Effects of selective serotonin reuptake inhibitors on intraocular pressure and anterior segment parameters in open angle eyes

Purpose: To evaluate the short- and long-term effects of selective serotonin reuptake inhibitors (SSRIs) on intraocular pressure (IOP) and anterior segment parameters in open angle eyes.

Materials and methods: This cross-sectional study included 325 eyes of 166 subjects. Subjects were divided into three groups: Group 1 included 116 eyes of 58 patients receiving SSRIs for 1?week–6?months, Group 2 included 102 eyes of 53 patients receiving SSRIs for longer than 6?months and Group 3 included 107 eyes of 55 healthy subjects not receiving any drugs. All of the patients receiving SSRIs were diagnosed as major depressive disorder. All groups were chosen to be similar in terms of age and gender. All patients underwent a detailed ophthalmologic examination including IOP measurement by Goldmann applanation tonometer and gonioscopy. Anterior segment parameters including pupil diameter (PD), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were assessed by a Scheimpflug system.

Results: Pupil diameter was significantly larger in patients receiving SSRIs for <6?months and ≥6?months than the control subjects (3.53?±?0.71?mm, 3.48?±?0.60?mm versus 3.11?±?0.72?mm, p?p?Conclusions: Selective serotonin reuptake inhibitors cause mydriasis which is persistent during the treatment. In depression patients with open angle eyes, short- and long-term use of SSRIs leads to decrease in IOP.     

Effect of trospium chloride therapy on intraocular pressure and tear secretion in overactive bladder patients

Purpose: To investigate the effect of trospium chloride, which has an anticholinergic effect, used in overactive bladder (OAB) treatment on the intraocular pressure (IOP) and tear secretion after 12 weeks of treatment.

Materials and methods: This prospective study was performed at a single center between October 2014 and January 2016. A detailed history was obtained from the female OAB patients at the eye outpatient department. After checking the exclusion criteria, oral trospium chloride 30?mg bd was started. The patients were followed-up in terms of drug effectiveness and ophthalmic and other side effects at the 4th and 12th weeks. All procedures were repeated at both of these time-points.

Results: The mean age of the patients was 48.98?±?11.98 years (range 19–75). The data of 80 OAB patients were evaluated in the study. Trospium chloride did not cause any significant change in the OAB patients regarding their 4th week and 12th week IOP measurements (p?=?0.251, p?=?0.340, respectively). It was found to decrease tear secretion significantly at both time-points (p?=?0.020, p?=?0.001, respectively). Trospium chloride treatment of one patient (1.25%) was discontinued due to dry eye.

Conclusions: Trospium chloride decreases the symptoms in female OAB patients. Trospium chloride can be safely used in female OAB patients with normal IOP and no comorbidity as regards IOP changes as it did not cause a significant change in IOP in these patients. Pre-treatment and post-treatment dry eye symptoms of OAB patients about to start using trospium chloride should be queried beforehand as it can cause a statistically significant decrease in tear secretion. We concluded that it would be appropriate to refer the patients to an ophthalmologist before starting the drug if relevant symptoms are present.     

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.     

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.     

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.     

The ocular surface side effects of an anti-psychotic drug,clozapine

Purpose: The purpose of this study is to investigate the effects of long-term clozapine usage on tear film stability and corneal topographic parameters.

Material and methods: The study was conducted between March 2014 and November 2014. Thirty patients who were diagnosed of schizophrenia and have been under clozapine treatment for 2.73?±?0.73 years (range 2–4 years) were involved in this study (group 1). Thirty healthy subjects (group 2) who have statistically similar demographic features compared with the group 1, were involved as a control group. Full ophthalmologic examination with biomicroscopy and indirect ophthalmoscopy was applied. Corneal topographic parameters were measured using the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL) program.

