Additive effects of brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination in prostaglandin analog-treated Japanese glaucoma patients.

PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.

Additive effects and safety of fixed combination therapy with 1% brinzolamide and 0.5% timolol versus 1% dorzolamide and 0.5% timolol in prostaglandin-treated glaucoma patients.

PURPOSE: To compare the additive effects and safety of 1% brinzolamide/0.5% timolol fixed combination (BTFC) versus the low-dose regimen of 1% dorzolamide/0.5% timolol fixed combination (DTFC) in patients with open-angle glaucoma and ocular hypertension (OAG/OH) following treatment with prostaglandin analogues (PGAs). METHODS: A prospective, randomized, double-masked, multicentre, parallel-group and active-controlled study included 201 Japanese OAG/OH patients who had been treated with PGA. Efficacy was assessed as the change in intra-ocular pressure (IOP) from baseline after weeks 4 and 8. Safety was assessed with adverse event rates, ocular discomfort score, blur scale, blood pressure and heart rates, best-corrected visual acuity (BCVA) and slit lamp examinations. RESULTS: Intra-ocular pressure (IOP) change from baseline at 9 AM/11 AM pooled over the 8 weeks was -3.3/-3.3 mmHg in the BTFC group and -2.9/-3.4 mmHg in the DTFC group, demonstrating non-inferiority of BTFC to DTFC. Ocular irritation was frequently seen in DTFC group. Although blurred vision was frequently seen in BTFC group, it was transient and blurring became the equivalent 3 min after instillation between two groups. No noteworthy issue was observed in other safety outcome. CONCLUSION: Non-inferiority of BTFC to DTFC in IOP reduction was demonstrated after adding onto PGA therapy in Japanese OAG/OH patients. Although the score of blurred vision was transiently higher in BTFC than DTFC, treatment difference decreased and disappeared with time. Thus, BTFC can be considered as a safe and effective agent for glaucoma treatment.

Effects of Switching from Timolol to Brimonidine in Prostaglandin Analog and Timolol Combination Therapy.

PURPOSE: To assess the efficacy and safety of switching from timolol 0.5% to brimonidine 0.1% in patients with glaucoma treated with a prostaglandin analog (PGA) and timolol combination. METHODS: This prospective, open-label multicenter study enrolled patients with open-angle glaucoma or ocular hypertension who were being treated with a PGA and timolol. After baseline measurements, timolol was switched to brimonidine 0.1%, and patients were followed for 12 weeks. Patients visited at 4 and 12 weeks after switching. The main outcome measure was the change in intraocular pressure (IOP). For safety evaluations, hyperemia, formation of conjunctival follicles, superficial punctate keratopathy as a local side effect, blood pressure (BP), and heart rate (HR) were evaluated. RESULTS: One hundred seven patients participated in this study. Among them, 103 patients completed the study. The IOP values at baseline, 4 weeks, and 12 weeks after the transition were 15.7 ± 2.7, 14.3 ± 2.8, and 14.0 ± 2.8 mmHg, respectively. IOP was significantly reduced at 4 and 12 weeks compared with baseline (p<0.001). There were no significant changes in hyperemia or follicle formation. The superficial punctate keratopathy score was significantly reduced at 12 weeks compared with baseline (p<0.05). Systolic and diastolic BP values were significantly reduced and HR significantly increased after switching (p<0.05). CONCLUSION: Switching from timolol 0.5% to brimonidine 0.1% may not change IOP in the combination use of timolol 0.5% and a PGA and was well tolerated by patients without severe ocular or systemic side effects.

Colonic hydrogen generated from fructan diffuses into the abdominal cavity and reduces adipose mRNA abundance of cytokines in rats.

