An anterior chamber toxicity study evaluating Besivance, AzaSite, and Ciprofloxacin.
ABSTRACT We determined whether Besivance (Bausch & Lomb), AzaSite (Inspire Pharmaceuticals, Inc; both with DuraSite bioadhesive [InSite Vision, Inc]) and ciprofloxacin are toxic inside the anterior chamber.
Randomized, masked, placebo-controlled animal study.
Twenty New Zealand white rabbits (40 eyes) were randomized to 1 of 4 study groups: Besivance, AzaSite, ciprofloxacin, and balanced salt solution. Each eye was injected with 0.1 mL of the study medication. Clinical slit-lamp examinations were conducted at 24 and 48 hours after injection. All rabbits then were killed and all eyes were enucleated. We randomized eyes to either corneal vital staining or histopathologic examination. The main outcome measures were clinical and pathologic signs of toxicity.
The 2 DuraSite-based study groups (Besivance and AzaSite) showed clinically and pathologically significant differences when compared with the ciprofloxacin and balanced salt solution groups. Besivance and AzaSite eyes exhibited significantly similar and severe clinical damage, including severe corneal edema. Ciprofloxacin and balanced salt solution eyes appeared very similar and had only mild conjunctival injection and limbal vascularity. Vital staining and histopathologic evaluation revealed glaucomatous and toxic damage in eyes given DuraSite-based medications, whereas non-DuraSite groups showed minimal changes.
DuraSite blocks the trabecular meshwork and may be additionally toxic when introduced as a large bolus. Until the safety of these medications is established with further studies using smaller injected volumes, we recommend placement of a suture over a clear corneal wound if DuraSite-based medications are used.
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ABSTRACT: Purpose: The aim of the study was to evaluate the safety of besifloxacin ophthalmic suspension 0.6% as antibacterial prophylaxis in the surgical setting. Methods: Two prospective safety surveillance studies were conducted—one in the cataract surgery setting and the other in the laser-assisted in situ keratomileusis (LASIK) surgery setting. Cases from patients aged 18 years and above were eligible for inclusion. In both surveillance studies, data were collected from consecutive cases of routine primary cataract surgery and LASIK surgery, respectively, in which besifloxacin ophthalmic suspension 0.6% or moxifloxacin ophthalmic solution 0.5% was used as the topical perioperative prophylactic antibacterial medication as part of the clinician's routine standard of care. The primary safety endpoint was the incidence of treatment-emergent adverse events (TEAEs). Results: The cataract surgery surveillance study included 485 cases/eyes (besifloxacin, n = 333; moxifloxacin, n = 152), whereas the LASIK surveillance study included 456 cases/eyes (besifloxacin, n = 344; moxifloxacin, n = 112). In the cataract study, only 1 TEAE was reported in a besifloxacin case (mild hypersensitivity/allergic reaction considered possibly related to besifloxacin). No TEAEs were reported in the LASIK study. In both studies, surgical outcomes were similar with both treatments. The frequency of preoperative and/or postoperative dosing was generally lower for besifloxacin than that for moxifloxacin. Conclusions: In prospective safety surveillance studies of patients undergoing cataract extraction or LASIK, TEAEs associated with prophylactic use of besifloxacin ophthalmic suspension 0.6% were rare, and surgical outcomes with besifloxacin were similar to those with moxifloxacin ophthalmic solution 0.5%.Cornea 03/2014; 33(5). DOI:10.1097/ICO.0000000000000098 · 2.36 Impact Factor
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ABSTRACT: In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery.PLoS ONE 06/2014; 9(6):e100632. DOI:10.1371/journal.pone.0100632 · 3.53 Impact Factor
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ABSTRACT: Besifloxacin (BSF) is a synthetic chiral fluoroquinolone developed for the topical treatment of ophthalmic infections. The present study reports the development and validation of a microbiological assay, applying the cylinder-plate method, for determination of BSF in ophthalmic suspension. To assess this methodology, the development and validation of the method was performed for the quantification of BSF by high performance liquid chromatography (HPLC). The HPLC method showed specificity, linearity in the range of 20-80µgmL(-1) (r=0.9998), precision, accuracy and robustness. The microbiological method is based on the inhibitory effect of BSF upon the strain of Staphylococcus epidermidis ATCC 12228 used as a test microorganism. The bioassay validation method yielded excellent results and included linearity, precision, accuracy, robustness and selectivity. The assay results were treated statistically by analysis of variance (ANOVA) and were found to be linear (r=0.9974) in the range of 0.5-2.0µgmL(-1), precise (inter-assay: RSD=0.84), accurate (101.4%), specific and robust. The bioassay and the previously validated high performance liquid chromatographic (HPLC) method were compared using Student´s t test, which indicated that there was no statistically significant difference between these two methods. These results confirm that the proposed microbiological method can be used as routine analysis for the quantitative determination of BSF in an ophthalmic suspension. A preliminary stability study during the HPLC validation was performed and demonstrated that BSF is unstable under UV conditions. The photodegradation kinetics of BSF in water showed a first-order reaction for the drug product (ophthalmic suspension) and a second-order reaction for the reference standard (RS) under UVA light. UVA degraded samples of BSF were also studied in order to determine the preliminary in vitro cytotoxicity against mononuclear cells. The results indicated that BSF does not alter the cell membrane and has been considered non-toxic to human mononuclear cells in the experimental conditions tested.Talanta 02/2014; 119C:367-374. DOI:10.1016/j.talanta.2013.10.051 · 3.51 Impact Factor