0.2% Betamethasone Sodium Phosphate: A Multicenter, Randomized, Double-Masked Study to Compare Its Ocular Safety, Tolerability, and Efficacy to Vehicle in Cataract Surgery Subjects.

Purpose: To compare the preservative-free corticosteroid 0.2% betamethasone sodium phosphate BID (SURF-201) to vehicle BID in patients undergoing routine cataract surgery. Methods: Phase 2, multicenter, randomized (1:1 ratio), double-masked, vehicle-controlled, parallel-group study in patients scheduled for uncomplicated cataract surgery without the aid of a femtosecond laser. Subjects instilled topical medications for 16 days beginning the day before cataract surgery (Day -1), 1 dose administered at least 1 hour prior to cataract surgery (on Day 0) and 1 dose on the evening after cataract surgery, and then 2 doses administered each day through Day 15; patients were re-evaluated on Days 22 and 32 to ensure no rebound inflammation. Primary outcome was the difference in the proportion of subjects with anterior chamber cell (ACC) grade 0 between the two groups at Day 15. Secondary outcomes included pain scores and overall safety. Results: There was a statistically significant difference (P=0.004) in the proportion of subjects in the SURF-201 treatment group with an ACC grade of 0 at Day 15 (n=22/39 [56.4%]) compared to subjects in the vehicle treatment group (n=9/43 [20.9%]). There was no statistically significant difference (P=0.528) in the proportion of subjects in the SURF-201 treatment group who had a visual analog scale pain score of 0 at Day 15 (n=35/38 [89.7%]) compared to subjects in the vehicle group (n=33/40 [82.5%]). A slightly higher incidence of adverse events occurred in subjects in the SURF-201 treatment group (n=27/40 [67.5%]) compared to the vehicle treatment group (n=23/43 [53.5%]). Conclusion: SURF-201 is an effective topical, preservative-free corticosteroid when dosed BID for the treatment of postoperative inflammation and prevention of pain in a post-cataract population.

OCS-01 (Novel Topical Dexamethasone Formulation) in Inflammation and Pain Post Cataract Surgery: A Randomized, Double-Masked, Vehicle-Controlled Study.

PURPOSE: The goal of this study was to compare topical dexamethasone 1.5% in a novel formulation (OCS-01) once daily and BID versus vehicle for the treatment of inflammation and pain after cataract surgery. METHODS: This was a Phase II, double-masked, vehicle-controlled, randomized multicenter study. Adult patients with planned unilateral uncomplicated cataract surgery were randomized to receive OCS-01 once daily (n = 51), OCS-01 BID (n = 51), or matching vehicle (n = 51) for 15 days postsurgery. Primary end points were absence of anterior chamber cells (ACC; cells = 0) at Day 15 and absence of pain (score of "0") at postoperative Day 4. The Pearson χ2 test with a two-sided alpha = 0.1 was used to compare treatments. Safety was assessed in terms of adverse events and changes in intraocular pressure. FINDINGS: Treatment arms were generally similar in their baseline characteristics, with mean age ranging from 66 to 68 years, the proportion of male patients ranging from 29% to 37%, and 82% to 92% of each arm being White. On Day 15, a greater reduction in the percentage of eyes with ACC grade 0 was observed in the OCS-01 once daily (51%) and BID (66.7%) arms than in the vehicle arm (19.6%) (P = 0.0009 and P < 0.0001, respectively, using a Pearson χ2 test). On Day 4, the percentage of eyes with no pain was 72.5% (OCS-01 once daily), 62.7% (OCS-01 BID), and 45.1% (vehicle); statistical significance was reached for OCS-01 once daily (P = 0.005) and OCS-01 BID (P = 0.074) compared with vehicle. OCS-01 was well tolerated. A higher proportion of treatment-emergent adverse events, including ocular adverse events, were reported for the placebo group than for either OCS-01 group. IMPLICATIONS: OCS-01 once daily and BID were more effective than vehicle and well tolerated in the treatment of inflammation and pain after cataract surgery. CLINICALTRIALS: gov identifier: NCT04130802.

Simple Endoscopic Score of Crohn Disease and Magnetic Resonance Enterography in Children: Report From ImageKids Study.

