Comparison of morning versus evening dosing and 24-h post-dose efficacy of travoprost compared with latanoprost in patients with open-angle glaucoma

ABSTRACT

Objective: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and latanoprost at 24-h post-dose.

Research design and methods: Open-angle glaucoma patients not naïve to prostaglandin therapy and currently controlled on p.m.-dosed (2100) latanoprost (n?=?21) or travoprost (n?=?30) had baseline IOPs measured at 0900. In a randomized, single-masked, crossover design, patients received travoprost (Travatan) or latanoprost (Xalatan) at 0900 for 4?weeks, then were crossed over to receive the second prostaglandin for another 4?weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8?week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit.

Main outcome measure: Intraocular pressure (IOP).

Results: The mean IOP in the first period when all patients were dosed in the evening was assessed 12?h after dosing at 09:00 and it was similar in the two treatment groups (mean?±?standard deviation: 17.9?±?2.7?mmHg for travoprost versus 17.7?±?2.5?mmHg for latanoprost, p?=?0.812). In the a.m.-dosing crossover comparison, the 24-h post-dose IOP was significantly lower (?p?<?0.001) on travoprost (16.9?±?3.1?mmHg) compared to latanoprost (18.6?±?3.3?mmHg). In the exit survey, 51% of patients preferred a.m.-dosing.

Conclusions: a.m.-dosed travoprost is superior to a.m.-dosed latanoprost by 1.7?mmHg at 24-h post-dose.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

SUMMARY

Purpose: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.

Research, design and methods: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.

Main outcome measures: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.

Results: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1?month, 2?month and 3?month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 ± 0.9?mmHg vs 18.4 ± 1.8?mmHg, p < 0.001) at the 3?month check. The percentage of responders (IOP decrease ≥ 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.

Conclusions: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Treatment of patients with primary open-angle glaucoma with a fixed combination of brimonidine 0.2%/timolol 0.5%: multicenter,open-label,observational study in Germany*

ABSTRACT

Objective: At the introduction of the fixed-combination of brimonidine/timolol in Germany in 2006, a non-interventional, multicenter, observational, open-label study was initiated to evaluate efficacy, tolerability, and safety of this preparation in a broad patient population.

Methods: The study population comprised patients with bilateral primary open-angle glaucoma or ocular hypertension with insufficient intraocular pressure (IOP) control who participating physicians determined required a change of medication, and who switched to exclusive use of the new fixed-combination brimonidine 0.2%/timolol 0.5%. Patient demographics and information on specific risk factors were collected. IOP readings were recorded for each eye at treated baseline (previous therapy), 4 to 6 weeks, and 12 weeks after changing to twice-daily brimonidine/timolol. Tolerability was measured using a four-step scale ranging from excellent to poor. All adverse events were recorded.

Results: Mean treated baseline IOP (±SD) for all patients (N?=?861) was 20.8?±?3.5?mmHg. Five hundred sixty-five patients switched from monotherapy, 138 patients switched from other fixed combinations, and 158 patients had been using non-fixed combinations of up to four different active agents. The brimonidine/timolol fixed combination provided an additional IOP decrease in most pretreatment subgroups, with an overall reduction to 16.9?±?2.6?mmHg after 4 to 6 weeks and to 16.5?±?2.7?mmHg after 12 weeks. Both of these values were significantly lower than baseline IOP (p?<?0.001). A target pressure of <18?mmHg was achieved in 79.5% of all eyes at week 12. Tolerability of fixed-combination brimonidine/timolol was rated excellent or good by the physicians for 97.1% of patients, and by 93.4% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of brimonidine 0.2%/timolol 0.5% was effective, well tolerated, and safe in a broad POAG patient population.     

Evaluation of the effects on choroidal thickness of bimatoprost 0.03% versus a brinzolamide 1.0%/timolol maleate 0.5% fixed combination

Objective: To investigate the effects of two different medical treatment options on choroidal thickness (CT) in cases of open-angle glaucoma (OAG).

