Study of the additive effect of timolol and epinephrine in lowering intraocular pressure.

A randomised, double-masked clinical study was conducted in patients with primary open-angle glaucoma to determine if timolol and epinephrine have an additive effect in lowering intraocular pressure. Sixteen patients were randomly assigned to one of 2 treatment sequences (timolol alone, supplemented after 2 weeks with epinephrine, and vice versa). An initial additive effect in lowering intraocular pressure was found in both sequences. However, after several weeks of combined therapy complete loss of additive effect was found. Patients who were treated first with epinephrine for 2 weeks and then supplemented with timolol had significantly lower intraocular pressures for at least 2 weeks than patients in the reverse treatment sequence. Epinephrine treatment alone caused a significant increase in facility of outflow, but this effect did not occur with simultaneous timolol treatment. The results are discussed in terms of possible fundamental beta and alpha adrenergic influences on aqueous dynamics and their potential clinical relevance.     

The determination of additive effect and intraocular pressure lowering effects of 0.05% bromocriptine and 0.25% timolol

It has been confirmed that topically applied bromocriptine has a satisfactory intraocular pressure (IOP) lowering effect without serious ocular or systemic side effects. We compared the IOP lowering effects of 0.05% bromocriptine and 0.25% timolol and determined whether they have an additive effect in lowering IOP in normal volunteers.In a double-blind, randomised, prospective, single-dose study, we measured IOP in 24 ocular normotensive subjects before (baseline) and 2, 4 and 6 hours after topical instillation of the following drugs: timolol and bromocriptine alone (n : 14), timolol + bromocriptine, timolol + placebo, bromocriptine + placebo (n : 10).Both bromocriptine and timolol have a significant IOP lowering effect (p < 0.01) compared with the baseline value during the study period. There were no significant differences in IOP lowering effect between timolol and bromocriptine at 2 and 4 hours (p > 0.05), but timolol was more efficacious than bromocriptine at 6 hours (p < 0.05). An additive effect in lowering IOP was not found.Although timolol and bromocriptine have no additive effect in lowering IOP, topically applied bromocriptine may be used in the treatment of glaucoma.     

A short-term study of the additive effect of latanoprost 0.005% and brimonidine 0.2%

PURPOSE: To evaluate the short-term additive effects of latanoprost 0.005% and brimonidine 0.2%. METHODS: This study was a randomized, double-masked, cross-over study that included 32 patients (32 eyes) with primary open-angle glaucoma or exfoliation glaucoma. On baseline day, intraocular pressure (IOP) was measured at 10 AM and 11 PM. Baseline IOP values were obtained by calculating the mean values for both eyes. After this process, latanoprost 0.005% was prescribed once a day during the first 5 days at 10 PM as the first test drug. During the second 5 days, twice a day brimonidine 0.2% or a placebo, as the second test drug, was added to the latanoprost at 9 AM and 10 PM. After a 4-week washout period, latanoprost 0.005% was prescribed once a day during the first 5 days at 10 PM and during the second 5 days, the second test drug, brimonidine or a placebo, was added to latanoprost, and the two drugs were prescribed twice a day for 5 days. RESULTS: During the second 5 days, although an additional 2.53-3.10 mm Hg decrease in IOP was determined in the latanoprost+brimonidine group, there was no additional decrease in the latanoprost+placebo group. CONCLUSIONS: This study showed that brimonidine and latanoprost have an additive IOP-lowering effect in open-angle glaucoma patients in the short term.     

