Antibacterial efficacy of prophylactic besifloxacin 0.6% and moxifloxacin 0.5% in patients undergoing cataract surgery.

BACKGROUND: The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients. METHODS: This was a prospective, randomized, laboratory-masked clinical trial. Patients received besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints. RESULTS: Fifty-nine patients (n=28 besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin. CONCLUSION: Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.

Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population.

INTRODUCTION: The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. METHODS: A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. RESULTS: A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. CONCLUSION: The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring.

An update on the surgical management of pterygium and the role of loteprednol etabonate ointment.

Pterygium, a sun-related eye disease, presents as wing-shaped ocular surface lesions that extend from the bulbar conjunctiva onto the cornea, most commonly on the nasal side. Pterygia show characteristic histological features that suggest that inflammation plays a prominent role in their initial pathogenesis and recurrence. Appropriate surgery is the key to successful treatment of pterygia, but there is also a rationale for the use of anti-inflammatory agents to reduce the rate of recurrence following surgery. Multiple surgical techniques have been developed over the last two millennia, but these initially had little success, due to high rates of recurrence. Current management strategies, associated with lower recurrence rates, include bare sclera excision and various types of grafts using tissue glues. Adjunctive therapies include mitomycin C and 5-fluorouracil, as well as the topical ocular steroid loteprednol etabonate, which has been shown to have a lower risk of elevated intraocular pressure than have the other topical ocular steroids. Here, the surgical management of pterygium is presented from a historical perspective, and current management techniques, including the appropriate use of various adjunctive therapies, are reviewed, along with an illustrative case presentation and a discussion of the conjunctival forceps designed to facilitate surgical management. Despite thousands of years of experience with this condition, there remains a need for a more thorough understanding of pterygium and interventions to reduce both its incidence and postsurgical recurrence. Until that time, the immediate goal is to optimize surgical practices to ensure the best possible outcomes. Loteprednol etabonate, especially the ointment formulation, appears to be a safe and effective component of the perioperative regimen for this complex ocular condition, although confirmatory prospective studies are needed.

Loteprednol etabonate ophthalmic gel 0.5% following cataract surgery: integrated analysis of two clinical studies.

INTRODUCTION: We aimed to evaluate the safety and efficacy of loteprednol etabonate (LE) gel 0.5% compared with vehicle in the treatment of postoperative inflammation and pain following cataract surgery, using the integrated analysis of data from two identical, prospective, multicenter, randomized, double-masked, parallel-group, vehicle-controlled trials. METHODS: Patients with anterior chamber cell (ACC) inflammation ≥ grade 2 (6-15 cells) 1 day post-surgery were randomized to receive 1 or 2 drops of LE gel 0.5% or vehicle 4 times per day instilled in the study eye 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 endpoints included adverse events (AEs), changes from baseline in intraocular pressure (IOP) and visual acuity (VA), biomicroscopy, and funduscopy findings. Gel comfort was graded by patients according to drop sensation. RESULTS: The intent-to-treat population included 813 patients (409 LE gel 0.5% and 404 vehicle). At postoperative Day 8, 30.8% and 15.1% of patients randomized to LE gel 0.5% or vehicle, respectively, had complete resolution of ACC, while 74.3% and 43.8% of patients, respectively, had grade 0 pain (P < 0.001 for both). Tolerability assessments for ocular itching, photophobia, and tearing favored LE gel 0.5% compared with vehicle at different time points beginning at Day 3. Two patients in the LE gel 0.5% group and 1 patient in the vehicle group exhibited a transient treatment-emergent increase in IOP ≥ 10 mmHg. Treatment-related AEs were generally mild to moderate and occurred less frequently with LE gel 0.5% than with vehicle. Reports of treatment-related blurred vision were rare (n = 2, vehicle). CONCLUSION: LE gel 0.5% was efficacious and well tolerated in the treatment of postoperative pain and inflammation following ocular surgery, with minimal risk of IOP elevation.

Post-cataract outcomes in patients with noninfectious posterior uveitis treated with the fluocinolone acetonide intravitreal implant.

PURPOSE: To describe visual acuity (VA) and inflammation following cataract surgery in eyes with noninfectious posterior uveitis (NIPU) that were being treated with a fluocinolone acetonide (FA) intravitreal implant compared with those that were not. DESIGN: Post hoc, subgroup analysis of data from a 3-year, dose-masked, randomized, multicenter trial evaluating the FA implant for the treatment of NIPU. PARTICIPANTS AND CONTROLS: The subset of eyes that underwent cataract surgery during the 3-year trial. Eyes were either implanted with a 0.59- or a 2.1-mg FA implant, or, in the case of affected fellow eyes, received standard-of-care local treatment. MAIN OUTCOME MEASURES: VA, anterior and posterior chamber inflammation at 1 and 3 months after surgery, and rate of uveitis recurrence and serious postoperative ocular adverse events. RESULTS: Of 278 patients enrolled in the main trial, 132/142 phakic implanted eyes and 39/186 phakic non-implanted eyes underwent cataract surgery. Mean improvement in VA was significantly greater in implanted than non-implanted eyes at 1 (P = 0.0047) and 3 months (P = 0.0015) postoperatively; significantly fewer anterior chamber cells were seen in implanted than non-implanted eyes at 1 (P = 0.0084) and 3 months (P = 0.0002). Severity of vitreous haze was less in implanted than non-implanted eyes at 3 months postoperatively (P = 0.0005). The postsurgical uveitis recurrence rate was lower in implanted than non-implanted eyes (26.5% vs 44.4%; P = 0.0433). Glaucoma was reported in 19.7% of implanted eyes and no non-implanted eyes (P = 0.0008) postoperatively. CONCLUSION: In this post hoc subgroup analysis, eyes with NIPU treated with the FA intravitreal implant demonstrated better vision and less intraocular inflammation following cataract surgery than non-implanted eyes. Recurrent uveitic inflammation did not appear to be triggered by cataract surgery. Glaucoma occurred more frequently in implanted eyes.

Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial.

PURPOSE: We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME). DESIGN: Prospective, evaluator-masked, controlled, multicenter clinical trial. PARTICIPANTS: We included 196 eyes with refractory DME. METHODS: Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation. MAIN OUTCOME MEASURES: The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs). RESULTS: Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years. CONCLUSIONS: The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Human aqueous humor concentrations of besifloxacin, moxifloxacin, and gatifloxacin after topical ocular application.

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.

Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery.

BACKGROUND: To compare the safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% (LE ointment), a new topical ointment formulation, with vehicle for the treatment of inflammation and pain following cataract surgery. METHODS: Two randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies were conducted. Patients aged ≥18 years with a combined postoperative anterior chamber cells and flare (ACI) ≥ Grade 3 following uncomplicated cataract surgery participated in seven study visits. Patients self-administered either topical LE ointment or vehicle four times daily for 14 days. Efficacy outcomes included the proportion of patients with complete resolution of ACI and the proportion of patients with no (Grade 0) pain at postoperative day 8. Safety outcomes included the incidence of adverse events, ocular symptoms, changes in intraocular pressure and visual acuity, and biomicroscopy and funduscopy findings. RESULTS: Data from the two studies were combined. The integrated intent-to-treat population consisted of 805 patients (mean [standard deviation] age 69.0 [9.2] years; 58.0% female and 89.7% white). Significantly more LE ointment-treated patients than vehicle-treated patients had complete resolution of ACI (27.7% versus 12.5%) and no pain (75.5% versus 43.1%) at day 8 (P < 0.0001 for both). Fewer LE ointment-treated patients required rescue medication (27.7% versus 63.8%), and fewer had an ocular adverse event (47.2% versus 78.0%, P < 0.0001) while on study treatment. The most common ocular adverse events with LE ointment were anterior chamber inflammation, photophobia, corneal edema, conjunctival hyperemia, eye pain, and iritis. Mean intraocular pressure decreased in both treatment groups. Four patients had increased intraocular pressure ≥10 mmHg (three LE ointment and one vehicle) prior to rescue medication. Visual acuity and dilated funduscopy results were similar between the treatment groups, with the exception of visual acuity at visits 5 and 6, which favored LE ointment. CONCLUSION: LE ointment was efficacious and well tolerated in the treatment of ocular inflammation and pain following cataract surgery.

Concentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration.

PURPOSE: To evaluate the pharmacokinetic properties of besifloxacin, gatifloxacin, and moxifloxacin in the conjunctival tissue of healthy volunteers after topical application. METHODS: One-hundred eight (108) subjects were randomly assigned to receive one drop of besifloxacin (0.6% suspension), gatifloxacin (0.3% solution), or moxifloxacin (0.5% solution) ophthalmic formulations in one eye prior to conjunctival biopsy. Conjunctival samples were taken from subjects at either 15 minutes, 30 minutes, 2 hours, 6 hours, 12 hours, or 24 hours after dosing. RESULTS: All three fluoroquinolones reached a peak mean concentration 15 minutes after dosing. The mean concentrations of besifloxacin, gatifloxacin, and moxifloxacin at 15 minutes were 2.30 +/- 1.42 mug/g, 4.03 +/- 3.84 mug/g, and 10.7 +/- 5.89 mug/g, respectively. Concentrations decreased with each subsequent time point. At 24 hours after dosing, concentrations of besifloxacin were measurable in 4 of 6 subjects, compared with 3 of 6 subjects for gatifloxacin and 2 of 6 subjects for moxifloxacin. Besifloxacin had the greatest mean residence time (4.7 hours) in the conjunctival tissue. With regard to methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, besifloxacin had the greatest area-under-the-curve (AUC) to MIC(90) ratio. Nine percent (9%) of study subjects (N = 7) experienced a transient reduction in visual acuity. CONCLUSION: All three fluoroquinolones were well tolerated and reached levels in the conjunctiva above the MIC(90)s of methicillin-sensitive S. aureus and S. epidermidis for at least 2 hours.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

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 (> or =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 (> or =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< or =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.

Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results.

OBJECTIVES: To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. DESIGN: A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. MAIN OUTCOME MEASURES: Recurrence rate, vision, and complications. RESULTS: Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P < .01) and from 58% to 7%, 17%, and 41%, respectively, for the 2.1-mg dose group (P < .01). More implanted eyes than nonimplanted eyes had improved visual acuity (P < .01). Implanted eyes had higher incidences of intraocular pressure elevation (> or = 10 mm Hg) than nonimplanted eyes (P < .01), and glaucoma surgery was required in 40% of implanted eyes vs 2% of nonimplanted eyes (P < .01). Cataracts were extracted in 93% of phakic implanted eyes vs 20% of phakic nonimplanted eyes (P < .01). CONCLUSIONS: The FA implant significantly reduced uveitis recurrence and improved or stabilized visual acuity in subjects with noninfectious posterior uveitis. Most subjects required cataract extraction, and a significant proportion required intraocular pressure-lowering surgery. APPLICATION TO CLINICAL PRACTICE: The FA implant provides an alternative therapy for prolonged control of inflammation in noninfectious posterior uveitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00407082.

Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.

OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP