjunctivitis. Subjects treated with DM/T experienced more of an increase in IOP. Limitation: Although the single-masked design of this study could be considered a limitation, care was taken to ensure that the investigator was masked.

Efficacy and Tolerability of Besifloxacin Ophthalmic Suspension 0.6% Administered Twice Daily for 3 Days in the Treatment of Bacterial Conjunctivitis: A Multicenter, Randomized, Double-Masked, Vehicle-Controlled, Parallel-Group Study in Adults and Children

BACKGROUND Besifloxacin is a topical fluoroquinolone with potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains. Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5 days has been reported to be more effective than its vehicle in the treatment of bacterial conjunctivitis. Pharmacokinetic/pharmacodynamic modeling suggests that besifloxacin might also be effective given twice daily. OBJECTIVE This study evaluated the efficacy and tolerability of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days compared with vehicle (formulation without besifloxacin) in the treatment of adults and children with bacterial conjunctivitis. METHODS This was a multicenter, prospective, randomized, double-masked, vehicle-controlled, parallel-group study. Patients aged ≥1 year with bacterial conjunctivitis were randomized to receive besifloxacin ophthalmic suspension or vehicle administered twice daily for 3 days. There were 3 study visits: the baseline visit, visit 2 (day 4 or 5), and visit 3 (day 7±1). Participants recorded the times of medication instillation in a patient diary. The primary end points were clinical resolution and bacterial eradication of the baseline bacterial infection at visit 2 in patients with culture-confirmed bacterial conjunctivitis. Secondary end points were clinical resolution and bacterial eradication of the baseline bacterial infection at visit 3, individual clinical outcomes (ocular conjunctival discharge and bulbar conjunctival injection) at the follow-up visits, and microbial and clinical outcomes for overall bacterial species and individual gram-positive and gram-negative bacterial species. Tolerability assessments included ocular adverse events (AEs), changes in visual acuity, biomicroscopy and ophthalmoscopy findings, and nonocular AEs. RESULTS Of 202 patients randomized to treatment (mean [SD] age, 25.2 [24.3] years; 56.9% female; 76.7% white), 109 had culture-confirmed bacterial conjunctivitis (53 besifloxacin ophthalmic suspension, 56 vehicle). At visit 2, the besifloxacin ophthalmic suspension group had significantly greater rates of clinical resolution compared with the vehicle group (37/53 [69.8%] vs 21/56 [37.5%], respectively; P < 0.001), as well as significantly greater rates of bacterial eradication (46/53 [86.8%] vs 32/56 [57.1%]; P < 0.001). At visit 3, rates of bacterial eradication were also significantly greater in the besifloxacin ophthalmic suspension group compared with the vehicle group (46/53 [86.8%] vs 39/56 [69.6%]; P = 0.038). Results for the individual clinical outcomes and microbial and clinical outcomes by gram-positive and gram-negative species were consistent with the primary efficacy outcomes. The incidence of ocular AEs did not differ significantly between treatment groups (4/94 [4.3%] vs 8/98 [8.2%]). Ocular AEs in all treated eyes in the respective groups included bacterial conjunctivitis (3/157 [1.9%] and 5/154 [3.2%]), conjunctivitis (3/157 [1.9%] and 4/154 [2.6%]), and allergic conjunctivitis (2/157 [1.3%] and 1/154 [0.6%]). These events were of mild or moderate severity. Changes in visual acuity and biomicroscopy and ophthalmoscopy findings were comparable between groups. There were few nonocular AEs (2/94 [2.1%] vs 3/98 [3.1%]; P = NS), none of them considered treatment related. CONCLUSION In these adults and children with bacterial conjunctivitis, treatment with besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days was effective and well tolerated. ClinicalTrials.gov identifier: NCT00972777.

Besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days in the treatment of bacterial conjunctivitis in adults and children.

AbstractBackground and Objective: Besifloxacin ophthalmic suspension 0.6% given thrice daily for 5 days is safe and effective in the treatment of patients with bacterial conjunctivitis. This study evaluated the safety and efficacy of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days compared with vehicle in the treatment of bacterial conjunctivitis. Study Design: This was a multicenter, double-masked, randomized, vehicle-controlled, parallel-group study. Methods: A total of 474 patients aged ≥1 year with bacterial conjunctivitis were randomized in a 1 : 1 ratio to receive either besifloxacin ophthalmic suspension 0.6% or vehicle administered twice daily for 3 days. There were three study visits: day 1 (the baseline visit), day 4/5 (visit 2), and day 7±1 (visit 3). The co-primary efficacy endpoints were bacterial eradication and clinical resolution at day 4/5 in designated study eyes of patients with culture-confirmed bacterial conjunctivitis. Secondary efficacy endpoints were bacterial eradication and clinical resolution at day 7±1, individual clinical outcomes of ocular discharge and bulbar conjunctival injection at all visits; and microbial and clinical outcomes for overall bacterial species and individual Gram- positive and Gram-negative bacterial species at each follow-up visit. Safety endpoints included adverse events (AEs), changes in visual acuity and biomicroscopy findings at each visit, and changes in ophthalmoscopy findings at day 7±1. Results: Bacterial eradication and clinical resolution rates were significantly higher in the besifloxacin group than in the vehicle group (115/135 [85.2%] vs 77/141 [54.6%], p<0.001, and 89/135 [65.9%] vs 62/141 [44.0%], p<0.001, respectively) at day 4/5. Rates of bacterial eradication continued to be significantly greater in the besifloxacin group (115/135 [85.2%] vs 91/141 [64.5%], respectively; p<0.001) at day 7±1; however, the rates of clinical resolution did not differ significantly between the groups (103/135 [76.3%] and 94/141 [66.7%], p =0.209) at this visit. Ocular discharge and bulbar conjunctival injection at each visit were consistent with the primary outcomes. Clinical resolution and bacterial eradication with Gram-positive or Gram-negative organisms were consistent with the overall findings. All AEs in both groups were of mild or moderate severity and were considered unrelated to the treatment. Conclusion: Treatment with besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days was effective and safe in adults and children with bacterial conjunctivitis.

