Dataset Information

Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews.

ABSTRACT:

Aim

To evaluate the existing evidence on relative efficacy and tolerability of topical mono-compound intraocular pressure (IOP)-lowering drugs in treatment of primary open angle glaucoma (POAG) and ocular hypertension (OHT).

Methods

In this systematic review of systematic reviews/meta-analyses of randomized controlled trials a thorough and sensitive search of PubMed, Embase and Cochrane Databases was performed. Individual study methodological quality and quality of evidence were assessed using the AMSTAR checklist and the GRADE system, respectively. The relationships between individual drugs were evaluated based on the best available evidence.

Results

Of the 133 initial non-duplicate records, 16 studies met the inclusion criteria. Five achieved an overall "moderate" (none achieved "high") quality of evidence and evaluated prostaglandin analogues (PGAs) - latanoprost, travoprost, and bimatoprost; timolol; "other beta-blockers;" carbonic anhydrase inhibitors (CAI) as a group or dorzolamide separately; and brimonidine. "Moderate quality" refers to efficacy and incidence of conjunctival hyperemia. Quality of evidence regarding other tolerability aspects was low. PGAs should be considered equivalent regarding efficacy, but latanoprost was relevantly better tolerated than the other two. Non-PGA compounds did not relevantly differ between each other in either efficacy or safety. Timolol and brimonidine were relevantly less effective than all PGAs. The same was true for CAI vs bimatoprost. Regarding tolerability, timolol was superior to all PGAs and brimonidine and CAI were superior to bimatoprost.

Conclusion

No high quality evidence on relative efficacy and tolerability of the most commonly used mono-compound IOP-lowering drugs for POAG/OHT exists. Moderate quality evidence indicates latanoprost as a treatment with the most favorable trade-off between benefits and harms.

SUBMITTER: Daka Q

PROVIDER: S-EPMC4228301 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews.

Daka Qëndresë Q Trkulja Vladimir V

Croatian medical journal 20141001 5

<h4>Aim</h4>To evaluate the existing evidence on relative efficacy and tolerability of topical mono-compound intraocular pressure (IOP)-lowering drugs in treatment of primary open angle glaucoma (POAG) and ocular hypertension (OHT).<h4>Methods</h4>In this systematic review of systematic reviews/meta-analyses of randomized controlled trials a thorough and sensitive search of PubMed, Embase and Cochrane Databases was performed. Individual study methodological quality and quality of evidence were a ...[more]

PMID: 25358880

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Project description:ImportanceGlaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients.ObjectiveTo summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews.Data sourcesThe Cochrane Database of Systematic Reviews including studies published before June 1, 2021.Study selectionReviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy.Data extraction and synthesisData were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted.Main outcomes and measuresThe proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up.ResultsSix eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results.Conclusions and relevanceBased on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.

Project description:Medications to control intraocular pressure (IOP) are frequently preserved using benzalkonium chloride (BAK), which can negatively affect the ocular surface. Data are needed to assess efficacy and safety of prostaglandin drugs preserved with and without BAK. The present study compared the efficacy and safety of BAK-free travoprost 0.004% (TRAV) and BAK 0.02%-preserved bimatoprost 0.01% (BIM) during late-day time points in patients with open-angle glaucoma or ocular hypertension.This was a 12-week, phase 4, randomized, investigator-masked, crossover study. 84 patients with IOP ?24 and <36 mmHg were randomized 1:1 to receive once-daily TRAV or BIM for 6 weeks followed by an additional 6-week crossover period. IOP was measured at the end of each treatment period at 4, 6, and 8 pm. TRAV was considered noninferior to BIM if the upper limit of the 95% CI of the between-group difference in mean IOP was ?1.5 mmHg. Adverse events were assessed throughout the study.One patient discontinued due to allergic conjunctivitis, and 2 patients with missing data were excluded; 81 patients were included in the per-protocol population (mean ± SD age, 58.3 ± 11.4 years; TRAV/BIM, n = 41; BIM/TRAV, n = 40). After 6 weeks, mean IOP with TRAV (17.4 ± 2.7 mmHg; change from baseline, -6.0 mmHg) was similar to BIM (17.2 ± 2.6 mmHg; change from baseline, -6.3 mmHg); the between-group difference was 0.22 mmHg (95% CI, -0.22 to 0.67). Thus, noninferiority of TRAV versus BIM was demonstrated. Mean IOP at each time point and mean and percentage IOP change from baseline were not significantly different between treatments. All treatment-emergent adverse events were mild to moderate. The incidences of mild ocular hyperemia with TRAV and BIM were 31% and 39%, respectively; moderate hyperemia was observed in 2% of patients receiving BIM.Late-day IOP-lowering efficacy of BAK-free TRAV was noninferior to that of BAK 0.02%-preserved BIM; both reduced baseline IOP by 25%. Both treatments were well tolerated, although a higher incidence of moderate ocular hyperemia was observed with BIM.ClinicalTrials.gov identifier, NCT01464424; registered November 1, 2011.

Project description:IntroductionPharmacotherapy to lower intraocular pressure (IOP) is a mainstay of treatment aimed at delaying progression of visual field loss in ocular hypertension (OHT) and open-angle glaucoma (OAG), but some topical treatments are less effective in controlling IOP at night. Peak IOP may be related to glaucoma progression and can occur outside office hours. A phase 2 study was conducted to evaluate the IOP-lowering efficacy of netarsudil across the diurnal and nocturnal periods.MethodsThis was a randomized, double-masked, single-center, vehicle-controlled, 9-day study. After washout of any prior ocular hypotensive agents, 12 patients with OHT or OAG underwent baseline IOP assessment at 15:00, 18:00, 21:00, 00:00, 03:00, 06:00, 09:00, and 12:00 h on day 1/day 2. Participants were then randomized in a 2:1 ratio to netarsudil ophthalmic solution 0.02% (n = 8) or vehicle (n = 4) for 7 days of self-administered dosing each evening. IOP was assessed at the same time points on day 8/day 9. All measurements were conducted with a Perkins tonometer in habitual positions by day (seated) and at night (supine).ResultsBaseline mean 24-h IOP was 22.4 mmHg in the netarsudil group and 22.9 mmHg in the vehicle group. Netarsudil was associated with a reduction in mean nocturnal IOP (measurements at 21:00, 00:00, 03:00, 06:00 h) of 3.5 mmHg, which was significant relative to baseline nocturnal IOP (P < 0.001) and the reduction in the vehicle group (0.4 mmHg; P < 0.001 vs. netarsudil). Reduction in mean diurnal IOP with netarsudil (3.5 mmHg) was the same as the nocturnal reduction and statistically significant versus baseline (P < 0.001) and the vehicle group (0.9 mmHg; P < 0.01). The magnitude of IOP reductions with netarsudil was consistent at each time point assessed over the 24-h period. No adverse events were reported.ConclusionNetarsudil exhibited consistent IOP-lowering efficacy over a 24-h period in this short-term study.Trial registrationClinicaltrials.gov identifier: NCT02874846.

Project description:Prospective, multicenter, randomized, double-masked trials have shown latanoprost instilled once daily to be at least as effective as and generally superior to timolol administered twice daily and to be as effective as other frequently prescribed prostaglandin analogues. This study prospectively assessed the efficacy of latanoprost monotherapy in a large cohort of treatment-naive patients with a broad range of baseline intraocular pressure (IOP) levels treated in actual clinical practice settings.This prospective, open-label, multicenter, uncontrolled, phase IV study included treatment-naive ocular hypertension or open-angle glaucoma subjects initiating latanoprost once daily (evening). IOP levels were measured at baseline and after 1 and 3 months. The primary efficacy outcome was mean change in IOP from baseline to month 3. Analyses were stratified by baseline IOP: > or = 20 and <24 mmHg vs > or = 24 mmHg.Efficacy analyses (intent to treat) included 572 subjects: 20 to <24 mmHg group, N = 252; > or = 24 mmHg group, N = 320. Mean baseline IOP levels were 22.2 +/- 0.9 mmHg and 26.7 +/- 2.8 mmHg, respectively. At month 3, significant IOP reductions were seen in both groups (p < 0.0001, within-group differences); reductions were smaller in the 20 to <24 mmHg group (-6.3 +/- 2.4 vs -9.2 +/- 3.7 mmHg, respectively; -28.0 +/- 10.6% vs -34.1 +/- 11.9%, respectively). An IOP reduction of > or = 30% from baseline to month 3 was noted in 48.4% and 65.6% of subjects, respectively (p < 0.0001). At month 3, targets IOPs of < or = 18 mmHg were achieved by > or = 70% of subjects in both groups. Latanoprost was well tolerated with an adverse event profile similar to that reported in the literature.This "real world" study found once-daily latanoprost to be effective and safe in treatment-naive ocular hypertension or open-angle glaucoma patients. Patients with baseline IOP levels of 20 to <24 mmHg as well as > or = 24 mmHg benefitted from initial latanoprost therapy.NCT00647101.

Project description:Purpose:TAK-639 is a topical, nine-amino acid, synthetic, C-type natriuretic peptide analog in Phase 1 development for the treatment of ocular hypertension (OHT) and primary open-angle glaucoma (POAG). TAK-639 is postulated to lower intraocular pressure (IOP) through a novel mechanism of action (MOA) that increases trabecular meshwork outflow. We investigated the safety and tolerability of TAK-639 in subjects with OHT or POAG. Methods:This was a phase 1, multicenter, randomized, double-masked, placebo-controlled, single- and multiple-dose escalation study. Subjects (aged 18-90 years) with OHT or POAG were randomized 5:2 to TAK-639 or placebo. Three dose levels were planned (0.1%, 0.3%, 0.6% TAK-639), each with four dosing regimens (QD, BID, TID, QID). Safety measures included treatment-emergent adverse events (TEAEs) and ophthalmologic examinations. Pharmacokinetics and pharmacodynamics (reduction of IOP) were also evaluated. Results:In total, 63 subjects were randomized and received 0.1%, 0.3% and 0.6% TAK-639, as single dose, QD, or BID, and 0.1% and 0.3% TID. The study was terminated before 0.6% TID or QID dosing cohorts were studied; instead, 0.6% BID was repeated in a new cohort. TEAEs were instillation related and of mild-to-moderate intensity. There were no TEAEs leading to premature discontinuation, and no serious TEAEs. The most common treatment-related TEAEs were instillation site pain and transient corneal staining with fluorescein. There were no clinically significant concerns across dose groups for all other safety measures, including drop comfort, best corrected visual acuity, slit-lamp biomicroscopy, and corneal epithelial integrity. Little or no systemic exposure was observed. There was a marginal reduction in IOP in one cohort at the highest dose (0.6%) and regimen (BID) tested, suggesting biological plausibility of targeting the trabecular meshwork through this mechanism. Conclusion:TAK-639 was generally well tolerated up to 0.6% BID. Further non-clinical studies will improve understanding of the MOA and the penetration of TAK-639 to the anterior chamber.

Dataset Information

Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews.

Aim

Methods

Results

Conclusion

Publications

Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews.

Similar Datasets

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