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 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.     

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.     

Retrospective analysis of the effect of aflibercept loading dose on the retinal vessel diameters in patients with treatment-naive neovascular AMD*

Background: To evaluate the effects of intravitreal aflibercept (IVA) on retinal vessel diameters in patients with neovascular age-related macular degeneration (AMD).

Design, setting, and participants: A retrospective study conducted at the Kutahya Dumlupinar University Faculty of Medicine included 15 eyes of 15 patients with treatment naive neovascular AMD.

Methods: All eyes received IVA injections once per month for 3?months; untreated contralateral eyes were used as controls. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery-vein ratio (AVR) values were measured using a computer-based program before the first IVA injection and 30?days after the first, second, and third injections. The main outcome measurements were the central macular thickness (CMT), best-corrected visual acuity (BCVA), choroidal thickness, CRAE, CRVE, and AVR.

Results: Significant vasoconstriction of the retinal arterioles was observed in all eyes treated with IVA when compared to baseline (p?=?0.009). However, no significant differences were found for CRVE or AVR throughout the study period in treated eyes. In the control group, all parameters measured during each visit were similar to baseline measurements (p?>?0.05). The mean BCVA significantly improved at the end of the loading dose of IVA, when compared to baseline (p?=?0.006). After the IVA injections, the mean CMT and choroidal thickness were significantly reduced at all visits, compared to baseline (p?Conclusions: The current study showed that IVA led to significant retinal arteriolar vasoconstriction and choroidal thinning, which may cause reduced retinal blood flow.     

Acute effects of caffeine on choroidal thickness and ocular pulse amplitude

Objective: To explore ocular changes in healthy people after caffeine consumption.

Methods: This prospective observational study was carried out with students of the Turgut Özal University Medical Faculty from May 15 to 15 December 2014. Enrolled in the study were 17 healthy subjects (n?=?17 eyes), with a median age of 24 (IQR 1), ranging between 21 and 26 years. The control group (6 females, 11 males) aged between 23 and 28 (median 25 years [IQR 4.75]). For study, one eye from each participant was randomly selected. To obviate the effect of diurnal variations, tests were performed at the same time of the day (10:00?a.m.–12:00?p.m.). Each subject was given an ophthalmologic examination before the study to exclude those with undiagnosed ocular disease. Version 6.0 Cirrus high-definition optical coherence tomography (HD-OCT) (Carl Zeiss Meditec, Dublin, CA) was used to measure CT at the fovea, and 1500?μm nasal and 1500?μm temporal to the fovea. After baseline OCT measurements, participants were asked to have 200?mg oral caffeine intake or a placebo capsule (200?mg lactose powder). Two further OCT measurements were applied at the first and fourth hours of caffeine intake. All participants also had intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements recorded before, first and fourth hours of caffeine intake. IOP and OPA were measured using the dynamic contour tonometry (DCT) (Swiss Micro Technology AG, Port, Switzerland).

Results: The groups showed no significant difference by means of age, gender, spherical refraction and axial length (p?>?0.05). Baseline choroidal thickness measurements of the study and control group showed no significant difference. Oral caffeine intake caused a significant reduction in choroidal thickness compared with baseline, at all three measurement points, (p?<?0.05). There were no significant changes in IOP and OPA measurements compared with the baseline values (p?>?0.05). The choroidal thickness still continued to decrease for at least 4?h following caffeine intake; whereas, the difference between 1 and 4?h was not statistically significant (p?>?0.05). However, choroidal thicknesses, IOP and OPA values of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 and 4?h after placebo intake (p?>?0.05).

Conclusions: We found no significant change in IOP and OPA following oral 200?mg caffeine intake, while CT significantly decreased, for at least 4?h.     

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema

Objective: To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Methods: Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT) >?275?μm, duration >?6 months) received three injections of 2.5?mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. Results: At 18 weeks, the mean BCVA (0.68?±?0.40 logMAR, p?=?0.45) and CFT (453?±?169?μm, p?=?0.58) did not show any significant change compared to baseline (0.74?±?0.42 logMAR and 521?±?151?μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295?±?42 μ (p?=?0.01). However, no significant difference was observed for BCVA during this period (p?=?0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p?<?0.001 and p?=?0.01, respectively). Conclusions: Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.     

Efficacy of intravitreal dexamethasone implant for the treatment of macular oedema after pars plana vitrectomy for rhegmatogenous retinal detachment: long-term outcomes

Abstract

Purpose: To investigate the efficacy and safety of intravitreal dexamethasone implant as initial and only treatment for macular oedema after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD).

