Preservative-Free versus Benzalkonium Chloride-Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial.

Purpose: To evaluate the safety and efficacy of a preservative-free latanoprost 0.005% formulation (T2345) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) compared to benzalkonium chloride-preserved latanoprost 0.005% (BPL) formulation in the United States (US). Patients and Methods: A prospective, randomized, multicenter, observer-masked, parallel-group study enrolled 335 patients diagnosed with POAG or OHT from 31 US sites who had adequately controlled intraocular pressure (IOP; ≤18 mm Hg) with latanoprost monotherapy. After a ≥72-hour washout period, patients were randomized to T2345 (n=165) or BPL (n=170) groups. Study drugs were dosed once-daily from Day 0 to Day 84 in one or both eyes. The study eye was the eye with lower IOP at baseline. The primary efficacy measure was the between-group comparison of the mean IOP values in the study eye at each time point (8 AM, 10 AM, and 4 PM on Days 15, 42, and 84). Safety measurements included ocular and systemic treatment-emergent adverse events (TEAEs). Results: Both T2345 and BPL adequately controlled IOP with 95% CIs within 1.5 mm Hg in the study eye at all assessed time points. The percentages of patients with diurnal IOP <18 mm Hg at Day 84 were 73.1% vs 78.7% for the T2345 and BPL groups, respectively. Adverse events were generally mild-to-moderate and primarily ocular. Fewer patients in the T2345 group experienced ocular TEAEs (13.9% vs 22.5%, respectively) and TEAEs with a suspected relationship to the study medication compared with the BPL group (5.5% vs 11.8%, respectively). The most common ocular TEAEs were instillation site pain and conjunctival hyperemia. Conclusion: In patients with POAG or OHT, both T2345 and BPL maintained IOP at or below clinically meaningful values for the duration of the study. T2345 showed a favorable safety profile, with numerically lower incidences of ocular TEAEs than BPL.

Comparison of Outcomes of Resident-performed Ahmed Valve Implantation vs Trabeculectomy.

AIMS: To compare outcomes of resident-performed Ahmed valve surgery vs trabeculectomy in a Veteran Affairs medical facility. MATERIALS AND METHODS: A retrospective cohort of 103 eyes in 91 patients receiving Ahmed valve (valve) or trabeculectomy (trab) performed at a Veterans Administration Medical Center by residents in their third year of training. The primary outcomes included intraocular pressure (IOP), treatment failure, and complications over 1 year. RESULTS: Of 103 eyes, 44 received valve and 59 received trab. Primary open-angle glaucoma was primary diagnosis more often in trab, while neovascular glaucoma predominated in the valve group (p < 0.001). Preoperative mean IOP was 35.1 ± 11.8 and 24.5 ± 7.1 mm Hg for valve and trabeculectomy respectively (p < 0.001), but at 1 year the IOP difference between groups was not statistically significant (p = 0.064). Overall, 11 (25.0%) and 11 (18.6%) eyes met any criteria for failure for valve and trab respectively. At 1 year, 22.5% of valves had IOP > 21 mm Hg vs only 4.3% of trab (p = 0.02). Complications were infrequent. There were no intraoperative complications for valve, whereas five for trab. Most common immediate complication for valve was hyphema. Both groups had low rates of choroidal effusions and reoperation. CONCLUSION: Ahmed valve implantation and trabeculectomy produce significant reductions in IOP when performed by residents-in-training. Valves tend to be used more frequently in patients with secondary glaucoma. Although complication profiles differ between procedures, both are safe and well tolerated when performed by resident physicians. CLINICAL SIGNIFICANCE: This study provides support for evidence-based patient counseling that supervised, resident-performed Ahmed valve implantation and trabeculectomy are indeed safe and effective. How to cite this article: Sharpe RA, Kammerdiener LL, Wannamaker KW, Fan J, Sharpe ED. Comparison of Outcomes of Resident-performed Ahmed Valve Implantation vs Trabeculectomy. J Curr Glaucoma Pract 2016;10(2):60-67.

