Topical timolol for treatment of persistent granulation tissue in the setting of severe hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a potentially debilitating dermatological disease that negatively impacts patients' quality of life. Severe cases can be further complicated by persistent granulation tissue at the ostia of sinus tracts, which may prove recalcitrant to standard interventions. Herein we report such a case in which a patient experienced significant improvement from severe HS but was left with persistent granulation tissue that complicated his course of recovery. When standard interventions failed, we elected to begin treatment with topical timolol. After three months, the majority of the granulation tissue had regressed and has remained quiescent after 12 months of follow up. The patient has tolerated the treatment well and continues to use topical timolol daily as needed for flares. We believe that topical timolol can provide a practical and painless alternative to current invasive and expensive therapies for persistent granulation tissue associated with severe HS

Pharmacogenetics of ophthalmic topical β-blockers

Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications of polymorphisms in CYP2D6 are also discussed. Although the candidate-gene approach has facilitated significant progress in our understanding of the genetic basis of glaucoma treatment response, most drug responses involve a large number of genes, each containing multiple polymorphisms. Genome-wide association studies may yield a more comprehensive set of polymorphisms associated with glaucoma outcomes. An understanding of the genetic mechanisms associated with variability in individual responses to topical β-blockers may advance individualized treatment at a lower cost

Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.

BACKGROUND: Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown. METHODS: We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly. RESULTS: During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year. CONCLUSIONS: Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.

A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine

Introduction. Daily oral beta-adrenoreceptor antagonist has been shown to be effective in preventing migraine headaches. Timolol 0.5% ophthalmic solution is a non-selective beta-adrenoreceptor antago- nist, where the primary use is for glaucoma. There have been case reports that timolol is effective in aborting or improving an acute migraine headache. The objective of this study was to assess the efficacy (decrease of ≥ 50% in pain scale at 120 minutes) of timolol 0.5% ophthalmic solution compared to placebo in acute treatment of migraine headache. Methods.We performed a randomized, double-blind, crossover, placebo-controlled, study. Study entry criteria required subjects to have one to eight migraine episodes per month. The primary outcome was comparison of the change in a visual analog pain scale (VAS) at 120 minutes after taking the study medication. Study subjects were given a pain scale with a range of 1 (no pain) to 10 (most severe pain) to complete after onset of migraine but before administration of study drops and 120 minutes after administration of study drops. Improve- ment was defined as a ≥ 50% decrease in pain scale. Results. Nineteen subjects completed the study and were used for analysis. The primary outcome changes in pain scale, 120 minutes after dose, showed a similar decrease for placebo and drug with a slightly wider 95% CI for placebo. Six subjects in each arm experi- enced a ≥ 50% decrease in pain scale. Conclusion. These results support that timolol 0.5% ophthalmic solution is not an efficacious treatment for acute migraine headache

Role of fixed-combination brinzolamide 1%/timolol 0.5% in the treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension

Brinzolamide 1%/timolol 0.5% is a new fixed-combination for the treatment of open-angle glaucoma or ocular hypertension. Brinzolamide/timolol has a favorable safety profile, with an incidence of ocular burning and stinging <5%. Published data show that brinzolamide 1%/timolol 0.5% and dorzolamide 2%/timolol 0.5% have similar efficacies for lowering intraocular pressure (IOP). There is some evidence that brinzolamide/timolol may be more comfortable. Although patients receiving brinzolamide/timolol may experience more blurred vision on instillation, some data show a preference for brinzolamide/timolol over dorzolamide/timolol. Although available data to assess the role of brinzolamide/timolol in daily clinical practice are still limited, these first results suggest the agent to be a reasonable alternative for patients who do not reach target IOP with monotherapy

A Study of the Safety and Efficacy of Travoprost 0.004%/Timolol 0.5% Ophthalmic Solution Compared to Latanoprost 0.005% and Timolol 0.5% Dosed Concomitantly in Patients with Open-Angle Glaucoma or Ocular Hypertension

