Timolol Drops Research Articles

Large ulcerated hemangioma treated with topical timolol drops

Infantile hemangiomas (IH) are the most common benign tumors of infancy and undergo spontaneous remission by about four to five years of age. Usually, only superficial and uncomplicated hemangiomas are treated by topical timolol while larger and complicated hemangiomas require oral propranolol or corticosteroids. Uncommonly reported in the literature is that even larger complicated IHs on low-risk sites can be treated with timolol drops locally. Our case is unique, as we treated a large ulcerated IH with oral and topical antibiotics and only topical timolol drops with rapid and complete resolution of symptoms.

An Investigation Comparing the Efficiency of Timolol 0.5% with Brimonidine 0.2% in Managing the Increase in Intraocular Pressure Subsequent to Nd-Yag Laser Capsulotomy

Objective: Conducting a comparison between the efficacy of Timolol 0.5% eye drops and Brimonidine 0.2% eye drops in managing the elevation of intraocular pressure post Nd-YAG laser capsulotomy. Study Design: Employed a randomized controlled trial. Methodology: The research involved 80 patients (one eye per patient) aged between 45 and 70, diagnosed with posterior capsular opacification scheduled for Nd-YAG laser capsulotomy at the Department of Ophthalmology, Mathuradas Mathur Hospital (Dr. S. N. M. C.) in Jodhpur. The patients were divided into two groups, X and Y, each consisting of 40 individuals. Baseline intraocular pressure was measured using an applanation tonometer before administering eye drops. Group X received a single drop of Timolol 0.5%, while group Y received a single drop of Brimonidine 0.2% one hour prior to capsulotomy. Intraocular pressure was recorded at 1 hour and 4 hours post the laser procedure. Results: Both groups comprised 40 patients each. The baseline IOP was 16±2.16 for group X and 15±2.56 for group Y. There was no statistically significant variance between the two groups in mean IOP changes at 1 hour following Nd-YAG laser capsulotomy. However, after 4 hours, the mean reduction in IOP was -1.54 mmHg for group X and -1.85 mmHg for group Y (p<0.5). Conclusion: Our study indicates that both Timolol 0.5% eye drops and Brimonidine 0.2% eye drops are similarly effective in controlling elevated intraocular pressure after Nd-YAG laser capsulotomy

Timolol 0.5% ophthalmic solution influences cardiac function in healthy cats.

The aim of this study was to ascertain the effect of a drop of timolol 0.5% ophthalmic solution on the systolic function of the left ventricle (LV) and left atrium (LA), and to confirm if timolol helped appraisal of diastolic function by reducing heart rate (HR) and separating the transmitral outflow waves from tissue Doppler imaging (TDI). A total of 41 client-owned healthy cats underwent two echocardiograms 20 mins apart. The timolol group (33 cats) received a drop of timolol solution after the first examination. Standard and speckle-tracking echocardiography evaluated the LV and LA function of both groups at the two time points evaluated. Timolol reduced HR (19%), and fractional shortening from LV (20.3%) and LA (16.6%). Septal S' decreased by 51% (from 7.7 to 5.2 cm/s) and lateral S' dropped by 43.1% (7.3 to 5.1 cm/s). Most longitudinal techniques did not change after timolol, including the mitral annular plane systolic excursion from the interventricular annulus, tricuspid annular plane systolic excursion, LV longitudinal strain and LV tissue motion annular displacement. The isovolumic relaxation time increased by 15.2% (from 54 to 64.6 ms), with most cats presenting this variable above the reference (>60 ms). Timolol did not support diastolic assessment, enabling evaluation in only 2/11 cats when using lateral TDI and 1/9 cats using septal TDI. Regarding side effects, miosis occurred in 18 cats (54.5%). Timolol reduced systolic function, decreasing standard echocardiographic variables. Regarding diastolic evaluation, although timolol decreased HR, it did not separate the mitral diastolic waves, as expected.

Traumatic Hyphema.

