Efraim Duzman

Glaucoma treatment with once-daily levobunolol.

Although twice-daily instillation of topical beta-blockers is the standard regimen for treatment of increased intraocular pressure, once-daily therapy might improve patient compliance and provide greater safety. In a three-month, double-masked clinical trial, 92 patients with open-angle glaucoma or ocular hypertension received levobunolol 0.5% or 1% or timolol 0.5% once daily, in both eyes. Overall mean decreases in intraocular pressure were significantly greater in the groups treated with levobunolol than in the group treated with timolol. Intraocular pressure decreases averaged 7.0 mm Hg with levobunolol 0.5%, 6.5 mm Hg with levobunolol 1%, and 4.5 mm Hg with timolol. The intraocular pressures of 72% (18 of 25 patients) of those treated with levobunolol 0.5%, 79% (22 of 28 patients) of those treated with levobunolol 1%, and 64% (16 of 25 patients) of those treated with timolol were successfully controlled during the study. Heart rate and blood pressure decreases were minimal with both levobunolol and timolol. Study results indicated that once-daily treatment with levobunolol and, to a lesser extent, timolol is sufficient to control intraocular pressure successfully and safely.

Levobunolol: A Beta-adrenoceptor Antagonist Effective in the Long-term Treatment of Glaucoma

We compared the ocular-hypotensive efficacy and systemic and ocular safety of an ophthalmic solution of levobunolol (0.5% and 1%) twice daily, with timolol (0.5%) twice daily in a long-term double-masked study of 391 patients with open-angle glaucoma or ocular hypertension. Patients received the test medication in both eyes for up to two years. Over the two-year period, both concentrations of levobunolol reduced mean IOP by 27% (range, -6 to -8 mmHg). This ocular-hypotensive effect was sustained throughout the study and was similar to that produced by timolol. Slight decreases in mean heart rate and blood pressure were observed. No unexpected adverse ocular or systemic reactions were reported. The results of these studies indicate that levobunolol is an effective therapy for the long-term treatment of glaucoma.

Levobunolol vs timolol for open-angle glaucoma and ocular hypertension.

A group of 162 patients with chronic open-angle glaucoma or ocular hypertension were treated twice daily for up to 15 months with one of the following topical ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. Overall mean reductions in intraocular pressure were 8 mm Hg for patients receiving 0.5% levobunolol or timolol and 8.2 mm Hg for patients receiving 1% levobunolol. There were no significant differences between levobunolol and timolol in mean reductions in intraocular pressure, percent of patients with adequately controlled intraocular pressure, or life-table estimates of the probability of successful treatment.

A Clinical Evaluation of the Effects of Topically Applied Levobunolol and Timolol on Increased Intraocular Pressure

Data from two short-term double-masked studies using 24 and 16 subjects suggest that topically applied levobunolol safely and effectively treats open-angle glaucoma and ocular hypertension. The onset of effect of a single drop of 0.5% levobunolol occurred within the first hour, producing a maximal hypotensive effect of more than 8 mm Hg after two hours. An intraocular pressure deceased of greater than or equal to 2 mm Hg was still observed after 24 hours for both concentrations of levobunolol tested (0.5% and 1%). Intraocular pressure decreases of more than 9 mm Hg persisted during a one-month trial in which patients were treated twice daily, confirming the results obtained in the 24-hour study. Systemic effects of both timolol (0.5%) and levobunolol (0.5% and 1%) included a consensual intraocular pressure-decreasing effect in the untreated eye and clinically significant reductions in heart rate. Diastolic blood pressure was decreased at two and four hours after administration of 0.5% levobunolol.

The Ocular Hypertensive Effect of 0.25% Fluorometholone in Corticosteroid Responders

Fourteen subjects known to be corticosteroid responders participated in a double-masked, randomized study comparing the ocular hypertensive effect of 0.25% fluorometholone suspension with that of 0.1% dexamethasone sodium phosphate. Subjects instilled one drop of fluorometholone in one eye and one drop of dexamethasone in the fellow eye four times daily for up to six weeks. Although both medications increased intraocular pressure, endpoint substitution analysis demonstrated that mean intraocular pressure increases from baseline in the eyes treated with fluorometholone were significantly lower than those in the eyes treated with dexamethasone at weeks 2, 4, and 6 (P less than or equal to .05). Also, mean maximum intraocular pressure was significantly lower in the eyes treated with fluorometholone than in the eyes treated with dexamethasone (P = .001). These results indicated that 0.25% fluorometholone is less likely to increase intraocular pressure in corticosteroid responders than 0.1% dexamethasone.

Minimum Concentration of Levobunolol Required To Control Intraocular Pressure in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension

In a double-masked, randomized, comparison titration study to determine the effective dose of topically applied levobunolol, three concentrations of levobunolol (0.25%, 0.5%, and 1%) and of timolol (0.125%, 0.25%, and 0.5%) were evaluated in patients with mild open-angle glaucoma or ocular hypertension. Following a washout of ocular hypotensive medication, twice-daily treatment in both eyes was initiated with the lowest of the three doses of either drug. The concentration was increased if intraocular pressure remained uncontrolled. Intraocular pressure was controlled in 63% (15 of 24) of the patients tested with the lowest concentration of levobunolol and 69% (18 of 26) with the lowest concentration of timolol. Overall, 75% (18 of 24) of the patients in the levobunolol group and 73% (19 of 26) of the patients in the timolol group had adequately controlled intraocular pressure. At the lowest concentrations tested, mean decreases from baseline in intraocular pressure ranged from 6 to 8 mm Hg in both treatment groups.

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.

A Dose-Response Study of Piloplex for Duration of Action

The duration of reduction in intraocular pressure after single-dose administration of three concentrations of piloplex and the vehicle of the drug was evaluated in 12 patients with open-angle glaucoma in a randomized, double-masked, crossover study. Piloplex lowered intraocular pressure in a dose-related fashion, with a duration of action of at least 14 hours.

Ophthalmic Rods: New Ocular Drug Delivery Devices

Ophthalmic Rods, new drug delivery devices for ophthalmic medications, are 2-inch-long plastic rods coated with an ocular diagnostic or therapeutic agent. When the drug-coated tip of the rod is brought into contact with the conjunctiva, the medication dissolves into the tear film. We evaluated the safety, comfort, and ease of use of Ophthalmic Rods coated with fluorescein (30 micrograms) in 28 volunteers. Seventy-nine percent (22 of 28) of the patients rated the device as superior to eyedrops, citing cleanliness, comfort, and ease of application as the primary advantages. Ophthalmic Rods effectively delivered fluorescein to the eye and were found to be safe in patients with various refractive conditions, including those with compromised near vision and accommodation.

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.