Tear cytokine response to multipurpose solutions for contact lenses

Purpose An increased risk of corneal infiltrative events has been noted with the use of certain contact lenses and multipurpose solutions (MPS). This study was designed to evaluate tear cytokine assay as a sensitive, objective, and quantitative measure of the ocular surface response to contact lens/MPS and to consider the assay’s clinical relevance in the context of other measures of ocular surface response. Methods Two MPS, ReNu® Fresh™ (RNF) and Opti-Free® RepleniSH (OFR), were used with daily wear silicone hydrogel contact lenses in a randomized, prospective crossover study involving 26 subjects. Clinical data collection (conjunctival hyperemia, ocular surface sensitivity, solution induced corneal staining (SICS) test score, and subjective responses) and tear cytokine assays were conducted masked. Responses were tracked as change from baseline throughout the experimental schedule. Results Similar response patterns for several inflammatory cytokines were seen throughout both phases: subjects who received OFR in Phase I had mean tear concentrations that were generally higher than those of the RNF Phase I group. OFR Phase I subjects had significant (P < 0.01) increases over baseline at day 1 and/or following washout for 13 cytokines (cc chemokine ligands [CCL] 3, CCL5, CCL11, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [INF]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-13, IL-15, IL-17, tumor necrosis factor [TNF]-α). These changes were not observed in RNF Phase I subjects, even though SICS test scores increased. Phase I OFR subjects also had increased dryness, while RNF Phase I subjects had decreased bulbar hyperemia. No changes were detected with respect to limbal hyperemia or surface sensitivity thresholds. Conclusion The tear cytokine assay can detect and differentiate contact lens/MPS induced increases in inflammatory cytokines. Changes in cytokine levels were consistent with measurement of hyperemia and dryness but not with SICS scores, thereby suggesting a proinflammatory response to OFR compared to RNF that is not related to SICS test score. Tear cytokine profiles may be useful for reconciling clinical relevance of test results and in revealing signaling involved in the development of corneal infiltrative events.

Safety and Tolerability of Loteprednol Etabonate 0.5% and Tobramycin 0.3% Ophthalmic Suspension in Pediatric Subjects

BackgroundLoteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension (LE/T) is indicated for steroid-responsive inflammatory ocular conditions where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. LE/T was shown to be safe in healthy volunteers and patients aged 18 years and older with minimal effect on intraocular pressure (IOP).ObjectiveThe aim of the study was to evaluate the safety of LE/T in pediatric subjects by examining data from two clinical studies.MethodsTwo randomized, multicenter, double-masked, parallel-group (one two-arm, the other four-arm) studies were conducted in subjects aged 0–6 years (N = 245). One study assessed LE/T compared with vehicle in the management of lid inflammation (n = 108) and the other compared LE/T with loteprednol etabonate ophthalmic suspension 0.5% (LE), tobramycin ophthalmic solution 0.3% (tobramycin), and vehicle in the treatment of blepharoconjunctivitis (n = 137). In the first study, subjects were randomized to LE/T or vehicle administered four times daily (qid) for the first 7 days followed by twice daily (bid) for 7 days along with warm compresses bid for the entire 2 weeks. In the second study, subjects were randomized to LE/T, LE, tobramycin, or vehicle administered qid for 14 days. Treatment-emergent ocular and non-ocular adverse events (AEs) and bilateral vision were assessed at all study visits in both studies. In addition, in the lid inflammation study, IOP was assessed at all visits. The primary safety endpoint in both studies was the incidence of treatment-emergent AEs.ResultsThe incidence of LE/T treatment-emergent AEs was low. A total of four ocular AEs were reported for three LE/T-treated subjects in the first study (conjunctivitis [two events], meibomian gland dysfunction, and corneal staining), and one ocular AE was reported for an LE/T-treated subject in the second study (eye pain). A total of 13 non-ocular AEs were reported for eight LE/T-treated subjects in the two trials. The most prevalent non-ocular AEs were pyrexia (three events) and rash (two events). There were no differences in the incidence of specific ocular and non-ocular AEs between the LE/T group and the comparator treatment group. In both studies, there were no clinically meaningful reductions in vision at follow-up visits. Mean IOP and IOP changes from baseline, assessed in the lid inflammation study, were not different between LE/T and vehicle treatment groups at any study visits.ConclusionThe results of these two clinical trials demonstrate the short-term safety of treatment with topical LE/T in pediatric subjects (0–6 years of age) with lid inflammation or blepharoconjunctivitis.