Roger Vogel

Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (vismed, rejena).

PURPOSE To evaluate the efficacy and safety of 0.18% sodium hyaluronate ophthalmic solution (Rejena, Vismed) compared with its vehicle for the treatment of signs and symptoms of dry eye disease. DESIGN Randomized, placebo-controlled clinical trial. METHODS A total of 444 subjects with dry eye disease were randomized 1:1 to active study drug (n = 221) or vehicle control (n = 223) in this multicenter, double-masked trial. Subjects instilled 1 to 2 drops, 3 to 6 times daily for 14 days, with evaluations at Days 7 and 14. The studys 2 primary efficacy endpoints were change from baseline at Day 7 in lissamine green staining scores (objective) and in global symptom frequency scores (subjective). Results were analyzed using Wilcoxon rank sum test and Student t test in the intent-to-treat (ITT) population with last observation carried forward (LOCF). RESULTS At Day 7, the differences between the active and vehicle groups in change from baseline for lissamine green staining score (P = .050, Wilcoxon; P = .029, t test) and global symptom frequency score (P = .050, Wilcoxon; P = .017, t test) were both statistically significant. There were no clinically relevant safety findings related to the use of Rejena. CONCLUSIONS This study demonstrated the clinical efficacy of Rejena in the treatment of dry eye disease in both a primary objective endpoint and a primary subjective endpoint when compared to its vehicle. The study results also supported the well-known safety profile of Rejena.

Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis.

PURPOSE The aim of this study was to evaluate the efficacy and safety of difluprednate ophthalmic solution 0.05% (Durezol; Alcon Laboratories, Fort Worth, TX) compared with prednisolone acetate ophthalmic suspension 1% (Pred Forte; Allergan, Inc., Irvine, CA) for endogenous anterior uveitis. METHODS In this phase 3, multicenter, randomized, noninferiority trial, 90 patients with endogenous anterior uveitis [>10 anterior chamber (AC) cells and an AC flare score of ≥2 in at least 1 eye] received either difluprednate 4x /day (QID) (n=50) or prednisolone 8x/day (n=40) for 14 days, followed by a 2-week tapering regimen. The main outcome measure was change from baseline in AC cell grade on day 14. RESULTS At day 14, mean AC cell grade improvement for difluprednate-treated patients was similar to prednisolone-treated patients (2.1 vs. 1.9, respectively), proving noninferiority. At day 14, 68.8% of difluprednate patients had AC cell clearing (grade 0:≥ 1cell) compared with 61.5% of prednisolone patients. In the prednisolone-treated group, 12.5% of patients were withdrawn because of investigator-determined lack of efficacy; no difluprednate-treated patients were withdrawn for this reason (P=0.01). Clinically significant intraocular pressure elevation occurred in 3 difluprednate-treated patients (6.0%) and 2 prednisolone-treated patients (5.0%). CONCLUSIONS Difluprednate administered QID is at least as effective as prednisolone administered 8x/day in resolving the inflammation and pain associated with endogenous anterior uveitis. Difluprednate provides effective treatment for anterior uveitis and requires less frequent dosing than prednisolone acetate. CLINICAL TRIAL REGISTRATION Trial NCT00501579 was registered at the National Institutes of Health Registry in July 2007 ( http://clinicaltrials.gov/ct2/show/NCT00501579?term=sirion&rank=4 ).

The safety and efficacy of topical norfloxacin compared with placebo in the treatment of acute, bacterial conjunctivitis

Two hundred and eighty-four patients with acute conjunctivitis were enrolled in a double-masked study comparing norfloxacin ophthalmic solution with placebo. The proportion of patients who were clinically improved after 5 days treatment was 88.1 % in the norfloxacin group and 71.6% in the placebo group (p<0.01). The proportion of patients who had all organisms eradicated, including the coagulase-negative staphylococci, after two to three days treatment was 52.7% for norfloxacin and 23.9% for placebo (p<0.01) and 64.7% and 26.3% (p<0.01) respectively when the coagulase-negative staphylococci were not included. Adverse experiences occurred in 4.2% of the patients receiving norfloxacin compared to 7.1% of the placebo patients. None of the adverse experiences was serious.

Randomized, Double-Masked, Placebo-Controlled Study to Assess the Ocular Safety of Mirabegron in Healthy Volunteers

PURPOSE This study assessed the effect of mirabegron on ocular safety in healthy volunteers. METHODS This was an 8-week, randomized, double-masked, placebo-controlled study. PARTICIPANTS Consenting adults aged ≥18 years with a normal intraocular pressure (IOP, ≥10 to ≤21 mmHg) were eligible to enter the study. Of the 321 randomized subjects, 305 completed the study. Subjects were randomized 1:1 to a supratherapeutic dose of oral mirabegron 100 mg or placebo once daily for 56 days. The IOP was measured at screening, baseline, day 10, and day 56/end of treatment using Goldmann applanation tonometry. Visual acuity and biomicroscopy were also evaluated. The primary endpoint was the mean change from baseline in the IOP at 56 days or end of treatment with mirabegron versus placebo. Secondary outcome variables included change from baseline to day 10 in the IOP, and increases in the IOP of ≥6 mmHg and ≥10 mmHg in either eye from baseline to day 10 and day 56. RESULTS The mean (standard error, SE) IOP at baseline was 15.3 (0.16) mmHg for mirabegron and 15.4 (0.16) mmHg for placebo; values at day 56 were 15.0 (0.16) mmHg and 15.2 (0.17) mmHg, respectively. The adjusted mean IOP change from baseline to day 56 was -0.3 mmHg for mirabegron and -0.2 mmHg for placebo (-0.1 mmHg difference [95% confidence interval, CI, -0.4 to 0.3]). For the primary endpoint, mirabegron was noninferior to placebo, based on the prespecified limit of 1.5 mmHg. No statistically significant treatment effects on the IOP were seen at day 10. No subject discontinued due to increased IOP. Clinically significant increases from baseline in the IOP occurred rarely and only with placebo treatment. Changes in the visual acuity and biomicroscopy were not suggestive of a mirabegron effect. No treatment-emergent adverse event (AE) of glaucoma was reported. CONCLUSIONS Mirabegron 100 mg orally once daily for 8 weeks of treatment does not increase the IOP, and was generally safe and well tolerated.

