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Precis: In pooled phase III analyses, once-daily netarsudil 0.02% resulted in intraocular pressure (IOP) reduction that was noninferior to twice-daily timolol 0.5%, with minimal treatment-related serious or systemic adverse events (AEs). Ocular AEs were generally tolerable., Purpose: The purpose of this study was to assess the efficacy and safety of the Rho kinase inhibitor netarsudil in patients with open-angle glaucoma or ocular hypertension., Patients and Methods: Pooled analysis of data from the ROCKET-1 to 4 phase III studies of once-daily (PM) netarsudil or twice-daily timolol in patients with open-angle glaucoma or ocular hypertension. The primary efficacy measure was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP <25 mm Hg., Results: In the pooled primary efficacy population (netarsudil, n=494; timolol, n=510), once-daily netarsudil was noninferior to twice-daily timolol at all 9 timepoints through month 3. Mean treated IOP ranged from 16.4 to 18.1 mm Hg among netarsudil-treated patients and 16.8 to 17.6 mm Hg among timolol-treated patients. In the pooled safety population (n=839 in each treatment group), treatment-related serious AEs occurred at similar frequencies in each treatment group (netarsudil, 0.1%; timolol, 0%). The most common ocular AE, conjunctival hyperemia (netarsudil, 54.4%; timolol, 10.4%), was graded as mild in 77.6% (354/456) of affected netarsudil-treated patients., Conclusions: Once-daily netarsudil resulted in IOP lowering that was noninferior to twice-daily timolol, with tolerable ocular AEs that were generally mild and self-resolving. As a first-in-class agent in the United States, with a novel mechanism of action, netarsudil may provide a useful therapeutic option for patients who would benefit from IOP lowering.

Introduction: New open-angle glaucoma (OAG) and ocular hypertension (OHT) therapies that reduce treatment burden and improve outcomes relative to currently available agents are needed. Netarsudil, a novel Rho kinase inhibitor approved by the US Food and Drug Administration, reduces intraocular pressure (IOP) by increasing trabecular outflow. Two phase 3 superiority studies compared a fixed-dose combination (FDC) of netarsudil and the prostaglandin latanoprost with each active component for IOP-lowering efficacy., Methods: Pooled efficacy and safety data were analyzed from MERCURY-1 and -2 studies in patients with OAG or OHT. Patients instilled one drop of netarsudil (0.02%)/latanoprost (0.005%) FDC (n = 483), netarsudil (0.02%, n = 499), or latanoprost (0.005%, n = 486) into each eye once-daily between 20:00 and 22:00. IOP was measured at 08:00, 10:00, and 16:00 at weeks 2, 6, and the primary endpoint at month 3., Results: Baseline mean diurnal IOP was 23.6, 23.6, and 23.5 mmHg in netarsudil/latanoprost FDC, netarsudil, and latanoprost groups, respectively. Mean diurnal IOP in each group was 15.3, 18.1, and 17.5 mmHg at week 2, 15.7, 18.4, and 17.4 mmHg at week 6, and 15.8, 18.4, and 17.3 mmHg at week 12. The netarsudil/latanoprost FDC met criteria for superiority compared with each active component (p < 0.0001 for all nine time points). At month 3, among patients randomized to netarsudil/latanoprost FDC or latanoprost, 58.4% vs 37.3% (p < 0.0001) achieved IOP ≤ 16 mmHg. Among patients randomized to netarsudil/latanoprost FDC or netarsudil or latanoprost, 30.9% vs 5.9% (p < 0.0001) vs 8.5% (p < 0.0001) achieved at least a 40% reduction from baseline in mean diurnal IOP. Pooled safety results were consistent with individual MERCURY studies., Conclusion: Once-daily netarsudil/latanoprost FDC produced statistically significant and clinically relevant reductions in mean IOP that were statistically superior to IOP reductions achieved by netarsudil and latanoprost monotherapy. Results of the pooled efficacy and safety analyses were consistent with the individual studies., Trial Registration: ClinicalTrials.gov identifiers, NCT02558400 and NCT02674854.

