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.     

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.     

Intraocular pressure reduction in the untreated fellow eye after selective laser trabeculoplasty

ABSTRACT

Objective: To investigate the effect of selective laser trabeculoplasty (SLT) on the intraocular pressure (IOP) of untreated fellow eyes in patients with open-angle glaucoma.

Study design: Retrospective chart review.

Patients and methods: Charts of all patients who underwent SLT at the University of Texas Southwestern Medical Center at Dallas between September 2003 and May 2006 were reviewed. Each patient had IOP measurements by Goldmann applanation tonometry in both eyes preoperatively, and at 1 hour, 2 weeks, 3 months, and 6 months postoperatively. Patient age, gender, diagnosis, central corneal thickness (CCT), previous intraocular surgeries, and degrees of laser treatment were tabulated for each patient. Patients with a history of previous glaucoma surgery in either eye were excluded as were those who underwent any change in glaucoma medications or further laser or surgical intervention in either eye within 6 months of SLT. Data were analyzed using a paired two-tailed t-test, an unpaired two-tailed t-test, ANOVA, and linear regression.

Results: A total of 43 patients were included through 6 months of follow-up. Mean reduction in IOP in the treated eye was 3.9?±?0.6?mmHg or 18.8% (p?<?0.001) at final exam. Mean IOP reduction in the fellow untreated eye was 2.1?±?0.5?mmHg or 11.2% (p?<?0.01). Patients with higher preoperative IOPs had a greater reduction in IOP in both eyes (p?<?0.001 for treated eyes, and p?=?0.02 for untreated eyes). Patients who were on a larger number of glaucoma medications preoperatively had a greater response in both eyes (treated eye p?=?0.002, untreated eye p?=?0.008). There was no significant difference in IOP response in either eye based on age, gender, CCT, degrees of treatment, or phakic status.

Conclusions: SLT produces a sustained and statistically significant IOP reduction in the fellow untreated eyes of patients with open-angle glaucoma. The results of our study support a biological mechanism of action for SLT. Limitations of this study include its retrospective design, relatively small sample size, a possible effect of increased compliance with medical therapy following SLT, and an inherent bias of excluding patients who underwent a change in medications or further laser or surgical therapy during the period under review.     

Accelerated corneal collagen cross-linking for progressive keratoconus

Purpose: To evaluate the efficacy of accelerated corneal cross-linking (CXL) procedure for progressive keratoconus.

Materials and methods: Twenty-three eyes of 23 patients undergone accelerated CXL procedure were evaluated preoperatively and postoperatively at 1st, 3rd and 6th month for uncorrected distant visual acuity (UDVA), best corrected distant visual acuity (CDVA), spherical error, cylindrical error, spherical equivalent (SE), keratometric values and thinnest corneal thickness (TCT) values with corneal topography by Scheimpflug camera and endothelial cell density (ECD).

Results: The mean UDVA was improved from 0.97?±?0.41 logarithm of minimal angle of resolution (logMAR) to 0.76?±?0.45 logMAR at the 6th month after CXL (p?=?0.332). The mean CDVA was improved from 0.49?±?0.30 logMAR to 0.34?±?0.22 logMAR at the 6th month after CXL (p?=?0.026). The mean sphere was decreased from ?4.47?±?4.1 diopter (D) to ?3.79?±?3.86?D and the mean cylinder was decreased from ?5.60?±?2.2?D to ?4.55?±?1.98?D and the mean SE was decreased from ?7.22?±?4.48?D to ?6.36?±?4.34?D at the 6th month after CXL (p?=?0.128, p?=?0.002 and p?=?0.045, respectively). Flat keratometry, steep keratometry, mean keratometry and maximum keratometry were significantly reduced at the 6th month after CXL (p?=?0.025, p?p?=?0.004 and p?=?0.03, respectively). TCT and ECD were not changed significantly the 6th month after CXL (p?=?0.135 and p?=?0.082, respectively).

Conclusion: Accelerated CXL procedure was effective to stabilize progression of keratoconus with significant reduction in topographic keratometric values and significant increase in CDVA in 6 months.     

Reduced central corneal thickness in patients with isotretinoin treatment

Context: It is well known that oral isotretinoin treatment causes numerous ocular side-effects.

Objective: To investigate the effect of systemic isotretinoin treatment on central corneal thickness (CCT) values due to meibomian gland disease (MGD).

Participants: In this prospective study, 47 patients (27 men, 20 women) with nodulocystic acne vulgaris treated with oral isotretinoin (0.8?mg/kg daily) were included.

Methods: All patients were analyzed with the Pentacam Scheimpflug topography at baseline, on the 3rd and 6th month of treatment. Main outcome measures were MGD scores and CCT.

Results: The mean age of patients was 25.1?±?4.4 years. The mean MGD scores were significantly higher at 3rd month (1.3?±?0.9) and 6th month (1.5?±?1.0) of treatment compared with baseline (1.1?±?0.9) (p?p?p?=?0.038, r?=??0.221).

Conclusion: Isotretinoin treatment causes higher MGD scores. A statistically significant decrease in CCT due to MGD was detected at 6th month of treatment.     

The effects of smoking on corneal endothelial cells: a cross-sectional study on a population from Isfahan,Iran

Purpose: The aim of this study is to compare the effect of smoking in corneal endothelial cell number and morphology by specular microscopy on a non-smoker population.

Methods: Our cross-sectional study was performed on 150 participants from a non-smoker population. Non-contact specular microscopy (Tomey Corporation Inc., Nagoya, Japan) was performed in the center of the cornea of all subjects. The cell density (CD), average cell size (AVG), percent of hexagonality (HEX%) and central corneal thickness (CCT) were calculated and compared in both groups.

Results: Totally, 76 eyes of 76 smokers and 74 eyes of 74 non-smokers were enrolled in the study from 2015 to 2016. The mean age of smokers and non-smokers were 48.61?±?17.04 and 46.39?±?13.02, respectively. The mean number of pack/year among the smokers was 17.36?±?14.68. Also, the mean values of AVG and CD were significantly different for these two groups (p?=?0.011 and p?=?0.039, respectively). Other corneal endothelial variables did not show a significant difference between smokers and non-smokers (p?>?0.05). However, smokers with severe nicotine dependency had significantly greater AVG and lower CD in comparison with the non-smokers (p?=?0.004 and p?=?0.013, respectively).

Conclusion: Our study showed that smoking can cause significant changes in some of the corneal endothelial variables, but not all of them.     

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.     

Long-term intraocular pressure changes after intravitreal injection of bevacizumab

Purpose: To assess the long-term intraocular pressure (IOP) changes after the intravitreal injection of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for treatment of age-related macular degeneration (AMD) and diabetic macular edema (DME) patients and evaluate the correlation factors.

Material and methods: Patients with neovascular AMD or DME underwent treat-and-extended anti-VEGF regimen in one eye and followed more than 12 months were enrolled in this study. We set three criteria of IOP elevation: (1) the IOP of the treated eye increased above the contralateral eye for at least two consecutive visits; (2) the IOP of the treated eye increased above the pre-injection IOP for at least two consecutive visits; (3) and the IOP of the treated eye increased more than 5?mmHg above the baseline IOP for at least two consecutive visits. We used mixed model univariate and multivariate analysis to assess the association between IOP elevation and independent parameters including age, sex, lens status, the number of injections, and underlying disease.

Results: In total 152 patients, 83 patients with AMD and 69 patients with DME, were included in this study. Mean follow-up time was 18.7 months, with a maximum of 50 months. In IOP elevation, 54 eyes (35.6%) showed an IOP increase above that of the contralateral eye (criteria 1), 50 eyes (33.4%) showed an IOP increase above the baseline IOP (criteria 2), and an IOP increase greater than 5?mmHg above the baseline IOP observed in nine eyes (5.9%) (criteria 3). In the univariate analysis, lens status and total number of injections were statistically significant for criteria 2 and 3 (all ps?<?0.05). However, in the multivariable analysis, only the number of intravitreal injections was statistically correlated with sustained IOP elevation for criteria 2 and 3 (p?<?0.001 and p?=?0.039, respectively).