A 7-year-old boy presented to the emergency department (ED) with acute onset of left eye pain and blurry vision after accidentally shooting himself in the left eye with a Nerf gun. His examination was notable for an abnormal appearance of the left eye (Figure 1). There was no periorbital swelling, and extraocular movements were intact without diplopia. Visual acuity was 20/20 in the right eye and 20/40 in the left eye. He was diagnosed with traumatic hyphema. The patient was initially discharged from the ED and treated as an outpatient with cyclopentolate drops, timolol drops, and prednisolone acetate drops.

Evaluation of age, gender, prenatal characteristics, and treatment results of 380 babies with infantile hemangioma.

e22018 Background: Infantile hemangiomas' incidence is 5% & are locally proliferated vascular structures. Methods: Fourhundred cases were analyzed,380 are presented. Results: Majority pts dx between 0-3 mos(88.8%), females (64.5 %), 26.6% had preterm birth,21.8% lbw 2500g. Maternal characteristics 17.1% were > age35, 8.5% multipar, 61.5% multiple gestation. Placental anomaly in 5.5%, preeclampsia in 10.3%, gestational diabetes in 7%, intervention in pregnancy 4.9%, smoking 7.6%, hyperemesis 29.9%. Treatment modality was topical timolol drops in 41.9%, oral propranolol solution in 37.6%, wait&see group 13.5%,surgical excision in 5.6%. Conclusions: Hemangioma, a multifactorial disease, lbw is an important risk factor.Oral propranolol solution for the babies <1yr of age avoided the use of intralesional steroids. It is essential to treat the babies especially who have the risk of developing amblyopia or other functional/cosmetic sequelae.

How the tophic problems and the rubbing eye behavior may aggravate the presence of keratoconus in trisomy 21

AbstractPurposeDown syndrome is a congenital anomaly caused by non‐dislocation of chromosome 21. Ocular features in trisomy 21 patients, such as changes in corneal collagen composition as well as thinning predisposing to keratoconus are well appreciated. We present a case of unilateral acute corneal hydrops in a young adult with trisomy 21, and the management to prevent corneal perforation yielding a successful visual outcome.MethodA 20‐year‐old man presented in our emergency department due to sudden visual loss and severe left ocular pain. Visual acuity was 20/200 in the right eye, and finger counting in the left. Anterior segment examination revealed pigmented endothelial cells and endothelial cell count reduced to 2583 CD/mm2 in the right eye, as well as a very large central corneal leukoma and corneal ectasia in the right eye. Corneal topography confirmed the presence of an acute corneal hydrops in the left eye as well as milder keratoconus in the right.ResultsApart from topical steroid drops, oral acetazolamide and timolol drops were used to reduce the intraocular pressure on a decompensated cornea with reduced endothelial cell count. Penetrating keratoplasty was eventually necessary. Due to intolerance and insufficient patient ability to use form‐stable contact lenses, a cross‐linking procedure was performed to stabilize the right eye. Both surgeries lead to best‐corrected acuity of 20/50 OU without a need for additional contact lens correction. Surface issues related to trisomy 21 were addressed using topical lubricants.ConclusionIn the presented case, preexisting keratoconus, worsened by frequent eye rubbing of abnormal collagen composition corneas, permits transmission of mechanical forces to thinner exposed tissue, leading to acute hydrops. The extensive corneal tissue damage that occurred with stromal scarring left necessitates keratoplasty to successfully restore vision. This case highlights the need for preventive ophthalmic examinations in patients of trisomy 21 to rule out the presence of keratoconus. The timely application of lubricants, as well as anti‐histamines and mast cell stabilizers could reduce the eye rubbing behavior that aggravates corneal anomalies in such mentally handicapped individuals. This may reduce progression and eventual need for surgical interventions.

Interventions to slow progression of myopia in children.

Background Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such as retinal detachments, choroidal atrophy, cataracts and glaucoma. Interventions that have been explored to slow the progression of myopia include bifocal spectacles, cycloplegic drops, intraocular pressure-lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose of this review was to systematically assess the effectiveness of strategies to control progression of myopia in children.

Therapeutic Effects of Hab Shabyar on Open-Angle Glaucoma: A Double-Blinded, Randomized, Placebo-Controlled Trial.

