Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.</p><p><b>METHODS</b>In this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.</p><p><b>RESULTS</b>Of the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).</p><p><b>CONCLUSIONS</b>Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.</p>

Expression of TNF-? and TNF-R1 in retinal glial cells of a rat chronic elevated intraocular pressure model / 中国病理生理杂志

AIM:In order to study the effects of retinal glial cells on glaucomatous retinal ganglion cells damage,expression of TNF-? and TNF-R1 in retinal glial cells was observed in rat model with chronic elevated intraocular pressure glaucoma.METHODS:(1)Rats were rendered elevated intraocular pressure by ligating 2 episcleral veins with subconjunctival injection of 5-Fu.(2)Four weeks after operation,immuno-histological assays were carried out on cryostat sections.The co-expressions of TNF-?-GFAP,TNF-?-OX42,TNFR-1-GFAP,and TNFR-1-NeuN were observed via a confocal laser scanning microscope,respectively.RESULTS:(1)Elevated intraocular pressure was consistently maintained for up to 4 weeks in model group.(2)The co-expressions of TNF-? and GFAP,TNF-? and OX42 were detected in retina in treatment group,respectively.(3)The co-expressions of TNFR-1 and GFAP were also detected in retina,but the co-expressions of TNFR-1 and NeuN were not detected in retina in treatment group.CONCLUSION:TNF-? that activated retinal glial cells may play an important role in glaucomatous retinal ganglion cell damage.