Role of the TM

The trabecular meshwork (TM) is the primary outflow pathway, responsible for up to 80% of aqueous outflow humor, followed by the uveoscleral outflow pathway.1 Nitric oxide deficiency is believed to play a role in chronic TM contraction.2

Glaucomatous eyes have shown a ~40% reduction in nitric oxide markers compared with normal eyes.3

Glaucomatous eyes have shown a ~40% reduction in nitric oxide markers compared with normal eyes.3

Dual-action VYZULTA

VYZULTA is the only PGA that delivers nitric oxide as part of a dual MOA with latanoprost acid to increase outflow and reduce IOP.4,5

NITRIC OXIDE (NO) improves trabecular meshwork (TM) permeability to increase outflow and reduce IOP4,5

Works on trabecular meshwork

animation comparing glaucoma and normal eyes showing how nitric oxide targets the primary outflow pathway to improve TM permeability

LATANOPROST ACID opens the interstitial spaces of the uveoscleral pathway to decrease IOP4,5

Works on uveoscleral pathway

animation showing how latanoprost acid opens the interstitial spaces of the uveoscleral pathway

Go deeper into the dual MOA of VYZULTA and how nitric oxide inhibits both rho kinase and calcium signaling to relax the TM.6,7

Facilitating outflow through cellular relaxation

Human TM cells were stained for F-actin (green) to assess for stress fiber formation and cellular contraction. F-actin (filamentous actin) is a protein polymer that regulates the shape and mechanical properties of cells.5

Contracted TM cells

Bright green fluorescence signifies contracted state

Normal TM cells

In vitro model of healthy TM

Normal TM cells

Normal TM cells

In vitro model of healthy TM

Contracted TM cells

Contracted TM cells

Bright green fluorescence signifies contracted state

Contracted TM cells
+ latanoprost

Latanoprost alone has marginal effect on contracted TM cells2

Contracted TM cells treated with
latanoprostene bunod (LBN)

LBN causes cellular relaxation, altering the contracted TM cells so they appear similar to healthy TM cells6,7

Contracted TM cells treated with latanoprostene bunod (LBN)

Contracted TM cells treated with latanoprostene bunod (LBN)

LBN causes cellular relaxation, altering the contracted TM cells so they appear similar to Thealthy TM cells6,7

Contracted TM cells + latanoprost

Contracted TM cells + latanoprost

Latanoprost alone has marginal effect on contracted TM cells2

The clinical significance of in vitro data is unknown.

IOP=intraocular pressure; LBN=latanoprostene bunod; PGA=prostaglandin analog; SLT=selective laser trabeculoplasty.

INDICATION

VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

IMPORTANT SAFETY INFORMATION

  • Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent
  • Gradual changes to eyelashes, including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation
  • Use with caution in patients with a history of intraocular inflammation (iritis/uveitis). VYZULTA should generally not be used in patients with active intraocular inflammation
  • Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs. Use with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema
  • There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products that were inadvertently contaminated by patients
  • Contact lenses should be removed prior to the administration of VYZULTA and may be reinserted 15 minutes after administration
  • Most common ocular adverse reactions with incidence ≥2% are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%)

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please click here to see full Prescribing Information.

References: 1. Winkler NS, Fautsch MP. Effects of prostaglandin analogues on aqueous humor outflow pathways. J Ocul Pharmacol Ther. 2014;30(2-3):102-109. 2. Aliancy J, Stamer WD, Wirostko B. A review of nitric oxide for the treatment of glaucomatous disease. Ophthalmol Ther. 2017;6(2):221-232. 3. Galassi F, Renieri G, Sodi A, Ucci F, Vannozzi L, Masini E. Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma. Br J Ophthalmol. 2004;88(6):757-760. 4. VYZULTA. Prescribing Information. Bausch & Lomb Inc. 5. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of endothelin-1-induced trabecular meshwork cell contractility by latanoprostene bunod. Invest Ophthalmol Vis Sci. 2015;56(6):4108-4116. 6. Suzuki H, Kimura K, Shirai H, et al. Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration. Arterioscler Thromb Vasc Biol. 2009;29(2):217-224. 7. Dismuke WM, Mbadugha CC, Ellis DZ. NO-induced regulation of human trabecular meshwork cell volume and aqueous humor outflow facility involve the BKCa ion channel. Am J Physiol Cell Physiol. 2008;294(6):C1378-C1386.

Expand

INDICATION

VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

IMPORTANT SAFETY INFORMATION

  • Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent