Congenital arthrogryposis: an inherited limb deformity in pedigree Suffolk lambs.

Thirty of 52 pedigree Suffolk lambs (58 per cent) were born with arthrogryposis characterised by bilateral flexion rigidity of the metacarpophalangeal and carpal joints. The recent introduction of a breeding ram was identified as the only significant risk factor in the flock, and embryo transfer was used to test the hypothesis that the arthrogryposis was an inherited disorder associated with the introduction of this ram. Two adult ewes that had previously produced lambs with arthrogryposis by the ram and four of its affected daughters were available as donors, and 20 crossbred ewes were used as recipients. Ten Suffolk-crossed ewes that had no known familial relationship with the ram were also mated by the ram as controls and they produced 10 normal lambs. Following embryo transfer, 19 lambs were born, of which seven were stillborn; arthrogryposis was evident in 10 of the 12 live lambs. Analysis of the data suggested that in the population under study, arthrogryposis was inherited as an autosomal recessive condition.

Levobunolol 0.5% and timolol 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy.

PURPOSE: To evaluate the prophylactic effect of levobunolol 0.5%, timolol 0.5%, or vehicle in reducing the incidence of postoperative intraocular pressure (IOP) spikes of 5 and 10 mm Hg or more in patients having neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Miami Vision Center, Coral Gables, Florida; Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Cincinnati Eye Institute, Cincinnati, Ohio; South Texas Cataract and Glaucoma Center, San Antonio, Texas; Mid-South Eye Foundation, Memphis, Tennessee, USA. METHODS: This prospective, double-masked, randomized study comprised 144 patients having Nd:YAG laser posterior capsulotomy in one eye. One drop of the test medication was administered preoperatively and one drop on the evening after surgery; IOP was measured preoperatively and 1,2,3 and 24 hours postoperatively. RESULTS: Intraocular pressure elevations of 5 mm Hg or more were seen in 1 of 60 patients (2%) in the levobunolol group, 4 of 54 (7%) in the timolol group, and 10 of 28 (36%) in the vehicle group. These elevations occurred significantly more frequently in the vehicle group than in the levobunolol (P < .001) or timolol (P < .004) groups. Elevations of 10 mm Hg or more were found in 2 of 28 patients (7%) treated with vehicle but were not observed in the patients treated with levobunolol or timolol. CONCLUSIONS: Levobunolol 0.5% or timolol 0.5% administered preoperatively and again in the evening after Nd:YAG laser capsulotomy effectively blunted the IOP rise that frequently follows laser surgery.

Brimonidine tartrate: a one-month dose response study.

BACKGROUND: Brimonidine tartrate is a relatively selective alpha2-agonist that effectively reduces mean intraocular pressure (IOP) and the incidence of IOP spikes after laser trabeculoplasty. The authors were interested in evaluating the dose response of brimonidine when applied topically for a longer duration in patients with elevated IOPs. METHODS: The authors conducted a 1-month, multicentered, double-masked, randomized, placebo-controlled, parallel clinical study in 194 patients with ocular hypertension or glaucoma (mean IOP, 25.6 +/- 3.2 mmHg). The authors administered three concentrations of brimonidine (0.08%, 0.2%, and 0.5%) or placebo bilaterally every 12 hours for 1 month. The authors evaluated the following parameters: IOP, heart rate, blood pressure, visual acuity, pupil size, basal tear secretion as well as patient comfort at baseline, day 1, week 1, week 3, and week 4. RESULTS: All concentrations of brimonidine significantly reduced IOP, compared to baseline and placebo, at all follow-up visits. Maximum mean IOP decreases from baseline of 20.8%, 27.2%, and 30.1% were observed for the 0.08%, 0.20%, and 0.5% treatment groups, respectively. On days 1 and 21, the 0.2% and 0.5% treatment groups exhibited significantly greater IOP decreases than did the 0.08% group. After the initial steep decline in IOP, the effect decreased slightly and stabilized at day 14 at the level that was maintained throughout the study. The most frequent side effects reported were fatigue and dry mouth. No significant changes in heart rate were reported. Statistically significant decreases in mean blood pressure without clinical symptoms were observed within the 0.2% and 0.5% treatment groups. CONCLUSION: Brimonidine 0.2% is well tolerated, efficacious, and shows potential as an agent in the long-term treatment of elevated IOP.

A double-masked comparison of betaxolol and dipivefrin for the treatment of increased intraocular pressure.

Noncardioselective beta-adrenoceptor antagonists are used for treatment of increased intraocular pressure. Because these agents may be absorbed systemically, their use is of concern in patients with restricted pulmonary function. We compared the efficacy of betaxolol, a cardioselective beta-adrenoceptor antagonist, and dipivefrin, an alpha/beta-adrenergic agonist. Seventy-six patients with open-angle glaucoma or ocular hypertension were randomly assigned to receive either betaxolol 0.5% or dipivefrin 0.1%. Patients were examined at two weeks, one month, two months, and three months. Intraocular pressure reductions were similar, with a mean decrease of 4.1 mm Hg in the betaxolol group and 3.5 mm Hg in the dipivefrin group. Both treatments caused similar minor increases in heart rate, typical with alpha-adrenergic agonists but atypical with beta-blockers. Stinging or burning in the betaxolol group was significantly (P = .008) greater than in the dipivefrin group. Our findings suggest that betaxolol and dipivefrin therapy are effective, equivalent ocular hypotensive agents.

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.

Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study.

The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.

A comparison of the ocular hypotensive efficacy of twice-daily 0.25% levobunolol to 0.5% timolol in patients previously treated with 0.5% timolol.

Treatment with noncardioselective beta-adrenoceptor antagonists (e.g., 0.5% timolol or 0.5% levobunolol) is standard practice for lowering elevated intraocular pressure (IOP). However, because there are risks and side effects associated with the use of these agents, a lower, yet still effective, dose may be preferred. We gave 0.5% timolol twice daily for 30 days to 143 patients. In a double-masked, randomized fashion, we then assigned patients to continue to receive 0.5% timolol twice daily or 0.25% levobunolol twice daily for 8 weeks. The mean unmedicated baseline IOP for both groups was approximately 25 mm Hg. After 30 days of timolol pretreatment, the mean IOP in both groups decreased to approximately 19 mm Hg (p = 0.210). After the 30-day timolol pretreatment period, and subsequent randomization to either 0.5% timolol or 0.25% levobunolol treatment, there was little change in overall mean IOP (0.03 mm Hg decrease for levobunolol, 0.06 mm Hg increase for timolol; p = 0.811) from the timolol pretreatment baseline. One patient assigned to the timolol treatment group was terminated from the study due to inadequate control of IOP. We conclude that the mean IOP lowering effect of 0.25% levobunolol is equivalent to 0.5% timolol, and switching patients from twice-daily 0.5% timolol to twice-daily 0.25% levobunolol poses no significant risk of decreased ocular hypotensive efficacy.

Efficacy and safety of once-daily levobunolol for glaucoma therapy.

We studied the ocular hypotensive efficacy and safety of 0.5% levobunolol hydrochloride and 0.5% timolol maleate administered topically once daily for 3 months in 91 patients (46 in the levobunolol group and 45 in the timolol group) with primary or secondary open-angle glaucoma or ocular hypertension. In this randomized double-masked parallel clinical study, intraocular pressure (IOP) was successfully controlled in 78% of the patients who received levobunolol and 89% of those who received timolol. The overall mean decrease in IOP was 5.6 mm Hg (decrease of 23%) in the levobunolol group and 6.7 mm Hg (26%) in the timolol group, a nonsignificant difference. In both groups the overall mean IOP during treatment was significantly lower than the pretreatment value (p less than 0.001). For both treatment groups changes in heart rate and blood pressure were minimal. We conclude that both 0.5% levobunolol and 0.5% timolol administered once daily are effective and safe in lowering IOP in most patients with ocular hypertension or open-angle glaucoma.

Prophylactic treatment of intraocular pressure elevations after neodymium: YAG laser posterior capsulotomies and extracapsular cataract extractions with levobunolol.

The prophylactic effect of topical 0.5% levobunolol on intraocular pressure (IOP) elevations after neodymium:YAG (Nd:YAG) laser posterior capsulotomies and extracapsular cataract extractions (ECCEs) was investigated in two separate, double-masked, placebo-controlled studies. In study 1, 42 patients received either levobunolol or vehicle 1 hour before a unilateral Nd:YAG laser posterior capsulotomy. Elevated IOP (greater than or equal to 10 mmHg) occurred in up to 38% of those in the vehicle group and none in the levobunolol group. Mean IOP increased up to 6 mmHg in the vehicle group, whereas it decreased up to 3 mmHg in the levobunolol group. In study 2, 41 patients received either levobunolol or vehicle immediately after a unilateral ECCE involving the use of a viscoelastic preparation and the implantation of a posterior chamber intraocular lens (PC IOL). The incidence of IOP elevations (greater than or equal to 10 mmHg) was up to 40% in the vehicle group and 19% in the levobunolol group. Mean IOP increased up to 9 mmHg in the vehicle group and up to 2 mmHg in the levobunolol group. Thus, marked elevations in IOP after posterior capsulotomies or ECCEs may be minimized by prophylactic treatment with levobunolol.

A multicenter evaluation of levobunolol (Vistagan) in Germany.

We evaluated the efficacy and safety of 0.5% levobunolol HC1 (Vistagan) in 2,041 glaucoma patients at 143 sites in the Federal Republic of Germany. This study was a 3-month, open-label, noncomparative trial of levobunolol administered twice daily. Eighty-five percent of the patients completed the study period with well-controlled intraocular pressure (IOP). Treatment was discontinued in the remaining 15%: 7% for adverse reactions, 1% for lack of drug efficacy, and 7% for reasons unrelated to the study treatment. Efficacy, ocular drug tolerance, and systemic safety were judged as good to very good in approximately 80% of the patients. This large, postapproval study confirms previous findings of several well-controlled clinical trials indicating that levobunolol is an effective drug for the treatment of elevated IOP and is safe and comfortable for most patients.

Plasma levobunolol levels following topical administration with reference to systemic side effects.

We determined the plasma level of levobunolol in normal volunteers after a single topical instillation of 0.5 or 1% levobunolol in both eyes, and after twice-daily instillations for 1 week. Levobunolol levels were detected within 1 h following acute instillation. During the study, mean plasma levels ranged from 0.1 to 0.3 ng/ml for the 0.5% group and 0.3 to 0.6 ng/ml for the 1% group. The highest individual plasma level was 1.2 ng/ml, which occurred in 1 patient receiving 1% levobunolol. After 1 week of twice-daily instillation mean plasma levels were similar to those observed after acute instillation. Minimal cardiovascular changes were observed in the 0.5% group while decreases in heart rate and systolic blood pressure were observed in the 1% treatment group.