Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin.

The crystalline lenses of hypercholesterolemic patients were assessed before and after 48 weeks of treatment with lovastatin or placebo to determine the effect of lovastatin on the human lens. Patients were given a biomicroscopic (slit-lamp) examination of the lens, and a previously validated, standardized classification system was used to describe the findings. A total of 8,245 patients were randomly assigned in equal numbers to treatment with placebo or lovastatin 20 or 40 mg once or twice daily in this double-blind, parallel-group study. Statistical analyses of the distribution of cortical, nuclear and subcapsular opacities at 48 weeks, adjusted for age and presence of an opacity at baseline, showed no significant differences (p less than 0.01) between the placebo and lovastatin-treated groups. Visual acuity assessments at week 48 were also not found to have significantly different distributions among treatment groups. Moreover, no significant differences were found among the groups in the frequencies of greater than or equal to 2-line worsening in visual acuity with concurrent progression in lenticular opacity, cataract extraction, or any spontaneously reported adverse ophthalmologic experience. No evidence was found for an effect of lovastatin on the human lens after 48 weeks of treatment.

Levobunolol. A three-month efficacy study in the treatment of glaucoma and ocular hypertension.

The ocular hypotensive effect and the safety of levobunolol hydrochloride (0.5% and 1%) were compared with vehicle in this double-masked study of 42 patients with chronic open-angle glaucoma or ocular hypertension. After a washout of ocular hypotensive medication, patients received one of the three test treatments in both eyes twice daily for three months. Both concentrations of levobunolol produced significant reductions in intraocular pressure, while decreases in vehicle-treated patients were minimal. Over the three-month study period, average pressure reductions were approximately 9.0 mm Hg in patients receiving either concentration of levobunolol and 0.5 mm Hg in patients receiving vehicle. Fewer patients were terminated from the study for inadequately controlled intraocular pressure in the levobunolol groups than in the vehicle group. No patients were terminated for drug-related adverse experiences.

Evaluation of timolol maleate combination therapy in chronic open-angle glaucoma.

In an eight-week study, timolol maleate ophthalmic solution 0.25% was administered twice daily with either pilocarpine 2% four times a day, epinephrine 2% twice a day, carbachol 1.5% four times a day, or 250 mg of acetazolamide twice a day to 44 patients with chronic open-angle glaucoma. Compared to baseline readings on standard therapy alone, mean intraocular pressure was significantly reduced after addition of timolol maleate to each of the regimens. Mean facility of outflow was unaffected. No clinically significant ocular irritation or changes in visual acuity, pupil size, or vital signs were observed in any patient. Timolol maleate appears to be effective and well tolerated when administered with other antiglaucoma medications in patients with open-angle glaucoma.

The effect of d-timolol on intraocular pressure in patients with ocular hypertension.

The stereoisomer form of timolol used in the treatment of glaucoma is l-timolol. Although d-timolol is a less potent beta-adrenergic receptor blocker than l-timolol, several laboratory studies have found that d-timolol has ocular hypotensive effects. Thus, d-timolol may be a useful therapeutic agent for glaucoma that has fewer systemic side effects than l-timolol. We conducted a randomized, double-masked, single-drop study of the effects of d-timolol and placebo on intraocular pressure in 34 patients with ocular hypertension. d-Timolol significantly lowered intraocular pressure for the six-hour duration of the study. No patients receiving the drug reported subjective side effects. There was no change in visual acuity, pupil size, or results of external ocular or slit-lamp examinations during the study. No changes in pulse rate or blood pressure were attributable to the drug.

Safety and effectiveness of concomitant administration of dipivefrin and timolol maleate.

Dipivefrin, an epinephrine prodromal drug, was used in conjunction with timolol maleate to evaluate the safety and effectiveness of combined therapy. Seventeen patients who had used timolol maleate for at least six months added dipivefrin (Group 1) and seven patients who had used dipivefrin for at least six months added timolol maleate (Group 2). Intraocular pressure decreased further in both groups. Side effects were most prominent in Group 1.

Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level.