Background/Aims: To compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% in fixed combination with the unfixed combination of latanoprost 0.005% and timolol 0.5% in open-angle glaucoma or ocular hypertension patients with IOP levels below 18 mmHg on the unfixed combination of latanoprost 0.005% and timolol 0.5%. Methods: Following a 30-day open-label run-in with latanoprost QD PM and timolol QD AM, subjects with intraocular pressure below 18 mmHg were randomized to continue concomitant latanoprost QD PM and timolol QD AM or switch to travoprost 0.004%/timolol 0.5% QD AM and vehicle QD PM in masked fashion and were followed for 3 months. The primary efficacy endpoint was mean IOP reduction from baseline. Results: There were no clinically relevant or statistically significant differences in mean IOP, mean IOP change from baseline, or percentage IOP change from baseline between the two treatment groups. Between-group differences in mean IOP were within ±0.3 mmHg at all time points (p ≥ 0.384), and between-group differences in mean IOP change from baseline were within ±0.4 mmHg at all time points. Overall, 88% of patients whose IOP was less than 18 mmHg on the unfixed combination of latanoprost and timolol remained well controlled on the same regimen in the masked portion of the study, compared with 92% who remained well controlled after switching to travoprost/timolol. Conclusion: Travoprost 0.004%/timolol 0.5% administered once daily and concomitant administration of timolol 0.5% and latanoprost 0.005% produce similar maintenance of IOP-lowering effect in patients who were previously well controlled on concomitant administration of latanoprost and timolol. Patients who are well controlled on latanoprost and timolol concomitant therapy can be switched to once-daily therapy with travoprost 0.004%/timolol 0.5% with no expected compromise in the safety and efficacy of their treatment

A COMPARATIVE STUDY OF DORZOLAMIDE + TIMOLOL VS. BRIMONIDINE + TIMOLOL FIXED COMBINATION THERAPY IN THE MANAGEMENT OF PRIMARY OPEN ANGLE GLAUCOMA

Background:&nbsp;To compare the efficiency of dorzolamide + timolol fixed combination vs. the Brimonidine + timolol fixed combination in the management of primary open-angle glaucoma&nbsp;Materials and methods: A prospective study conducted over a period of 6 months with a total of 69 patients having primary open angle glaucoma (POAG) who completed a follow up of 6 months at a tertiary care hospital. Detailed history of the patient was obtained and patients were assessed for best corrected visual acuity, base line IOP with Goldmann applanation tonometer and detailed anterior and posterior segment examination. They were categorized into two groups according to the combinations prescribed by the ophthalmologist as follow: group 1-dorzolamide+timolol and group 2-brimonidine+timolol. A follow up evaluation of each patient was done at 1, 3 and 6 months after baseline visit.&nbsp;Results:&nbsp;During our study the baseline IOP for dorzolamide + timolol group was 25.7 ±4.25 mm Hg and for brimonidine + timolol group was 26.3 ±5.86 mm Hg. During 6 months treatment, the mean reduction in IOP was 7.83 mm Hg (29.4%) in dorzolamide + timolol group and 9.39 mm Hg (35.6%) in brimonidine + timolol group.&nbsp;Conclusion:&nbsp;Our study showed that brimonidine + timolol combination has superiority over dorzolamide + timolol to reduce the IOP in newly diagnosed patients with POAG The value of IOP reduction in our study in brimonidine + timolol group was 9.39 mm Hg (35.6%) and 7.83 mm Hg (29.4%) in dorzolamide + timolol group. KEYWORDS:&nbsp;Primary open angle glaucoma, brimonidine, timolol, dorzolamide

A COMPARATIVE STUDY OF DORZOLAMIDE + TIMOLOL VS. BRIMONIDINE + TIMOLOL FIXED COMBINATION THERAPY IN THE MANAGEMENT OF PRIMARY OPEN ANGLE GLAUCOMA