Methods: This study included 14 patients, who were diagnosed with macular oedema after PPV for RRD and who were treated with intravitreal dexamethasone implant. Patients were examined at the time of macular oedema diagnosis (baseline) and 1, 6 and 12?months after treatment, using best corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT).

Results: The mean BCVA at baseline was 0.72?±?0.29 logMAR and improved significantly to 0.37?±?0.21, 0.42?±?0.19 and 0.35?±?0.22 logMAR at month 1, 6 and 12 after treatment with dexamethasone implant. The mean central retinal thickness (CRT) was 623?±?142?μm at baseline and decreased significantly to 339?±?163?μm, 428?±?131?μm and 356?±?147?μm at month 1, 6 and 12 after treatment. Total resolution of macular oedema was observed in 10 out of 14 patients (71.4%) at month 12. Ellipsoid zone was intact in 71.4% of patients at the end of the follow-up, while 71.4% of patients received only one implant until the end of the 12-month follow-up. No adverse events were observed.

Conclusions: Intravitreal dexamethasone implant was found to be effective and safe as initial treatment for macular oedema after PPV for RRD.     

Evaluation of the clinical effectiveness in routine practice of fluocinolone acetonide 190 µg intravitreal implant in people with diabetic macular edema

Abstract

Objective: The aim of the Iluvien Clinical Evidence study in the UK (ICE-UK) was to assess the real-world effectiveness of fluocinolone acetonide (FAc) 190?µg intravitreal implant for the treatment of clinically significant chronic diabetic macular edema (DME) in routine clinical practice.

Methods: This retrospective study collected data from patient medical records in 13 ophthalmology centers for people with DME prescribed FAc intravitreal implant between April 1, 2013 and April 15, 2015. Visual acuity (VA) and intraocular pressure (IOP) measurements were collected for 12 months prior to and after implant.

Results: Two hundred and eight people, contributing 233 eyes, treated with FAc implant were included. Mean age was 68.1 years and 62% were male. In the 12 months prior to FAc implant, VA declined. Median (interquartile range, IQR) VA was 0.66 (0.48–1.00) LogMAR units (equivalent to 52.0 ETDRS letters) at implant, improving to 0.60 (0.38–0.90) LogMAR units (55.0 letters) at 12 months post-implant (p?<?0.001). In total, 44%, 30%, and 18% of people achieved an improvement in ETDRS score of ≥5, ≥10, and ≥15 letters, respectively, over the same period. A small but significant (p?<?.001) increase in median IOP was observed (median?=?15.0, IQR?=?13.0–18.0?mmHg at implant to 18.0, 15.0–21.0?mmHg at 12 months). In the 12 months following implant, additional IOP-lowering therapy was prescribed in 15% of subjects previously not requiring such therapy.

Conclusion: Following FAc implant, an overall significant improvement in VA was observed over a period of 12 months, accompanied by a significant but small increase in IOP.     

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.     

Evaluation of the clinical effectiveness of fluocinolone acetonide 190 µg intravitreal implant in diabetic macular edema: a comparison between study and fellow eyes

Abstract

Objectives: To compare visual and anatomical outcomes between eyes treated with fluocinolone acetonide (FAc) 190 µg intravitreal implant for clinically significant chronic diabetic macular edema (DME) and fellow eyes not treated with FAc implant using data from the Iluvien Clinical Evidence study in the UK (ICE-UK) study.

Methods: In this retrospective cohort study, data on people attending hospital eye services and treated with the FAc implant between April 1, 2013 and April 15, 2015 were collected. Changes in visual acuity (VA), central foveal thickness (CFT) and intraocular pressure (IOP) were compared between study eyes (intervention) and fellow eyes.

Results: A total of 208 people were selected. Mean age was 68.1 years and 62% were male. Mean change in VA was ?0.09 LogMAR units for study eyes and 0.04 LogMAR units for fellow eyes at 12 months post-implant (p?<?.001). Over the same period, ≥5 letter, ≥10 letter and ≥15 letter improvements in Early Treatment Diabetic Retinopathy Study (ETDRS) score were achieved by more FAc treated eyes than by fellow eyes (41% versus 23%, p?<?.001; 28% versus 11%, p?<?.001; and 18% versus 4%, p?<?.001 at 12 months, respectively). Differences in the mean change in CFT (?113?µm versus ?13?µm, p?<?.001) and IOP (3.2?mmHg versus ?0.2?mmHg, p?<?.001) were also observed between study and fellow eyes at 12 months.

Conclusion: Visual acuity improved in study eyes over the 12 months following FAc implant and worsened in fellow eyes. Over the same period, study eyes showed a larger improvement in central foveal thickness. Intraocular pressure worsened in study eyes only. Change in visual acuity, central foveal thickness and intraocular pressure between FAc implant and the end of the 12-month follow-up period differed significantly between study and fellow eyes.     