Background: Open-angle glaucoma (OAG) is one of the leading causes of blindness worldwide. This study evaluates the therapeutic effects of hab shabyar in patients with open-angle glaucoma. Materials and Methods: In this clinical randomized controlled trial, 50 patients with OAG were randomized into two groups. The intervention group received a drop of timolol plus 500 mg of hab shabyar every 12 hours. The placebo group received a drop of timolol every 12 hours plus 500 mg of wheat germ as a placebo. The intraocular pressure in patients with OAG was measured in each group and compared before the intervention (t1), one month (t2), and two months (t3) after the intervention. Results: The mean decrease in intraocular pressure for the right eye on three times in the intervention group was statistically significant, but the mean decrease in the placebo group was not significant. Similar results were obtained for the left eye at t1 when compared to t3. The intervention group patients expressed more satisfaction changes than the placebo group (P≤0.001). Conclusion: Our study demonstrated that consumption of timolol plus hab shabyar instead of consuming timolol alone was probably more effective for reducing intraocular pressure in patients with OAG.

Therapeutic Effects of Hab Shabyar on Open-Angle Glaucoma: A Double-Blinded, Randomized, Placebo-Controlled Trial

Background: Open-angle glaucoma (OAG) is one of the leading causes of blindness worldwide. This study evaluates the therapeutic effects of hab shabyar in patients with open-angle glaucoma. Materials and Methods: In this clinical randomized controlled trial, 50 patients with OAG were randomized into two groups. The intervention group was received a drop of timolol plus 500 mg of hab shabyar every 12 hours. The placebo group was received a drop of timolol every 12 hours plus 500 mg of wheat germ as a placebo. The intraocular pressure in patients with OAG was measured in each group and compared at before the intervention (t1), one month (t2), and two months (t3) after the intervention. Results: The mean decrease in intraocular pressure for the right eye at three times in the intervention group was statistically significant, but the mean decrease in the placebo group was not significant. Similar results were obtained for the left eye at t1 when compared to t3. The patients in the intervention group expressed more satisfaction than the patients in the placebo group (P≤0.001). Conclusion: Our study demonstrated that consumption of timolol plus hab shabyar instead of consuming of timolol alone was probably more effective for reducing intraocular pressure in patients with OAG.[GMJ.2019;In press:e1218]

Therapeutic Effects of Hab Shabyar on Open-Angle Glaucoma: A Double-Blinded, Randomized, Placebo-Controlled Trial

Background: Open-angle glaucoma (OAG) is one of the leading causes of blindness worldwide. This study evaluates the therapeutic effects of hab shabyar in patients with open-angle glaucoma. Materials and Methods: In this clinical randomized controlled trial, 50 patients with OAG were randomized into two groups. The intervention group received a drop of timolol plus 500 mg of hab shabyar every 12 hours. The placebo group received a drop of timolol every 12 hours plus 500 mg of wheat germ as a placebo. The intraocular pressure in patients with OAG was measured in each group and compared before the intervention (t1), one month (t2), and two months (t3) after the intervention. Results: The mean decrease in intraocular pressure for the right eye on three times in the intervention group was statistically significant, but the mean decrease in the placebo group was not significant. Similar results were obtained for the left eye at t1 when compared to t3. The intervention group patients expressed more satisfaction changes than the placebo group (P≤0.001). Conclusion: Our study demonstrated that consumption of timolol plus hab shabyar instead of consuming timolol alone was probably more effective for reducing intraocular pressure in patients with OAG. [GMJ.2020;9:e1218]

A drug utilization study in glaucoma patients in ophthalmology out patient department in a tertiary care hospital

Background: According to World Health Organization (WHO) studies Glaucoma is a chronic progressive symptomatic disease that damages retinal cells and is one of the leading cause of preventable blindness worldwide. Availability of newer topical agents has modernized the management of glaucoma.Methods: A prospective observational study was carried out from August 2016 to December 2016 at ophthalmology Out Patient Department of L.G General Hospital, Ahmedabad by authours after the approval of the Institutional Ethics Committee.Results: Out of total 101 patients, 71 were males and 30 were females. Average age of patient is 54 years. Common variant of Glaucoma was Primary Open Angle Glaucoma in 57.4% of patients. Average number of drugs per prescription was 2 (45%). Most commonly used Fixed Dose Combination was Brimonidine +Timolol Drops which was used in 87 (86.1%) patients. Most commonly used adjuvant drug was Tab. Acetazolamide (60% of patients).Conclusions: Common variant of Glaucoma was Primary Open Angle Glaucoma in 57.4% of patients. Most commonly used Fixed Dose Combination was Brimonidine+Timolol Drops which was used in 87 (86.1%) patients and commonly used Single drug therapy is Tab. Acetazolamide in (60% of patients).

