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

Timothy L Comstock1 Michael R Paterno1 Angele Singh1 Tara Erb1 Elizabeth Davis21Bausch and Lomb Inc., Rochester, NY, USA; 2Minnesota Eye Consultants, Bloomington, MN, USABackground: 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.Keywords: loteprednol etabonate, ophthalmic ointment, postoperative inflammation, postoperative pain, cataract surgery, intraocular pressur

Multipurpose Solutions and Rates of Biocidal Efficacy

Objective: To investigate the hypothesis that reasonable levels of disinfection are achievable over relatively short exposure durations of microorganisms to multipurpose solutions, this study examined the stand-alone disinfection efficacy at 10, 20, and 30 min of five different multipurpose solutions products, each against five different pathogens eye care practitioners may encounter in their contact lens practice. Methods: ReNu MultiPlus, ReNu Multi-Purpose, AQuify, OptiFree Express, and OptiFree RepleniSH were evaluated for their microbiocidal efficacy using the stand-alone method at 10, 20, and 30 min of exposure to either Fusarium solani, Candida albicans, Staphylococcus aureus, Serratia marcescens, or Pseudomonas aeruginosa. Results: Solutions which showed significantly higher rates of disinfection at 30 min were ReNu MultiPlus against Fusarium solani and Candida albicans, and both ReNu MultiPlus and AQuify against Staphylococcus aureus and Serratia marcescens. There were no statistically significant differences at 30 min amongst solutions against Pseudomonas aeruginosa. Conclusions: The product attribute of rapid rate of disinfection may give a greater level of assurance to practitioners when patients are noncompliant and do not follow the recommended time period for lens disinfection. The results of this study, however, should not be interpreted as a recommendation to use any of the solutions tested for a disinfection period less than the recommended soak time. Patient compliance with recommended lens care regimens is essential in minimizing the risk of contamination of contact lenses and lens care accessories

Pharmacokinetics of Indinavir and Ritonavir Administered at 667 and 100 Milligrams, Respectively, Every 12 Hours Compared with Indinavir Administered at 800 Milligrams Every 8 Hours in Human Immunodeficiency Virus-Infected Patients

Human immunodeficiency virus (HIV) patients on nucleoside or nucleotide reverse transcriptase inhibitors with HIV RNA at <1,000 copies/ml were randomized in an open-label study to administration of combined indinavir/ritonavir (IDV/RTV) at 667/100 mg every 12 h (q12h) or IDV alone at 800 mg q8h to determine the regimens' pharmacokinetics. On day 14, plasma IDV and RTV levels were determined over 24 h. Noncompartmental pharmacokinetics (minimum concentration of drug in serum [C(min)], area under the concentration-time curve from 0 to 24 h [AUC(0-24)], and maximum concentration of drug in serum [C(max)]) were expressed as geometric mean values with 90% confidence intervals (CI). The primary hypothesis was that the lower bound of the protocol-specified 90% CI for the geometric mean C(min) ratio of the combination compared to IDV alone regimen would be ≥2. Twenty-seven patients were enrolled, and 24 (15 male; average age, 42 years) completed the study. The C(min), AUC(0-24), and C(max) for IDV/RTV compared to IDV alone were 1,511 versus 250 nM, 119,557 versus 77,034 nM · h, and 10,428 versus 10,407 nM, respectively. Corresponding relationships for IDV/RTV compared to IDV alone were a 6.0-fold increase in C(min) (90% CI, 4.0, 9.3), an increase in AUC(0-24) (1.5-fold, 90% CI, 1.2, 2.0), and no increase in C(max). Adverse events were similar and generally mild, with no cases of nephrolithiasis. The geometric mean ratio of IDV C(min) for IDV/RTV compared to IDV was at least 2 by a lower bound of the 90% CI, satisfying the primary hypothesis. The C(max) was not increased, suggesting an IDV/RTV 667/100-mg toxicity profile may be similar to that of unboosted IDV

Gender influences the response to experimental silica-induced lung fibrosis in mice

Accumulating evidence suggests that gender can have a profound effect on incidence and severity of a variety of pulmonary diseases. To address the influence of gender on the development of silica-induced pulmonary fibrosis, we instilled 0.2 g/kg silica into male and female C57BL/6 mice and examined the fibrotic and inflammatory response at 14 days postexposure. Both silica-exposed male and female mice had significant increases in total lung hydroxyproline compared with saline controls. However, silica-exposed female mice had significantly less total lung hydroxyproline than silica-exposed male mice. This observation was confirmed by color thresholding image analysis. Interestingly, silica-exposed female mice had significantly more inflammatory cells, the majority of which were macrophages, as well as higher levels of the macrophage-specific chemokines MCP-1 and CCL9 in whole lung lavage compared with silica-exposed male mice. We also show that at baseline, estrogen receptor α (ERα) mRNA expression is lower in female mice than in males and that ERα mRNA expression is decreased by silica exposure. Finally, we show that the response of ovariectomized female mice to silica instillation is similar to that of male mice. These observations together show that gender influences the lung response to silica

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

Introduction: Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. Methods: Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (Ktrans, ve, kep, and vp). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P &lt; 0.05. Results: mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5&nbsp;mm (3.0). ROI volume was 278&nbsp;mm3 (222). ADC was 1.07 (0.27) × 10–3&nbsp;mm2/s. DCE metrics were Ktrans 0.085/min (0.063), ve 0.060 (0.052), kep 1.20/min (0.32), and vp 1.48&nbsp;% (0.82). Patients with &gt;33&nbsp;% monosomy 3 had higher Ktrans and higher ve values than those with disomy 3 or ≤33&nbsp;% monosomy (P &lt; 0.01). There were no significant differences between ADC (P = 0.07), kep (P = 0.37), and vp with respect to monosomy 3. Conclusion: mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma