Comparison of the impact of Ripasudil and Dorzolamide on intraocular pressure in patients on prostaglandin analogues

Update on Microinvasive Glaucoma Surgery.

The purpose of the study was to determine the 24-h effects of pilocarpine 2% ophthalmic solution on intraocular pressure (IOP) and ocular perfusion pressure (OPP) when used in addition to prostaglandin analog (PGA) therapy. Twenty-seven patients with ocular hypertension (OHTN) or open angle glaucoma who were receiving stable monotherapy with a PGA were admitted to an inpatient sleep laboratory for 24-h monitoring of IOP, blood pressure (BP), and heart rate over 2 separate visits. The first baseline visit was performed under PGA monotherapy only. During the second 24-h visit, pilocarpine 2% was administered four times daily in addition to their normal PGA dosing. For each study visit, measurements of all study metrics were performed every 2 h in the habitual position. OPP was calculated as 2/3[diastolic BP +1/3(systolic BP - diastolic BP)] - IOP. During the diurnal period, pilocarpine significantly reduced IOP from a baseline of 18.2 ± 0.5 mmHg on PGA monotherapy to 17.1 ± 0.4 mmHg, P < 0.01. Similarly, pilocarpine significantly lowered IOP during the nocturnal period from 21.1 ± 0.7 to 20.0 ± 0.6 mmHg, P < 0.01. Mean OPP was unchanged from baseline levels after the addition of pilocarpine in both the diurnal and nocturnal periods. Mean systolic BP was significantly reduced during the nocturnal period only (-3.16 ± 1.5 mmHg, P = 0.03). In patients taking PGA monotherapy, the addition of pilocarpine can significantly lower IOP throughout the diurnal and nocturnal periods, but has no effect on OPP.

This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of -5.76mmHg and -7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: -2.01, -0.60; P = 0.0003). The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124.

BackgroundWe have shown a decrease in mean intraocular pressure (IOP) by switching to travoprost/timolol fixed combination (TTFC) in subjects receiving prostaglandin analogue (PGA) monotherapy and requiring additional medication in a previous report. For analyzing factors affecting IOP reduction, baseline IOP and preceding PGA were selected as statistically and clinically significant factors. In this report, we examine IOP-lowering effect and adverse drug reactions by preceding PGA.MethodsPatients with primary open angle glaucoma or ocular hypertension who received monotherapy with one of four PGAs (travoprost, latanoprost, tafluprost, or bimatoprost) for at least 3 months at 26 institutions and were determined to require additional medication by their primary physician were included. IOP reduction and adverse events were examined at 4, 8, and 12 weeks for each of four PGAs after switching to TTFC.ResultsIn total, 157 patients who could be followed up for at least 4 weeks after switching to TTFC were included in the efficacy analysis. Multiple regression analysis was performed, and baseline IOP and PGA were found to be significant factors to IOP reduction. IOP reduction at week 12, adjusted with the regression model, was −3.5, −1.8, and −1.4 mmHg in the tafluprost, latanoprost, and travoprost groups, whereas it was −0.5 mmHg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8–14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch.ConclusionClinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns.

PurposeTo assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP) had been insufficiently controlled on prostaglandin analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC).MethodsThis prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to once-daily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12.ResultsOf 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost). In the total population, mean IOP was significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001) in the prior travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1% reduction). Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12, TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the patients themselves, and for 94.7% of patients (54 of 57) by their physicians.ConclusionWhen TTFC replaced PGA monotherapy in patients whose IOP had been uncontrolled, the outcome was a significant reduction in IOP and an acceptable safety and tolerability profile. Most patients and investigators preferred TTFC to prior PGA monotherapy.