Effect of timolol maleate gel-forming solution on intraocular pressure, pupil diameter, and heart rate in normal and glaucomatous cats.

To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution (GFS) on intraocular pressure (IOP), pupil diameter (PD), and heart rate (HR) in normal cats and cats with feline primary congenital glaucoma (FCG). A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes (OU) every 2 h (PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma.

Effects of 0.5% Timolol Maleate Ophthalmic Solution on Heart Rate and Selected Echocardiographic Indices in Apparently Healthy Cats.

BackgroundEchocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta‐blocker used in glaucoma is safe and transiently decreases HR in clinical trials.HypothesisAdministration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects.AnimalsTwenty‐five apparently healthy cats.MethodsElectrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR.ResultsAcclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed (P < .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20, P = .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first‐degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats.Conclusions and clinical importanceOcular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function.

Paroxetine markedly increases plasma concentrations of ophthalmic timolol; CYP2D6 inhibitors may increase the risk of cardiovascular adverse effects of 0.5% timolol eye drops.

Although ophthalmic timolol is generally well tolerated, a significant fraction of topically administered timolol can be systemically absorbed. We investigated the effect of the strong CYP2D6 inhibitor paroxetine on the pharmacokinetics of timolol after ophthalmic administration. In a four-phase crossover study, 12 healthy volunteers ingested either paroxetine (20 mg) or placebo daily for 3 days. In phases 1-2, timolol 0.1% gel, and in phases 3-4, timolol 0.5% drops were administered to both eyes. Paroxetine increased the plasma concentrations of timolol with both timolol formulations to a similar degree. The geometric mean ratio (95% confidence interval) of timolol peak concentration was 1.53-fold (1.23-1.91) with 0.1% timolol and 1.49-fold (0.94-2.36) with 0.5% timolol, and that of timolol area under the plasma concentration-time curve (AUC) from time 0 to 12 hours was 1.61-fold (1.26- to 2.06-fold) and 1.78-fold (1.21-2.62), respectively. During paroxetine administration, six subjects on 0.5% timolol drops, but none on 0.1% timolol gel, had plasma timolol concentrations exceeding 0.7 ng/ml, which can cause systemic adverse effects in patients at risk. There was a positive correlation between the AUC from time 0 to 13 hours of paroxetine and the placebo phase AUC from time 0 to infinity of timolol after timolol 0.5% drops (P < 0.05), and a nonsignificant trend after timolol 0.1% gel, consistent with the role of CYP2D6 in the metabolism of both agents. In the orthostatic test, heart rate immediately after upright standing was significantly lower (P < 0.05) during the paroxetine phase than during the placebo phase at 1 and 3 hours after 0.5% timolol dosing. In conclusion, paroxetine and other CYP2D6 inhibitors can have a clinically important interaction with ophthalmic timolol, particularly when patients are using 0.5% timolol formulations.

Intraocular Pressure-reducing Effects of Latanoprost Versus Timolol in Chinese Patients With Chronic Angle-closure Glaucoma

