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Aim The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods Subjects with OAG or OHT, on 0–3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12. Results A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study ( p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study ( p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased. Conclusion The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials. Trial Registration ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019).

Purpose A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. Methods Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% ( n = 49). IOP was measured at baseline, day 1–2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. Results Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint ( P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. Conclusion The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. Trial Registry ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Purpose    To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda ® ) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort ® ) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). Methods MERCURY-3 was a 6-month prospective, double–masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. Results Overall, 430 patients were randomized (NET/LAT, n  = 218; BIM/TIM, n  = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n  = 184; BIM/TIM, n  = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). Conclusions Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

•This study was necessitated to bridge this knowledge gap by systematically evaluating the effect of timolol in the sequential treatment of angle-closure crisis (AACC), aiming to provide clearer guidance for clinical treatment.•This study clarifies that timolol eye drops do not significantly enhance the success rate of AACC sequential treatment compared to placebo.•This study prompts a re-evaluation of treatment protocols for AACC, suggesting that reliance on timolol eye drops may need revision.•It highlights the potential for research into more effective treatments and could lead to changes in clinical practice, steering toward multimodal treatment strategies. To observe and compare the efficacy of timolol eye drops in sequential treatment of acute angle-closure crisis (AACC). In this prospective, randomized, double-blind case-control study, patients diagnosed with AACC at the Affiliated Hospital of Hebei University from April 2021 to October 2023 were continuously enrolled. The patient data were collected and randomly divided into timolol group (group A) and placebo group (group B). All patients were sequentially treated with drug therapy, anterior chamber paracentesis, and argon laser peripheral iridoplasty. The primary outcomes were decreased intraocular pressure (IOP), success rate, and treatment time. At 2 hours, 4 hours, and 6 hours after the start of treatment, the reduction in IOP in group A was 13.87 ± 13.85 mm Hg, 28.42 ± 12.87 mm Hg, and 35.69 ± 8.51 mm Hg, respectively, and the number of controlled eyes was 23 (29.87%), 51 (66.23%), and 71 (92.20%), respectively. The reduction in IOP in group B was 15.88 ± 14.95 mm Hg, 28.17 ± 13.63 mm Hg, and 33.90 ± 13.59 mm Hg, respectively, and the number of controlled eyes was 30 (36.59%), 58 (70.73%), and 75 (91.46%) eyes, respectively. Among patients whose crises were relieved, the times for AACC relief were 3.29 ± 1.31 hours in group A and 3.38 ± 1.34 hours in group B. There were no significant differences in IOP reduction, numbers of eyes remission, and times for AACC relief between the 2 groups at each point of sequential treatment (P > 0.05). In the sequential treatment of AACC, timolol is not helpful to improve the success rate of treatment.

In this study, we aimed to investigate the efficacy and safety of combined fractional carbon dioxide laser and topical timolol maleate 0.5% solution versus topical timolol maleate 0.5% solution alone in inflammatory acne. Thirty adult patients with inflammatory facial acne were randomized in this study. The patients received 3 biweekly sessions of fractional CO2 laser on one side of the face followed by topical timolol maleate ophthalmic solution 0.5% once daily for 7 days on both sides. Outcome was evaluated 2 weeks after the first session, 2 weeks after the last session, and 1 month after the last session by lesion count, erythema, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction. Side effects were also evaluated. Trial registration (IRB No. 417, 30/10/2023). At 2 weeks after the first session, there were insignificant differences between both sides regarding lesion count, erythema, hyperpigmentation, and qualitative global scarring grading ( p value = 0.8, 0.05, 0.7, 0.1 respectively). At 2 weeks after the last session, the erythema on the combined side was reduced by a mean of 0.2 ± 0.4 SD compared to timolol only side with significant difference between both sides ( p value = 0.03), while there were insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction ( p value = 0.1, 0.5, 0.8, 0.3 respectively). Recurrence was detected at one month after the last session. No side effects were reported. Combined fractional CO2 laser and topical timolol maleate 0.5% solution were significantly more effective than topical timolol maleate 0.5% solution alone in reduction of erythema of inflammatory facial acne in adolescent men with Fitzpatrick’s skin type III-IV at 2 weeks after 3 biweekly sessions with insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction. Further and larger studies are still needed.

Beta-blockers prevent variceal bleeding in patients with cirrhosis who already have esophageal varices. In this randomized, placebo-controlled trial, timolol (a nonselective beta-blocker) did not prevent esophageal varices in patients with cirrhosis who had portal hypertension. In this trial, timolol did not prevent esophageal varices in patients with cirrhosis who had portal hypertension. Nonselective beta-adrenergic blockers reduce portal pressure through a reduction in portal venous inflow 1 , 2 as a result of a decrease in cardiac output (β 1 -adrenergic blockade) and splanchnic blood flow (β 2 -adrenergic blockade). Randomized, controlled trials have demonstrated that nonselective beta-blockers prevent variceal hemorrhage in patients with varices. 3 Decreasing portal pressure at earlier stages may prevent gastroesophageal varices. In fact, an experimental study demonstrated that beta-blockers prevent the development of portosystemic collateral vessels. 4 Therefore, we conducted a study to evaluate the efficacy of nonselective beta-blockers in preventing gastroesophageal varices and to assess whether baseline and sequential measurements of . . .