Methods: Sixty-seven eyes newly diagnosed with OAG and 52 healthy eyes constituting the control group were included in the study. Glaucomatous eyes were randomly divided into two subgroups; Group I was started on bimatoprost 0.03% and Group II on a brinzolamide 1.0%/timolol maleate 0.5% fixed combination (BTFC). Intraocular pressure (IOP), ocular pulse amplitude (OPA) and subfoveal CT measurements were performed in all eyes in the study before treatment and on weeks 2, 4 and 8 after treatment.

Results: Mean initial IOP values in groups I and II and the control group were 25.5?±?4.7, 25.1?±?5.2 and 16.1?±?2.9?mmHg, mean OPA values were 3.7?±?1, 3.6?±?1.4 and 2.4?±?0.6?mmHg and mean CT values were 269.4?±?83, 264.5?±?84.4 and 320.1?±?56.6?μm, respectively. Eight weeks after treatment, mean IOP values in Groups I and II and the control group were 18.3?±?2.6, 18.1?±?3.4 and 15.7?±?2.9?mmHg, mean OPA values were 2.9?±?1.2, 2.8?±?1.5 and 2.3?±?0.8?mmHg and mean CT values were 290.2?±?87.3, 271.8?±?82.5 and 319.3?±?56.8?μm, respectively. No significant difference was determined in terms of the decrease in IOP and OPA obtained after treatment in Group I and Group II. However, a significant difference was observed between the two groups in terms of choroidal thickening after treatment.

Conclusion: The use of topical ocular hypotensive medication in eyes with OAG results in an increase in CT. This increase is relatively greater with bimatoprost 0.03% therapy compared to BTFC.     

Influence of switching to travoprost on intraocular pressure of uncontrolled chronic open-angle glaucoma patients compliant to previously-used topical medication

ABSTRACT

Objective: To investigate the influence of switching to travoprost on intraocular pressure (IOP) of chronic open-angle glaucoma (COAG) patients.

Research design and methods: Multicentre, open-label, non-comparative, 12‐week, phase IV study conducted at 10 academic and hospital centres in Hungary. Patients’ compliance to use of the pre-study medication was confirmed at a visit 10 days before the baseline measurements, and compliance was monitored throughout the study period.

Results: Of the 203 COAG patients three (1.48%) ceased travoprost medication due to ocular hyperaemia, and one subject was lost from follow-up. Self-reported compliance was optimal except for two patients. For the per-protocol analysis 197 patients were evaluable. IOP of the 37 per-protocol patients receiving additional travoprost medication decreased from 23.1 ± 3.2?mmHg (mean ± SD) to 17.3 ± 2.6?mmHg at week 12 (?p < 0.001). Switching the 121 per-protocol patients from latanoprost to travoprost IOP decrease from 20.8 ± 3.5?mmHg to 17.7 ± 2.4?mmHg (?p < 0.001). IOP of the 11 patients switched from topical non-selective beta-blockers to travoprost decreased from 20.1 ± 2.1?mmHg to 15.7 ± 1.5?mmHg (?p < 0.001). For the whole per-protocol population (n = 197) IOP decreased from 21.0 ± 3.4?mmHg to 17.4 ± 2.4?mmHg (?p < 0.001). Defining responders as having an IOP decrease > 2.0?mmHg or ≥ 5?mmHg at week 12, the responder rate was respectively 62.9% or 31% for the total study population; 86.5% or 54.1% when travoprost was added to the established therapy; 54.5% or 24.0% if latanoprost was switched to travoprost; and 90.9% or 36.4% for those who switched from beta-blockers.

Conclusion: Travoprost provided a clinically and statistically significant IOP decrease in uncontrolled COAG patients whose self-reported compliance to their previous topical medication was optimal. Our results suggest that the IOP reduction found after switching to travoprost is not explainable by improved compliance due to the clinical study situation.     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%*

ABSTRACT

Purpose: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan^?) compared to latanoprost 0.005% (Xalatan^?) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension.

Methods: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients’ IOP was measured throughout two consecutive 24‐h periods every 4?h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4?h throughout two 24‐h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9?mmHg and 80% power to detect a difference of 2.5?mmHg between treatments.

Results: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (?p < 0.05) at 12, 16, 20, 24, 36, 40, and 48?h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24‐h period of the week 2 visit as well as for the 48‐h visit were statistically lower (?p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated.