Association of strength of religious adherence with attitudes regarding glaucoma or ocular hypertension.

BACKGROUND: To evaluate the impact of religious adherence on a patient's outlook on disease in a glaucoma population. METHODS: A prospective survey analysis of patients with open-angle glaucoma or ocular hypertension evaluating self-reported global religious adherence, adherence to specific basic activities and knowledge of faith ('maturity') and 'comfort' (ability to cope, attitude toward glaucoma, motivation to take medication and God's concern). This specific analysis was limited to self-professed Christians. RESULTS: 248 patients were included and religious adherence was correlated to religious activity and knowledge (p < 0.0001). Patients who scored as adherent on at least 1 of 4 maturity questions had greater benefit than less adherent patients from each of the 5 comfort questions (p < 0.0001). We found an increased statistical separation on each of the 5 comfort questions between religiously adherent and less adherent individuals for patients who scored as adherent on any 2 (n = 40), 3 (n = 50) or all 4 (n = 57) of the maturity questions (p < 0.001). CONCLUSIONS: This study suggests, at least for the Christian faith, that religious patients are subjectively more prone to cope with treatment and that religiosity increases the self-confidence, and possibly the quality of life, of patients with glaucoma or ocular hypertension. Whether this necessarily translates into better glaucoma practices remains to be demonstrated by further studies.

A comparison of dorzolamide/timolol-fixed combination versus bimatoprost in patients with open-angle glaucoma who are poorly controlled on latanoprost.

PURPOSE: The aim of this study was to evaluate the intraocular pressure (IOP) efficacy and safety of dorzolamide/timolol in fixed combination (DTFC) versus bimatoprost in open-angle glaucoma (OAG) patients poorly controlled (> or =21 mmHg) on latanoprost. METHODS: This was a prospective, double-masked, randomized, controlled, cross-over evaluation. After a 6-week wash-out period, the patients then returned for baseline diurnal curve testing every 2 h (8 AM to 8 PM). Patients with an IOP of 22-29 mmHg inclusive at 8 AMwere randomized to either bimatoprost dosed each evening or DTFC twice-daily. Patients returned in 8 weeks for the Period 1 diurnal curve and were switched to the opposite treatment. Patients again returned in 8 weeks for the Period 2 diurnal curve. RESULTS: Of the 29 patients, mean untreated baseline IOP (visit 2) was 24.6 +/- 2.6 mmHg and treatment mean IOP was statistically lower with bimatoprost 17.6 +/- 2.0 mmHg than for DTFC 18.8 +/- 2.5 mmHg (P = 0.03), as was the IOP range (P = 0.02) and IOP peak (P = 0.003). No significant differences were found between DTFC and bimatoprost at individual time points after a modified Bonferroni correction (>0.02). DTFC demonstrated a greater incidence of stinging or burning (n = 12) than bimatoprost (n = 0; P = < 0.0001). CONCLUSIONS: This study suggests that OAG patients generally can obtain similar IOP control at individual time points (when a Bonferroni correction is considered) by switching to either DTFC or bimatoprost, but overall diurnal control is statistically better with bimatoprost.

Success rates for switching to dorzolamide/timolol fixed combination in timolol responders who are insufficiently controlled by latanoprost monotherapy.