Hydrogen (H2) protects against inflammation-induced oxidative stress. Nondigestible saccharides (NDSs) enhance colonic H2 production. We examined whether colonic H2 transfers to tissues in the abdominal cavity and whether it affects expression of proinflammatory cytokines. In Expts. 1 and 2, rats were fed diets containing fructooligosaccharides [FOSs; 25 (Expt. 1) and 50 g/kg (Expts. 1 and 2)] for 7 and 14 d, respectively. The no-FOS diet was used as the control diet. At the end of the experiment, H2 excretion and the portal H2 concentration were significantly greater in the FOS group than in the control group. In the FOS group, the arterial H2 concentration was no more than 1.5% of the portal H2 concentration (P = 0.03). The H2 concentration in abdominal cavity tissues, especially adipose tissue, in the FOS group was 5.6- to 43-fold of that in the control group (P < 0.05). The H2 content in the abdominal cavity in the FOS group was 11-fold of that in the control group (P < 0.05). In Expt. 3, rats were fed a high-fat diet containing FOS and inulin (50 g/kg) for 28 d. The area under the curve for H2 excretion between 0 and 28 d and portal and adipose H2 concentrations were significantly higher in the FOS and inulin groups than in the high-fat control group. Adipose mRNA abundance of nuclear factor kappa-light-chain-enhancer of activated B cells 1 was lower in the FOS group than in the control group (P = 0.02) and those of interleukin-6 and chemokine (C-C motif) ligand 2 tended to be lower (P < 0.11). Colonic H2 generated from NDS diffuses to the abdominal cavity before transferring to abdominal tissues. Reduced cytokine expression by FOS feeding might be dependent on increased colonic H2. Colonic H2 may have important implications in the suppressive effect on metabolic syndrome via oxidative stress.

S100A9 in BALF is a candidate biomarker of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, and the prognosis remains poor. On the other hand, other fibrotic interstitial pneumonias such as idiopathic nonspecific interstitial pneumonia (I-NSIP) and collagen vascular disease-associated interstitial pneumonia (CVD-IP) resemble IPF, but they respond to therapy and the prognosis is better. We searched for biomarkers to distinguish IPF from other fibrotic interstitial pneumonias and investigated whether S100A9 could be useful for discriminating types of fibrotic interstitial pneumonia based on our preliminary proteomic findings. METHODS: We measured S100A9 levels in serum and bronchoalveolar lavage fluid (BALF) from 28 patients with IPF, 15 with I-NSIP, 20 with cryptogenic organizing pneumonia (COP), 35 with CVD-IP and 23 healthy individuals (controls) using enzyme-linked immunosorbent assays. S100A9 in the lung was also immunohistochemically localized. RESULTS: S100A9 levels in BALF, but not in serum, were significantly elevated in patients with IPF compared with I-NSIP, COP, CVD-IP and healthy individuals. S100A9 immunoreactivity was localized mainly in macrophages and neutrophils in lung specimens from patients with IPF. The results of receiver operating characteristic (ROC) curve analysis showed that BALF S100A9 levels had sufficient specificity and sensitivity to distinguish IPF from I-NSIP and CVD-IP. CONCLUSION: S100A9 in BALF might serve as a candidate biomarker to discriminate between IPF and other fibrotic interstitial pneumonias.

Filtering bleb modification with a THC:YAG (Holmium) laser.

OBJECTIVE: To present a method for remodeling oversized blebs using the THC:YAG laser and describe its use in treating hypotony and bleb leaks. METHODS: Retrospective medical record review of 13 patients who underwent holmium laser bleb revision. RESULTS: Thirteen eyes of 13 patients were analyzed. All the patients had an oversized bleb and 2 patients presented an associated late-onset leaking bleb. Mean preoperative IOP was 4.1 mm Hg. THC:YAG laser energy was applied to the bleb to remodel and/or close the leak. After a mean follow up of 17.3 months, the mean IOP was 7.84 mm Hg +/- 2.3. Postsurgery complications included hyphema and the inadvertent rupture of a conjunctival microcyst. Visual acuity improved in 9 of the eyes and remained stable in 4 of the eyes. CONCLUSION: The THC:YAG laser can be used effectively to sculpt large blebs, reduce symptoms associated with large blebs, increase IOP in hypotonous eyes, and under specific circumstances, close bleb leaks.