Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study.

OBJECTIVE: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. RESULTS: Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI): -0.33, 0.76]; 400 U: 0.42 [95% CI: -0.26, 1.10]; 200 U: -0.03 [95% CI: -0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. CONCLUSIONS: There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. GOV IDENTIFIER: NCT02230956.

Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain.

OBJECTIVES: OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA). METHOD: We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain). RESULTS: The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization. CONCLUSIONS: Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.

Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA was effective and well tolerated for prophylaxis of headache in patients with chronic migraine (CM) in two randomized, double-blind, placebo-controlled, phase 3 trials. To further assess the safety and tolerability of onabotulinumtoxinA in CM prophylaxis in adults, the pooled safety data from four double-blind, placebo-controlled trials were analyzed. METHODS: The pooled analysis included two phase 2 and two phase 3 double-blind, placebo-controlled trials. The safety population was 2436 patients, 1997 of whom received ≥1 dose of onabotulinumtoxinA. The studies shared similar dosing intervals (approximately 12 weeks) with doses between 75 and 260 U. Safety assessments included adverse events (AEs), physical examination and clinical laboratory tests. RESULTS: OnabotulinumtoxinA was safe and well tolerated, with a low discontinuation rate (3.4%) due to AEs. The majority of patients in this pooled analysis received doses between 150 and 200 U, with an average of 163 U per treatment cycle. Of the 1997 patients who received any onabotulinumtoxinA injections, 1455 patients (72.9%) reported at least one AE. Neck pain (12.6%) was the most common onabotulinumtoxinA-associated AE, followed by muscle weakness (8.0%), musculoskeletal stiffness (6.1%) and eyelid ptosis (4.6%). Serious AEs were infrequent, occurring in 5.4% of patients who received any onabotulinumtoxinA treatment and 3.0% of patients receiving placebo. AEs were consistent with the known tolerability profile of onabotulinumtoxinA. CONCLUSIONS: Multiple treatments with onabotulinumtoxinA at doses of 75-260 U administered every 12 weeks, and up to five treatment cycles, were well tolerated for the prophylaxis of headache in adults with CM.

OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.

OBJECTIVE: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study. MATERIALS AND METHODS: PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported. RESULTS: Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials. CONCLUSIONS: This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial.

OBJECTIVES: This is the second of a pair of studies designed to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX) for prophylaxis of headaches in adults with chronic migraine. METHODS: PREEMPT 2 was a phase 3 study, with a 24-week, double-blind, placebo-controlled phase, followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections of onabotulinumtoxinA (155U-195U; n = 347) or placebo (n = 358) every 12 weeks for two cycles. The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21-24 post-treatment. RESULTS: OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint, frequency of headache days per 28 days relative to baseline (-9.0 onabotulinumtoxinA/-6.7 placebo, p < .001). OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons. OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few patients (3.5% onabotulinumtoxinA/1.4% placebo) discontinued due to adverse events. CONCLUSIONS: The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine. Repeated onabotulinumtoxinA treatments were safe and well tolerated.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.

OBJECTIVES: This is the first of a pair of studies designed to assess efficacy, safety and tolerability of onabotulinumtoxinA (BOTOX) as headache prophylaxis in adults with chronic migraine. METHODS: The Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1 (PREEMPT 1) is a phase 3 study, with a 24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxinA (155 U-195 U; n = 341) or placebo (n = 338) (two cycles). The primary endpoint was mean change from baseline in headache episode frequency at week 24. RESULTS: No significant between-group difference for onabotulinumtoxinA versus placebo was observed for the primary endpoint, headache episodes (-5.2 vs. -5.3; p = 0.344). Large within-group decreases from baseline were observed for all efficacy variables. Significant between-group differences for onabotulinumtoxinA were observed for the secondary endpoints, headache days (p = .006) and migraine days (p = 0.002). OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. CONCLUSIONS: There was no between-group difference for the primary endpoint, headache episodes. However, significant reductions from baseline were observed for onabotulinumtoxinA for headache and migraine days, cumulative hours of headache on headache days and frequency of moderate/severe headache days, which in turn reduced the burden of illness in adults with disabling chronic migraine.

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial.