To compare the efficacy and safety of latanoprost and timolol in Chinese patients with chronic angle-closure glaucoma (CACG), who had undergone laser or surgical peripheral iridotomy but who continued to experience elevated intraocular pressure (IOP) levels. This 8-week, randomized, open-label, parallel, active-controlled study was conducted at 4 sites in China. Subjects were 18 to 75 years of age; had primary, unilateral, or bilateral CACG with an IOP between 21 and 35 mm Hg inclusive at screening; and had undergone peripheral iridotomy at least 1 month before study entry. Subjects were randomized (1:1) to receive 1 drop of latanoprost 0.005% (PM) or 1 drop of timolol 0.5% twice daily (AM and PM). Follow-up was at weeks 1, 2, 4, and 8. Primary efficacy endpoint: change in average IOP from baseline to week 8. One hundred forty-two subjects were randomized into the latanoprost and timolol group; the analysis population included 141 subjects (latanoprost, n=71; timolol, n=70). Mean baseline average IOP levels were 24 mm Hg in both groups. The least square mean change from baseline to week 8 was -6.7 mm Hg for latanoprost versus -4.9 mm Hg for timolol [least square mean difference=1.8 mm Hg (95% confidence interval, 0.7-2.9); P<0.001]. Latanoprost was associated with significantly lower mean average IOP levels at each visit (P<0.05). Both treatments were well tolerated and no treatment-emergent adverse event was considered by investigators to be severe. Once-daily administration of latanoprost 0.005% was significantly more effective in reducing IOP in Chinese patients with CACG than twice-daily instillation of timolol 0.5%. Both agents were well tolerated.

Treatment of superficial infantile hemangiomas with timolol: Evaluation of short-term efficacy and safety in infants

Timolol has been demonstrated to be efficacious in the topical treatment of superficial infantile hemangiomas (IHs). We conducted a prospective study to evaluate the short-term efficacy and safety of timolol in the treatment of superficial IH in Chinese infants. From March to November 2012, 124 patients with superficial IHs were included in the prospective study. The patients were divided into two groups: treatment (101 patients, the timolol drops were administered on the surface of the lesions three times daily, and erythromycin ointment was applied around the lesions) and observation (23 patients, without treatment). The results were categorized into three grades: class 1 (ineffective), class 2 (controlled growth) and class 3 (promoted regression). Within one week of the initiation of timolol treatment, a number of the lesions became softer and lighter in color. Four months following the initiation of timolol treatment, the overall response was class 1 in eight patients (7.9%), class 2 in 36 patients (35.6%) and class 3 in 57 patients (56.4%). Complete tumor regression was observed in 12 patients. No adverse effects were recorded during the treatment period. Among the patients in the observation group, there were 15 class 1 patients (65.2%), seven class 2 patients (30.4%) and only one class 3 patient (4.3%). In conclusion, timolol is an effective and safe treatment for superficial IH. In addition, it may be used in the treatment of proliferative superficial IH, particularly in infants within 6 months of age.

Topical timolol for the treatment of epistaxis in hereditary hemorrhagic telangiectasia

Epistaxis is the most common problem affecting patients with hereditary hemorrhagic telangiectasia (HHT). Approximately 90% of patients with HHT experience epistaxis that can range in severity from a social nuisance to lifethreatening hemorrhages. Until recently, the treatment of significant epistaxis in these patients consisted of surgery. Surgical options have included laser photocoagulation, septal dermoplasty, and modified Young's procedure [1]. Recently, the vascular endothelial growth factor (VEGF) inhibitor bevacizumab has shown promise as a medical treatment for HHT-related epistaxis [2]. Propranolol is a nonselective β-blocker that has been shown to be useful for the treatment of infantile hemangiomas [3]. Timolol is also a nonselective β-blocker and is commonly used in the treatment of glaucoma. It has been used topically for the treatment of superficial hemangiomas [4]. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis related to HHT. This report describes a case of epistaxis in a patient with HHT that was improved with the use of topical timolol drops. A 48-year-old man with a known diagnosis of HHT presented with frequent epistaxis. His past treatment had included nasal cauterization with silver nitrate as a child and topical bevacizumab. His epistaxis had improved after topical bevacizumab on several occasions. The effect would last for several months with retreatment needed when the nosebleeds became more frequent. Six months after his last treatment, he was experiencing 3 to 4 nosebleeds a day. Some would last for more than 30 minutes. It was decided to try topical timolol at that time. He began using timolol 0.5% ophthalmic solution and placed 1 drop in each nostril 3 times a day. Within 3 to 4 days, he noticed a significant reduction in the frequency and severity of his epistaxis. A month after the initiation of treatment, his nosebleeds had decreased to an average of 1 to 2 per week, and they lasted less than 5 minutes when they occurred. There was no change in blood pressure or heart rate during the treatment. Topical timolol has been used to treat superficial hemangiomas in infants. The mechanism of action of βblockers in the treatment of hemangiomas is currently unknown but may be related to vasoconstriction, endothelial cell apoptosis, and decreased VEGF expression [5]. Vascular endothelial growth factor levels have been shown to be elevated in patients with HHT and may play a role in the development of nasal telangiectasia [6]. Therefore, it was theorized that timolol could be a viable option in the treatment of epistaxis in patients with HHT. The patient described in this report had both a rapid and persistent response to treatment as is seen in infants with hemangiomas that are treated with β-blockers. The initial response may be secondary to the vasoconstrictive properties of timolol. The longer term effect may be due to endothelial cell apoptosis as well as decreased VEGF expression. The potential advantage of topical timolol compared with bevacizumab includes greater availability of the medication without the need for compounding, ease of application, and decreased cost. Although this is a single case report, the results are encouraging, and further study will allow a greater understanding of the potential use of topical β-blockers in this patient population.