Conclusions: Our results suggest that under long-term monitoring, with a treat-and-extended regimen, intravitreal bevacizumab injections were associated with sustained IOP elevation. In particular, multiple intravitreal injections could be associated with sustained IOP elevation.     

Effect of chronic smoking on lens nucleus as assessed by Pentacam HR lens densitometry in young adults

Objective: To evaluate the effects of chronic tobacco smoking on lens nucleus by Pentacam HR lens densitometry (LD) in young adults.

Design: Prospective cross-sectional case series.

Methods: Thirty subjects (23?M, 7 F) who were chronic cigarette smokers (≥10 cigarettes/day for at least 2 years) (group 1) and another 30 subjects (23?M, 7 F) who did not smoke (group 2), were included in this study. The patients were matched for age and sex between the groups. The exclusion criteria were any history of ocular surgery, any systemic disorders and any ocular diseases except for mild refractive disorders. Lens densitometry measurements were done with the Pentacam HR (Oculus, Wetzlar, Germany). The Schirmer test and pachymetry measurements were also performed.

Results: Mean age of the patients for both groups was 28.90?±?8.20 years (range: 18–40 years). Mean lens densitometry (LD) measurements of Group 1 (chronic cigarette smoking group) were higher than those of Group 2 (control group) in all LD techniques; however only mean “peak” LD measurements showed a statistically significant difference between these two groups (Group 1: 8.67?±?0.61, Group 2: 8.44?±?0.70, p?=?0.04). The mean Schirmer test value was 12.43?±?5.60?mm in Group 1 and 13.00?±?4.26?mm in Group 2 (p?=?0.55). The mean central corneal thickness (CCT) value was 564.23?±?34.61?µm in Group 1 and 550.47?±?32.94?µm in Group 2 (p?=?0.03).

Discussion: The Pentacam HR LD seems to be an important option for the evaluation of lens nucleus in young adults, because it gives objective and quantitative data.

Conclusion: Although chronic smoking increases lens nucleus density in young adults, the effect is not statistically significant when compared with the control group.     

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.     

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.     

Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biological agent therapy

Purpose: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents.

Methods: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer’s II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed.

Results: Thirty-eight patients with a mean age of 53.00?±?8.19 years were in group 1 and 18 patients with a mean age of 51.00?±?9.54 years were in group 2. The mean duration of RA was 6.89?±?7.96 years in group 1 and 5.70?±?9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer’s II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05).

Conclusions: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.     

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections

Background: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration.

Methods: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3?months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale.

Results: A total of 90 patients were included in the study. 43.3% n?=?39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n?=?11 amongst study eyes vs 4.4%, n?=?4 amongst control, fellow eyes (p?p?=?0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p?=?0.02).

Conclusion: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.     

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.     

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.     

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.     

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.     

Effects of chronic smoking on central corneal thickness,endothelial cell,and dry eye parameters

Objective: To evaluate the effect of chronic cigarette smoking on dry eye parameters, endothelial cells, and corneal thickness.

Design: Prospective cross-sectional case series.

Methods: In this cross-sectional study, 49 eyes of 49 chronic smokers (smoker group) and 53 eyes of 53 age-matched, healthy non-smokers (non-smoker group) were enrolled. All participants underwent measurements of tear breakup time (TBUT), central corneal thickness (CCT) measurements with contact pachymeter and the Schirmer test with anesthesia. Corneal endothelial cells were evaluated by non-contact specular microscopy and photographed for analysis of cell density and hexagonality and the coefficient of variation in cell size.

Results: The mean Schirmer score and TBUT value were significantly lower in the smoker group compared to the non-smoker group (p?=?0.015) and p?p?>?0.05). However, a lower percentage of endothelial hexagonal cells were observed in smokers than non-smokers (p?Discussion and conclusion: Our results suggest that cigarette smoking seems to affect the Schirmer score, TBUT value, and hexagonal cells of the corneal endothelium.     

Spectral domain-optical coherence tomographic findings in patients with ankylosing spondylitis under anti-tumor necrosis factor-alpha therapy

Objective: To evaluate the effect of tumor necrosis factor-alpha (TNF-α) blockade on the thickness of the peripapillary retinal nerve fiber layer (RNFL), the ganglion cell-inner plexiform layers (GCIPL), and the macula in ankylosing spondylitis (AS) patients under anti-TNF-α therapy.

Materials and methods: Twenty-one patients with AS received etanercept, or adalimumab, or infliximab for at least 6 months. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were measured before and 6 months after the beginning of the treatment. Peripapillary RNFL, four regional fields (superior, inferior, nasal, and temporal), GCIPL, and macular thicknesses of the patients were analyzed by optical coherence tomography before the treatment, at 3 months and 6 months after the beginning of the treatment.

Results: The mean BASDAI, ESR, and CRP values were 5.2?±?1.5, 31.6?±?21.7, and 15.7?±?13.9, respectively, at the beginning of the treatment and 2.3?±?1.7, 21.3?±?15.1, and 10.1?±?10.3, respectively, 6 months after the beginning of treatment. There were significant differences among the mean BASDAI, ESR, and CRP values at the beginning of treatment and 6 months later (p?p?=?0.007, and p?=?0.009, respectively). There were no significant differences among peripapillary RNFL (p?=?0.24), four regional fields (p?=?0.98, p?=?0.23, p?=?0.09, p?=?0.47), GCIPL (p?=?0.25), or macular (p?=?0.33) thicknesses of the patients during anti-TNF-α treatment. In addition, the mean intraocular pressure levels throughout the follow-up did not show significant variation on repeated-measures ANOVA (p?=?0.77).

Conclusions: TNF-α blockade does not seem to influence RNFL, GCIPL, or macular thickness of patients with AS in the short term.     

Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the electrophysiologic function of retina

Context: Since we had observed electroretinographic (ERG) abnormalities in some patients undergoing photochemotherapy with normal eye examination, we decided to investigate the effects of this therapy on retinal function.

Objective: To investigate the effects of oral photochemotherapy (8-methoxypsoralen?+?Ultraviolet-A) on electrophysiologic function of retina.

Materials and methods: Patients with vitiligo, psoriasis or eczema were enrolled. Patients with any abnormal eye exam or a positive drug or family history for retinal disease were excluded. Baseline standard ERG was provided with the RETIport32 device. The second ERG was performed 6 months after the first and at least 1 week after the last photochemotherapy session (mean number of sessions: 45?±?11). The outcome measures were changes in rod response, standard combined response, single-flash cone response, 30-Hz flicker (N1-P1) and oscillatory potentials amplitudes.

Results: Forty patients were enrolled; 20 of them (mean age: 31.1?±?12 years) completed the study. The mean rod response b-wave amplitude decreased from 88.9?±?47.5 to 86.4?±?36.6 and standard combined response b-wave amplitude decreased from 266.52 to 261.85?µV (p?=?0.422 and p?=?0.968, respectively) and the standard combined response a-wave amplitude increased from 155.4?±?40.0 at baseline to 165.1?±?48.4 in the follow-up ERG (p?=?0.092). The mean single-flash cone response a-wave amplitude decreased insignificantly in the follow-up ERG trace (34.5?±?13.7 and 29?±?15.4, respectively, p?=?0.242). The mean single-flash cone response b-wave amplitude showed an insignificant increase (p?=?0.087). The amplitudes of 30-Hz flicker wave and oscillatory potentials did not change significantly in the follow-up ERG (p?=?0.551 and p?=?0.739, respectively).

Conclusion: Since no significant change in ERG traces was observed, oral photochemotherapy seems safe for retinal electrophysiologic function.