Conclusion: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

Three-month,randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT

Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.

Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n?=?101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n?=?79).

Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.

Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.

Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p?=?0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p?=?0.213). Patients on brimonidine–timolol reported less burning (p?<?0.001), stinging (p?<?0.001), and unusual taste (p?<?0.001) than patients on dorzolamide–timolol.

Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.     

Intraocular pressure reduction with travoprost/timolol fixed combination,with and without adjunctive brinzolamide,in glaucoma

ABSTRACT

Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension.

Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004?%?, then switched to evening travoprost 0.004?%?/timolol 0.5?%?fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1?%?ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period.

Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p?<?0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences.

Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Intraocular pressure lowering effect of brinzolamide 1.0% as adjunctive therapy to latanoprost 0.005% in patients with open angle glaucoma or ocular hypertension: an uncontrolled, open-label study

PURPOSE: A prospective study was conducted to evaluate the intraocular pressure (IOP) lowering effect of brinzolamide 1.0% ophthalmic suspension as an adjunctive therapy with latanoprost 0.005% ophthalmic solution in patients with open angle glaucoma or ocular hypertension. PATIENTS AND METHODS: Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy. The IOP values at 1 month, 2 months, and 3 months were compared with those measured immediately before adding brinzolamide to the regimen (baseline). The incidence of adverse events such as conjunctival hyperemia and corneal epithelial defect were also examined. RESULTS: The baseline IOP was 21.1 +/- 4.8 mmHg (mean +/- standard deviation). After 1 month, 2 months, and 3 months of therapy IOP was 16.9 +/- 4.5 mmHg, 16.6 +/- 4.0 mmHg, and 15.9 +/- 3.1 mmHg, respectively, showing significant reductions in IOP at all the measuring time-points during the study compared with the baseline value (p < 0.01). Conjunctival hyperemia developed in one patient after 1 month and in another after 2 months; however, both were mild, and therapy was continued. Corneal epithelium defect was observed in 3 patients. One of them had mild defect before brinzolamide was added to the regimen. Increase of eye discharge was seen in one patient. No serious side effects were otherwise observed. CONCLUSION: The addition of brinzolamide to a latanoprost 0.005% regimen may further lower intraocular pressure in patients with open angle glaucoma or ocular hypertension.     

Efficacy,tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter,open-label observational study*

ABSTRACT

Objective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort^?) among German patients.

Methods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n?=?606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.

Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7?±?3.5?mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6?±?2.7?mmHg (p?<?0.001 vs. baseline) after 4–6 weeks and to 16.1?±?2.6?mmHg (p?<?0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18?mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.     

Preservative-free versus preserved brimonidine %0.15 preparations in the treatment of glaucoma and ocular hypertension: short term evaluation of efficacy,safety, and potential advantages

Abstract

Purpose: To compare the efficacy, safety, and potential advantages of the preservative-free versus preserved brimonidine %0.15 preparations in patients with primer open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: Forty-two eyes of the 21 treatment-naive patients with POAG or OHT were enrolled in this study. Eyes were randomly assigned to receive brimonidine-purite 0.15% or preservative-free brimonidine 0.15% two times daily. Efficacy of the two eye drops was assessed by measuring the intraocular pressure (IOP) at 9–10 am at baseline and week 4. Safety and potential advantages of the drops were evaluated at weeks 4 in terms of ocular symptoms and tear parameters. Ocular symptom values of the patients were evaluated with a scale of 0–4 (0?=?no discomfort and 4?=?severe discomfort).

Results: Both of the brimonidine tartrate formulations resulted in statistically similar IOP reduction (preserved formulation; ?5.2?mmHg [22.9% reduction] preservative-free formulation; ?5.7?mmHg [24.1% reduction], p?=?0.37). It was found that brimonidine tartrate formulations with and without topical preservatives did not produce a statistically significant difference in pain, stinging, and blurred vision at the upon instillation (p?>?0.05). However, the burning sensation was significantly higher in the preservative-free formulation at the first instillation compared to the preserved formulation (p?=?0.01). Also, there was no statistically significant difference between the two formulations in terms of symptoms (itching, burning, tearing, stinging, and photophobia) and tear parameters during the day (p?>?0.05).