Dyspnea on Exertion and Ground-Glass Infiltrates in an Ex-Smoker

Dyspnea on Exertion and Ground-Glass Infiltrates in an Ex-Smoker

Changing Antiglaucoma Therapy from Timolol to Betaxolol: Effect on Ocular Blood Flow

The aim of the present study was to investigate the effect of a therapy change from timolol to betaxolol on ocular blood flow in patients with open-angle glaucoma. This randomized double-blind study comprised 34 consecutive patients with open-angle glaucoma, already treated with either timolol alone or in combination with other antiglaucoma agents. The patients were randomly allocated to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Ocular blood flow measurement as well as systemic hemodynamic and intraocular pressure (IOP) measurements were performed at baseline and 1 week and 1 and 3 months after the therapy change. Visual field testing was performed at baseline and at 3 months. After 3 months of treatment with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal blood flow were significantly altered. The power to detect a 9% change in pulsatile choroidal blood flow and a 20% change in retinal blood flow in the present study was 90%. The IOP was not significantly altered in either group. In contrast, visual fields slightly improved after betaxolol treatment compared to baseline (p = 0.047), but this effect was not significant versus timolol. Changing therapy from timolol to betaxolol has no effect on ocular blood flow in patients with open-angle glaucoma.

Timolol concentrations in rat ocular tissues and plasma after topical and intraperitoneal dosing.

Topical beta-blockers, such as timolol, have been used extensively in the medical treatment of glaucoma to lower intraocular pressure (IOP). Recently, these drugs have been shown to have effects on the retinal and optic nerve circulation as well as potential neuroprotective properties. In the current study, the concentration of timolol attained in the cornea, iris-ciliary body, retina, vitreous, and plasma was measured after topical or intraperitoneal administration in rats to determine the relative contributions of each route to intraocular timolol concentrations. One group of rats received one drop of commercially available 0.5% timolol in the right eye and two drops in the left eye for 3 to 12 days. Another group of rats received one drop of 0.5% timolol in one eye only and concentrations were studied in the ocular tissues at 15, 30, 60, 120, and 240 minutes after instillation. The final group of rats received a single intraperitoneal injection of timolol ranging in concentration from 5 to 75 mg/kg after which tissue and plasma concentrations were measured 30 minutes after injection. All tissue and plasma concentrations were measured by high performance liquid chromatography. Rats that received topical timolol daily for 3 to 12 consecutive days accumulated timolol concentrations of 2.3 to 4.4 microg/g in cornea, 198 to 326 microg/g in iris, 0.05 to 0.11 microg/ml in vitreous, and 0.17 to 0.77 microg/g in retina. In rats that received a single drop of timolol in one eye, the tissue concentrations were higher in the treated eye than in the untreated eye in all cases except for vitreous. In these experiments, timolol levels in plasma were either low or not detectable. Increasing timolol doses administered intraperitoneally resulted in corresponding increased tissue and plasma concentrations. Absorption of drug into the systemic circulation plays a significant role in delivering timolol to the retina and vitreous in addition to a local ocular route. A clear dose-response relationship exists in all ocular tissues studied after an intraperitoneal dose of timolol. High doses of timolol were required to achieve measurable concentrations of drug in the ocular tissues via our high performance liquid chromatography assay suggesting that a significant hepatic first-pass effect may be involved after an intraperitoneal injection of timolol.