A comparison of the fixed combination of latanoprost and timolol with the unfixed combination of brimonidine and timolol in patients with elevated intraocular pressure. A six month, evaluator masked, multicentre study in Europe

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of fixed combination (FC) latanoprost/timolol with unfixed combination (UFC) brimonidine/timolol in patients with increased IOP. METHODS: In this 6 month, randomised, evaluator masked, parallel group European study, patients with glaucoma or ocular hypertension and IOP > or =21 mm Hg on monotherapy or >16 mm Hg on dual therapy received either FC latanoprost/timolol at 8:00AM or UFC brimonidine/timolol at 8:00AM and 8:00PM. The primary outcome was the difference from baseline to month 6 in mean diurnal IOP reduction. RESULTS: 325 of 334 randomised patients were included in intent to treat analyses (FC latanoprost/timolol, 163; UFC brimonidine/timolol, 162). Baseline diurnal IOP levels were similar: FC latanoprost/timolol, 26.4 (SD 2.7) mm Hg; UFC brimonidine/timolol, 26.5 (SD 2.8) mm Hg (p = 0.851). At month 6, levels were 16.9 (SD 2.8) mm Hg in FC latanoprost/timolol patients and 18.2 (SD 3.1) mm Hg in UFC brimonidine/timolol patients (p<0.001). No adverse events were reported by 76.4% and 75.5% of patients receiving FC latanoprost/timolol versus UFC brimonidine/timolol, respectively. Larger proportions of brimonidine/timolol treated patients reported study medication related adverse events (18.6% v 7.3%) and discontinued study participation because of this (10.8% v 1.8%). CONCLUSION: Fixed combination latanoprost/timolol administered once daily is both more effective and better tolerated than twice daily dosing with UFC brimonidine/timolol.     

A comparison of the effects of timolol and epinephrine on intraocular pressure.

We conducted a double-masked, six-week crossover study comparing bilateral twice-a-day therapy with timolol maleate (0.1%, 0.25%, and 0.5%) and epinephrine hydrochloride (0.5%, 1.0%, 2.0%) in 36 otherwise untreated patients. Increasing concentrations of each drug were administered until an arbitrary level of control was achieved before each of the six-week follow-up periods. Seventeen patients were controlled by both drugs and four patients were controlled by neither drug. Timolol, but not epinephrine, was effective in ten patients, whereas epinephrine, but not timolol, was effective in two patients. Three patients did not complete the study. The mean decrease in intraocular pressure from baseline was significantly greater with timolol than with epinephrine both before crossover and overall at both the lowest and highest concentrations of drug used. Significantly toxicity was produced in four patients during treatment with epinephrine, but in no patients during treatment with timolol.     

Additive intraocular pressure reducing effect of topical timolol during systemic beta-blockade

The effect on intraocular pressure (IOP) of topical timolol was studied in 30 patients with arterial hypertension treated with oral alprenolol, metoprolol or timolol. No patient had any known eye disorder. Topical administration of timolol induced a significant reduction of IOP regardless if the patients had systemic beta-blockade or not. Treatment with topical timolol alone was equally effective in reducing IOP as combined topical and oral therapy. Patient compliance was checked with plasma concentrations of the different beta-blockers.     

A follow-up study on the intraocular pressure response of timolol eye drops (author's transl)

In 22 open-angle glaucoma patients a total of 39 eyes were treated with Timolol 0.25% twice daily for an average period of 12.6 months. The relative intraocular pressure decrease at the beginning of the study was 47% of the untreated pressure level. This initial response declined to a 23% pressure decrease at the end of the study. In 8 eyes treatment had to be discontinued because of insufficient pressure control and in one patient because of subjective intolerance. In two patients (4 eyes) a complete loss of response of Timolol therapy was observed. The phenomenon of slowly diminishing drug effectiveness was not related to the untreated pressure levels in the patients covered by this study. In 5 eyes there was evidence of a rebound effect after discontinuation of Timolol therapy.     

Effects of short term increase of intraocular pressure on optic disc cupping

AIMS—To evaluate the effect of acute elevation of intraocular pressure (IOP) on optic disc cupping.
METHODS—10 emmetropic and 10 myopic volunteers were included in this study. The cup area (CA) and cup volume (CV) of the optic disc were determined with the Heidelberg retina tomograph (HRT). After baseline determinations, a suction cup was used to increase the intraocular pressure (IOP) to 20-25 mm Hg above the baseline and HRT images were obtained.
RESULTS—Baseline IOP was 13.5 (SD 1.3) mm Hg and 12.6 (2.6) mm Hg in the emmetropic and myopic groups, respectively. The IOP was elevated to 35.4 (3.3) mm Hg and 34.4 (2.5) mm Hg in the emmetropic and myopic groups, respectively. When compared with their baseline values, the cupping variables (CA and CV) were significantly increased (p<0.05) during the suction treatment in both emmetropic and myopic subjects.
CONCLUSION—There was a significant enlargement in the optic disc cupping during the artificial increment of intraocular pressure in both emmetropic and myopic eyes. In non-glaucomatous eyes the optic nerve head has a partially dynamic topography dependent upon the level of IOP.

