The Efficacy, Safety, and Satisfaction Associated with Switching from Brinzolamide or Brimonidine to Brinzolamide/Brimonidine in Open-Angle Glaucoma Patients.

We evaluated switching from brinzolamide 1% or brimonidine 0.1% to a fixed-combination of brinzolamide 1% and brimonidine 0.1%, and then determined the efficacy, safety, and satisfaction associated with these changes in glaucoma patients. This prospective, nonrandomized study evaluated a total of 31 enrolled glaucoma patients who underwent treatment with at least brinzolamide 1% or brimonidine 0.1%. Patients were administered a brinzolamide/brimonidine fixed-combination ophthalmic suspension (BBFC) after being switched from their original brinzolamide 1% or brimonidine 0.1% therapy. All other intraocular pressure (IOP)-lowering medications currently being used were continued. IOP, superficial punctate keratopathy (SPK), and conjunctival hyperemia data obtained at baseline and then at 4 and 12 weeks were evaluated. To assess the changes in treatment satisfaction, this study utilized the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). There was a significant decrease in the mean baseline IOP from 15.7 ± 4.9 mmHg to 13.6 ± 4.4 (p = 0.001) and 13.5 ± 3.9 mmHg (p = 0.002) at 4 and 12 weeks, respectively. Evaluation of the incidence of conjunctival hyperemia or SPK score showed there were no significant changes noted at any time point. The TSQM-9 score demonstrated there was a significant increase for effectiveness after switching from brinzolamide 1% or brimonidine 0.1% to BBFC. After switching from brinzolamide 1% or brimonidine 0.1% to BBFC, there was a significant decrease in the IOP. Patients were aware of the effectiveness of switching from brinzolamide 1% or brimonidine 0.1% to BBFC.

The Efficacy, Safety and Satisfaction Associated with Switching from Brinzolamide 1% and Brimonidine 0.1% to a Fixed Combination of Brinzolamide 1% and Brimonidine 0.1% in Glaucoma Patients.

We evaluated glaucoma patients for the efficacy, safety and satisfaction associated with switching from brinzolamide 1% and brimonidine 0.1% to a fixed combination of brinzolamide 1% and brimonidine 0.1%. A total of 22 glaucoma patients were enrolled and completed this prospective, nonrandomized study that evaluated patients who underwent treatment with at least brinzolamide 1% and brimonidine 0.1%. Patients on brinzolamide 1% and brimonidine 0.1% were switched to a brinzolamide/brimonidine fixed-combination ophthalmic suspension (BBFC). Evaluations of intraocular pressure (IOP), superficial punctate keratopathy (SPK) and conjunctival hyperemia were conducted at baseline and at 4 and 12 weeks. The Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) was utilized to assess the change in treatment satisfaction. At baseline and at 4 and 12 weeks, the IOP was 15.0 ± 4.1, 14.8 ± 4.1 and 14.8 ± 4.1 mmHg, respectively. There were no significant differences observed at any of the time points. However, the SPK score significantly decreased at 12 weeks, even though no significant differences were observed for the conjunctival hyperemia incidence at any of the time points. After switching from brinzolamide 1% and brimonidine 0.1% to BBFC, there was a significant increase in the TSQM-9 score for convenience and global satisfaction. Both an improvement in the degree of SPK and an increase in treatment satisfaction occurred after switching from brinzolamide 1% and brimonidine 0.1% to BBFC, even though there were sustained IOP values throughout the 12-week evaluation period.

Effect of trabeculectomy on visual field progression in Japanese progressive normal-tension glaucoma with intraocular pressure < 15 mmHg.

We examined the effectiveness of trabeculectomy in decreasing the slope of mean deviation (MD) in Japanese patients with progressive normal-tension glaucoma (NTG) at low intraocular pressure (IOP) levels. The charts of patients who had undergone initial trabeculectomy with adjunctive mitomycin C for progressive NTG with medically controlled IOP < 15 mmHg in 2010-2013 were retrospectively reviewed. Seventeen eyes of 13 NTG patients who had undergone at least 5 times of visual field (VF) examinations in both of preoperatively and postoperatively with postoperative follow-up of ≥ 2 years were enrolled. Preoperative and postoperative MD slopes were compared to evaluate the effectiveness of trabeculectomy in slowing progression of VF. Mean IOP (8.1 ± 2.9 mmHg) and number of IOP-lowering medications (0.8 ± 1.5) were significantly lower postoperatively than preoperatively (13.9 ± 0.9 mmHg; P < 0.001 and 3.0± 0.4; P < 0.0001). In total, 91.7% of eyes with single-digit IOP postoperatively showed improvement in MD slope, whereas only 20.0% of eyes with IOP ≥ 10 mmHg postoperatively showed the improvement. Three eyes (17.6%) showed a decrease in visual acuity (VA) of ≥ 0.1 unit; this group had a lower mean postoperative IOP (6.0 ± 1.0 vs. 8.6 ± 3.0 mmHg; P = 0.1717) and a higher mean IOP reduction rate (56.2 vs. 38.5%; P = 0.8296) than eyes with a VA decrease of < 0.1 unit or no change. Thus, in this analysis of Japanese NTG patients with medically controlled IOP < 15 mmHg, achieving an IOP < 10 mmHg with trabeculectomy was beneficial for reducing the VF progression rate in progressive NTG at low IOP levels. However, an IOP < 7 mmHg by surgery would be required careful attention to VA decline.

Sustainability of Intraocular Pressure Reduction of Travoprost Ophthalmic Solution in Subjects with Normal Tension Glaucoma.