PURPOSE: We aimed to investigate the safety and efficacy of dorzolamide/timolol fixed combination (DTFC) in timolol responders with ocular hypertension or open-angle glaucoma who switched to DTFC because of insufficient control on latanoprost. METHODS: We carried out a prospective, open-label cohort study with an active-historical control in which qualifying patients must have been treated with latanoprost monotherapy for at least 4 weeks, must have demonstrated insufficiently controlled intraocular pressure (IOP) (> or = 19 mmHg at 08.00 hours), and must have shown a decrease in IOP at 2 hours after timolol instillation of > or = 3 mmHg or > or = 15%. Patients then began DTFC dosed at 08.00 hours and 20.00 hours and discontinued latanoprost. Patients were evaluated again after 4 and 12 weeks. RESULTS: In 57 patients IOP was further reduced by 2.4 +/- 3.3 mmHg at 08.00 hours (p < 0.0001) and by 3.5 +/- 3.3 mmHg at 10.00 hours (p < 0.0001) after switching to DTFC. Responses to the Comparison of Ophthalmic Medications for Tolerability (COMTol) questionnaire showed no difference between DTFC and latanoprost for in terms of overall preference, typical daily activities, limitation of activities, compliance, satisfaction or quality of life (p > 0.05). However, greater frequency in burning and/or stinging (p < 0.0001) and bitter taste (p < 0.0001) were observed with DTFC, whereas unusual taste (p = 0.02) and itchy eyes (p = 0.05) were associated with latanoprost. CONCLUSIONS: This study suggests that patients who are insufficiently controlled on latanoprost monotherapy, and who are timolol responders, can generally achieve further IOP reduction and similar tolerance levels when changed to DTFC.

The clinical impact and incidence of periocular pigmentation associated with either latanoprost or bimatoprost therapy.

PURPOSE: To evaluate the incidence and characteristics of periocular pigmentation with latanoprost versus bimatoprost. METHODS: A retrospective, active-controlled comparison of consecutive patients treated with latanoprost or bimatoprost for 12 months evaluating patients to determine the incidence, characteristics, and reversibility of periocular pigmentation. RESULTS: Periocular pigmentation was found in 1% patients treated with latanoprost and 6% patients treated with bimatoprost within 12 months of beginning treatment (p = 0.004). CONCLUSIONS: This study suggests that periocular pigmentation may develop after treatment with latanoprost or bimatoprost.

A persistency and economic analysis of latanoprost, bimatoprost, or beta-blockers in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The aim of this study was to evaluate differences in the persistency and treatment costs for latanoprost, bimatoprost, or beta-blockers in open-angle glaucoma or ocular hypertensive patients. METHODS: This study was a retrospective, multicenter, parallel, active-controlled comparison of patients who were prescribed with ocular hypotensive monotherapy between September 1996 and August 2002. RESULTS: 1,182 patients were included. The Kaplan Meier life table analysis showed that latanoprost was continued longest among the groups for the first year of therapy (p=0.02). A significant difference existed between groups in the final intraocular pressure for latanoprost (17.3+/-3.9, N=357), for bimatoprost (18.0+/-3.6, N=146), and for the beta-blockers (17.9+/-3.7, N=335) (p=<0.0001). The average number of visits was statistically higher for beta-blockers (3.3), compared to latanoprost (2.9) and bimatoprost (3.1) (p=0.01). Further, the mean number of medicine changes was greater for bimatoprost (0.45) and beta-blockers (0.47) than for latanoprost (0.27) (p=0.0008). The cost of visits and medications was lowest for beta-blockers ($119.3+/-$78.9) and highest for bimatoprost ($163.8+/-$51.2) (p<0.0001). CONCLUSIONS: Patients were more persistent with latanoprost and demonstrated lower intraocular pressure, fewer visits, and fewer medicine changes when compared to bimatoprost or beta-blocker therapy. In contrast, the beta-blocker group provided lower overall cost.

Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily.

PURPOSE: To evaluate the efficacy and safety of the timolol maleate/latanoprost fixed combination (TLFC) given once each evening versus brimonidine and timolol solution given twice daily as concomitant therapy in primary open-angle glaucoma or ocular hypertension patients. METHODS: Qualified subjects were begun on timolol alone twice daily for 1 month and then randomized to either TLFC or brimonidine and timolol concomitant therapy for 6 weeks. Patients were then switched to the other treatment regimen. Intraocular pressures (IOPs) were measured every 2 hours between 08 : 00 and 20 : 00 hours at baseline and at the end of periods 1 and 2. RESULTS: This study found that in 32 subjects the IOP diurnal curve on timolol alone (20.9 +/- 2.8 mmHg) decreased to 17.9 +/- 3.2 mmHg when patients were treated with TLFC and to 19.0 +/- 2.4 mmHg when patients were treated with brimonidine and timolol (p = 0.02). Intraocular pressures at individual time-points were statistically similar between the groups at the 08 : 00 trough and 2 and 4 hours after dosing. However, beyond 4 hours after dosing, TLFC-treated subjects demonstrated a trend towards lower IOPs at each 2-hour time-point that was not statistically significant after a Bonferroni correction (p

Timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily to patients with primary open-angle glaucoma or ocular hypertension.