Keywords: optic disc; intraocular pressure; compliance; glaucoma     

The effects of timolol on cataract extraction and intraocular pressure

We studied the effect of timolol on post-operative intraocular pressures (IOPs) in a control and experimental group of 30 eyes, each in patients who had uncomplicated intracapsular cataract extractions, most with iris clip lenses. Closure of the eye in each case was with three 6-0 silk sutures preplaced in a morticed incision. Six control eyes had IOP increases of 6 mm Hg or more within 24 hours of surgery. One patient treated with timolol had an IOP increase of 6 mm Hg or more. The differences in IOP between the control and experimental groups were statistically significant at the .01 level. The pressure lowering ability of timolol appears to be prophylactic as well as therapeutic. It is well suited for pseudophakic eyes as pressure reduction is not associated with pupillary alterations.     

曲伏前列素与噻吗洛尔降眼压效果的对比研究

目的观察曲伏前列素(苏为坦)降眼压(intraocular pressure,IOP)效果及安全性。方法以噻吗洛尔为对照采用随机、单盲、平行对照试验,选取原发性开角型青光眼、高IOP症和抗青光眼术后高IOP患者。试验组30例(30眼)滴用曲伏前列素滴眼液,每天1次;对照组20例(20眼)滴用噻吗洛尔滴眼液,每天2次,共观察4周。观察的指标包括IOP、视力、血压、脉搏、眼部症状和体征以及不良反应。结果曲伏前列素与噻吗洛尔相比昼夜降IOP效果稳定、持续降IOP效果恒定。曲伏前列素组有16例出现了结膜充血,有2例出现睫毛增粗增长,1例眼睑皮肤颜色增加,无其他明显不良反应。结论曲伏前列素滴眼液对控制IOP是有效、稳定和安全的,有望成为理想的一线抗青光眼药物。     

Long term effect on intraocular pressure of phacotrabeculectomy compared to trabeculectomy

AIM: To compare the long term mean intraocular pressure (IOP) reduction after non-augmented single site phacotrabeculectomy with that after trabeculectomy and to determine the relation between preoperative IOP and IOP reduction. METHODS: A group of 44 consecutive patients with chronic open angle glaucoma who underwent phacotrabeculectomy were matched to a trabeculectomy control group and the results of surgery were compared. Linear regression analysis of preoperative IOP and IOP reduction was undertaken. RESULTS: The mean IOP reduction was significantly less in the phacotrabeculectomy group (6.7 (SD 2.1) mm Hg) than in the trabeculectomy group (11.0 (1.4) mm Hg) (p=0.0017). There was a significant difference in surgical success between the groups. The preoperative IOP was significantly related to the postoperative reduction in IOP in both groups (p<0.001). CONCLUSIONS: In elderly white patients with chronic open angle glaucoma, phacotrabeculectomy is not as effective as trabeculectomy in reducing IOP. In both procedures the magnitude of IOP reduction is proportional to the preoperative IOP.     

Effects of timolol on intraocular pressure following ocular adrenergic denervation

The effects of timolol on the elevation of intraocular pressure induced by orogastric water-loading were studied in conscious pigmented rabbits which had undergone unilateral, superior cervical ganglionectomy. Each rabbit was studied without timolol treatment and with unilateral 2% timolol treatment, either to the innervated eye or to the denervated eye, 90 min before water-loading. Timolol, applied to the innervated eye, significantly reduced the elevation of intraocular pressure in that eye, but not in the fellow eye. Timolol, applied to the denervated eye, did not affect the elevated intraocular pressure in either the denervated or the fellow eye. These results demonstrate that ocular adrenergic innervation participates in the mechanism of ocular hypotensive action of timolol in water-loaded pigmented rabbits.     

Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure

PURPOSE: To compare the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure (IOP) in patients with ocular hypertension or early glaucomatous changes. DESIGN: Prospective, open-label, experimental study with crossover design. METHODS: Eighteen patients with ocular hypertension or early glaucomatous changes (aged 41 to 79 years) each received topical treatments with timolol (0.5% Timoptic-XE), latanoprost (0.005% Xalatan), and no IOP-lowering medication, for at least 4 weeks. Timolol was given once in the morning upon awakening and latanoprost once in the evening at bedtime. At the end of each treatment period, the patient was housed in a sleep laboratory for 24 hours and IOP was measured every 2 hours using a pneumatonometer. Measurements were taken sitting and supine during the 16-hour diurnal/wake period and only supine during the 8-hour nocturnal/sleep period. Mean diurnal and nocturnal IOP levels were compared among the treatments with timolol, latanoprost, and no medication. RESULTS: In the diurnal period, the mean IOP under the timolol or the latanoprost treatment was significantly less than the mean IOP under no medication in both the sitting and the supine positions. There was no statistical difference between the timolol and latanoprost treatments. In the nocturnal period, supine IOP with timolol treatment was not different from the supine IOP with no medication but was significantly higher than supine IOP with the latanoprost treatment. CONCLUSION: Although both once-daily timolol and latanoprost were effective in lowering IOP during the diurnal period, only latanoprost reduced IOP during the nocturnal period.     

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.     

Effect of topical brimonidine on intraocular pressure after small incision cataract surgery

PURPOSE: To evaluate the effect of brimonidine 0.2% on intraocular pressure (IOP) after small incision cataract surgery. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective randomized study comprised 80 eyes of 40 patients scheduled for small incision cataract surgery in both eyes. In each patient, 1 eye was randomly assigned to receive 1 drop of brimonidine 0.2% or no treatment (control) immediately after surgery. The fellow eye received the other assigned treatment. All patients had standardized surgery by the same surgeon with sodium hyaluronate 1%, a temporal 3.5 mm sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The IOP was measured preoperatively as well as 6 and 20 to 24 hours and 1 week postoperatively. RESULTS: Six hours after surgery, the mean increase in IOP was 4.7 mm Hg +/- 6.1 (SD) in the brimonidine group and 4.6 +/- 5.3 mm Hg in the control group. In each group, 17 eyes (43%) had an IOP increase of 5 mm Hg or more. Twenty to 24 hours after surgery, the mean increase in IOP was 1.5 +/- 4.2 mm Hg in the brimonidine group and 1.6 +/- 4.4 mm Hg in the control group. There were no statistically significant between-group differences at any measurement. CONCLUSIONS: In both groups, IOP significantly increased 6 hours and 20 to 24 hours after small incision cataract surgery. Brimonidine 0.2% failed to reduce the IOP increase observed after small incision cataract surgery.     

The effect of timolol eye drops on the intraocular pressure in simple glaucoma (author's transl)

The intraocular pressure response to timolol ophthalmic solution, a beta-adrenergic blocking agent, was tested in two groups of open angle glaucoma patients using the 0,1% and the 0,5% solution. The 0.5% concentration gave a mean IOP reduction of 13 mm Hg in 39 glaucomatous eyes, corresponding to 46% of the pretreatment pressure level. The 0,1% concentration resulted in an average pressure decrease of 11,5 mm Hg in 22 glaucomatous eyes, corresponding to 40% of the pretreatment pressure levels. With both solutions a reduction of the first day's response was noted after repeated administration of timolol. In all patients tested timolol was tolerated well subjectively and objectively without any side effects. Timolol did not affect blood pressure or pulse rate. Tear production was not reduced after topical application of timolol. Pupillary diameter and facility of outflow were not changed significantly under therapy. It is concluded, that timolol acts primarily by reduction of aqueous inflow. The advantages of timolol as antiglaucomatous drug not affecting visual functions like miotics are discussed.