INTRODUCTION: We examined the sustainability of the intraocular pressure (IOP)-lowering efficacy of travoprost (0.004%) ophthalmic solution in subjects with normal tension glaucoma (NTG). METHODS: Travoprost ophthalmic solution was given once daily at 9 PM to subjects with newly diagnosed NTG or with NTG who had not received any ocular hypotensives within the previous 30 days. IOP was measured at three time points (9 AM, 1 PM, and 5 PM) at baseline and week 12 visits, and at one time point (9 AM) at week 4 and week 8 visits. Conjunctival hyperemia, superficial punctate keratopathy, and other adverse events were evaluated during the observation period. RESULTS: Thirty subjects (12 males and 18 females; mean age 65.6 years) from 32 subjects enrolled were included in the efficacy analysis. The mean IOPs (±standard deviation) of 16.6 ± 1.4, 15.7 ± 1.8, and 15.7 ± 2.2 mmHg at 9 AM, 1 PM, and 5 PM, respectively, at baseline reduced significantly to the mean IOPs of 13.0 ± 1.8, 12.7 ± 1.8, and 12.8 ± 1.6 mmHg, respectively, at week 12 (P < 0.0001 for every time point). Together with the mean IOPs of 13.4 ± 1.9 mmHg at week 4 and 13.2 ± 1.9 mmHg at week 8, the pooled IOP during the observation period for up to 12 weeks showed a statistically and clinically significant reduction of IOP at 9 AM. (3.4 mmHg or 20.3% reduction from baseline, P < 0.0001). There were no adverse events leading to treatment discontinuation. CONCLUSION: This multi-center collaborative study suggests that IOP-lowering efficacy of travoprost ophthalmic solution persists during the day at the clinically relevant level in subjects with NTG. FUNDING: Alcon Japan Ltd. TRIAL REGISTRATION: University Hospital Medical Information Network, UMIN ID: 000011621.

Safety and efficacy of a fixed versus unfixed brinzolamide/timolol combination in Japanese patients with open-angle glaucoma or ocular hypertension.

BACKGROUND: The purpose of this study was to assess the safety and efficacy of fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) compared with concomitant brinzolamide 1% and timolol 0.5% (BRINZ + TIM) in Japanese patients with open-angle glaucoma (primary open-angle, exfoliation, pigmentary) or ocular hypertension. METHODS: This randomized, double-masked, multicenter, parallel-group, positive-control, Phase III study was conducted in Japan and included patients aged ≥20 years. Baseline intraocular pressure was assessed after 4 weeks of treatment with timolol 0.5%. Patients were randomized to twice-daily BRINZ/TIM-FC or BRINZ + TIM for 8 weeks (treatment phase). The primary endpoint was mean intraocular pressure reduction from baseline to week 8 at 11 am, at which time noninferiority of BRINZ/TIM-FC versus BRINZ + TIM was evaluated. Data were analyzed using repeated-measures analysis of covariance and t-tests. Adverse events and ophthalmic/physiologic variables were assessed. RESULTS: In total, 319 patients of mean age 64±12 years were enrolled in the treatment phase. BRINZ/TIM-FC and BRINZ + TIM were associated with reductions in mean intraocular pressure from baseline throughout the study (ranges -2.5 to -3.4 mmHg and -2.7 to -3.3 mmHg, respectively). Mean between-group differences in intraocular pressure reduction ranged from 0 to -0.3 mmHg; the upper limit of the 97.5% confidence interval for week 8 at 11 am was <1.1 mmHg, indicating noninferiority of BRINZ/TIM-FC. Treatment-related adverse events were observed in 3% and 12% of patients receiving BRINZ/TIM-FC and BRINZ + TIM, respectively. No substantial changes in other safety parameters were reported. CONCLUSION: Twice-daily BRINZ/TIM-FC reduced intraocular pressure by levels similar to concomitant BRINZ + TIM in Japanese patients with open-angle glaucoma or ocular hypertension and was noninferior to BRINZ + TIM. Both treatments were well tolerated.

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients.

PURPOSE: To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. RESULTS: The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p=0.0147) and NTG (4/28, 14.2%, p=0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p=0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p=0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p=0.0076), and a significantly higher rate of surgery and/or laser history (p=0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. CONCLUSIONS: Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open- angle glaucoma in this Japanese population.

The incidence and pathology of conjunctival ulceration in Behçet's syndrome.

AIMS: To describe the results of a study of the incidence of conjunctival ulceration and its pathology as a manifestation of Behçet's syndrome. METHODS: The authors reviewed retrospectively medical charts of 152 patients with Behçet's syndrome seen at the uveitis service of Okayama University Hospital from January 1995 to December 1999. Criteria used to diagnose Behçet's syndrome in this study required the presence of oral aphthous ulceration plus any two of three other manifestations-genital ulceration, eye lesions such as iridocyclitis and uveoretinitis, or skin lesions such as erythema nodosum. The presence of conjunctival ulceration was determined in patients with Behçet's syndrome through standardised ophthalmological examinations. A biopsy of the conjunctival ulceration was performed in one patient. The incidence of conjunctival ulceration in patients with Behçet's syndrome was calculated and the clinical and pathological features of this ulceration were examined. RESULTS: Four of 152 patients (2.6%) developed conjunctival ulceration in concordance with exacerbation of their systemic symptoms. Histopathological examinations of a conjunctival biopsy specimen in one patient revealed intraepithelial and perivascular infiltration with neutrophils and lymphocytes, consistent with Behçet's syndrome. The conjunctival ulcerations of the study patients showed good response to topical corticosteroids or topical steroids plus oral colchicine. CONCLUSIONS: Conjunctival ulceration should be noted as an uncommon but possible manifestation of Behçet's syndrome. Accordingly, routine examination of the conjunctiva is recommended in patients with Behçet's syndrome, and Behçet's syndrome should be included in a list of differential diagnoses for patients with conjunctival ulcerations.