Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP.

Anterior juxtascleral delivery of anecortave acetate in eyes with primary open-angle glaucoma: a pilot investigation.

PURPOSE: To describe the intraocular pressure (IOP)-lowering effects in eyes with open-angle glaucoma (OAG) after treatment with an anterior juxtascleral depot of anecortave acetate. DESIGN: Prospective, interventional case series. METHODS: Seven eyes of six subjects with OAG, with uncontrolled IOP while being administered one or more topical medications, received 24 mg anecortave acetate delivered by anterior juxtascleral depot. IOP was assessed at baseline and regularly after treatment for up to 24 months. RESULTS: Mean IOP before anecortave acetate treatment was 31.3 +/- 11.3 mm Hg and dropped by 9.5 +/- 4.5 mm Hg (32.7% +/- 16.8%) within one week after treatment. This IOP reduction was sustained through six months (8.4 +/- 5.4 mm Hg [29.6% +/- 12.4%]) and 12 months (9.5 +/- 5.7 mm Hg [34.0% +/- 15.9%]) after a single anecortave acetate treatment. The injection process was well tolerated, and no eyes experienced any injection-related or drug-related serious adverse events. CONCLUSIONS: Both the anterior juxtascleral depot of a drug and anecortave acetate may be promising candidates for IOP reduction in eyes with OAG. Additional studies are required to establish better their efficacy and safety, optimal dosing frequency, mechanism of action, and potential additivity to other IOP-lowering therapies.

Intraocular pressure-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination compared with brinzolamide 1% and timolol 0.5%.

PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination with brinzolamide 1% or timolol 0.5% alone in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter study. PARTICIPANTS: Five hundred twenty-three patients were randomized to the study treatments. METHODS: Patients with OAG or OHT were recruited to the study. Qualifying eyes had IOPs of 24 to 36 mmHg at 8 am and 21 to 36 mmHg at 10 am on 2 eligibility visits after an appropriate washout period from previous treatment. Patients were assigned randomly to either brinzolamide 1%/timolol 0.5%, brinzolamide 1% (Azopt; Alcon Laboratories, Fort Worth, TX), or timolol 0.5%, dosed twice daily and were followed up while receiving therapy for 6 months. At selected sites, additional IOP measurements were performed at 12 pm, 4 pm, and 8 pm during the 2 eligibility visits, at month 3, and at month 6. MAIN OUTCOME MEASURE: Mean IOP. RESULTS: Brinzolamide 1%/timolol 0.5% produced statistically significant and clinically relevant reductions from baseline ranging from 8.0 to 8.7 mmHg, which were statistically and clinically superior to that of either brinzolamide 1% (5.1-5.6 mmHg) or timolol 0.5% (5.7-6.9 mmHg). No safety concerns were identified based on an assessment of ocular and cardiovascular parameters and a review of adverse events. CONCLUSIONS: Brinzolamide 1%/timolol 05% is superior in IOP-lowering efficacy to either brinzolamide 1% or timolol 0.5%.

Efficacy of brinzolamide and levobetaxolol in pediatric glaucomas: a randomized clinical trial.

PURPOSE: To describe the safety and clinical response on elevated intraocular pressure (IOP) of brinzolamide and levobetaxolol in pediatric patients under 6 years of age. METHODS: A double-masked, randomized design. Pediatric patients were randomized to brinzolamide suspension, 1%, or levobetaxolol suspension, 0.5%, both dosed twice daily. IOPs at 9 AM were taken at screening, baseline, and weeks 2, 6, and 12. A descriptive study with mean change from baseline IOP, the primary efficacy parameter. RESULTS: Seventy-eight evaluable patients (32 brinzolamide and 46 levobetaxolol). Patients on no prestudy IOP-lowering therapy randomized to brinzolamide had mean IOP change from baseline ranging from -4.1 mm Hg (week 2) to -5.0 mm Hg (week 6). When all brinzolamide patients are considered, there was little mean change from baseline IOP due to the large number of patients enrolled without a washout of prior IOP-lowering therapy. Levobetaxolol patients had mean change from baseline, ranging from -1.8 mm Hg (week 6) to -2.9 mm Hg (week 2). Levobetaxolol patients on no prestudy therapy had mean IOP change from baseline ranging from -2.9 mm Hg (week 12) to -4.0 mm Hg (week 2). Brinzolamide was more efficacious for glaucoma associated with systemic or ocular abnormalities and less efficacious for primary congenital glaucoma. Levobetaxolol was most efficacious for primary congenital glaucoma. Adverse events were predominantly nonserious and did not interrupt patient continuation in the study. CONCLUSIONS: Both brinzolamide and levobetaxolol were well tolerated. Both drugs provided clinically relevant IOP reductions for patients not on a previous medication, although efficacy is, in part, contingent upon diagnosis.