Purpose: To compare the ocular hypotensive efficacy and safety of a fixed-dose combination (FDC) of the Rho kinase inhibitor netarsudil and latanoprost vs monotherapy with netarsudil or latanoprost., Design: Three-month primary endpoint analysis of a randomized, double-masked, phase 3 clinical trial., Methods: Adults with open-angle glaucoma or ocular hypertension (unmedicated intraocular pressure [IOP] >20 and <36 mm Hg at 8:00 AM) were randomized to receive once-daily netarsudil/latanoprost FDC, netarsudil 0.02%, or latanoprost 0.005% for up to 12 months. The primary efficacy endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3., Results: Mean treated IOP ranged from 14.8-16.2 mm Hg for netarsudil/latanoprost FDC, 17.2-19.0 mm Hg for netarsudil, and 16.7-17.8 mm Hg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < .0001), lowering IOP by an additional 1.8-3.0 mm Hg vs netarsudil and an additional 1.3-2.5 mm Hg vs latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP ≤15 mm Hg was 43.5% for netarsudil/latanoprost FDC, 22.7% for netarsudil, and 24.7% for latanoprost. No treatment-related serious adverse events were reported; treatment-related systemic adverse events were minimal. The most frequent ocular adverse event was conjunctival hyperemia (netarsudil/latanoprost FDC, 53.4%; netarsudil, 41.0%; latanoprost, 14.0%), which led to treatment discontinuation in 7.1% (netarsudil/latanoprost FDC), 4.9% (netarsudil), and 0% (latanoprost) of patients., Conclusions: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to netarsudil and latanoprost across all 9 time points through month 3, with acceptable ocular safety., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the ocular hypotensive efficacy and safety of a once-daily (pm) fixed-dose combination (FDC) product containing netarsudil 0.02% and latanoprost 0.005% with monotherapy with netarsudil or latanoprost. Netarsudil is a Rho kinase inhibitor that lowers intraocular pressure (IOP) primarily by increasing trabecular (conventional) outflow. Latanoprost is the most frequently prescribed of the prostaglandin analogs, which lower IOP primarily by increasing uveoscleral outflow., Design: Three-month, double-masked, randomized (1:1:1), phase 3, superiority study., Participants: Patients had unmedicated IOP > 20 to <36 mmHg at 8:00 am and met other standard criteria for open-angle glaucoma and ocular hypertension., Methods: Randomization to once-daily (pm) netarsudil/latanoprost FDC, netarsudil, or latanoprost for 3 months., Main Outcome Measures: Mean IOP at 8:00 am, 10:00 am, and 4:00 pm at week 2, week 6, and month 3 (intent-to-treat). Statistical superiority was concluded if the P value for the comparison of netarsudil/latanoprost FDC with each component was <0.05 and the difference in mean IOP (netarsudil/latanoprost FDC minus comparator) was <0 for all time points at all visits. Safety was recorded throughout the treatment period., Results: A total of 750 patients were enrolled, with 90.2%, 89.4%, and 94.4% completing 3 months of treatment with netarsudil/latanoprost FDC, netarsudil, and latanoprost, respectively. Least-squares mean treated IOP ranged from 15.3 to 16.5 mmHg for netarsudil/latanoprost FDC, 17.4 to 19.8 mmHg for netarsudil, and 17.1 to 18.1 mmHg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < 0.0001), lowering IOP by an additional 2.2 to 3.3 mmHg versus netarsudil and an additional 1.5 to 2.4 mmHg versus latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP ≤ 15 mmHg was 42.1% for netarsudil/latanoprost FDC, 15.8% for netarsudil, and 18.3% for latanoprost. No treatment-related serious adverse event (AE) was observed. Treatment-related systemic AEs were minimal. The most frequent ocular AE was conjunctival hyperemia (netarsudil/latanoprost FDC, 54.5%; netarsudil, 42.7%; latanoprost, 22.3%), which was generally mild., Conclusions: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to its individual components at all 9 time points over 3 months, with tolerable ocular safety. This FDC offers a reduced treatment burden that may improve adherence and clinical outcomes., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the intraocular pressure (IOP)-lowering efficacy and safety of netarsudil once daily (QD) and timolol twice daily (BID)., Design: Double-masked, randomized, phase 3, noninferiority study., Methods: Patients with open-angle glaucoma or ocular hypertension (unmedicated baseline IOP >20 to <30 mm Hg at 8:00 AM) were randomized to netarsudil ophthalmic solution 0.02% QD (PM) or timolol ophthalmic solution 0.5% BID. The primary endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP <25 mm Hg (per-protocol population). Safety was recorded over the 6-month treatment period., Results: A total of 186 patients from each treatment arm were included in the primary efficacy analysis. Netarsudil QD met the criteria for noninferiority to timolol BID. Mean treated IOP ranged from 16.3 to 17.9 mm Hg for netarsudil and 16.7 to 17.6 for timolol, with mean reductions from baseline of 3.9 to 4.7 mm Hg and 3.8 to 5.2 mm Hg, respectively. In prespecified secondary analyses, netarsudil demonstrated noninferiority to timolol in patients with baseline IOP <27 mm Hg and <30 mm Hg. The IOP-lowering effects of netarsudil were sustained over 6 months of treatment. No treatment-related serious adverse event (AE) was reported for either study drug. However, statistically significant reductions in mean heart rate were recorded at all study visits for the timolol group. The most frequent ocular AE among netarsudil-treated patients was conjunctival hyperemia (47.9%), which was predominately mild., Conclusions: Netarsudil QD (PM), a first-in-class IOP-lowering medication, was noninferior to timolol BID and was associated with tolerable ocular AEs., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the intraocular pressure (IOP)-lowering performance and safety of an ab interno gelatin stent (XEN 45 Gel Stent, Allergan plc, Irvine, California, USA), a minimally invasive glaucoma surgery device, in refractory glaucoma., Design: Single-arm, open-label, multicenter clinical study., Methods: Following mitomycin C pretreatment, the stent was placed ab interno in patients who failed prior filtering/cilioablative procedure or had uncontrolled IOP on maximum-tolerated medical therapy, with medicated IOP ≥20 and ≤35 mm Hg and visual field mean deviation ≤-3 dB. Primary performance outcomes: patients (%) achieving ≥20% IOP reduction from baseline on the same or fewer medications and mean IOP change from baseline at month 12. Procedure-related complications and ocular adverse events (AEs) were assessed., Results: Sixty-five patients were implanted (intent-to-treat/safety population). At 12 months, 75.4% (46/61; observed data) reported ≥20% IOP lowering from baseline on the same or fewer medications. Mean IOP change from baseline was -9.1 mm Hg (95% confidence interval [CI]: -10.7, -7.5) (n = 52; observed data) at 12 months, excluding patients with missing data (n = 4) and those requiring a glaucoma-related secondary surgical intervention (n = 9). Mean medication count decreased from 3.5 (baseline) to 1.7 (12 months). No intraoperative complications or unexpected postoperative AEs were reported. Most AEs were mild/moderate; common AEs included needling (without sight-threatening complications), nonpersistent loss of best-corrected visual acuity, and transient hypotony (requiring no surgical intervention)., Conclusions: The gelatin stent reduced IOP and medication use without raising unexpected safety concerns, offering a minimally invasive surgical option for refractory glaucoma patients., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety and intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost sustained-release implant (Bimatoprost SR)., Design: Phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial., Methods: At baseline following washout, open-angle glaucoma patients (n = 75) were administered Bimatoprost SR (6 μg, 10 μg, 15 μg, or 20 μg) intracamerally in the study eye; the fellow eye began topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or a single repeat treatment with implant was allowed. The primary endpoint was IOP change from baseline. The main safety measure was adverse events. Results through month 6 are reported., Results: Bimatoprost SR provided rapid, sustained IOP lowering. Overall mean IOP reduction from baseline through week 16 in study eyes was 7.2, 7.4, 8.1, and 9.5 mm Hg with the 6-μg, 10-μg, 15-μg, and 20-μg dose strengths of implant, respectively, vs 8.4 mm Hg in topical bimatoprost-treated pooled fellow eyes (data censored at rescue/retreatment). Rescue/retreatment was not required in 91% and 71% of study eyes up to week 16 and month 6, respectively. Adverse events in study eyes usually occurred within 2 days after the injection procedure and were transient. Conjunctival hyperemia with onset later than 2 days after the injection procedure was more common with topical bimatoprost than Bimatoprost SR (17.3% vs 6.7% of eyes)., Conclusions: Bimatoprost SR demonstrated favorable efficacy and safety through 6 months. All dose strengths were comparable to topical bimatoprost in overall IOP reduction through week 16. A single administration controlled IOP in the majority of patients for up to 6 months., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/aims: To evaluate the ocular hypotensive efficacy of fixed-dose combinations of the Rho kinase inhibitor and norepinephrine transport inhibitor AR-13324 (0.01% and 0.02%) and latanoprost (PG324 Ophthalmic Solution) relative to the active components AR-13324 0.02% and latanoprost 0.005%, used bilaterally at night., Methods: This was a double-masked, randomised, parallel comparison study in patients with open-angle glaucoma or ocular hypertension. After washout, patients were randomised to one of four treatment arms and treated for 28 days. The primary efficacy variable was mean diurnal intraocular pressure (IOP) at day 29., Results: We randomised 298 patients, of whom 292 (98%) completed the study. Mean unmedicated diurnal IOPs (study eye) was 25.1, 25.1, 26.0 and 25.4 in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively. On day 29, mean diurnal IOP decreased to 17.3, 16.5, 18.4 and 19.1 mm Hg, respectively. For the primary efficacy variable of mean diurnal IOP at day 29, PG324 0.02% met the criterion for statistical superiority relative to both latanoprost and AR-13324 0.02% (p<0.0001), providing additional IOP lowering of 1.9 and 2.6 mm Hg, respectively. PG324 0.01% also met the criterion for superiority. The most frequently reported adverse event was conjunctival hyperaemia with an incidence of 41% (30/73), 40% (29/73), 14% (10/73) and 40% (31/78) in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively., Conclusions: In this short-term study, the fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations. The only safety finding of note was transient asymptomatic conjunctival hyperaemia which was typically of mild severity., Trial Registration Number: NCT02057575., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To report 3-year results evaluating the effect on safety and efficacy of canaloplasty to treat open-angle glaucoma when combined with cataract surgery., Patients and Methods: This was a retrospective subset analysis of a prospective, international, multicenter study evaluating 133 eyes of 133 adult, open-angle glaucoma patients who underwent canaloplasty with tensioning suture placement. Eighty-two phakic eyes that received canaloplasty alone were compared with 51 eyes that underwent cataract surgery before or during canaloplasty., Results: Phakic eyes that received combined cataract-canaloplasty surgery (phacocanaloplasty) had a mean±SD baseline IOP of 23.5±5.2 mm Hg and mean glaucoma medication usage of 1.5±1.0 decreasing to a mean IOP of 13.6±3.6 mm Hg on 0.3±0.5 medications at 3 years postoperatively. Pseudophakic eyes undergoing canaloplasty had a mean baseline IOP of 23.9±5.2 mm Hg on a mean of 1.8±0.8 glaucoma medications decreasing to 15.6±3.5 mm Hg on 1.1±0.8 medications at 3 years. In phakic eyes, reductions in IOP were significantly greater and less postoperative IOP lowering medication was needed after undergoing phacocanaloplasty compared to eyes which had canaloplasty alone., Conclusions: Clear corneal phacoemulsification performed before or in combination with canaloplasty is a safe and effective surgical procedure to reduce IOP in adult patients with open-angle glaucoma.