This study aimed to evaluate the effect of combining dexmedetomidine infusion with a modified Trendelenburg position on intraocular pressure (IOP) in patients undergoing robot-assisted laparoscopic surgery (RALS). In a single-center, prospective, 2 × 2 factorial randomized controlled trial, 160 patients scheduled for RALS were allocated to one of four groups: control (normal saline + traditional position), modified position alone, dexmedetomidine alone, or the combination of both. IOP was measured at baseline, during key surgical phases, and after extubation. The primary outcome was IOP during surgery. Secondary outcomes included the incidence of cardiovascular adverse events and the requirement for vasoactive drugs. A total of 153 patients completed the study protocol. Both dexmedetomidine and the modified position significantly reduced IOP during surgery (main effect of drug: F = 35.2, P < 0.001; main effect of position: F = 28.7, P < 0.001). Critically, a statistically significant interaction was observed between the two interventions (F = 4.8, P = 0.030), indicating a synergistic effect. The combination group demonstrated the greatest reduction in IOP from time points T2 to T4, ranging from 3.6 to 4.8 mmHg lower than the control group. There were no significant differences in the overall incidence of adverse events among the groups. In conclusion, for patients undergoing prolonged robotic laparoscopic surgery (with a mean operative time of 217 minutes), the combined use of dexmedetomidine infusion and a modified Trendelenburg position provides an effective and synergistic strategy for intraocular pressure control. This approach offers a practical means to enhance intraoperative ocular safety during such lengthy procedures. Chinese Clinical Trial Registry ChiCTR2300072961.

Comparison of the Effects of Latanoprost, Travoprost, and Bimatoprost on Circadian Intraocular Pressure in Patients with Glaucoma or Ocular Hypertension

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Objective Analysis and comparison of country-level data from the VISIONARY study, examining treatment outcomes with the topical fixed-dose combination of preservative-free tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) who were insufficiently treated with or unable to tolerate either beta-blocker or prostaglandin analogue (PGA) topical monotherapy. Methods A European, prospective, observational study was conducted in 11 countries. Adults with OAG/OHT were switched to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Statistical analysis examined changes in mean standard deviation (SD) intraocular pressure (IOP) from baseline at Week 4, Week 12 and Month 6. Data were documented for each eye separately at baseline and during follow up visits, with the eye reported to have the higher IOP (mmHg), as measured using Goldmann applanation tonometry, being selected for analysis (study eye). Country-level subanalysis examined outcomes by prior monotherapy, diagnosis and timing of dosing for those countries recruiting ≥20 patients (Country-level Subanalysis Population). Two-sided paired t-test was used to assess significance regarding mean IOP reduction from baseline and a compound symmetry covariance model was used in cross-country comparisons regarding variation in IOP change from baseline. Treatment-related adverse events (AEs) were evaluated. Results Mean (SD) age among patients recruited to the VISIONARY study ranged between 63.9 (11.8) and 72.4 (10.6) years across all countries. The majority of participants (>50%) were female in each country. The Country-level Subanalysis Population included 551 eyes. Mean (SD) IOP was significantly reduced from baseline in each country at Week 4, Week 12 and Month 6 (p < .0001). Mean IOP reduction at Month 6 ranged from 5.0 mmHg (22.6%, Hungary) to 7.8 mmHg (31.8%, Latvia) and varied significantly between countries (p < .001). The greatest reductions were in Latvia and Russia, where baseline IOP was highest. Country-level IOP reductions were significant irrespective of prior monotherapy, diagnosis or dosing time (p < .0001). Most treatment-related AEs occurred in the UK (26 events, 73% mild). One serious AE was reported (Russia, status asthmaticus). Tolerability with PF tafluprost/timolol FC therapy was rated as good/very good by most patients (85.7–100%) in all countries. Conclusion Subanalysis of VISIONARY study data revealed significant IOP reductions following a switch to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Cross-country variation was likely due to baseline IOP differences. Within country, outcomes were consistent regardless of diagnosis, dosing or prior monotherapy. Treatment was generally well tolerated.

To determine the efficacy of locally produced Latanoprost in reducing the intraocular pressure (IOP) in patients with Primary open-angle glaucoma (POAG). Open-label, non-comparative, observational case study with non-probability purposive sampling. A total of 48 patients (94 eyes) of either gender were recruited from glaucoma clinic with the diagnosis of POAG, having IOP of more than 21mmHg. Patients were commenced on locally produced Latanoprost (Vislat 0.005%). IOP was subsequently measured at 4weeks and 12weeks, respectively. The primary end point was reduction in IOP at 12weeks after the initiation of treatment. A total of 48 patients (94 eyes) were recruited from glaucoma clinic. The average IOP of our patients at baseline was 28.6±8.1mmHg, decreasing to 21.3±10.6mmHg at 4weeks, indicating a drop of 19.1% (P<0.001). IOP further decreased to 20.3±8.7mmHg after 3months of treatment indicating a decrease of 23.3% (P<0.001). A decrease in IOP occurred in 51 eyes (71.8%) at 4weeks after treatment, improving to 54 eyes (76%) at 3-month follow-up. Twenty eyes (28.1%) did not show any change in IOP at 4weeks. However, after 3-month follow-up only 17 eyes (23.9%) did not reveal any change in IOP. Our results showed a decrease in IOP of 19.1% after 4weeks, increasing to 23.3% at 12weeks in cohort of 37 patients (72 eyes) treated with locally produced Latanoprost (Vislat 0.005%).