Background:&nbsp;To compare the efficiency of dorzolamide + timolol fixed combination vs. the Brimonidine + timolol fixed combination in the management of primary open-angle glaucoma&nbsp;Materials and methods: A prospective study conducted over a period of 6 months with a total of 69 patients having primary open angle glaucoma (POAG) who completed a follow up of 6 months at a tertiary care hospital. Detailed history of the patient was obtained and patients were assessed for best corrected visual acuity, base line IOP with Goldmann applanation tonometer and detailed anterior and posterior segment examination. They were categorized into two groups according to the combinations prescribed by the ophthalmologist as follow: group 1-dorzolamide+timolol and group 2-brimonidine+timolol. A follow up evaluation of each patient was done at 1, 3 and 6 months after baseline visit.&nbsp;Results:&nbsp;During our study the baseline IOP for dorzolamide + timolol group was 25.7 ±4.25 mm Hg and for brimonidine + timolol group was 26.3 ±5.86 mm Hg. During 6 months treatment, the mean reduction in IOP was 7.83 mm Hg (29.4%) in dorzolamide + timolol group and 9.39 mm Hg (35.6%) in brimonidine + timolol group.&nbsp;Conclusion:&nbsp;Our study showed that brimonidine + timolol combination has superiority over dorzolamide + timolol to reduce the IOP in newly diagnosed patients with POAG The value of IOP reduction in our study in brimonidine + timolol group was 9.39 mm Hg (35.6%) and 7.83 mm Hg (29.4%) in dorzolamide + timolol group. KEYWORDS:&nbsp;Primary open angle glaucoma, brimonidine, timolol, dorzolamide

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Purpose: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. Methods: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Results: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg ± 0.23) than in the dorzolamide/timolol group (17.3 mmHg ± 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. Conclusions: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.publishersversionPeer reviewe

Current Knowledge and Attitudes Concerning Cost-Effectiveness in Glaucoma Pharmacotherapy: A Glaucoma Specialists Focus Group Study.

Background:Rising healthcare costs motivate continued cost-reduction efforts. To help lower costs associated with open-angle glaucoma (OAG), a prevalent, progressive disease with substantial direct and indirect costs, clinicians need to understand the cost-effectiveness of intraocular pressure (IOP)-lowering pharmacotherapies. There is little published information on clinicians' knowledge and attitudes about cost-effectiveness in glaucoma treatment. Purpose:This pilot focus group study aimed to explore clinician attitudes and perspectives around the costs and cost drivers of glaucoma therapy; the implementation of cost-effectiveness decisions; the clinical utility of cost-effectiveness studies; and the cost-effectiveness of available treatments. Methods:Six US glaucoma specialists participated in two separate teleconferencing sessions (three participants each), managed by an independent, skilled moderator (also a glaucoma specialist) using a discussion guide. Participants reviewed recent publications (n=25) on health economics outcomes research in glaucoma prior to the sessions. Results:Participants demonstrated a clear understanding of the economic burden of glaucoma therapy and identified medications, diagnostics, office visits, and treatment changes as key cost drivers. They considered cost-effectiveness an appropriate component of treatment decision-making but identified the need for additional data to inform these decisions. Participants indicated that there were only a few recent studies on health economics outcomes in glaucoma which evaluate parameters important to patient care, such as quality of life and medication adherence, and that longitudinal data were scant. In addition to efficacy, participants felt patient adherence and side-effect profile should be included in economic evaluations of glaucoma pharmacotherapy. Recently approved medications were evaluated in this context. Conclusion:Clinicians deem treatment decisions based on cost-effectiveness data as clinically appropriate. Newer IOP-lowering therapies with potentially greater efficacy and favorable side-effect and adherence profiles may help optimize cost-effectiveness. Future studies should include: clinicians' perspectives; lack of commercial bias; analysis of long-term outcomes/costs; more comprehensive parameters; real-world (including quality-of-life) data; and a robust Markov model