Conclusions: Although topical preservative-free brimonidine tartrate treated eyes had a more burning sensation at the first drop, the two formulations were similar in terms of ocular tolerability in the short term period. Also, both formulations were found to reduce IOP at a similar rate.     

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL).

Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups.

Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85?±?8.41 and 38.66?±?10.47 years, mean spherical equivalent (SE) values were ?0.15?±?0.4 and 0?±?0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58?±?3.41?mmHg, 23.69?±?0.56?mm, 84.3?±?5.83?μm and 92.3?±?3.51?μm in the smokers group and 18.5?±?2.91?mmHg, 23.45?±?0.72?mm, 86.11?±?8.02?μm and 97.66?±?8.23?μm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18?±?26.14, 117.05?±?5.51, 64.95?±?8.67 and 63.5?±?6.88?μm in the smokers group and 130.81?±?11.8, 123.55?±?11.03, 72.44?±?9.84 and 58.44?±?7.48?μm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p?>?0.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p?=?0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p?=?0.01 and p?=?0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p?=?0.96 and p?=?0.07, respectively).

Discussion: Smoking may affect RNFL thickness but not GCIPL.     

The short-term and long-term adverse ocular effects of fesoterodine fumarate

Aim: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA).

Method: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4?mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically.

Results: The mean age of 120 women was 52.06?±?9.39 years (30–70 years). The mean PD, IOP and AA values were 4.12?±?0.61?mm (3.00–5.70?mm), 15.58?±?1.74?mmHg (11–20?mmHg) 2.28?±?1.26?Diopter (D) (0.50–5.50?D) at baseline; 4.68?±?0.65?mm (3.20–5.80?mm), 16.11?± 1.72?mmHg (11–20?mmHg), 1.68?±?1.04?D (0.25–4.50?D) at 30th day; and 4.28?±?0.58?mm (3.10–5.70?mm), 16.09?±?1.96?mmHg (11–19?mmHg), 2.18?±?1.19?D (0.50–5.00?D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p?<?0.001 for each), the changes in IOP values were not as such (p?=?0.642). Visual complaint was not observed in any patient.

Discussion: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.     

Effect of mydriasis induced by topical 0.5% tropicamide instillation on the corneal biomechanical properties in healthy individuals measured by ocular response analyzer

Purpose: This observational study aims to investigate the effects of tropicamide (0.5%) on corneal biomechanical properties, with the ocular response analyzer (ORA), in healthy individuals.

Methods: Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) measurements of 38 (21 female and 17 male) healthy individuals, before and after 30?min of 0.5% tropicamide instillation, were performed by using the ORA.

Results: The mean CH, CRF, IOPg and IOPcc measurements of the eyes were 10.2?±?1.9?mmHg, 10.3?±?2.1?mmHg, 15.7?±?3.4?mmHg, 16.4?±?3.3?mmHg pre-tropicamide, and 10.4?±?1.7?mmHg, 10.3?±?2.1?mmHg, 15.3?±?3.4?mmHg, 15.8?±?2.7?mmHg post-tropicamide, respectively. The differences between the pre- and post-tropicamide measurements of the eyes were insignificant (p?=?0.184, p?=?0.659, p?=?0.294, p?=?0.150, respectively; paired t-test).

Conclusions: A tropicamide instillation does not lead to significant changes in the corneal biomechanical properties. Therefore, it can be used safely in disease, i.e. in the diagnosis and follow-up ORA as it does not cause any change.     

A meta-analysis of topical prostaglandin analogues intra-ocular pressure lowering in glaucoma therapy

ABSTRACT

Objective: To compare the ef?cacy of latanoprost, bimato­prost and travoprost for lowering IOP in patients with glaucoma.

Research design and methods: In order to carry out this meta-analysis, randomized trials (2001–2004) were identi?ed on Medline and EMBASE using the following key words: glaucoma, ocular hypertension (OHT), random­ization, trial, latanoprost, bimatoprost and travoprost. The studies had to compare at least two prostaglandin analogues as mono-therapy. Cross-over experimental designs were excluded. The main outcome measure was IOP at ?nal visit. Statistical analyses included random effects, pooled estimates of treatment effects, tests for publication bias, and random-effects models to obtain adjusted treatment effects on ?nal IOP after lowering for baseline IOP, and duration of follow-up. Random effects Poisson regression models were used to estimate the adjusted effects of treatments on response rates (IOP < 18?mmHg).