Purpose: To report 3-year results of the safety and efficacy of canaloplasty, a procedure involving circumferential viscodilation and tensioning of the inner wall of Schlemm canal to treat open-angle glaucoma., Setting: Multicenter surgical sites., Design: Nonrandomized multicenter clinical trial., Methods: This study comprised adult open-angle glaucoma patients having canaloplasty or combined cataract-canaloplasty surgery. Qualifying preoperative intraocular pressures (IOPs) were at least 16 mm Hg with historical IOPs of at least 21 mm Hg. A flexible microcatheter was used to viscodilate the full circumference of the canal and to place a trabecular tensioning suture. Primary outcome measures included IOP, glaucoma medication use, and adverse events., Results: Three years postoperatively, all study eyes (n = 157) had a mean IOP of 15.2 mm Hg ± 3.5 (SD) and mean glaucoma medication use of 0.8 ± 0.9 compared with a baseline IOP of 23.8 ± 5.0 mm Hg on 1.8 ± 0.9 medications. Eyes with combined cataract-canaloplasty surgery had a mean IOP of 13.6 ± 3.6 mm Hg on 0.3 ± 0.5 medications compared with a baseline IOP of 23.5 ± 5.2 mm Hg on 1.5 ± 1.0 medications. Intraocular pressure and medication use results in all eyes were significantly decreased from baseline at every time point (P<.001). Late postoperative complications included cataract (12.7%), transient IOP elevation (6.4%), and partial suture extrusion through the trabecular meshwork (0.6%)., Conclusion: Canaloplasty led to a significant and sustained IOP reduction in adult patients with open-angle glaucoma and had an excellent short- and long-term postoperative safety profile., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate 2-year postsurgical safety and efficacy of canaloplasty (circumferential viscodilation and tensioning of the inner wall of Schlemm canal) to treat open-angle glaucoma (OAG)., Setting: Multicenter surgical sites., Methods: This international prospective study comprised adult OAG patients having glaucoma surgery or combined glaucoma-cataract surgery. Qualifying preoperative intraocular pressure (IOP) was at least 16 mm Hg and historical IOP, at least 21 mm Hg. The full circumference of the canal was viscodilated and a trabecular tensioning suture placed with a microcatheter. Primary outcome measures included IOP and glaucoma medication use., Results: At 24 months, all 127 eyes (127 patients) had a mean IOP of 16.0 mm Hg +/- 4.2 (SD) and mean glaucoma medication use of 0.5 +/- 0.8 (baseline values 23.6 +/- 4.8 mm Hg and 1.9 +/- 0.8 medications). Eyes with canaloplasty alone had a mean IOP of 16.3 +/- 3.7 mm Hg and 0.6 +/- 0.8 medications (baseline values 23.2 +/- 4.0 mm Hg and 2.0 +/- 0.8 medications). Eyes with combined glaucoma-cataract surgery had a mean IOP of 13.4 +/- 4.0 mm Hg and 0.2 +/- 0.4 medications (baseline values 23.1 +/- 5.5 mm Hg and 1.7 +/- 1.0 medications). The IOP and medication use results at all time points were statistically significant versus baseline (P <.001). The late postoperative follow-up identified 3 patients with elevated IOP. No other serious ocular or nonocular complications were reported., Conclusion: Canaloplasty was safe and effective in reducing IOP in adult patients with OAG.

Purpose: To evaluate the safety and efficacy of circumferential viscodilation and tensioning of the inner wall of Schlemm's canal in a new surgical procedure for the treatment of open-angle glaucoma (OAG)., Setting: Fourteen clinical sites in the United States and Germany., Methods: In this international multicenter prospective study of adult patients with OAG having glaucoma surgery, patients with qualifying preoperative intraocular pressure (IOP) of at least 16 mm Hg or higher and open angles were eligible. Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months preoperatively. After a nonpenetrating dissection technique to expose Schlemm's canal was performed, a flexible microcatheter (iTrack 250A, iScience Interventional) was used to dilate the full circumference of the canal by injecting sodium hyaluronate 1.4% (Healon GV) during catheterization. A suture loop was placed in the canal to apply tension to the trabecular meshwork. High-resolution ultrasound imaging was used to assess Schlemm's canal and anterior segment angle morphology, including distension of the trabecular meshwork caused by the tensioning suture. Data analysis was performed in 2 groups: Group 1, in which patients met all inclusion criteria, and Group 2, made up of Group 1 patients who had successful suture placement., Results: Group 1 comprised 94 patients and Group 2, 74 patients. The mean baseline IOP in Group 1 was 24.7 mm Hg+/-4.8 (SD) on a mean of 1.9+/-1.0 medications per patient. In Group 2 (patients with sutures), the mean IOP was 16.1+/-4.7 mm Hg 3 months postoperatively, 15.6+/-4.0 mm Hg at 6 months, and 15.3+/-3.8 mm Hg at 1 year. Medication use dropped to a mean of 0.6+/-0.9 per patient at 12 months. Suture tensioning was an apparent contributing factor in achieving surgical success. Patients with measurable trabecular meshwork distension from suture tension had a mean IOP of 15.9+/-5.2 mm Hg at 6 months and 14.5+/-3.0 mm Hg at 12 months. Surgical and postsurgical adverse events were reported in 15 of 94 patients (16%) and included hyphema (3), elevated IOP greater than 30 mm Hg (3), Descemet's tear (1), hypotony (1), choroidal effusion (1), and exposed closure suture with eyelid edema and erythema epiphora (1); 4 patients were subsequently converted to trabeculectomy., Conclusion: Circumferential viscodilation and tensioning of Schlemm's canal was a safe and effective surgical procedure to reduce IOP in adult patients with OAG.

