As gatekeepers to eyecare, optometrists are often the first line of clinicians to interface with patients for their vision needs. We play a key role in the diagnosis and management of a wide range of ocular conditions, particularly chronic diseases such as glaucoma. At present, there are approximately 3 million people living with glaucoma in the United States.1 A leading cause of irreversible blindness, the course of glaucoma involves progressive and irreparable damage to the optic nerve, even before there is perceived vision loss.2 Early diagnosis and treatment aimed at controlling intraocular pressure (IOP) have been proven to delay glaucoma progression and preserve vision. However, diagnosis is difficult – approximately 50 percent of patients are undiagnosed.3 As optometrists, we are key to addressing this gap, and significant progress has been made to broaden our scope of practice to include glaucoma care. We are involved in multiple facets of the disease, from diagnosis to prescribing and monitoring the effectiveness of pharmacologic treatment options.
The majority of today’s glaucoma therapies were approved for use more than twenty years ago; however, in November 2017, VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% was approved for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension.4 Since the most frequently prescribed ophthalmic medication for glaucoma treatment currently is a prostaglandin analog, most providers will be comfortable with VYZULTA. But what makes it novel is that it is the first and only FDA approved nitric oxide-releasing agent with a dual mechanism of action that targets both the trabecular meshwork and uveoscleral pathways at the intracellular level to lower IOP in glaucoma patients.4-6 Once administered, VYZULTA is metabolized into latanoprost and butanediol mononitrate which releases nitric oxide.4 Latanoprost, as demonstrated through years of experience, works on the uveoscleral outflow pathway to increase aqueous outflow, while the nitric oxide moiety of VYZULTA relaxes the trabecular meshwork and aids aqueous outflow through the primary outflow pathway of the eye.4-6 Nitric oxide relaxes the trabecular meshwork by inhibiting Rho kinase and calcium signaling, two major causes of trabecular meshwork contraction.6-12
Every 1 mmHg of IOP reduction yields a 10 percent to 19 percent reduction in progression of visual field loss.13 Additionally, achieving a 20 percent to 30 percent reduction of IOP from baseline or a target IOP of less than 18 mmHg has been proven to slow progression of visual field loss.13
In two Phase 3 clinical studies that compared once-daily VYZULTA to twice-daily timolol 0.5% in 774 patients with open-angle glaucoma or ocular hypertension, VYZULTA demonstrated up to 9 mmHg mean IOP reduction from baseline (P=0.002) and a 32 percent reduction in mean IOP from baseline at Month 3.14-16 In a Phase 2, dose-ranging study (VYZULTA arm: N=83; Xalatan arm: N=82), VYZULTA achieved a 35 percent mean reduction in mean IOP at day 28 compared to approximately 30 percent for latanoprost 0.005%.17 Additionally, 68 percent of patients treated with VYZULTA achieved a mean diurnal IOP reduction of ≤18 mmHg compared to only 48 percent of latanoprost 0.005%-treated patients (P=0.05).18
The safety of VYZULTA was also confirmed in these studies. The most common adverse reaction was conjunctival hyperemia at 6 percent and less than 1 percent of patients discontinued therapy due to ocular adverse reactions.4 Please see Important Safety Information below.
We should consider VYZULTA as a first-line treatment option for glaucoma because it is a nitric oxide-releasing agent with a dual mechanism of action that works on two outflow pathways.4-6 With early intervention being crucial to preserving vision, VYZULTA’s proven effectiveness, overall safety profile, and once-daily dosing make it a good addition to the glaucoma armamentarium and can enhance our confidence in managing patients afflicted with this disease.
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%)
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Dr. Zerbinopoulos sees patients at the Rhode Island Eye Institute. Dr. Zerbinopoulos is a paid advisor and speaker for Bausch + Lomb. This article was sponsored by Bausch + Lomb.
1. National Eye Institute. Open-angle Glaucoma Defined. nei.nih.gov/eyedata/glaucoma. Accessed November 1, 2018.
2. National Eye Institute. Glaucoma: The ‘silent thief’ begins to tell its secrets. nei.nih.gov/news/pressreleases/012114. Accessed November 29, 2018.
3. Glaucoma Research Foundation. Glaucoma Facts and Stats. www.glaucoma.org/glaucoma/glaucoma-facts-and-stats.php. Accessed November 26, 2018.
4. VYZULTA Prescribing Information. Bausch & Lomb Incorporated. 2018.
5. Krauss AH, Impagnatiello F, Toris CB, et al. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2alpha agonist, in preclinical models. Exp Eye Res. 2011;93:250-255.
6. 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.
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:C1378-C1386.
8. Dismuke WM, Liang J, Overby D, Stamer WD. Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility. Exp Eye Res. March 2014;120:28-35.
9. Thoonen R, Sips PY, Bloch KD, Buys ES. Pathophysiology of hypertension in the absence of nitric oxide/cyclic GMP signaling. Curr Hypertens Rep. Feb 2013;15(1):47-58.
10. Buys ES, Potter LR, Pasquale LR, Ksander BR. Regulation of intraocular pressure by soluble and membrane guanylate cyclases and their role in glaucoma. Front Mol Neurosci. 2014;7:38.
11. Schneemann A, Dijkstra BG, van den Berg TJ,et al. Nitric oxide/guanylate cyclase pathways and flow in anterior segment perfusion. Graefes Arch Clin Exp Ophthalmol. 2002;240:936-941.
12. Wiederholt M, Sturm A, Lepple-Wienhues A. Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide. Invest Ophthalmol Vis Sci. 1994;35:2515-2520.
13. VanVeldhuisen, Paul C, et al. The Advanced Glaucoma Intervention Study (AGIS): The Relationship Between Control of Intraocular Pressure and Visual Field Deterioration. Am J Ophthalmol. 2000;130(4): 429-440.
14. Medeiros FA, Martin KR, Peace J, et al. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. Am J Ophthalmol. 2016;168:250-259.
15. Weinreb RN, Scassellati Sforzolini B, Vittitow J, Liebmann J. Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study. Ophthalmology. 2016;123:965-973.
16. Weinreb RN, Liebmann JM, Martin KR, Kaufman PL, Vittitow JL. Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings. J Glaucoma. 2018;27:7-15.
17. Weinreb RN, Ong T, Scassellati Sforzolini B, et al for the VOYAGER study group. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015;99:738-745.
18. Data on file. Bausch & Lomb Incorporated.
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