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Hyperaemia was similar across treatments.Conclusions LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28days was well tolerated.Clinical trial number NCT01223378.Clinical TrialDrugsGlaucomaIntraocular pressureTreatment MedicalIntroductionGlaucoma is a leading cause of blindness worldwide.1 3 Intraocular pressure (IOP) is the primary risk factor for glaucoma,3 ,4 and lowering IOP to prevent optic nerve injury is the only proven effective treatment.3 ,5 9 Topical prostaglandin analogues, such as latanoprost, are considered first line treatment to lower IOP due to their safety and efficacy.10 12 BOL 303259 X, also known as latanoprostene bunod (LBN), is a new IOP lowering agent that, when exposed to ubiquitous esterases in the ocular environment, is cleaved into latanoprost acid, a prostaglandin F2 receptor agonist, and butanediol mononitrate, a nitric oxide (NO) donating moiety. LBN exhibited potent and effective IOP lowering activity in three ocular hypertensive glaucoma animal models.13NO donors relax the trabecular meshwork (TM) and increase aqueous humour outflow.14 17 They activate the large conductance calcium activated potassium channel, or BKCa ion channel, involved in reducing TM cell volume.17 19 NO donors may trigger, among other things, reduction of actomyosin contractility and disassembly of the actin cytoskeleton and cell adhesion system in the cells of the conventional outflow pathway, causing cell shape changes and overall relaxation of the TM and inner wall of Schlemm’s canal leading to decreased resistance to aqueous humour outflow.8 ,20 ,21 Experimental data to date on the role of NO in modulating IOP through the conventional pathway were the focus of a recent review.17 In contrast, latanoprost acts by increasing the outflow of aqueous humour primarily through the uveoscleral pathway, consequently decreasing the IOP.22 There is a substantial reduction in IOP beginning approximately 3 4h after latanoprost exposure and the reduction is sustained for at least 24h.23It is hypothesised that the use of the novel single entity, LBN, with the combined actions of latanoprost acid and NO will provide greater IOP reduction than latanoprost 0.005% while maintaining the convenience of a once daily dosing regimen.