A study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to latanoprost 0.005% and timolol 0.5% dosed concomitantly in patients with open-angle glaucoma or ocular hypertension.

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

Effects of travoprost on aqueous humor dynamics in patients with elevated intraocular pressure.

PURPOSE: To determine the mechanism by which travoprost 0.004% reduces intraocular pressure (IOP) in patients with ocular hypertension or primary open angle glaucoma. DESIGN: This is a randomized, double-masked, placebo-controlled, single center study of 26 patients scheduled for 3 visits (baseline, day 15, and days 17 to 18) following screening. METHODS: After appropriate washout of all ocular medications, baseline IOPs were taken and travoprost 0.004% was administered once-daily in the evening for 17 consecutive doses to 1 eye and its vehicle to the fellow eye in a randomized, masked fashion. On day 15, beginning 12 hours after the 14th consecutive dose, IOP was measured by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, and episcleral venous pressure by venomanometry. Uveoscleral outflow was determined by mathematical calculation. Two days later, the last drop of drug/vehicle was given at 2000 hours. Fluorophotometry and tonometry measurements were repeated between 2200 and 0600 hours. Treated eyes were compared with contralateral control eyes or baseline measurements, and daytime measurements were compared with nighttime measurements using paired t tests. RESULTS: Travoprost-treated eyes showed a significant (P<0.001) decrease in daytime IOP compared with baseline (26%) or to vehicle-treated eyes (22%), and an increase in daytime outflow facility (P=0.001; 64%). The increase in uveoscleral outflow was not statistically significant. At night, the IOPs of travoprost-treated eyes remained 21% to 24% below baseline daytime values. Seated and supine IOPs in control eyes were significantly (P<0.04) lower at 2200 hours than 1700 hours (P<0.04). Supine IOPs were higher than seated IOPs in both control and treated eyes (P<0.001). Aqueous flow was significantly (P<0.001) reduced at night in both travoprost (30%) and vehicle-treated (25%) eyes when compared with daytime values. No other comparisons were statistically significant. CONCLUSIONS: Travoprost seems to lower IOP by increasing trabecular outflow facility. An effect on uveoscleral outflow cannot be ruled out.

Travoprost 0.004% with and without benzalkonium chloride: a comparison of safety and efficacy.

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.

Pooled results of two randomized clinical trials comparing the efficacy and safety of travoprost 0.004%/timolol 0.5% in fixed combination versus concomitant travoprost 0.004% and timolol 0.5%.

PURPOSE: To compare the IOP-lowering efficacy of the fixed combination of travoprost 0.004%/timolol 0.5% dosed once daily in the morning with the concomitant administration of travoprost 0.004% dosed once daily in the evening and timolol 0.5% dosed once daily in the morning. METHODS: This was an analysis of pooled data from two similarly designed prospective, randomized, controlled clinical trials comparing the fixed combination and concomitant therapy. RESULTS: Mean IOP ranged from 15.7 to 16.8 mmHg for the fixed combination group, and from 15.1 to 16.4 mmHg for the concomitant group. Mean IOP reductions were up to 9.0 mmHg in the fixed combination group, and up to 8.8 mmHg in the concomitant group. The differences in mean IOP change between treatment groups ranged from -0.2 to +0.9 mmHg across visits and time points. The safety profile was generally similar between groups. An exception was the incidence of ocular hyperemia, which was 13.7% with the fixed combination and 20.8% with concomitant therapy (p = 0.02). CONCLUSION: The fixed combination of travoprost 0.004% and timolol 0.5% provides IOP-lowering efficacy that is similar to concomitant administration of travoprost 0.004% dosed once daily in the evening and timolol 0.5% dosed once daily in the morning.

The safety and intraocular pressure-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1.

PURPOSE: The safety and intraocular pressure (IOP)-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1 were evaluated and compared with brimonidine tartrate 0.15% preserved with chlorine dioxide in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter equivalence study. PARTICIPANTS: Eight hundred forty-two patients randomized to the study treatments. METHODS: Patients with OAG or OHT and with qualifying IOP (22-36 mmHg at 8 am on 2 eligibility visits after an appropriate washout period from previous treatment) were assigned randomly to either brimonidine tartrate 0.15% preserved with polyquaternium-1 (brimonidine PQ) or brimonidine tartrate 0.15% preserved with chlorine dioxide (brimonidine P) dosed 3 times daily and were followed up for 6 months. Approximately one half of the study sites continued to follow up their patients for an additional 6 months to obtain longer-term safety data. RESULTS: Brimonidine PQ produced statistically significant and clinically relevant reductions from baseline ranging from 4.3 to 6.5 mmHg, which were statistically and clinically equivalent to brimonidine P at all 18 visit days and times. No safety concerns were identified based on an assessment of ocular and cardiovascular parameters. Patient discontinuations resulting from adverse events were similar for both groups and most of these were a result of signs or symptoms of ocular allergic reaction. CONCLUSIONS: Brimonidine PQ is equivalent in IOP-lowering efficacy and safety to brimonidine P.