Fifty-eight healthy, normolipidemic adult men participated in a prospective, masked, randomized crossover study designed to compare the effects of two topical nonselective beta-adrenergic antagonists, carteolol and timolol, on plasma high-density lipoprotein cholesterol levels. Two eight-week treatment periods were separated by an eight-week drug-free period. Carteolol 1.0% or timolol 0.5% was used, one drop twice daily, in both eyes without nasolacrimal occlusion. Fresh plasma was assayed for levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I and B-100. With indistinguishable effects on intraocular pressure, carteolol and timolol induced different (P = .013) decrements in high-density lipoprotein cholesterol levels. Carteolol treatment decreased high-density lipoprotein cholesterol levels by 3.3% (-0.04 mmol/l) and raised the ratio of total to high-density lipoprotein cholesterol levels by 4.0% (0.15 unit); timolol treatment decreased high-density lipoprotein cholesterol levels by 8.0% (-0.10 mmol/l) and raised the ratio of total to high-density lipoprotein cholesterol levels by 10.0% (0.37 unit). There was no differential drug effect on the other lipid variables measured. Ocular nonselective beta-adrenergic antagonist therapy can produce clinically relevant decrements in high-density lipoprotein cholesterol levels in healthy men.

Timolol hemihydrate vs timolol maleate to treat ocular hypertension and open-angle glaucoma.

PURPOSE: We compared the therapeutic efficacy and safety of timolol hemihydrate to timolol maleate in patients with ocular hypertension and chronic open-angle glaucoma. METHODS: We conducted this three-month study as a multicentered, masked, parallel group comparison. Both the 0.25% and 0.5% concentrations were evaluated against similar concentrations of timolol maleate. Dosing was twice daily. An open-label, nine-month study followed the masked portion of the protocol, in which all patients received either 0.25% or 0.5% timolol hemihydrate. A total of 371 patients were included in both the 0.25% and 0.5% studies. RESULTS: We found statistically similar intraocular pressures with both the 0.25% (18.3 and 18.6 mm Hg for the hemihydrate and maleate groups, respectively) and 0.5% (19.9 and 19.5 mm Hg for the hemihydrate and maleate groups, respectively) concentrations of timolol hemihydrate and timolol maleate after three months of masked treatment. Likewise, peak intraocular effect at two hours after taking the medication was statistically similar between medicines at both concentrations. Likewise, both ocular and systemic safety were similar between the maleate and hemihydrate preparations at both concentrations. In the nine-month open-label protocol, therapeutic efficacy (19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations, respectively) and safety of timolol hemihydrate were similar to effect and safety of the three-month protocol. CONCLUSIONS: This study suggests that timolol hemihydrate had an ocular hypotensive efficacy and safety profile statistically equivalent to that of timolol maleate for up to three months of therapy. Timolol hemihydrate showed efficacy and safety similar to that observed within the first three months, for up to one year of therapy.

A YAG laser technique to facilitate removal of posterior chamber intraocular lenses from the capsular bag.

A technique is presented which facilitates repositioning or removal of a decentered capsular bag-fixated posterior chamber intraocular lens. The anterior lens capsule in front of the encapsulated haptic loop is disrupted with the YAG laser. This frees the loop from the capsular bag so a dialing maneuver will not stress the posterior capsule or zonule.

Comparison of the properties of AMVISC and Healon.

A standardized investigation to compare the biophysical characteristics of two sodium hyaluronate products, AMVISC and Healon, was conducted. Results showed that the two products exhibited similar biophysical properties. AMVISC exhibited an average kinematic viscosity of 41,554 centistokes and a calculated average molecular weight of 2.04 X 10(6) daltons. Healon exhibited an average kinematic viscosity of 47,271 centistokes and a calculated average molecular weight of 2.43 X 10(6) daltons.

Carteolol hydrochloride: controlled evaluations of its ocular hypotensive efficacy relative to its vehicle, and, in combination with pilocarpine, relative to timolol.

Carteolol is a noncardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity. In the two studies presented in this report, we sought (a) to evaluate the absolute efficacy of carteolol (i.e., vs. its vehicle) over an extended period and (b) to evaluate the utility of carteolol versus that of timolol when used concomitantly with pilocarpine. Study 1 was a double-masked, randomized, 6-week evaluation conducted in 64 patients of 1% carteolol HCl, 2% carteolol HCl, and its vehicle given twice daily in both eyes. From an unmedicated baseline intraocular pressure (IOP) of 23-25 mm Hg, mean reductions in the carteolol treatment groups ranged from 5.8 to 6.6 mm Hg (23-26% reduction). Mean reductions in heart rate were six to seven beats/min, two beats/min, and one beat/min in the 1% carteolol, 2% carteolol, and vehicle groups, respectively. Study 2 was a double-masked, randomized, 12-week evaluation of 1% carteolol HCl, 2% carteolol HCl, and 0.5% timolol in combination with pilocarpine, either 2% or 4%, in 67 patients. From an unmedicated baseline IOP of 24-29 mm Hg, mean reductions from this unmedicated baseline with combination beta-adrenoceptor antagonist/pilocarpine treatment ranged from 6 to 10 mm Hg in all groups (24-40%). Mean decreases in heart rate ranged from one to six beats/min, with no meaningful differences among the treatment groups. Based on the efficacy of twice-daily carteolol in reducing IOP by approximately 25%, as well as its efficacy when used concomitantly with pilocarpine, we suggest that clinicians may find carteolol a useful addition to their pharmacopeia in the treatment of elevated IOP.