Follow up of retinal nerve fiber layer thickness with optic coherence tomography in patients receiving anti-tubercular treatment may reveal early optic neuropathy

Purpose: To evaluate the effect of anti-tubercular treatment on retinal nerve fiber layer (RNFL) thickness and the efficiency of optic coherence tomography (OCT) on early diagnosis of optic neuropathy.

Methods: Twenty patients diagnosed with either pulmonary or extra-pulmonary tuberculosis which were treated with anti-tubercular treatment (isoniazid (INH), rifampicin, ethambutol (ETM), and pyrazinamide) were enrolled in the study. RNFL thicknesses of the patients were measured via OCT, at baseline (before starting anti-tubercular treatment) and after the two-month treatment period. Standard ophthalmologic examinations were also performed.

Results: Compared to baseline values, after the two-month treatment period, thinning was detected in the right eye’s average and superior quadrant RNFLs (p?=?0.024 and p?=?0.006 respectively) and in the left eye’s average, superior quadrant, and inferior quadrant RNFLs (p?=?0.001, p?=?0.008, p?Conclusion: We displayed that patients receiving INH and ETM, which were the basic medicines of anti-tubercular treatment, experienced thinning in RNFL after the two-month treatment period. Patients receiving these drugs can be followed via OCT in terms of reduction in RNFL thicknesses for early diagnose of INH and ETM toxicity.     

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.     

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.     

Postmarketing surveillance of serious adverse events associated with the use of rofecoxib from 1999–2002

ABSTRACT

Objective: The authors performed a postmarketing database analysis to evaluate the incidence of cardiovascular and other serious adverse events (SAEs) reported to the US Food and Drug Administration's Adverse Event Reporting System (AERS) involving the use of rofecoxib.

Research design and methods: The authors studied all adverse events involving rofecoxib reported to the AERS from inception of the drug until 2002. An emphasis was placed on cardiovascular and other SAEs of interest categorized using the high level group terms hemorrhage, edema, thrombosis, embolism, and death.

Results: There were 31,024 reports of SAEs associated with the use of rofecoxib, which was considered primary suspect in 97.8% of these reports. There were 3915, 3677, 1653, 1917, and 233 reports of hemorrhage, edema, death, thrombosis, and embolism, respectively. Relative to the overall population in this dataset, reports of hemorrhage, death, thrombosis, and embolism consisted of a greater proportion of males. The mean age for patients that reported hemorrhage, death, and thrombosis was older, whereas the mean age for embolism and edema was younger than the overall population in this dataset. Aspirin was the most commonly reported concomitant medication (7.4% of reports) followed by acetaminophen (5.4%). Reports containing concomitant use of anti-coagulants, Cox-1, and nonselective inhibitors (each p?<?0.001) but not Cox-2 inhibitors were associated with increased age while only anti-coagulants and Cox-1 inhibitors (each p?<?0.001) were associated with more males. Reports containing concomitant use of an anti-coagulant or an NSAID accounted for a disproportionate incidence of hemorrhage, edema, embolism, and death. Most notably, the odds of a hemorrhagic event for those reporting concomitant use of an anti-coagulant, Cox-1, non-selective, or Cox-2 inhibitor was 3.05 (p?<?0.001), 3.07 (p?<?0.001), 2.07 (p?<?0.001), and 1.18 (p?<?0.001), respectively. Some weaknesses of this type of analysis are the retrospective nature of such a study, the inability to find causality, and that the data can contains multiple reports from any one individual.

Conclusions: It can be postulated that in addition to the risk of heart attack and stroke, rofecoxib users were at increased risk of hemorrhage, in addition to other thrombotic and embolic adverse events, which was exacerbated in those taking blood thinners or NSAIDs.     

Effects of pioglitazone on metabolic control and blood pressure: a randomised study in patients with type 2 diabetes mellitus

SUMMARY

Aim: This Swiss multicentre study examined the efficacy and safety of oral pioglitazone in patients with type 2 diabetes.

Methods: Patients were randomised to pioglitazone at once-daily doses of 30mg for 20 weeks (n?=?76), 30?mg for 12 weeks followed by 45?mg for 8 weeks (n?=?74), or 45?mg for 20 weeks (n?=?84); 94.9% of patients completed 12 weeks and 88.9% completed all 20 weeks. Almost all (96.6%) patients received pioglitazone in combination with other anti-diabetic treatments.