Patients' and physicians' perceptions of the travoprost dosing aid: an open-label, multicenter study of adherence with prostaglandin analogue therapy for open-angle glaucoma or ocular hypertension.

OBJECTIVE: This study describes patients' and physicians' perceptions of issues related to dosing adherence with topical therapies for lowering intraocular pressure before and after use of the travoprost dosing aid (Travatan Dosing Aid, Alcon Research Ltd., Fort Worth, Texas). METHODS: The study had an open-label, multicenter, single-treatment-arm design that included sequential patients with open-angle glaucoma (with or without pigment dispersion or pseudoexfoliation component) or ocular hypertension who were taking any prostaglandin analogue monotherapy. Ten participating physicians were chosen on the basis of factors such as their experience, qualifications, and previous clinical study participation. The study consisted of 2 visits: screening and week 4. Patients were asked to complete a survey about their medication adherence before study entry at the screening visit and at study exit during the week-4 visit. In addition, each physician was asked to complete an entry and exit survey on each patient as well as a survey to provide feedback on the travoprost dosing aid. RESULTS: Of the 87 enrolled patients, 6 did not complete the exit survey; therefore, 81 patients were included in the intent-to-treat analysis. Mean (SD) age at enrollment was 65.4 (11.6) years; 61.7% (50/81) of the patients were women and 60.5% (49/81) were white. Most patients (96.3% [78/81]) had open-angle glaucoma. Participating physicians perceived that problems involving dosing and adherence were reduced after patients used the dosing aid. Physicians indicated that they would recommend continued use of the travoprost dosing aid for 91.3% (73/80) of patients. All 10 participating physicians said that they would recommend the dosing aid to patients in the future. Of the 81 patients, the majority (68.8% [55/80]) indicated that they would like to continue using the travoprost dosing aid. For 67.5% (54/80) of patients, dosing adherence as recorded by the travoprost dosing aid was >70%. The dosing lever (39.7% [31/78]) and the visual alarm (29.5% [23/78]) were the 2 most favored features of the dosing aid reported by all evaluable patients. The majority of patients (58.8% [47/80]) indicated that they were "relieved" or "very relieved" that the doctor was able to monitor when they dosed their medication; few (7.5% [6/80]) were "concerned" or "very concerned" that the doctor was able to monitor their dosing. CONCLUSIONS: The travoprost dosing aid was perceived to be effective in reminding this group of patients to take their medication as prescribed. In this study, the device was well accepted by both patients and physicians.

A three-month, multicenter, double-masked study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to travoprost 0.004% ophthalmic solution and timolol 0.5% dosed concomitantly in subjects with open angle glaucoma or ocular hypertension.

PURPOSE: The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension. METHODS: This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure. RESULTS: Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) was < or =1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups. CONCLUSIONS: A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.

Efficacy and safety of a fixed combination of travoprost 0.004%/timolol 0.5% ophthalmic solution once daily for open-angle glaucoma or ocular hypertension.

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.

The safety and efficacy of travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution.

PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution (Trav/Tim) to its components travoprost 0.004% ophthalmic solution, TRAVATAN, (Trav) and timolol 0.5% ophthalmic solution (Tim) in patients with open-angle glaucoma or ocular hypertension. DESIGN: Randomized multicenter, double-masked, active-controlled, parallel group study. METHODS: Two hundred sixty-three patients with open-angle glaucoma or ocular hypertension were randomized to receive Trav/Tim once daily AM (and vehicle PM), Trav once daily PM (and vehicle AM), or Tim twice daily (AM and PM). Efficacy and safety were compared across treatment groups over 3 months. RESULTS: Trav/Tim produced a mean IOP decrease from baseline of 1.9 mm Hg to 3.3 mm Hg more than Tim, with a significant decrease in mean IOP at each of the nine study visits (P < or = .003). Trav/Tim decreased mean IOP by 0.9 mm Hg to 2.4 mm Hg more than Trav, with a significant decrease in mean IOP at seven of the nine study visits (P < or = .05). The adverse event profile for Trav/Tim was comparable to Trav or Tim alone. CONCLUSIONS: Over the 3 months of treatment, Trav/Tim produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by either Trav or Tim alone. The clinical results that Trav/Tim was safe and well tolerated with an incidence of adverse events was comparable to the results of Trav or Tim alone. Trav/Tim provides both more effective IOP reduction than its components and the benefits of once-daily dosing.