Results: K₁ value was measured as 43.39?±?0.17?D (43–43.50?D) and K₂ value was measured as 43.39?±?0.06?D (43.30–43.50?D) in groups 1 and 2, respectively. In groups 1 and 2, K₂ values were noted as 43.86?±?0.27?D (43.50–44.50?D) and 43.72?±?0.18?D (43.50–44.00?D), respectively. Central corneal thickness was found to be 523.93?±?15.66?µm (495–554?µm) and 550.13?±?1.03?µm (520–580?µm) in groups 1 and 2, respectively. Corneal apex thickness was 525.86?±?15.75?µm (497–556?µm) in group 1 and 551.60?±?14.99?µm (521–581?µm) in group 2. The corneal thickness of thinnest location was 520.93?±?15.60?µm (492–551?µm) and 548.06?±?15.17?µm (518–578?µm) in groups 1 and 2, respectively. Corneal volume was determined as 58.13?±?3.46?mm³ (52–64?mm³) in group 1 and 60.73?±?3.76?mm³ (54–66?mm³) in group 2. The Schirmer test showed thichkness of 3.33?±?0.72?mm (2–4?mm) and 13.60?±?1.59?mm (11–16?mm) in groups 1 and 2, respectively. The mean fluorescein break-up time was 5.40?±?1.50?s (3–8?s) and 12.46?±?1.40?s (10–14?s) in groups 1 and 2, respectively. There was a statistically significant difference in the Schirmer test, fluorescein break-up time, central corneal thickness, corneal apex, and the thinnest corneal location thickness between the two groups.

Conclusion: Clozapine may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities. Because of these corneal alterations, one should be aware of evaluating patients having diseases like glaucoma or preoperative selection of corneal refractive surgery candidates.     

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion

Objective: To evaluate the effects of dexamethasone (DEX) implant (Ozurdex®) on corneal endothelium in patients with retinal vein occlusion complicated with macular edema.

Materials and methods: Patients (n?=?31) received 1–3 intravitreal DEX implants in one eye. Measurements were intraocular pressure (IOP) at baseline and 1, 3, and 6 months after the first intravitreal injection and corneal specular microscopy and central corneal thickness (CCT) at baseline and 1 and 6 months. We analyzed endothelial cell density (ECD), coefficient of variation of cell size (CV), and percentage of hexagonality.

Results: Mean follow-up period was 9.7?±?3.3 months. Mean number of injections was 1.5?±?0.8. Mean IOP values were 15.6?±?2.6?mm Hg at baseline, 17.7?±?3.6?mm Hg at one month, 16.4?±?4.1?mm Hg at three months, and 16.0?±?2.7?mm Hg at six months. There was a significant difference in mean IOPs at one month and six months (p?=?0.008). There were no significant differences in mean ECD (p?=?0.375), CV (p?=?0.661), percentage of hexagonality (p?=?0.287), and CCT (p?=?0.331).

Conclusion: Although intravitreal injection of 0.7?mg DEX causes moderate elevation of IOP, it does not seem to have detrimental effects on corneal endothelium at six months.     

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.     

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.     

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea

Objectives: The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz) in Korean patients with overactive bladder (OAB) in routine clinical practice. Methods: This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator’s discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.

Results: A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24?hours decreased by 4.0, 2.4, and 0.8, respectively (all p?<?0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.

Conclusion: These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.     

Brimonidine purite 0.1% versus brinzolamide 1% as adjunctive therapy to latanoprost in patients with glaucoma or ocular hypertension

ABSTRACT

Objective: To evaluate the efficacy and tolerability of brimonidine purite 0.1% in comparison to brinzolamide 1% when used as adjunctive therapy to latanoprost 0.005% in patients with glaucoma or ocular hypertension.

Methods: Randomized, single-center, investigator-masked, parallel-group clinical study. Patients with IOP?≥?18?mmHg while on once-daily latanoprost were randomized to adjunctive treatment with brimonidine purite TID (n?=?20) or brinzolamide TID (n?=?20) for 3 months. Intraocular pressure (IOP) was measured at 8 a.m., 10 a.m., and 4 p.m. at latanoprost-treated baseline and after 1 and 3 months of latanoprost and adjunctive therapy. A patient questionnaire was administered to evaluate the tolerability of eye drop instillation.