PURPOSE: To investigate the efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution (Acular; Allergan, Inc, Irvine, California) in the treatment of moderate to severe anterior segment inflammation developing after unilateral cataract surgery with intraocular lens implantation. METHODS: Only patients who exhibited moderate or greater levels of cells and flare 1 day after surgery were included in this multicenter, double-masked, randomly assigned, parallel-group study. Topical ketorolac or vehicle solution (Allergan, Inc) was administered to the treated eye four times daily, starting the day after surgery and continuing for 14 days. RESULTS: Ketorolac was significantly more effective than the vehicle solution in reducing anterior chamber cells (P < or = .030) and flare (P < or = .025), conjunctival erythema (P < or = .046), ciliary flush (P < or = .006), tearing (P < or = .012), photophobia (P < or = .014), and pain (P < or = .049). Half as many patients from the ketorolac group (14/51) were discontinued from the study for lack of efficacy, compared with the vehicle group (28/51; P = .005). There was no significant difference between ketorolac and the vehicle solution in changes in visual acuity, intraocular pressure, biomicroscopic or ophthalmoscopic variables, or adverse events. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution is safe and provides substantial anti-inflammatory activity in the treatment of moderate to severe anterior segment inflammation developing after cataract surgery and intraocular lens implantation.

Effects of flurbiprofen and indomethacin on acute cystoid macular edema after cataract surgery: functional vision and contrast sensitivity.

We examined the effect of acute cystoid macular edema (CME) on contrast sensitivity. Eyedrops were instilled into the surgically treated eye f1p4 times daily for two days preoperatively and for three months postoperatively. Angiographic and clinical CME were measured, as were contrast sensitivity and Snellen acuity. Jaeger visual acuity equivalents were calculated and digital imaging techniques used to simulate visual function. We found that angiographic CME reduces functional vision as measured by contrast sensitivity and visual acuity over a large range of sizes. In patients treated with the flurbiprofen vehicle, those without CME had higher mean contrast sensitivity scores than those with CME; this increased over time. Those treated with flurbiprofen and indomethacin had slightly higher contrast sensitivity scores than vehicle-treated patients; this also increased over time, most notably in the higher spatial frequencies. Flurbiprofen treatment improved contrast sensitivity in patients with and without CME significantly at 12 cycles per degree. Flurbiprofen-treated patients with CME in general had higher contrast sensitivity scores than vehicle-treated patients. In this population of patients having cataract surgery, treatment with flurbiprofen or indomethacin reduced the loss of functional vision associated with CME.

Efficacy and safety of nonpreserved ketorolac ophthalmic solution in postoperative ocular pain following radial keratotomy.

PURPOSE: To investigate the efficacy and safety of nonpreserved ketorolac tromethamine 0.5% ophthalmic solution in relieving pain following radial keratotomy (RK). SETTING: Multicenter clinical trial. METHODS: Topical ketorolac was compared with its vehicle in a double-masked, randomized, parallel-group study involving 170 RK patients. Patients were treated with nonpreserved ketorolac 0.5% ophthalmic solution or the vehicle 4 times daily beginning immediately after surgery and continuing for 3 days or until they no longer had ocular pain. RESULTS: At several intervals, patients treated with ketorolac reported significantly greater pain relief and less pain intensity than patients treated with the vehicle. The time required for patients to first report "complete relief" or "no pain" was shorter in the ketorolac than in the vehicle group (P < or = .006). Patients in the ketorolac group used less escape medication (acetaminophen) (P < or = .001) and had fewer sleep difficulties (P < or = .031), fewer symptoms of ocular discomfort (P < or = .028), and less difficulty performing activities of daily living (P = .048). Patients treated with ketorolac experienced the same low rate of treatment-related adverse events as those treated with the vehicle and exhibited the same improvement in visual acuity and manifest refraction. CONCLUSIONS: Nonpreserved ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than, and as safe as, the vehicle in alleviating the postoperative pain associated with RK. This resulted in significant improvements in patient quality of life and less need for oral analgesics, suggesting that topical ketorolac is an appropriate treatment option for ocular pain following RK.

Intraocular availability and pupillary effect of flurbiprofen and indomethacin during cataract surgery.

PURPOSE: To compare the bioavailability and pupillary effect of flurbiprofen and indomethacin during phacoemulsification and intraocular lens implantation. SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS: In this prospective, randomized, double-masked study, 236 patients had cataract extraction by phacoemulsification and posterior chamber intraocular lens implantation. They received topical flurbiprofen 0.03% solution or indomethacin 1% suspension applied every 15 minutes for 60 to 75 minutes before surgery. An aqueous humor sample (100 microL) was taken immediately before the corneal incision was made. Pupil diameters (horizontal and vertical) were measured before aqueous humor sampling, after phacoemulsification, after irrigation and aspiration (I/A), and after acetylcholine instillation. RESULTS: Mean concentration of flurbiprofen and indomethacin in the aqueous humor was 59.8 ng/mL and 90.2 ng/mL, respectively (P < .001). The percentage of dose detected in the aqueous humor was 4.38% in the flurbiprofen group and 0.21% in the indomethacin group (P < .001). Pupil diameters were 7.2 and 7.3 mm presurgery and 7.0 and 7.0 mm after I/A in the flurbiprofen and indomethacin groups, respectively (P > .05). No adverse events were reported in either group. CONCLUSIONS: Although the absolute concentration of indomethacin was higher, the percentage of dose detected in the aqueous humor was 20 times greater in the flurbiprofen than in the indomethacin group. Flurbiprofen is absorbed 20 times more readily than indomethacin. Both drugs were equally effective in preventing miosis during cataract surgery.

