Dimanche 4 mai :
TITLE: NO-induced Regulation of Primary Human Trabecular Meshwork Cell Contractility by Latanoprostene Bunod
Results: LBN (1 - 100 µM) significantly increased cGMP levels in a dose dependent manner with an EC50 of 1.54 ± 1.33 µM, while latanoprost caused a minimal increase in cGMP at 100 µM only. The cGMP elevation was abolished by ODQ and was therefore sGC dependent. Effects of LBN on endothelin-1-induced MLC-2 phosphorylation were significantly greater than those of latanoprost. LBN caused a dramatic reduction in endothelin-1 induced actin stress fibers and vinculin localization at focal adhesions, while latanoprost was without effect. LBN significantly reduced endothelin-1 induced HTMC monolayer resistance increases to a greater extent than latanoprost over the dose range studied, indicating a greater reduction in cell contractility with LBN.
Conclusions: Data suggest that LBN mediates HTMC relaxation through activation of the cGMP signaling pathway and a subsequent reduction in MLC-2 phosphorylation. In all cases, effects observed with LBN were of a greater magnitude than those observed with latanoprost. This mechanism may underlie the additional IOP lowering effects of LBN over latanoprost observed in in vivo studies.
TITLE: Efficacy of Latanoprostene Bunod Ophthalmic Solution, 0.024%, in Lowering Intraocular Pressure Over 24-Hours in Normal Japanese Subjects (KRONUS)
Results: The mean age of the volunteers was 26.8 (range 20-39) years. Mean IOPs (± SD) on Day 0 were: 14.4mmHg (1.7), 13.9mmHg (1.5), 13.4mmHg (1.4), 13.0mmHg (1.3), 13.2mmHg (1.6), 14.0mmHg (1.7), 13.7mmHg (1.5), 13.5mmHg (1.7) and 13.4mmHg (1.6) with a 24-hour mean IOP of 13.6 mmHg (1.6). On Day 14 pressures were: 11.5mmHg (1.8), 9.8mmHg (1.4), 9.8mmHg (1.2), 9.9mmHg (1.2), 9.9mmHg (1.5), 9.8mmHg (1.7), 9.6mmHg (1.3), 9.4mmHg (1.3) and 10.1mmHg (1.1) with a 24-hour mean IOP of 10.0 mmHg (1.5). Intraocular pressures were taken at 8 PM, 10 PM, 12 AM, 2 AM, 4 AM, 8 AM, 10 AM, 12 PM and 4 PM, respectively. 14-day QD treatment with 0.024% Latanoprostene bunod reduced IOP at all time points (p < 0.001) with a mean 24-hour reduction of 3.6mmHg (1.5) or 26% from the baseline. Peak and trough IOP lowering occurred at 8 AM and 8 PM (12 and 24 hours following instillation) with a mean reduction of 4.2mmHg (1.8) or 30% and 2.8mmHg (2.2) or 20%, respectively. No significant adverse events were encountered.
Conclusions: Latanoprostene bunod, 0.024% dosed QD for 14 days significantly lowered IOP in normal Japanese subjects during the entire 24 hour period from 13.6 to 10.0 mmHg, corresponding to 27% reduction in mean 24-hour IOP. The current result suggests potential of this compound in providing sustained 24-hour IOP reduction to glaucoma patients not only with elevated, but also with normal IOP.
Mardi 6 mai :
TITLE: Efficacy of Latanoprostene Bunod Ophthalmic Solution 0.024% Compared With Timolol Maleate Ophthalmic Solution 0.5% in Lowering IOP over 24 hours in Subjects With Open Angle Glaucoma or Ocular Hypertension (CONSTELLATION)
Results: Mean change from baseline in IOP (mmHg) was 3.9±0.28 for latanoprostene bunod treated eyes and 2.4±0.29 for timolol treated eyes during the diurnal period; 2.75 ± 0.45 for latanoprostene bunod and 0.2±0.46 for timolol during the nocturnal period; and 3.5 ± 0.24 for latanoprostene bunod and 1.7±0.25 for timolol during the entire 24 hour period.
Conclusions: In this group of open angle glaucoma/ocular hypertensive patients, LBN 0.024% was shown to be superior to timolol with regard to IOP lowering during the entire 24 hour period measured (p<0.05), suggesting that treatment with LBN 0.024% may provide more effective and better sustained diurnal and nocturnal IOP reduction.
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