Results: Baseline mean diurnal IOP (± standard deviation, mmHg) on latanoprost was comparable between groups (brimonidine purite: 19.6?±?2.94; brinzolamide: 19.8?±?3.25; p = 0.846). Mean diurnal IOP at Month 3 was 16.3?±?2.63?mmHg with brimonidine purite and 17.8?±?2.19?mmHg with brinzolamide (?p = 0.028). Adjunctive use of brimonidine purite provided greater IOP lowering than brinzolamide at 10 a.m. (?p < 0.001) and 4 p.m. (?p = 0.050) and equivalent IOP lowering to brinzolamide at 8 a.m. (?p = 0.716). Blurred vision at Month 1 and bitter taste at Months 1 and 3 were more common upon instillation of brinzolamide eye drops.

Conclusion: Brimonidine purite 0.1% provided significantly lower IOP compared with brinzolamide 1% when used as adjunctive therapy to latanoprost. Both adjunctive therapies were well tolerated. Limitations of this study include the use of a single site and the sample size. Additional studies are needed to further evaluate these drugs as adjunctive therapy to prostaglandin analogs.     

Characteristics of antimuscarinic responders versus suboptimal responders in a randomized clinical trial of patients with overactive bladder symptoms

Objective: To assess the characteristics of tolterodine extended-release (ER) 4?mg responders and suboptimal responders (≤50% decrease in UUI episodes/24?h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8?mg in tolterodine suboptimal responders.

Methods: Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24?h at week ?2 received open-label tolterodine ER 4?mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4?mg for 1 week, 8?mg for weeks 2–12) or placebo once daily. Post-hoc analyses compared the percentage change from week ?2 to week 0 in UUI episodes/24?h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8?mg among tolterodine suboptimal responders.

Results: Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24?h at week ?2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24?h after tolterodine treatment at week 0 (80.0% versus 15.3%; p?p?=?.0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.

Conclusions: For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8?mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.     

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.     

Peri-implant soft-tissue parameters and crestal bone levels among narghile smokers and nonsmokers

This retrospective convenient sample case–control study investigated the peri-implant soft-tissue inflammatory parameters and crestal bone loss (CBL) among narghile smokers (NS) (Group I) and nonsmoking controls (Group II). Demographic data were collected using a questionnaire. Peri-implant plaque index (PI), bleeding-on-probing (BOP) and pocket-depth (PD) were assessed; and peri-implant CBL was measured on standardized digital bite-wing radiographs. Sample-size was estimated and statistical analysis were done using Mann–Whitney U-test. Level of significance was set at p?p?p?p?p?p?相似文献   

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.     

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.     

Efficacy and safety of the single pill combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not controlled by amlodipine 10 mg plus olmesartan 20 mg in free combination

ABSTRACT

Background and objective: For patients with moderate hypertension (grade 2, defined as systolic blood pressure [SBP] 160–179?mmHg and/or diastolic blood pressure [DBP] 100–109?mmHg), current guidelines recommend initial combination therapy and rapid dose-adjustment to achieve blood pressure goal. In this study we investigated the efficacy and tolerability of the single pill combination of amlodipine 10?mg plus valsartan 160?mg (A?10?+?Val 160) in patients not controlled by the free combination of amlodipine 10?mg plus olmesartan 20?mg (A?10?+?O 20).

Methods: In this prospective, open-label, non-randomized trial, 257 patients with mean sitting DBP of 100–109?mmHg at trough entered a 4 week treatment phase with A?10?+?O 20 in free combination once daily. Patients in whom DBP remained uncontrolled were switched in a second 4 week treatment phase to A?10?+?Val 160. The primary efficacy variable was the reduction in DBP at week 8 compared to week 4 in the intent-to-treat population.

Results: In the total cohort, baseline SBP/DBP of 164.2?±?9.8/103.6?±?2.1?mmHg decreased by 19.2?±?12.4/14.1?±?7.4?mmHg at week 4. In patients who did not achieve BP control (n?=?175), subsequent treatment with A?10?+?Val 160 for 4 weeks reduced SBP from 149.6?±?11.1 at week 4 by 7.9?mmHg at week 8 (95% CI: 6.1–9.6, p?<?0.0001) and DBP from 93.4?±?3.9?mmHg by 9.1?mmHg (95% confidence interval: 8.1–10.2, p?<?0.0001). The combination of A?10?+?Val 160 was well tolerated, and the observed adverse events (15.3% of patients in phase 2) were consistent with the known drug profiles.