Purpose To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). Study design Open-label, multicenter, Phase 3 study (NCT02822729). Methods Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16– < 22 mmHg (Group 1) or ≥ 22– ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients ( N  = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. Results Significant reductions in mean diurnal IOP from baseline occurred at every visit ( P  < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was −3.7 ± 0.3 mmHg (Group 1), −5.6 ± 0.5 mmHg (Group 2), and −8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. Conclusions In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia.

ObjectiveHalting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide.MethodsA single-centre, masked, prospective, placebo-controlled, crossover trial of 41 well-controlled open-angle glaucoma subjects with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination (DTFC) therapy was conducted. Subjects were randomized to preservative-free (PF) tafluprost and DTFC with either placebo or cyclosporine 0.1% drops for 6 months and were then crossed over to the opposite therapy. Oxford score of ocular staining was the primary outcome; osmolarity, matrix-metalloproteinase-9 (MMP-9) testing, tear film break-up time (TFBUT), meibomian gland dysfunction (MGD), punctum evaluation, adverse events and diurnal intraocular pressure (IOP) comprised secondary outcomes.ResultsGTR-OSD findings improved with PF therapy. At 6 months the triple PF with placebo group showed improvement compared to baseline in mean Oxford score (mean difference [MD]:−3.76; 95% confidence interval [CI]:−4.74 to −2.77; p < 0.001), osmolarity (MD:−21.93; 95%CI:−27.61 to −16.24 mOsm/l; p < 0.001), punctum stenosis (p = 0.008) and conjunctival hyperaemia (p < 0.001). Similar improvements occurred in the cyclosporine enhanced period, which also provided greater improvement in MMP-9 positivity (24 vs 66%; p < 0.001) and TFBUT (p = 0.022). The cyclosporine group was superior vs placebo in mean Oxford score (MD:−0.78; 95%CI:−1.40 to −0.15); p < 0.001), itchiness and objective adverse events (p = 0.034). Cyclosporine elicited more stinging vs placebo (63 vs 24%; p < 0.001). Both PF regimens reduced mean diurnal IOP more than preserved therapy (14.7 vs 15.9 mmHg; p < 0.001).ConclusionsChanging from preserved to PF glaucoma medications improves ocular surface health and IOP control. Topical cyclosporine 0.1% further reverses GTR-OSD.

Aim To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol 0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. Methods In this multicentre, randomised, parallel-group study, patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting differing regional regulatory requirements, included change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12, and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population. Results 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed statistically and clinically significant mean decreases from baseline in worse eye IOP and in average eye IOP at all follow-up time points (p<0.001). Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and equivalence to bimatoprost/timolol. Ocular adverse events were similar between treatment groups, with conjunctival hyperaemia being the most frequent. Most were mild or moderate in severity. Conclusions Bimatoprost/timolol PF demonstrated non-inferiority and equivalence in IOP lowering compared with bimatoprost/timolol, with no significant differences in safety and tolerability. Trial registration number NCT01177098.

Hereditary hemorrhagic telangiectasia is a rare vascular genetic disease. Epistaxis is the most frequent and disabling manifestation, and timolol appears to be a new therapeutic option as non-selective beta-blockers have in vitro and in vivo anti-angiogenic properties. Our main objective was to evaluate the efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. This study is a single-center, randomized, phase 2, double-blind placebo-controlled study with an allocation ratio of 1:1. It was proposed to patients with hereditary hemorrhagic telangiectasia monitored at the French Reference Center, and we included patients aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis. The treatment was self-administered by the patient with a posology of one spray (50 microL) of timolol 0.5% or placebo in each nostril twice a day for 28 consecutive days. The primary efficacy endpoint was mean monthly epistaxis duration, assessed by monitoring epistaxis grids. A total of 58 patients were randomized and treated. The baseline characteristics were similar in the 2 groups. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 26 patients receiving the drug in comparison with the placebo group (p = 0.54). Toxicity was low and no severe adverse events were reported. One limitation is that we included all HHT patients with nosebleeds and did not take into account history of nasal surgery or nasal crusts. Timolol, administered by nasal spray at a dose of 0.25 mg in each nostril twice a day for 28 consecutive days, did not improve epistaxis in patients with hereditary hemorrhagic telangiectasia at 4 months after the beginning of the treatment.