Flurbiprofen 0.03% for the control of inflammation following cataract extraction by phacoemulsification.

We conducted a double-masked, vehicle-controlled study to evaluate the anti-inflammatory effect of topical flurbiprofen in cataract surgery by phacoemulsification and implantation of a posterior chamber intraocular lens. The 233 patients were randomized to receive either flurbiprofen or vehicle immediately prior to and for two weeks following surgery. No concomitant corticosteroid use was allowed. The flurbiprofen group had significantly less anterior chamber cells and flare at day 7 and significantly less conjunctival erythema, corneal edema, and lid edema at day 14. The investigator's global effectiveness rating was higher in the flurbiprofen group at day 14. Blood-aqueous barrier disruption, as measured by aqueous fluorophotometry, was statistically significantly diminished in the flurbiprofen group. Burning and stinging were rated significantly greater in the flurbiprofen group than in the vehicle group. Foreign-body sensation and photophobia were significantly more severe in the vehicle group than in the flurbiprofen group. Flurbiprofen provided postsurgical anti-inflammatory efficacy in clinical signs of inflammation and in blood-aqueous barrier disruption, and also showed improved subjective signs.

Naftifine cream in the treatment of cutaneous candidiasis.

Naftifine, a member of a new class of synthetic antifungal drugs, the allylamines, was evaluated for the treatment of cutaneous candidiasis. In a double-blind, parallel-group clinical trial, sixty patients with cutaneous candidiasis were randomly assigned to receive either naftifine cream 1 percent or its vehicle twice a day for three weeks. Two weeks after the end of therapy, 77 percent of the naftifine-treated patients were mycologically cured (negative results on potassium hydroxide preparations and culture) and had no clinically apparent disease, compared with 3 percent of the patients treated with vehicle (p less than 0.001). Side effects reported with naftifine cream were few and minor.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine.

OBJECTIVE: To assess the effects of treatment with onabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and headache impact in adults with chronic migraine (CM). METHODS: The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles) followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites. An additional 40 U could be administered "following the pain." Prespecified analysis of headache impact (Headache Impact Test [HIT]-6) and HRQoL (Migraine-Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed. Because the studies were similar in design and did not notably differ in outcome, pooled results are presented here. RESULTS: A total of 1,384 subjects were included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696). Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups; 93.1% were severely impacted based on HIT-6 scores ≥60. At 24 weeks, in comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6 scores and the proportion of patients with HIT-6 scores in the severe range at all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001). CONCLUSIONS: Treatment of CM with onabotulinumtoxinA is associated with significant and clinically meaningful reductions in headache impact and improvements in HRQoL. CLASSIFICATION OF EVIDENCE: This study provides Class 1A evidence that onabotulinumtoxinA treatment reduces headache impact and improves HRQoL.

Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: a multicentre, double-blind, randomized, placebo-controlled, parallel-group study.

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX); Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3% female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had >or=50% decrease in tension headache days than did placebo (P

Ocufen (flurbiprofen) in the treatment of ocular pain after radial keratotomy.

Ocular pain is often treated with systemic analgesics, which are associated with some undesirable side effects. Because nonsteroidal anti-inflammatory drugs are thought to be peripheral analgesics, we decided to evaluate the local analgesic effect of flurbiprofen. After an initial study in 29 patients demonstrated that 0.03% flurbiprofen ophthalmic solution did not affect corneal sensitivity, a second trial was designed to test the analgesic efficacy and safety of this agent. In a multicenter, randomized, double-masked, parallel-group clinical trial, topically applied 0.03% flurbiprofen sodium ophthalmic solution was compared with its vehicle in 105 patients (53 females, 52 males) undergoing elective unilateral radial keratotomy. All patients received flurbiprofen or its vehicle before and every four hours after surgery for 14 days. Mean pain intensity variables were lower in the flurbiprofen group than the vehicle group after surgery. Clinically significant differences in pain relief (mean difference > or = 1 unit), favoring flurbiprofen, were seen at hours 2, 3, and 4, and on days 1 through 4, and on day 7. Statistically significant differences were seen at hours 2, 3, and 4. Sixteen patients (eight in each group) had adverse effects, most commonly transient burning. These studies suggest that topical 0.03% flurbiprofen safely and effectively relieves ocular pain without affecting corneal sensation.