Results: Nine studies were used in the analysis. Patient mean age varied from 56.7 to 68.8 years and baseline IOP ranged from 22.3 to 26.5?mmHg. Three hundred and seventy-eight patients were treated with bimatoprost, 385 with travoprost and 555 with latanoprost. Patients treated with travoprost and bimatoprost had lower IOP levels at the end of follow-up (–0.98?mmHg [95% CI: –2.08; 0.13; p = 0.08] and –1.04?mmHg [95% CI: –2.11;0.04; p = 0.06], respectively) than those treated with latanoprost. The combined effect of newer prostaglandin analogues (bimatoprost/travoprost) was an adjusted decrease of 1.00?mmHg [95% CI: –1.91;–0.10], p = 0.03], or a 17% higher adjusted response rate (Incidence Rate Ratio 1.17, 95% CI, 1.00–1.35, p = 0.04), compared to latanoprost.

Conclusion: Travoprost and bimatoprost may have greater ef?cacy in lowering IOP for patients with OHT or glaucoma.     

Ocular hypotensive efficacy of travoprost in patients unsuccessfully treated with latanoprost

SUMMARY

Objective: To evaluate the efficacy of travoprost 0.004% monotherapy in patients unsuccessfully treated with latanoprost monotherapy.

Research design and methods: Open-label, non-comparative study conducted at US academic and private practice clinics in adult patients with ocular hypertension or primary open-angle glaucoma who required a change in therapy (due to either inadequate efficacy or safety issues) as judged by the investigator. Intraocular pressure (IOP) was measured at entry and 30?days later.

Main outcome measures: Mean change in intra-ocular pressure (mm Hg).

Results: Reported here are 488 per-protocol patients from 330 centers who were using latanoprost monotherapy prior to study entry, and who received travoprost monotherapy during the study. Patients had a mean age of 69?years, were approximately two-thirds Caucasian, 60% female, predominantly brown or blue eyes, and 91% were diagnosed as having primary open-angle glaucoma. The mean days in treatment were 31.9 ± 6.4. Mean IOP at study entry was 21.2?mm Hg. Following travoprost monotherapy, this was reduced by a mean of 3.2?mm Hg to 18?mm Hg (?p < 0.0001, paired t-test). There were 21 adverse events reported in the intent-to-treat (ITT) population for an incidence of 3.5%. There were some limitations to the current study including: no washout period, no control therapy, single IOP determinations at the beginning and the end of the study; patient compliance with the initial therapy was not measured, and the study was not masked. This study reflects a real-life situation of what a clinician can expect when he changes a patient from latanoprost monotherapy to travoprost monotherapy.

Conclusion: This study showed that travoprost provided a statistically and clinically significant reduction (?p < 0.0001) in IOP of 3.2?mm Hg for patients who had not been successfully treated with latanoprost monotherapy. The results of this trial demonstrate the potential benefit of using travoprost as a replacement therapy in order to ensure adequate IOP control.     

Exenatide effects on diabetes,obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

ABSTRACT

Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A_1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of?≥?3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety.

Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5?µg exenatide, or 10?µg exenatide for 30 weeks, followed by 5?µg exenatide BID for 4 weeks, then 10?µg exenatide BID for ≥3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas.

Results: 217 patients (64% male, age 58?±?10 years, weight 99?±?18?kg, BMI 34?±?5?kg/m², A1C 8.2?±?1.0% [mean?±?SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (?1.1?±?0.1% [mean?±?SEM]) were sustained to 3 years (?1.0?±?0.1%; p?<?0.0001), with 46% achieving A1C?≤?7%. Exenatide progressively reduced body weight from baseline (?5.3?±?0.4?kg at 3 years; p?<?0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n?=?116) had reduced ALT (?10.4?±?1.5?IU/L; p?<?0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (?6.1?±?0.6?kg vs. ?4.4?±?0.5?kg; p?=?0.03), however weight change was minimally correlated with baseline ALT (r?=??0.01) or ALT change (r?=?0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n?=?151). Triglycerides decreased 12% (p?=?0.0003), total cholesterol decreased 5% (p?=?0.0007), LDL-C decreased 6% (p?<?0.0001), and HDL-C increased 24% (p <?0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison.

