Effects of D-Timolol and L-Timolol on Ocular Blood Flow and Intraocular Pressure
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Effects of D-timolol and L-timolol on IOP were compared with two rabbit models. When the drug solution was injected into vortex vein, 1% D-timolol produced ocular hypotension just like 0.5% L-timolol except D-timolol was less potent than L-timolol to lower the IOP. On the other hand, when 0.5% of D-timolol and L-timolol were instilled into the rabbit eye on IOP recovery model both agents showed equipotency to delayed the IOP recovery. Effects of D-timolol and L-timolol on ocular blood flow were also studied with two rabbit models. D-Timolol at 0.5% did not affect the ocular pulsatile blood flow measured with Langham's pneumatonometer whereas 0.5% L-timolol significantly suppressed it. D-Timolol (0.5%) was found to increase retinal and choroidal blood flows measured with laser Doppler method whereas L-timolol suppressed it. These results indicate that D-timolol though less potent than L-timolol to lower IOP, is superior over L-timolol to improve the blood flow in retina and choroid.Cite
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The intraocular pressure lowering effect in 30 patients with raised intraocular pressure and open angles following a single application in a randomised double-masked fashion of four concentrations of D-timolol (0.25%, 0.5%, 1.0%, and 2.0%), 0.25% L-timolol, and placebo are presented. The percentage reduction in intraocular pressure after four hours following single-drop instillation range from 20% to 25% in the D-timolol group, 32% in the L-timolol group, and only 8% in the placebo group of treated eyes.
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Argon laser iridotomy was performed in 123 eyes of 83 patients with primary angle-closure glaucoma. Sixty-three eyes received argon laser iridotomies with timolol pretreatment and the other 60 eyes served as controls. There were 43 eyes (71.7%) in the control group and 32 eyes (50.7%) in the timolol-pretreated group, whose intraocular pressure increased significantly over baseline level 2 hours after laser treatment. There was statistical difference in the incidence of intraocular pressure elevation in these two groups. Seven eyes (11.7%) in the control group and 4 eyes (6.2%) in the timolol-pretreated group had intraocular pressure elevation at least 11 mmHg over baseline. Additional 28 patients, who received argon laser iridotomy bilaterally, one eye with timolol pretreatment and the other eye served as a matched control, revealed that eyes which were timolol pretreated had statistically significant less intraocular pressure elevation.
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Administration of timolol to one eye is associated with a decrease in intraocular pressure in both eyes. To further investigate this effect the contralateral decrease in intraocular pressure was measured in a three arm crossover study using a 0.1 mg dose of timolol given topically to an eye, a 0.1 mg dose of timolol given lingually, and a placebo given topically. Two hours after topical timolol administration the mean intraocular pressure reduction in the fellow eye was 3.1 mm Hg compared with baseline (p = 0.0007). Two hours after lingual timolol administration the mean intraocular pressure reduction was 3.9 mm Hg compared with baseline (p = 0.0004). Two hours after topical administration of placebo the mean intraocular pressure reduction in the fellow eye was only 0.33 mm Hg (p = 0.6). These findings suggest the contralateral reduction in intraocular pressure from timolol is caused by systemic absorption. The significant intraocular pressure reduction obtained from lingual timolol raises the possibility that this route of drug administration may be useful in selected patients who cannot use eye drops.
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To report the change over time in intraocular pressure in patients treated with topical timolol or placebo.Ninety patients with untreated ocular hypertension, defined as elevated intraocular pressure and normal visual fields, were randomly assigned to treatment and prospectively observed at 3-month intervals for up to 10 years in a double-masked fashion. The study end point was one eye showing reproducible glaucomatous field defects; patients were also withdrawn if one eye showed intraocular pressure of 35 mm Hg or higher. For each treatment group and visit, the mean and median of all intraocular pressure measurements were calculated. Medians were also calculated for the timolol group, assuming a worst-case scenario in which all patients who reached the end point, or intraocular pressure of 35 mm Hg or more, were assumed to show higher intraocular pressure than those remaining in the study. Distributions of slopes for intraocular pressure over time were compared between treatment groups.Means and medians of follow-up intraocular pressure over time did not differ between timolol- and placebo-treated patients. This was also true when assuming a worst-case scenario. Slopes of intraocular pressure over time did not differ statistically between treatment groups.In agreement with other masked and controlled studies and in conflict with uncontrolled ones, the present study did not demonstrate long-term drift of intraocular pressure in patients with ocular hypertension treated with topical timolol.
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The timolol gel was developed for the simplification of multi-dose medications for glaucoma patients. This gel can be used once per day instead of twice per day of the aqueous form. It is necessary to understand the clinical effects of intraocular pressure maintained in glaucoma by there two forms of timolol.Fifty-two eligible patients were included and completed the 12-week study. In this randomized, open-label, two-period crossover study design, patients received either the gel form of 0.5% timolol once daily or the aqueous form of 0.5% timolol twice daily for the first 6 weeks, then crossed over to the other treatment form for the remaining 6 weeks. Intraocular pressure was measured at baseline, week 6 and week 12 at the end of the treatment period. The incidences of all the adverse events were recorded and summarized in each follow-up visit.No statistically significant difference in intraocular pressure was observed between the two different control treatment groups (p>0.05). However, stickiness and transient blurred vision was reported more often by patients using the gel form than the aqueous form of timolol.The gel form of 0.5% timolol used once daily offers a new alternative that is probably more convenient than the aqueous form of 0.5% timolol given twice daily in maintaining the intraocular pressure of patients with glaucoma.
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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.
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