The additive effects on intraocular pressure of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions: a prospective, randomized, multicenter study.

PURPOSE: To investigate the effectiveness of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions in improving the intraocular pressures (IOPs) in glaucoma patients. METHODS: We divided the 53 patients into two groups, those who had been treated with latanoprost and those who had been treated with nipradilol. We administered to the first group one dose of latanoprost daily for 12 weeks and to the second group one dose of nipradilol daily for 12 weeks. Each group then received both solutions for another 12 weeks; the latanoprost group received nipradilol and the nipradilol group received latanoprost. IOPs were measured at each 4-week visit. RESULTS: In the patients previously treated with latanoprost, the mean IOP was 19.6+/-2.5 mmHg at baseline, and 14.9+/-2.4 mmHg (23.7% reduction) after 12 weeks of latanoprost monotherapy. The addition of nipradilol decreased the IOP to 13.8+/-1.9 mmHg (29.0% reduction). In the group previously treated with nipradilol, the mean IOP was 20.2+/-3.1 mmHg at baseline, and 16.7+/-3.5 mmHg (17.1% reduction) after 12 weeks of nipradilol monotherapy. Addition of latanoprost decreased the IOP to 14.2+/-3.2 mmHg (29.5% reduction). CONCLUSION: Latanoprost and nipradilol are more effective as a combination therapy than each one by itself.

Phase III long-term study and comparative clinical study of nipradilol ophthalmic solution in patients with primary open-angle glaucoma and ocular hypertension.

Nipradilol (CAS 81486-22-8) is a non-selective beta-blocker with alpha-1 blocking and nitroglycerin-like vasodilating activities. In the present communication, the long-term efficacy and safety of nipradilol were investigated and the efficacy, safety and utility of topical nipradilol and timolol (CAS 91524-16-2) were compared in patients with primary open-angle glaucoma or ocular hypertension. In the long-term study, nipradilol for 1 year (52 weeks) was performed by registration method. 67 out of 68 patients were subjected to analysis and 57 patients (83.8 %) completed 52-week instillation. 0.25 % nipradilol was applied twice daily to patients. As a result, intraocular pressure (IOP) decreased significantly by 4.0 mmHg to 4.8 mmHg compared with the baseline without tachyphylaxis. The incidence of adverse events was 12.5 % at 52 weeks by analysis with Kaplan-Meier life-table method. It showed no significant trend of increase after 3 months. In the multi-centered double-masked comparative randomized study, 0.25 % nipradilol was assigned to 96 patients and 0.5 % timolol to 100 patients. Each patient was instilled nipradilol or timolol twice daily for 8 weeks. IOP significantly decreased by 4.2 mmHg and by 4.7 mmHg at 8 weeks and the incidence of adverse events was 10.5 % and 12.1 % in the nipradilol and timolol group, respectively. No significant between-group difference in IOP reduction or incidence of adverse events was seen. Topical nipradilol showed long-term ocular hypotensive effects and clinical safety in a 52-week study, and its efficacy and safety equivalent to timolol was confirmed in a 8-week comparative study.

Influence of topical betaxolol and timolol on visual field in Japanese open-angle glaucoma patients.

PURPOSE: To assess the effects of topical betaxolol and timolol on the visual field in Japanese open-angle glaucoma (OAG) patients. METHODS: This study was a multicenter, 2-year, prospective, randomized and double-masked study. Tests using the Humphrey 30-2 perimeter program were conducted every 6 months and the data of 95 patients were analyzed using regression analysis. Estimated regression coefficients for mean deviation (MD), corrected pattern standard deviation (CPSD), and total deviation (TD) values clustered into 15 sectors were obtained for each treatment group. RESULTS: Estimated slopes (dB/year) for MD and CPSD showed no significant difference from zero in either group. However, in the betaxolol group, estimated slopes (dB/year) for two adjacent sectors in the inferior arcuate area were significantly positive (P =.0135,.0116) while in the timolol group, no significant difference from zero was seen in any of the sectors. IOP changes from baseline in the timolol group were greater than in the betaxolol group, although no statistical significance was seen at any of the examination times. CONCLUSION: MD and CPSD showed no significant change in either group. In the betaxolol group, however, a significant trend in improvement of visual field performance was seen in the inferior arcuate subfield. Timolol reduced IOP more effectively than betaxolol in OAG patients.

The efficacy and safety of dose escalation of dorzolamide used in combination with other topical antiglaucoma agents.

We investigated the dose-escalation profile of dorzolamide used in combination with other antiglaucoma agents in patients with primary glaucoma and ocular hypertension. In a prospective, open-label study, 78 patients received dorzolamide 0.5% in addition to other topical antiglaucoma agents for > or =4 weeks. The concentration of dorzolamide was then escalated to 1.0% and intraocular pressure (IOP) measured every 4 weeks for 12 weeks. Dose escalation of dorzolamide from 0.5% to 1.0% resulted in a significant reduction in IOP throughout the 12 weeks of treatment at the higher dose. Mean baseline IOP was 19.7 mmHg. At 4, 8, and 12 weeks after dose escalation, mean IOP had decreased to 17.8 (-9.4%), 17.6 (-10.8%), and 17.5 (-10.7%) mmHg. No serious drug-related adverse effects were reported. These results indicate that dose escalation of dorzolamide from 0.5% to 1.0% is effective and well tolerated as adjunctive therapy for patients in whom IOP is insufficiently controlled by combination therapy.

Long-term effect of topically applied isopropyl unoprostone on microcirculation in the human ocular fundus.

PURPOSE: To investigate the long-term effect of 0.12% isopropyl unoprostone (Rescula) on microcirculation in the human ocular fundus. METHODS: A laser speckle tissue circulation analyzer was used to measure normalized blur (NB), a quantitative index of blood flow velocity, in the optic nerve head (ONH) and choroid-retina before and 4.5 hours after the instillation of a placebo into both eyes of 11 healthy volunteers. The intraocular pressure (IOP), blood pressure, and pulse rate were also recorded in this control experiment. Thereafter, a drop of unoprostone or a placebo was instilled into each eye in a double-blind manner twice a day for 21 days to form treated and untreated groups. RESULTS: After 21 days, the NB values in the ONH and choroid-retina had increased significantly and the IOP had decreased significantly in the unoprostone-treated eyes. Ocular perfusion pressure showed no significant change. CONCLUSIONS: These results suggest that long-term application of unoprostone can increase microcirculatory blood flow in the human ocular fundus, probably due to a reduction in vascular resistance.