Results: Mean HbA1c at baseline was 8.8?±?1.2%, and changes to endpoint were ?1.1?±?1.1%, ?1.1?±?1.4% and ?0.9?±?1.6%, respectively for the three dose groups (p?<?0.001 for each group). Triglyceride concentrations decreased in each group and the overall mean change during the study was ?0.58?mmol/l (p?<?0.001 versus baseline). HDL-cholesterol increased, with an overall mean change of 0.10?mmol?l^?1 (p?<?0.001 versus baseline). Blood pressure decreased from baseline, particularly for hypertensive patients with mean changes: systolic -10mmHg, p?<?0.001, diastolic-8mmHg, p?<?0.001 versus baseline. Serum alanine aminotransferase and γ-glutamyl transferase concentrations were significantly (p?<?0.001 for each) reduced during the study.

Conclusions: The study demonstrates the efficacy of pioglitazone 30?mg?day^?1 and 45?mg?day^?1 in the treatment of type 2 diabetes, with an improved lipid profile and decreased blood pressure in addition to improved glycaemic control.     

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.     

The effect of cigarette smoking on retinal nerve fiber layer thickness in patients with migraine

Context: Migraine is a frequent and disabling chronic neurological condition with complex pathophysiology. Both cigarette smoking and migraine may cause damage to the optic nerve. Objective: The primary objective of this study was to investigate the effect of cigarette smoking on retinal nerve fiber layer (RNFL) thickness in patients with migraine.

Materials and methods: Eighty-four consecutive patients diagnosed with migraine (34 smokers and 50 nonsmokers) and 66 age- and gender-matched healthy non-smoker controls were enrolled for this observational cross-sectional study. RNFL thickness was measured using spectral-domain optical coherence tomography (OCT) and then RNFL thickness in patients with migraine who smoke was compared to nonsmoking patients with migraine and healthy subjects.

Results: The average, superior, nasal and inferior RNFL thicknesses were significantly thinner in patients with migraine compared to the control group (p?<?0.001, p?=?0.02, p?<?0.001 and p?=?0.04, respectively). The average and inferior RNFL thicknesses were significantly reduced in smoker patients with migraine compared to the nonsmokers (p?=?0.011, p?=?0.045, respectively). Nonsmoker patients with migraine had significantly thinner average and nasal RNFL thicknesses than the control group (p?=?0.001, p?=?0.001, respectively).

Conclusion: Cigarette smoking may cause significant RNFL thinning in patients with migraine. OCT may be a feasible technique for determination of smoking-induced ocular damage in patients with migraine.     

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.     

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.     

The long-term anatomical and visual effect of intravitreal triamcinolone injection during vitrectomy for the treatment of idiopathic macular epiretinal membrane

Purpose: To compare the long-term anatomical and visual outcomes of patients with idiopathic epiretinal membrane (ERM) removed by vitrectomy and membrane peeling with or without the use of intravitreal injection of triamcinolone acetonide (IVTA).

Methods: A retrospective chart review was performed. Subjects who underwent vitrectomy and who were followed over 12 months were included. The study included two groups of patients. In group 1 (71 eyes), the patients underwent vitrectomy and membrane peeling without the use of IVTA. In group 2 (27 eyes), 2?mg of IVTA was given at the end of the surgery. The main outcome measures were best-corrected visual acuity (BCVA), central foveal thickness (CFT) determined by optical coherence tomography (OCT), the number of cataract surgeries, and the use of anti-glaucomatous drugs during the follow-up period.

Results: This study included 98 eyes with ERM from 98 patients. There was no significant difference between the two groups with respect to age, gender, pre- and postoperative lens status, BCVA, CFT, or length of the follow-up period. The mean age for all of the patients was 62.45?±?10.01 (mean ± SD) years, and the mean follow-up length was 20.58?±?9.64 (mean ± SD) months. In all cases, the mean best-corrected logarithm of minimum angle of resolution (logMAR) acuity improved from a preoperative value of 0.91?±?0.32 [Snellen equivalent (SE), 0.16?±?0.14] to a postoperative value of 0.46?±?0.36 (SE, 0.46?±?0.29) (P?<?0.0001). The CFT was reduced from a preoperative value of 473.46?±?96.91 μm to a postoperative value of 302.44?±?69.80 μm (P?<?0.0001). Six patients (22.2%) in group 2 required anti-glaucomatous drugs to control intraocular pressure (IOP) during the follow-up period, and three patients (4.2%) in group 1 required drugs to control IOP (P?=?0.012).

Conclusions: The postoperative visual outcomes for patients with idiopathic ERM were favorable, but CFT did not return to a normal level, even in eyes in which 2?mg IVTA was used. The IVTA use after ERM removal produced no significant benefits during long-term follow-up, but IVTA did increase the risk of increased IOP.