Purpose: To compare the safety and efficacy of travoprost 0.004% without benzalkonium chloride (BAC) to that of the marketed formulation of travoprost 0.004% in patients with open-angle glaucoma or ocular hypertension., Methods: The study was a double-masked, randomized, parallel group, multicenter, noninferiority design. Adult patients with open-angle glaucoma or ocular hypertension with qualifying intraocular pressure (IOP) on 2 eligibility visits received either travoprost 0.004% with BAC (n=346), or travoprost 0.004% without BAC (n=344) dosed once-daily each evening. Patients were followed for a period of 3 months. IOP measurements at 8 AM, 10 AM, and 4 PM were taken at study visits on week 2, week 6, and month 3., Results: Mean IOP reductions, across all 9 study visits and times ranged from 7.3 to 8.5 mm Hg for travoprost 0.004% without BAC and from 7.4 to 8.4 mm Hg for travoprost 0.004% with BAC. Statistical equivalence was also demonstrated for the comparison of mean IOP changes; 95% confidence limits were within +/-0.8 mm Hg at 9 of 9 study visits and times in both the per protocol and intent-to-treat data sets. Adverse events and the number of patients discontinued owing to adverse events were similar for both treatment groups. Adverse events due to hyperemia occurred in 6.4% and 9.0% of patients treated with travoprost 0.004% without BAC and travoprost 0.004% with BAC, respectively., Conclusion: Travoprost 0.004% without BAC is equivalent to travoprost 0.004% with BAC in both safety and efficacy.