To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy. An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined. The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group. Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

IntroductionThe efficacy of lowering intraocular pressure (IOP) and safety of switching to travoprost/timolol fixed combination ophthalmic solution (Duotrav®, Alcon Laboratories, Inc., Fort Worth, TX, USA) in patients with primary open-angle glaucoma, normal tension glaucoma or ocular hypertension undergoing prostaglandin analog (PGA) monotherapy was investigated.MethodsPatients treated with travoprost, latanoprost, tafluprost, or bimatoprost for ≥3 months and requiring additional medication were switched to Duotrav without washout. Baseline IOP was calculated from measurements at two visits during PGA monotherapy. IOP reductions at 4, 8, and 12 weeks after switching to Duotrav and adverse events were assessed.ResultsOf 162 patients enrolled, 157 patients (96.9%) with ≥4 weeks of follow-up after switching to Duotrav were analyzed. The mean IOP decreased significantly (baseline = 16.3 ± 3.1 mmHg; 4 weeks = 14.6 ± 3.1 mmHg, 8 weeks = 14.7 ± 3.3 mmHg, 12 weeks = 14.6 ± 3.2 mmHg; all P < 0.0001). When study eyes were divided into three groups according to baseline IOP (≥19 mmHg: 33 eyes, 21.0%; ≥15 to <19 mmHg: 78 eyes, 49.7%; <15 mmHg: 46 eyes, 29.3%), all groups showed significant IOP reductions (P = 0.0324 ~ P < 0.0001) after switching to Duotrav. Twenty-seven of 166 patients (16.3%) in the safety analysis experienced adverse events and 26/166 patients (15.7%) experienced adverse events, for which a relationship to Duotrav could not be ruled out. Adverse events in five patients led to treatment discontinuation (eye pruritus; eye irritation; increased blood pressure and rash; increased blurred vision; deepening of the eyelid sulcus and blepharoptosis). Twelve weeks after treatment switching, eyelash changes, blepharal pigmentation and deepening of the eyelid sulcus occurred in 42 (26.8%), 29 (18.5%), and 13 (8.3%) cases, respectively, among 157 patients with follow-up. There was no significant worsening from baseline for superficial punctate keratopathy (SPK) or conjunctival hyperemia after switching (SPK score: baseline = 0.58 ± 1.31; 12 weeks = 0.92 ± 1.76, P = 0.1819; conjunctival hyperemia score: baseline = 0.41 ± 0.64; 12 weeks = 0.49 ± 0.63, P = 0.3774).ConclusionOur findings confirm that switching to Duotrav® in PGA monotherapy patients shows IOP-lowering effect with minimal safety concerns.FundingJapan Association of Health Service and Alcon Japan. Ltd.Trial registrationUMIN Clinical Trials Registry identifier, UMIN000007028.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0246-9) contains supplementary material, which is available to authorized users.