Comparison of phacotrabeculectomy with 5-fluorouracil, mitomycin-C, and without antifibrotic agents.

BACKGROUND AND OBJECTIVE: To evaluate the potential benefits, complications, and prognostic risk factors for failure of phacotrabeculectomy performed with or without 5-fluorouracil (5-FU) and mitomycin-C (MMC). PATIENTS AND METHODS: Retrospective chart review of 78 patients who underwent phacotrabeculectomy during a 2-year period. Patients were divided into 3 groups, those who received 5-FU (N = 28). MMC (N = 29), or no antifibrotic agent (N = 21). RESULTS: All 3 groups had statistically significant lower intraocular pressures (IOP) on fewer antiglaucomatous medications at 6-month, 12-month, and last follow-up compared to preoperative levels (P < .05). Intraocular pressures were lower in the group that received MMC compared to the 5-FU group, but not in the group that did not receive antimetabolites, at all time intervals measured (P < .05). Black race was a strong predictor of failure of trabeculectomy (P = 009). No differences in final visual acuity or complications were found between groups. CONCLUSIONS: Phacotrabeculectomy is effective regardless of antimetabolite use. Race is a strong predictor of failure.

Effects of dapiprazole on the reversal of pharmacologically induced mydriasis.

The ability of a new alpha-adrenergic antagonist, dapiprazole, to reverse mydriasis produced by phenylephrine 2.5% or 10%, tropicamide 0.5%, and the combination of phenylephrine 2.5% and tropicamide 0.5% was investigated. A double masked crossover design was used to study both efficacy of mydriatic reversal and time course. The safety of administration was evaluated as well. Subjects were optometry students and their spouses. The results demonstrate that dapiprazole is safe and effective for reversing mydriasis produced by both concentrations of phenylephrine, and partially effective in reversing mydriasis in eyes treated with tropicamide 0.5%, alone, or in combination with 2.5% phenylephrine.

Retinal autoregulation in open-angle glaucoma.

The macular blood flow response to an induced change in intraocular pressure (autoregulation) was studied using the blue field entopic phenomenon in 11 open angle glaucoma patients, eight glaucoma suspects and 13 normal volunteers. A suction cup was used to raise the intraocular pressure (IOP) above its resting state (IOPrest). IOPmax, the highest acutely increased IOP for which blood flow can be maintained constant by autoregulation, was 24.9 +/- 1.5 mmHg (+/- 1 SD) in the glaucoma patients, 30.8 +/- 4.6 mmHg in the glaucoma suspects and 29.9 +/- 3.6 mmHg in the normal subjects. The values for IOPmax - IOPrest were 3.7 +/- 4.3 mmHg, 4.7 +/- 3.3 mmHg, and 14.3 +/- 3.1 mmHg, respectively. After the release of the suction cup, a hyperemic response was observed by 16 of 17 normal eyes, 10 of 14 glaucoma suspect eyes and only 9 of 19 glaucomatous eyes. These results suggest an abnormal autoregulation of macular retinal blood flow in open-angle glaucoma.

Argon laser trabeculoplasty in black and white patients with primary open-angle glaucoma.

The effect of argon laser trabeculoplasty (ALT) on lowering intraocular pressure (IOP) was studied retrospectively in 68 black patients and 42 white patients with uncontrolled primary open-angle glaucoma on maximally tolerated medical therapy. Patients with the diagnosis of pigmentary or pseudoexfoliation glaucoma and those having previous intraocular or laser surgery were excluded. While the mean age of the black patients (66.9 years) was lower than the white patients (72.2 years), the prelaser IOP was similar between the two groups: 26.2 mmHg for the black patients and 25.5 mmHg for the white patients. The mean IOP one year (18.4 mmHg for black patients and 18.4 mmHg for white patients) and two years (19.5 mmHg and 20.3 mmHg, respectively) after ALT was the same between the two groups of patients. A similar percentage of black (85%) and white (83%) patients showed more than a 15% decrease in IOP from their prelaser values one year after treatment. The IOP lowering effect of ALT decreased during the second post-operative year; but the diminished response was identical in patients of both races, with 71% of patients of both groups still showing greater than 15% reduction from their pre-laser IOP. We conclude that ALT is equally effective in lowering IOP for black and white patients with medically uncontrolled primary open-angle glaucoma.