Purpose: To compare the efficacy of a fixed combination of travoprost 0.004%/timolol 0.5% every day in the morning with a concomitant regimen of timolol 0.5% every day in the morning, plus travoprost 0.004% every day in the evening; and timolol 0.5% twice daily on the intraocular pressure (IOP) of subjects with open-angle glaucoma or ocular hypertension over 3 months., Design: Prospective, randomized, double-masked, parallel-group, active-controlled, multicenter trial., Methods: Patients comprised adult subjects (n = 403) of either gender with open-angle glaucoma or ocular hypertension in at least one eye. To qualify, the IOP had to be between 22 to 36 mm Hg in the same eye at two consecutive eligibility visits. The primary outcome variable was IOP measured with a Goldmann applanation tonometer., Results: Mean IOP ranged from 16.2 to 17.4 mm Hg with the combination travoprost/timolol compared with 15.4 to 16.8 mm Hg in the concomitant travoprost + timolol group, from baselines of 23.1 to 25.6 mm Hg and 22.9 to 25.0 mm Hg, respectively. The fixed combination of travoprost/timolol significantly lowered IOP by 7 to 9 mm, similar to the IOP reductions observed with concomitant therapy. The most frequent ocular adverse event was hyperemia that occurred in 14.3% and 23.4% of subjects treated with travoprost/timolol combination and concomitant travoprost + timolol, respectively., Conclusions: Travoprost/timolol combination produces greater IOP reductions than the positive control, timolol 0.5%, and reductions that were similar to concomitant travoprost + timolol. This study demonstrates that the fixed combination of travoprost/timolol produces significant and clinically relevant reductions of IOP in a once-daily dosing regimen.

Background: Primary congenital glaucoma is an uncommon autosomal recessive condition that results from a developmental defect in the trabecular meshwork and anterior chamber angle, manifesting in the neonatal or infantile period with increased intraocular pressure, corneal enlargement and edema, and optic nerve cupping with consequent loss of vision. Nothing is known about its genetic location., Patients and Methods: Linkage analysis was performed in 25 primary congenital glaucoma Saudi Arabian families with six polymorphic DNA markers on chromosome 1q in a region that has shown tight linkage to a locus for autosomal dominant juvenile-onset open angle glaucoma (GLC1A). Twenty-four of these families are highly consanguineous., Results: Each family was shown separately to exclude the 8-centimorgan (cM) interval containing the GLC1A locus. Four families independently demonstrated overlapping regions of exclusion (theta < or = -2) that spanned the entire 8-cM interval. Assignment of a primary congenital glaucoma locus in this region could be excluded by a cadre of 21 families because a primary congenital glaucoma disease locus did not segregate in an autosomal recessive manner on haplotypes constructed with markers in this region. For all families, no affected individuals demonstrated homozygosity of alleles in regions tightly linked to the GLC1A locus., Conclusion: These results exclude the 8-cM region on chromosome 1q shown to contain the GLC1A locus from containing a disease locus for primary congenital glaucoma in this population of 25 Saudi Arabian families.