Conclusion: Adjunctive exenatide treatment for ≥3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.     

Evaluation of an isotonic tear in combination with topical cyclosporine for the treatment of ocular surface disease

ABSTRACT

Purpose: To determine whether a new category of artificial tear product, carboxymethylcellulose 0.5% with compatible solutes (CMC-solutes) (Optive, Allergan, Inc., Irvine, California) improves clinical outcomes when used adjunctively with topical cyclosporine 0.05% (Restasis, Allergan, Inc., Irvine, California) for the treatment of ocular surface disease.

Methods: Nineteen patients with ocular surface disease treated with cyclosporine 0.05% for at least 3 months and who had previously used other artificial tears adjunctively were enrolled. Patients discontinued their previous artificial tear and used CMC-solutes, concomitant with topical cyclosporine 0.05%. Corneal evaluation and tear production parameters were evaluated before and during combined CMC-solutes/cyclosporine treatment. Patients also completed a questionnaire before and during treatment with combined CMC-solutes/cyclosporine. Follow-up was at 1 and 3 months.

Results: Most objective measures of ocular surface health were unchanged, but an improvement in conjunctival lissamine green staining and tear break-up time was found. Conjunctival lissamine green staining scores improved from 3.4 ± 2.5 to 1.9 ± 2.5 by Month 3 (?p = 0.004). Tear break-up time improved from 4.6 ± 3.9?s pre-treatment to 5.3 ± 3.8?s post-treatment (?p = 0.049). Ocular Surface Disease Index (OSDI) scores improved from 16.2 ± 9.4 at baseline to 11.5 ± 8.9 at month 3 (?p = 0.007). Subjectively, patients graded their ocular discomfort as 2.7 at baseline and as 2.3 at Month 3 (?p = 0.049). At Month 3, 89.5% of patients said they liked CMC-solutes as well or better than previous drops they had used. All patients said CMC-solutes provided similar or improved relief of symptoms of dry eye than previous eye drops. There were no tear-related adverse events reported.

Conclusions: In this study, CMC-solutes, when used in conjunction with cyclosporine 0.05%, provided patients with an improvement in objective signs and subjective symptoms of ocular surface disease compared to their previous artificial tears. Further studies are warranted.     

Changes in intraocular pressure following a switch from latanoprost monotherapy to latanoprost/timolol fixed combination therapy in patients with primary open-angle glaucoma or ocular hypertension: results from a clinical practice database

ABSTRACT

Aims: To assess the incremental change in intraocular pressure (IOP) levels in patients with primary open-angle glaucoma or ocular hypertension, insufficiently treated with topical ocular hypotensive monotherapy or combination therapy and changed to the latanoprost/timolol fixed-combination therapy (LTFC).

Methods: The glaucoma database of the Glasgow Royal Infirmary was reviewed retrospectively to identify patients ≥?18 years of age with primary open-angle glaucoma or ocular hypertension in at least one eye who had been switched to LTFC from a previous monotherapy or combination therapy. Ninety patients were identified, and 59 (66%) had changed to LTFC from latanoprost monotherapy (LM). The analysis focused on this subgroup because few patients were changed from any other single therapy. At least one documented patient visit following the change to LTFC was required. The within-subject difference in IOP levels (IOP on LM–IOP on LTFC) was calculated for each case, and the statistical significance of the mean change in IOP was analysed using a 2-sided Student's paired t-test with a 0.05 α level.

Results: The mean decrease in IOP after changing to LTFC from LM was 2.6?mmHg (95% confidence interval?=?1.6, 3.6), from 21.4 (SD?=?3.5) mmHg to 18.8 (SD?=?4.2) mmHg (p?=?0.002).

Conclusions: LTFC provides significant incremental IOP reduction in patients with primary open-angle glaucoma or ocular hypertension who require additional IOP reduction following treatment with LM.