PurposeTo assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open‐angle glaucoma (POAG) or ocular hypertension.MethodsWe searched PubMed, EMBASE and clinicaltrials.gov for studies that fit our inclusion criteria in this network meta‐analysis. Randomized controlled trials that report data on efficacy and safety of medications for POAG or ocular hypertension are included. Data on intra‐ocular pressure (IOP) lowering effect and incidence of adverse events including hyperaemia and ocular discomfort were extracted and used in mixed‐comparison analysis.ResultsThis study includes 72 randomized trials. Data were available on 12 medical treatments of POAG or ocular hypertension. Of 66 possible comparisons of outcome efficacy, 15 treatments were compared directly. Compared to prostaglandin analogues (PGA), beta‐blockers (BB) showed relatively weaker ability to lower IOP, followed by α2‐adrenergic agonists (AA) and carbonic anhydrase inhibitors (CAI). For dual therapy, regimens composed of a combination of PGA with another treatment demonstrated more powerful IOP lowering efficacy, while the combination of two non‐PGA drugs had lower efficacy in controlling IOP than PGA alone. There was no statistical significance in combinations that did not include PGA on efficacy of IOP control. In terms of tolerance, PGA alone leads to more severe hyperaemia than any other monotherapy regimen, while BBs have the lowest effect on the incidence of hyperaemia. Most dual therapy regimens containing PGA also lead to serious hyperaemia, with the exception of PGA + AA. Compared to regimens containing PGA, those with BB are less likely to cause hyperaemia.ConclusionOur network meta‐analysis showed that PGAs provide best IOP lowering effect among all the monotherapy regimen. Combination of PGA and other category of drugs leads to better IOP decrease. Combination of BB and another non‐PGA drug may have less ocular side‐effects than PGA alone.

Purpose:To evaluate the additive intraocular pressure–lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) as an adjunct to a prostaglandin analog (PGA) in patients with open-angle glaucoma or ocular hypertension insufficiently controlled with PGA monotherapy.Methods:In this Phase 4, double-masked trial, patients aged ⩾18 years, with a mean intraocular pressure of ⩾19 and <32 mm Hg in at least one eye were randomized (1:1) to receive BBFC + PGA (n = 96) or vehicle + PGA (n = 92) for 6 weeks. The primary endpoint was the mean change in diurnal intraocular pressure from baseline (averaged over 09:00 and 11:00 h) at Week 6.Results:The mean diurnal intraocular pressure at baseline was similar in the BBFC + PGA (22.8 mm Hg) and vehicle + PGA (22.9 mm Hg) groups. The least squares mean change in diurnal intraocular pressure from baseline at Week 6 was greater with BBFC + PGA (−5.59 mm Hg (95% confidence interval: −6.2 to −5.0)) than with vehicle + PGA (−2.15 mm Hg (95% confidence interval: −2.7 to −1.6)); the treatment difference was statistically significant in favor of BBFC + PGA (−3.44 mm Hg, (95% confidence interval: −4.2 to −2.7); p < 0.001). Ocular adverse events were reported in 21.1% and 8.7% of patients in the BBFC + PGA and vehicle + PGA groups, respectively. The most frequent ocular adverse event was ocular hyperemia (5.3%) in the BBFC + PGA group and blurred vision (2.2%) in the vehicle + PGA group.Conclusion:BBFC + PGA significantly reduced mean diurnal intraocular pressure than PGA alone in patients with open-angle glaucoma or ocular hypertension. The safety findings with BBFC + PGA were consistent with the known safety profile of the individual medications.

To compare intraocular pressure (IOP) control in eyes with or without clear corneal phacoemulsification following trabeculectomy. The study group included 30 eyes that underwent uneventful clear corneal phacoemulsification and foldable intraocular lens implantation following trabeculectomy without antimetabolites. Thirty eyes that had undergone filtering surgery without cataract extraction were selected as controls. Case and control groups were matched with respect to age, gender, IOP, number of glaucoma medications, glaucoma type (primary open-angle glaucoma/pseudoexfoliative glaucoma), trabeculectomy time and follow-up. Comparisons between the study and control groups (intergroup) and within the same group at different time-points (intragroup) were performed for IOP, glaucoma medications and bleb morphology. Success rates were investigated by Kaplan-Meier survival analysis and the factors influencing final success by logistic regression. Intraocular pressure (p = 0.04) and glaucoma medications (p = 0.001) increased during an average follow-up of 26.1 +/- 9.9 months in both groups. Intragroup differences became statistically significant after the 6-month visit, but intergroup differences remained insignificant. Bleb height decreased significantly following phacoemulsification in the study group (p = 0.017). Success rates decreased with time in both groups, with no intergroup difference (p = 0.46). The final success rate was negatively correlated with IOP and number of glaucoma medications used at the study entry, while there was a positive correlation between the baseline and final success rates. Trabeculectomy success decreased in a time-dependent manner in eyes with and without subsequent phacoemulsification. Uncomplicated clear corneal phacoemulsification was not found to have any additional unfavorable influence on IOP control in eyes with filtering blebs.