Carteolol, a nonselective beta-adrenergic antagonist with intrinsic sympathomimetic activity, was compared in 1% and 2% topical solutions with 0.5% timolol in 105 patients with primary open-angle glaucoma. In this double-masked, randomized 3-month trial, all three preparations significantly lowered intraocular pressure throughout the study, with no significant differences being observed. There were also no significant differences among the three preparations with regard to ocular or systemic adverse reactions, including heart rate and blood pressure.

Acute elevation of intraocular pressure frequently follows pupillary dilation in patients with primary open angle glaucoma. A retrospective study of 60 patients (116 eyes) with primary open angle glaucoma was done to assess the frequency and severity of intraocular pressure elevation following dilation with 2.5% phenylephrine hydrochloride (Neo-Synephrine) and 1% tropicamide (Mydriacyl). Significant pressure elevation (greater than 5 mm Hg) occurred in 37 eyes (32%). Marked pressure elevation (greater than 10 mm Hg) occurred in 14 eyes (12%). The only significant risk factor found was treatment with miotics. The change of intraocular pressure one hour after dilation was compared with the one-hour postoperative change in intraocular pressure in those patients (12 patients, 18 eyes) who subsequently underwent argon laser trabeculoplasty. No statistically significant correlation was found. There is a potential hazard of routine dilation of eyes with open angle glaucoma.

The authors compared the ocular hypotensive efficacy of two different treatment regimens of levobunolol 0.5% in a double-masked, randomized, controlled clinical trial. Seventy-one patients with open-angle glaucoma or ocular hypertension received levobunolol 0.5% as their sole glaucoma medication either on a once-daily or twice-daily treatment regimen for 3 months. Approximately 81% of the patients in the once-daily treatment group and 88% of subjects in the twice-daily treatment group successfully completed the 3-month study period. The overall mean decrease in intraocular pressure (IOP) was 4.5 mmHg in the once-daily group and 5.6 mmHg in the twice-daily group. These differences were not statistically different. For both treatment groups, effects on mean heart rate and blood pressure were minimal. The authors' data from this population suggest that once-daily treatment with levobunolol is an effective glaucoma regimen.

If the amount of visual field loss is less than expected from the amount of optic disk cupping in low-tension glaucoma compared with primary open-angle glaucoma, it might imply a difference between the two conditions in the type of optic nerve lesion produced. To test this hypothesis, three observers independently examined, in a masked fashion, optic disk stereoscopic photographs of 127 eyes with primary open-angle glaucoma and 71 eyes with low-tension glaucoma. For each stereoscopic photograph the observer predicted whether the visual field loss would be mild, moderate, or severe. The visual field were then classified, according to the number of sectors defective on the Goldmann perimeter chart, as having mild (1 to 15 sectors), moderate (16 to 30 sectors), or severe (more than 30 sectors) visual field loss. For no observer did the frequency of underpredictions or overpredictions in the two conditions differ significantly. The results of this study, thus, did not support the theory that the optic disk damage in primary open-angle glaucoma differs from that in low-tension glaucoma.

We compared the pattern of visual field loss in 148 patients with primary open-angle glaucoma and 63 patients with secondary glaucoma. The frequency with which each location in the visual field was defective was similar in the two conditions. The most common visual field defects in both varieties of glaucoma were superior arcuate scotomas and superior nasal steps. The similar distribution of visual field defects in primary and secondary glaucomas is consistent with a common mechanism for optic disc damage.

Thirty-seven eyes with open-angle glaucoma were treated by trabeculectomy and 34 eyes were treated by thermosclerostomy. Thermosclerostomy lowered intraocular pressure to a slightly greater extent than trabeculectomy; however, the average difference was not statistically significant except for the second year. After five years, IOPs were less than 22 mm Hg without additional medications or surgery in 24 (65%) of eyes undergoing trabeculectomy and in 14 (41%) of eyes undergoing thermosclerostomy. When eyes were included that were treated with medication or additional glaucoma or cataract surgery, over 90% of eyes in each group had an IOP less than 22 mm Hg. Visual acuity declined frequently in both groups, and progression of cataract was the most common cause. Loss of visual acuity occurred much more frequently in patients who were older than 60 years than in younger patients.