Conclusions: In a study designed to reflect typical clinical practice, in patients not controlled by the free combination of A?10?+?O 20, the single pill combination of A?10?+?Val 160 produced a statistically and clinically significant additional BP reduction and was well tolerated. Potential limitations of the design (open-label, non-controlled design, short term treatment) have to be taken into account.     

Attaining United States and European Guideline LDL-C Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SUMMARY

Objectives: The primary objective was to assess the effects of rilmenidine monotherapy and in combination with perindopril on blood pressure (BP) in patients assessed with grade 1 or 2 essential hypertension. The study also examined the effects of 2-year rilmenidine monotherapy on left ventricular hypertrophy (LVH) and on diastolic function of the left ventricle, along with the effects of rilmenidine on left ventricular mass index in hypertensive patients with no LVH, and the relationship between BP reduction and any change in LVH.

Research design and methods: Mild-to-moderate hypertensive patients (n?=?500) were enrolled in a multicentre 2-year open study and treated with rilmenidine (1-2?mg per day) monotherapy or rilmenidine plus perindopril (2, 4 or 8?mg per day) if control of hypertension was not achieved with rilmenidine monotherapy within 12 weeks. Blood pressure was recorded at regular intervals by the investigators and LVH measured by centralised single-blind echocardiographic reading.

Results: Rilmenidine monotherapy (average dose 1.42?mg) produced a significant decrease in BPfrom the baseline of 163?±?10/100?±?5?mmHg to 134?±?10/86?±?7?mmHg at 1 year and to 136?±?10/84?±?7?mmHg at 2 years (p?2 at 2 years (p?Conclusions: Long-term rilmenidine monotherapy was shown to be efficient in controlling BP and in reducing LVH. The addition of perindopril to rilmenidine monotherapy proved to be effective and well tolerated in those patients who did not respond to rilmenidine alone.     

Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study

Abstract

The aims of this study were to design and characterize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLN) with and without modification of low molecular weight chitosan (CS) and compare their potentials for ocular drug delivery. Low molecular weight CS was obtained via a modified chemical oxidative degradation method. SLN with CS (CS-SLN-MTZ) and without CS (SLN-MTZ) were prepared according to a modified emulsion-solvent evaporation method. SLN-MTZ and CS-SLN-MTZ were 199.4?±?2.8?nm and 252.8?±?4.0?nm in particle size, ?21.3?±?1.9?mV and +31.3?±?1.7?mV in zeta potential, respectively. Physical stability studies demonstrated that CS-SLN-MTZ remained stable for at least 4 months at 4?°C, while SLN-MTZ no more than 2 months. A prolonged in vitro release profile of MTZ from CS-SLN-MTZ was obtained compared with SLN-MTZ. Furthermore, CS-SLN-MTZ presented a better permeation property in excised rabbit cornea. In vivo studies indicated that the intraocular pressure lowering effect of CS-SLN-MTZ (245.75?±?18.31?mmHg?×?h) was significantly better than both SLN-MTZ (126.74?±?17.73?mmHg?×?h) and commercial product Brinzolamide Eye Drops AZOPT® (171.17?±?16.45?mmHg?×?h). The maximum percentage decrease in IOP of CS-SLN-MTZ (42.78?±?7.71%) was higher than SLN-MTZ (27.82?±?4.15%) and was comparable to AZOPT (38.06?±?1.25%). CS-SLN-MTZ showed no sign of ocular irritancy according to the Draize method and the histological examination.     

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers

Context: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system.

Objective: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats.

Material and methods: Animals were randomized into control, kernel extract (100 and 200?mg/kg/d, orally), dexamethasone (0.03?mg/kg/d, subcutaneously), dexamethasone?+?kernel (100 and 200?mg/kg/d, separately), and dexamethasone?+?captopril (25?mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX).

Results: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128?±?7 vs. 105?±?3?mmHg, p?p?p?p?Conclusion: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.