OBJECTIVES: We aimed to explore the ability of magnetic resonance enterography (MRE) to impute the simple endoscopic score of Crohn disease (SES-CD) in children with CD, in whom failure of ileal intubation is common and may impair SES-CD calculation in clinical studies. METHODS: This is a substudy of the prospective ImageKids study in which children with CD underwent ileocolonoscopy (scored by SES-CD) and MRE (scored on a 100 mm visual analogue scale [VAS] and by MaRIA). Mucosal healing (MH) was defined as SES-CD <3, MRE-VAS <20 mm, and/or MaRIA <7. RESULTS: A total of 237 children (22 centers, age 11.5 ±â€Š3.3 years), were enrolled. Ileal intubation has failed in 40 of 237 (17%). The agreement between SES-CD and MRE was 75% (k = 0.508, P < 0.001) in the ileum, and 68% to 85% in the colonic segments (k = 0.21-0.50, P < 0.001). The sensitivity and specificity of ileal MRE-VAS for MH were 91.7% (95% confidence interval 0.84-0.96) and 53.1% (95% confidence interval 0.43-0.63), respectively. The ileal MaRIA score (calculated in 33/40) was higher in the children without ileal intubation than in the others (20.5 ±â€Š7.1 vs 15.1 ±â€Š10.8, respectively, P = 0.0018). In 7% (16/237) of children, isolated active ileal disease would have been missed when considering SES-CD only. A multivariable model predicted the ileal SES-CD subscore from the MaRIA: SES-CDileum = 1.145 + 0.169 × MaRIAileum rounded to the nearest whole number (R = 0.17). Applying this model to the children without ileal intubation revealed that 29 of 33 (88%) had ileal disease; 8 of 29 patients (28%) with normal colonic SES-CD had imputed ileal SES-CD ≥3. CONCLUSIONS: MRE is useful for imputing the ileal disease in pediatric clinical studies, overcoming the problem of ileal nonintubation.

A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma.

PURPOSE: To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma. DESIGN: Double-masked, randomized, and vehicle-controlled study. METHODS: Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once-daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site. Part 3 was a multisite trial that evaluated intraocular pressure (IOP)-lowering efficacy of the MTD administered nightly for 1 week in 50 patients with minimum IOP of 24 mm Hg at 8 AM, with a main outcome measure of mean diurnal IOP at day 8 compared to baseline (ClinicalTrials.govNCT02743780). RESULTS: There was no difference in favor of MGV354 for IOP lowering; change from baseline to day 8 in mean diurnal IOP was -0.6 mm Hg for MGV354-treated patients and -1.1 mm Hg for vehicle-treated patients in Part 3, with a confidence interval of -0.7 to 1.7. The most common adverse events reported after MGV354 administration were conjunctival and ocular hyperemia. CONCLUSIONS: Overall, MGV354 0.1% demonstrated no statistically significant effect compared to vehicle in lowering IOP based on the study's main outcome measure. MGV354 produced ocular hyperemia consistent with its pharmacology.

Safety, efficacy, and intraoperative characteristics of DisCoVisc and Healon ophthalmic viscosurgical devices for cataract surgery.

PURPOSE: To evaluate the safety and efficacy of DisCoVisc ophthalmic viscosurgical device (OVD, Alcon Laboratories, Inc) with respect to a comparator, Healon OVD (Advanced Medical Optics, Inc). PATIENTS AND METHODS: In this prospective study, patients with cataracts were randomized to an OVD, and then received phacoemulsification and injection of an intraocular lens. After each surgery, unmasked investigators completed subjective questionnaires about OVD characteristics during each stage of the procedure. Masked technicians evaluated objective safety parameters of intraocular pressure (IOP) and endothelial cell density, with 90 days of follow-up. RESULTS: The DisCoVisc OVD group (128 eyes) and the Healon OVD group (121 eyes) had statistically similar outcomes for IOP and for endothelial cell loss. Subjectively assessed viscosity was statistically different (P < 0.0001), with Healon OVD most often rated "cohesive" and DisCoVisc OVD most often rated "both dispersive and cohesive". Workspace maintenance differed between groups (P < 0.0001), with workspace most frequently rated "full chamber maintained" when using DisCoVisc OVD and most frequently rated "workspace maintained" when using Healon OVD. "Flat" or "shallow" workspace ratings occurred only in the Healon OVD group. CONCLUSION: DisCoVisc OVD had both cohesive and dispersive properties, and was safe and effective for every stage of cataract surgery.

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.

PURPOSE: To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). SETTING: Five private ophthalmology practices throughout the United States. METHODS: Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E(2) (PGE(2)) inhibition. RESULTS: Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (C(max)). The C(max) of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE(2) aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible. CONCLUSION: Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.

Reemergence of canine Echinococcus granulosus infection, Wales.

As a consequence of large-scale outdoor slaughter of sheep during the 2001 foot and mouth disease (FMD) outbreak in the United Kingdom and the possibility of increased risk for transmission of Echinococcus granulosus between sheep and dogs, a large survey of canine echinococcosis was undertaken in mid-Wales in 2002. An Echinococcus coproantigen-positive rate of 8.1% (94/1,164) was recorded on 22% of farms surveyed, which compares to a rate of 3.4% obtained in the same region in 1993. Positivity rates between FMD-affected properties and unaffected ones did not differ significantly. Significant risk factors for positive results in farm dogs were allowing dogs to roam free and the infrequent dosing (>4-month intervals) of dogs with praziquantel. When these data are compared to those of a previous pilot hydatid control program in the area (1983-1989), an increase in transmission to humans appears probable.