Efficacy of a sunscreen containing butyl methoxydibenzoylmethane against ultraviolet A radiation in photosensitized subjects.

Topical formulations containing a new chemical entity, the ultraviolet A absorber Parsol 1789 (butyl methoxydibenzoylmethane), were evaluated as agents for protecting human skin against ultraviolet A (UVA) radiation. Healthy subjects were photosensitized to UVA radiation by ingestion of 8-methoxypsoralen (0.6 mg/kg). After 90 minutes, five formulations (vehicle, vehicle + butyl methoxydibenzoylmethane, vehicle + butyl methoxydibenzoylmethane + padimate O, vehicle + padimate O, and a marketed sunscreen containing padimate O, oxybenzone, and octyl salicylate) were applied in a randomized, double-blind manner to areas on the lower part of the back. Thirty minutes later, sites in the five treated areas and in a sixth unprotected area were exposed to graduated doses of UVA radiation. Test sites were evaluated for erythema 48 and 72 hours after UVA exposure, and for melanogenesis approximately 2 weeks later. The combination of butyl methoxydibenzoylmethane + padimate O demonstrated significantly greater protection than the combination of padimate O, oxybenzone, and octyl salicylate.

Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery.

PURPOSE: To compare the efficacy and safety of ketorolac 0.5% ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation. DESIGN: Multicenter clinical study. PARTICIPANTS: One hundred four patients were prospectively randomized, 52 patients in treatment group, 52 patients in control group. METHODS: Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospective, double-masked, randomized, parallel group study. Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled. MAIN OUTCOME MEASURES: The main outcome measures include inflammation (cell, flare, ciliary flush), intraocular pressure and visual acuity. RESULTS: Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation, including: anterior chamber cells (P: = 0.002) and flare (P: = 0.009), conjunctival erythema (P: = 0.010), ciliary flush (P: = 0.022), photophobia (P: = 0.027), and pain (P: = 0.043). Five times as many patients were dropped from the study for lack of efficacy from the vehicle group (22/52) than from the ketorolac group (4/52; P: = 0.001). Ketorolac was found to be equally as safe as vehicle in terms of adverse events, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery, while being as safe as vehicle.

Reduction of inflammation following cataract surgery by the nonsteroidal anti-inflammatory drug, flurbiprofen.

In this double-masked clinical trial, 72 patients undergoing cataract extraction surgery received a topical loading dose of 0.03% flurbiprofen or vehicle before surgery and one drop four times daily for 2 weeks after surgery. The severity of conjunctival hyperemia, aqueous humor cells, and aqueous humor flare was lower in the flurbiprofen-treated group than in the vehicle-treated group at all follow-up visits; the differences were significant on day 14. Four patients treated with flurbiprofen and two treated with vehicle exhibited postoperative hyphemas. Treatment with flurbiprofen appeared to decrease the severity of inflammation following cataract extraction surgery.

Prednisolone acetate-gentamicin combination following cataract surgery.

One-hundred-eleven patients participated in a 21-day, open-label study to evaluate the therapeutic efficacy and safety of a prednisolone acetate 1%-gentamicin 0.3% ophthalmic suspension to control inflammation and prevent infection after cataract surgery. Beginning the day after surgery, the medication was instilled qid for the next 21 days. No postoperative infection was noted, and postoperative inflammation, which was mild immediately after surgery, decreased steadily during follow-up. The results of this study suggest that a prednisolone acetate-gentamicin combination used for three weeks after cataract surgery is safe and has a positive therapeutic effect on postoperative inflammation and infection.

Once-daily naftifine cream 1% in the treatment of tinea cruris and tinea corporis.

Seventy patients with tinea cruris or tinea corporis were treated with naftifine cream 1% or vehicle once daily for 4 weeks in this double-blind, randomized study. After two weeks, the patients using naftifine had a significantly higher mycologic cure rate than the vehicle-treated patients (79% vs. 31%, p less than 0.001), and they showed significantly better resolution of signs and symptoms. Statistically significantly differences favoring naftifine over its vehicle were found throughout the treatment period and 2 weeks posttreatment.