A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study

Weinreb, Robert N.; Ong, T.; Sforzolini, Baldo Scassellati; Vittitow, Jason L; Singh, Kuldev; Kaufman, Paul L.

doi:10.1136/bjophthalmol-2014-305908

Cited by 141 publications

(158 citation statements)

References 21 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…This radical affects an early step in the replication cycle of influenza viruses and NO has been shown to severely impair the replication of influenza A and B viruses 11. In the outflow physiology, NO has been reported to contribute to the physiological regulation of aqueous humor outflow and to lower intraocular pressure in various animal models and human patients 5, 12, 13, 14, 15…”

Section: Introductionmentioning

confidence: 99%

Progress and Promise of Nitric Oxide‐Releasing Platforms

2018

View full text Add to dashboard Cite

Nitric oxide (NO) is a highly potent radical with a wide spectrum of physiological activities. Depending on the concentration, it can enhance endothelial cell proliferation in a growth factor‐free medium, mediate angiogenesis, accelerate wound healing, but may also lead to tumor progression or induce inflammation. Due to its multifaceted role, NO must be administered at a right dose and at the specific site. Many efforts have focused on developing NO‐releasing biomaterials; however, NO short half‐life in human tissues only allows this molecule to diffuse over short distances, and significant challenges remain before the full potential of NO can be realized. Here, an overview of platforms that are engineered to release NO via catalytic or noncatalytic approaches is presented, with a specific emphasis on progress reported in the past five years. A number of NO donors, natural enzymes, and enzyme mimics are highlighted, and recent promising developments of NO‐releasing scaffolds, particles, and films are presented. In particular, key parameters of NO delivery are discussed: 1) NO payload, 2) maximum NO flux, 3) NO release half‐life, 4) time required to reach maximum flux, and 5) duration of NO release. Advantages and drawbacks are reviewed, and possible further developments are suggested.

show abstract

Section: Introductionmentioning

confidence: 99%

Progress and Promise of Nitric Oxide‐Releasing Platforms

2018

View full text Add to dashboard Cite

show abstract

“…Current topical medications for glaucoma typically increase the uveoscleral outflow of aqueous humor (prostaglandin analogues) or reduce aqueous humor production (betaadrenergic blockers, alpha-adrenergic agonists, carbonic anhydrase inhibitors). The only drugs that increase the conventional outflow that are readily available at the time of this writing are cholinergic agonists who have miosis and ciliary spasm as significant side effects 2 although NO donors are on the horizon that relax the TM to increase outflow 3 . In the present study we examine the hypotensive effect of RKI-1447, which was originally introduced as an anti-tumor agent in breast cancer treatment 4 .…”

Section: Introductionmentioning

confidence: 99%

Ocular Hypotension, Actin Stress Fiber Disruption and Phagocytosis Increase by RKI-1447, a Rho-Kinase Inhibitor

Dang¹,

Wang²,

Shah³

et al. 2018

Preprint

View full text Add to dashboard Cite

Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods:Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67×10 7 pigment particles/ml) for 48 hours before being subjected to the RKI-1447 (n=16) or the vehicle control (n=12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis.

show abstract

“…33 Latanoprostene bunod (Vyzulta; NOdonating latanoprost) was shown to lower IOP by 1.3 mm Hg better than latanoprost. 18 In preclinical species, NO donors and a cGMP analog lower IOP in rabbits and nonhuman monkeys.…”

Section: Discussionmentioning

confidence: 99%

“…8,16,17 Vyzulta lowered IOP by an additional 1þ mm Hg better than Xalatan alone in glaucoma patients, and the effect was maintained up to 24 hours on day 28 in patients with glaucoma or ocular hypertension. 18 The preclinical and clinical effects of these and other potential new IOP-lowering drug classes have been recently discussed in a review paper 4 and by others. 19,20 The NO/sGC/cGMP pathway also appears to be dysregulated in glaucoma as well as other nonocular diseases/dysfunctions, including pulmonary hypertension, atherosclerosis, thrombosis, inflammation, erectile dysfunction, renal fibrosis/ failure, liver cirrhosis, and arterial hypertension.…”

mentioning

confidence: 99%

A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing

Prasanna

Ferrara

Adams

et al. 2018

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. The nitric oxide/soluble guanylate cyclase/protein kinase G (NO/sGC/PKG) is known to be involved in the regulation of intraocular pressure (IOP) and may be dysregulated in glaucoma. The purpose is to demonstrate that the sGC activator MGV354 lowers IOP in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. METHODS.Changes to cGMP were assessed in primary human trabecular meshwork (hNTM) cells and binding studies were conducted using human sGC full-length protein. Ocular safety tolerability, exposure, and efficacy studies were conducted in rabbit and monkey models following topical ocular dosing of MGV354.RESULTS. sGC was highly expressed in the human and cynomolgus monkey outflow pathways. MGV354 had a 7-fold greater Bmax to oxidized sGC compared to that of reduced sGC and generated an 8-to 10-fold greater cGMP compared to that of a reduced condition in hTM cells. A single topical ocular dose with MGV354 caused a significant dose-dependent reduction of 20% to 40% (versus vehicle), lasting up to 6 hours in pigmented rabbits and 24 hours postdose in a cynomolgus monkey model of glaucoma. The MGV354-induced IOP lowering was sustained up to 7 days following once-daily dosing in a monkey model of glaucoma and was greater in magnitude compared to Travatan (travoprost)-induced IOP reduction. Mild to moderate ocular hyperemia was the main adverse effect noted.CONCLUSIONS. MGV354 represents a novel class of sGC activators that can lower IOP in preclinical models of glaucoma. The potential for sGC activators to be used as effective IOPlowering drugs in glaucoma patients could be further determined in clinical studies.Keywords: soluble guanylate cyclase, monkey model of glaucoma, IOP, ODQ, cGMP, glaucoma T he estimated number of glaucoma cases globally is over 60 million, and primary open angle glaucoma accounts for >70% of the total cases. In the United States alone, over 120,000 patients are blind from this disease, accounting for 9% to 12% of all cases of blindness.1 Lowering of intraocular pressure (IOP) is the current gold standard for reducing visual field (VF) loss in glaucoma. However, up to 45% of patients who achieved an IOP-lowering target of 25% to 30% (6 to 8 mm Hg) from baseline IOP by medical treatment continued to show progressive VF loss. Every 1 mm Hg higher mean IOP in the follow-up period was associated with 13% higher risk of progressive VF loss for the study population, whereas each mm Hg reduction was associated with a 10% reduction in disease progression. Rhopressa and latanoprost, which lowered IOP by 1 to 3 mm Hg greater than the monotherapy comparators over 3 months of dosing in patients with glaucoma.5 IOP lowering via the NO/ cGMP signaling pathway is also well known. This is a key pathway in several physiologic processes, including platelet inhibition, smooth muscle relaxation, and neurotransmission. NO is the endogenous ligand of soluble guanylate cyclase (sGC). Binding of NO to the heme domain of sGC results in sGC activation and production ...

show abstract

A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study

Cited by 141 publications

References 21 publications

Progress and Promise of Nitric Oxide‐Releasing Platforms

Progress and Promise of Nitric Oxide‐Releasing Platforms

Ocular Hypotension, Actin Stress Fiber Disruption and Phagocytosis Increase by RKI-1447, a Rho-Kinase Inhibitor

A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing

Contact Info

Product

Resources

About