OBJECTIVE: To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily. DESIGN: Prospective multicenter, randomized, double-masked, crossover comparison study. METHODS: Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days. RESULTS: Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial. CONCLUSIONS: This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.

The safety and efficacy of timolol 0.5% in xanthan gum versus timolol gel forming solution 0.5%.

PURPOSE: To evaluate the efficacy and safety of timolol maleate 0.5% gel forming solution (TXE, Merck) versus timolol maleate 0.5% gel forming solution (TXG, Falcon) in primary open-angle glaucoma and ocular hypertension patients. METHODS: Following a washout period patients were randomly begun on either TXE or TXG each given once each morning for six weeks (Period 1). Patients then were crossed over to the opposite medicine for Period 2. Following each 6-week treatment period the intraocular pressure was obtained at 08:00 trough and +2 and +8 hours post-dosing. Anterior segment staining and photography were performed to assess surface irritation. RESULTS: Thirty-two patients were enrolled in this study; 28 completed. The diurnal intraocular pressure as well as the 08:00 trough and +2 hour post dosing pressures were statistically equal between groups, although a trend to a lower mean pressure was observed in the TXE (17.9 +/- 3.2 mm Hg) compared to the TXG (18.6 +/- 3.4 mm Hg) group. However, eight hours after dosing the pressure was 17.5 +/- 3.2 mm Hg in the TXE group and 18.9 +/- 3.3 mm Hg in the TXG group (P = 0.0019). Safety was similar between groups, including corneal and conjunctival staining, conjunctival hyperemia graded by anterior segment photography and at the slit lamp, and unsolicited and solicited side effects. Vision recovery after instillation was similar between groups. CONCLUSIONS: TXE demonstrates a lower intraocular pressure eight hours after dosing than does TXG, but safety appears similar between products.

An economic analysis of switching to latanoprost from a beta-blocker or adding brimonidine or latanoprost to a beta-blocker in open-angle glaucoma or ocular hypertension.

BACKGROUND: In treating patients with ocular hypertension or primary open-angle glaucoma, if a single agent cannot successfully control the pressure, additional medications may be prescribed. The cost of treatment may become expensive, especially with multiple drug therapy. Thus, prescribing techniques that help minimize costs may be beneficial to patients when medically appropriate. OBJECTIVE: To evaluate differences in drug and visit costs after switching to latanoprost 0.005% monotherapy (LM) versus adding latanoprost 0.005% once daily (Lbeta) or brimonidine 0.2% twice daily (Bbeta) in patients uncontrolled on beta-blocker therapy alone. METHODS: This study included 148 consecutive qualified charts of open-angle glaucoma or ocular hypertension patients within the first year of follow-up after switching from beta-blocker monotherapy to latanoprost or adding latanoprost or brimonidine. RESULTS: The Bbeta group demonstrated the highest costs per month, followed by the Lbeta group, then the LM group. A trend existed in the Lbeta group to a lower pressure than the Bbeta or the LM groups. A greater mean change in medication per patient per month was seen in the Bbeta group compared to the latanoprost treatment groups. Additionally, a greater number of visits per month occurred in the Bbeta than in the LM and Lbeta groups. The Bbeta group also reported significantly more tearing and fatigue. CONCLUSIONS: This study suggests that in patients uncontrolled on beta-blocker therapy, switching to latanoprost, when medically appropriate, may provide a further mean reduction in intraocular pressure and save costs compared to adding latanoprost or brimonidine.