Effect of Timolol versus Pilocarpine on Visual Field Progression in Patients with Primary Open-angle Glaucoma

BACKGROUND Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.

Topically Administered Norfloxacin Compared with Topically Administered Gentamicin for the Treatment of External Ocular Bacterial Infections

In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin-treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin-treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram-positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin.

Penetration of Intravenously Administered Cefoxitin into the Aqueous Humor of Inflamed Human Eyes

Intravenous injections of cefoxitin (2-g doses for adults and 40 mg/kg of body weight doses for children) were administered 90 minutes to two hours before surgery. All nine eyes had anterior segment inflammation. Samples of aqueous humor removed during surgery showed a mean cefoxitin concentration of 6.22 micrograms/ml, almost three times the concentration reported in uninflamed eyes. The greater penetration may have been the result of a breakdown in the blood-aqueous barrier. There were no complications.

Feasibility of an antiviral clinical trial requiring cross-country shipment of conjunctival adenovirus cultures and recovery of infectious virus

Purpose. Accurate and timely laboratory diagnosis of adenovirus from conjunctival cultures is essential to ensure appropriate enrollment, and detection of residual infectious virus is essential to evaluate antiviral efficacy in any multicenter national clinical trial. As part of a feasibility study, we investigated those variables that might affect the successful recovery of infectious adenovirus from patient conjunctival cultures after cross-country shipment. Materials and methods. Simulated adenovirus conjunctival cultures were prepared in viral transport media to evaluate the effect of four variables (adenovirus serotype, initial concentration, initial storage temperature [−20°C, 0°C, 20°C], and preshipment storage times [1–5 days]) on the recovery of infectious adenovirus by a central laboratory in St. Paul, MN, following air shipment from Pittsburgh, PA. Upon arrival, the internal temperatures of the containers were recorded, and the samples were cultured on A549 cells using standard tube and/or shell vial culture. Results. Overall, adenovirus was recovered in 352/354 (99.4%) of the samples when the initial titer was greater than 1.0 PFU/ml. Adenovirus serotype, initial storage temperature, and preshipment storage times had no adverse effect on virus recovery. Conclusions. Simulated conjunctival samples could successfully be shipped cross-country at ambient temperatures to a commercial laboratory for adenovirus isolation by culture. Having demonstrated feasibility, a clinical trial was subsequently carried out that confirmed the ease of shipment and recovery of infectious adenovirus from conjunctival cultures.

The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The Norfloxacin-Chloramphenicol Ophthalmic Study Group.

Two hundred and forty-six patients with signs of acute bacterial conjunctivitis and/or blepharitis were randomised to receive either norfloxacin or chloramphenicol for one week in this double-masked parallel group study. Ninety-two per cent of the norfloxacin-treated patients and 93% of the chloramphenicol-treated patients were rated as either clinically improved or cured at the end of the treatment period.Based upon pre-treatment bacteriological cultures, 31.3% of the patients had significant bacterial infection of the lids and/or conjunctiva. All of these culture-positive patients were rated as either clinically improved or cured. Based upon post-treatment cultures, 72 of 82 strains of Gram-positive and Gram-negative bacteria were erradicated or suppressed following treatment with either norfloxacin or chloramphenicol. However six of 41 strains persisted for norfloxacin and four of 41 for chloramphenicol. Two norfloxacin-treated patients and three chloramphenicol-treated patients had adverse experiences, predominantly ocular discomfort, which required cessation of drug therapy.Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the lids and/or conjunctiva. In this study, norfloxacin was clinically and microbiologically similar in activity to chloramphenicol.

The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections

Two hundred and forty-six patients with signs of acute bacterial conjunctivitis and/or blepharitis were randomised to receive either norfloxacin or chloramphenicol for one week in this double-masked parallel group study. Ninety-two per cent of the norfloxacin-treated patients and 93% of the chloramphenicol-treated patients were rated as either clinically improved or cured at the end of the treatment period.Based upon pre-treatment bacteriological cultures, 31.3% of the patients had significant bacterial infection of the lids and/or conjunctiva. All of these culture-positive patients were rated as either clinically improved or cured. Based upon post-treatment cultures, 72 of 82 strains of Gram-positive and Gram-negative bacteria were erradicated or suppressed following treatment with either norfloxacin or chloramphenicol. However six of 41 strains persisted for norfloxacin and four of 41 for chloramphenicol. Two norfloxacin-treated patients and three chloramphenicol-treated patients had adverse experiences, predominantly ocular discomfort, which required cessation of drug therapy.Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the lids and/or conjunctiva. In this study, norfloxacin was clinically and microbiologically similar in activity to chloramphenicol.