US Pharm. 2022;47(2):25-28.

ABSTRACT: Glaucoma is a term describing diseases of the ocular nerve. It is the leading worldwide cause of irreversible blindness. Primary open-angle glaucoma, representing approximately 75% of glaucoma cases, is asymptomatic in early stages and can lead to tunnel vision and blindness. Pharmacotherapy is a common first-line treatment to prevent disease progression. Common therapeutic options include topical ophthalmic prostaglandin analogs, beta-blockers, alpha-2-adrenergic agonists, carbonic anhydrase inhibitors, miotics, rho kinase inhibitors, and oral carbonic anhydrase inhibitors. Patients with glaucoma often struggle to adhere to treatment regimens. Patient education and therapy designed to match patient-specific factors are key to achieving optimal outcomes.

Glaucoma describes a group of ophthalmic diseases characterized by damage to the ocular nerve and subsequent vision loss that are often associated with elevated intraocular pressure (IOP).1 Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and is present in approximately 3 million people in the United States.2,3 Although there are several different types of glaucoma, the two main types are open-angle and closed-angle (or narrow-angle) glaucoma. Both types can be primary, with no identifiable association with known ocular or systemic disorders, or secondary to another cause or disease state.3


An examination of intraocular fluid flow is key to understanding the difference between the two main subtypes. Aqueous humor is an intraocular fluid with a composition resembling blood plasma that provides nutrients to and removes wastes from avascular structures of the eye. Produced in the ciliary body, this fluid flows through the posterior and anterior chambers of the eye to be returned to the aqueous veins through a space between the iris and cornea called the angle.4 Within the angle, fluid filters through a spongy tissue called the trabecular meshwork and drains out via Schlemm’s canal. Flow out of the eye can be disrupted in two main ways. In closed-angle glaucoma, outward flow is disrupted when movement of the iris narrows or completely blocks the angle. Flow can also be decreased by obstructions within the trabecular meshwork, as often occurs in open-angle glaucoma.

Elevated IOP results when fluid influx exceeds outflow.4,5 Although elevated IOP is commonly present in patients with glaucoma and is strongly associated with optic nerve damage, it is not required for the disease to occur. Problems with microcirculation, excitotoxicity, oxidative stress, and immune factors may also contribute to optic nerve damage.6 IOP that is elevated without any concurrent optic nerve damage is classified as ocular hypertension and may lead to glaucoma if not properly managed.5

In acute closed-angle glaucoma, angle closure results in a rapid increase in IOP, often causing sudden severe eye pain, headache, blurred vision, halos around bright lights, nausea, and vomiting. This is an ocular emergency requiring immediate medical attention. Open-angle glaucoma, in contrast, is often asymptomatic in the early stages. As approximately 75% of all glaucoma cases involve open angles, primary open-angle glaucoma will be the focus of this primer.3


According to the National Glaucoma Research Foundation, individuals with high IOP, a family history of glaucoma, thin corneas, and cupping of the optic nerve are at highest risk for open-angle glaucoma.7 Age is also strongly associated with the disease, beginning at age 40 years for African Americans and age 60 years for the general population. Individuals with diabetes, hypertension, prior eye injury or surgery, and a history of long-term corticosteroid use may also be at an elevated risk.7,8 When glaucoma is already present, a persistently elevated IOP, poor medication adherence, and lower ocular perfusion pressure are associated with more rapid disease progression.7,9


Poorly managed glaucoma can lead to tunnel vision and even blindness. As the disease is largely asymptomatic in the early stages, many sufferers remain undiagnosed for years, with Hispanic and African Americans being at particularly high risk.10 In more advanced disease, patients may experience dramatically reduced quality of life. Vision impairment may interfere with reading, driving, and even walking. Patients with glaucoma are at an increased risk of falls and involvement in motor vehicle collisions.11


Treatment of POAG aims to preserve visual function and maintain patient quality of life.9 Reduction of IOP is the primary therapeutic goal to prevent progression. A 25% reduction in IOP compared with baseline has been shown to slow progression, slow rate of visual field loss, and protect against further functional losses of vision and blindness.3,9 This treatment target should be individualized and take patient-specific factors into consideration. In patients with severe or rapidly progressing damage to the optic nerve or with other risk factors, a more aggressive IOP target may be justified. A less aggressive target may be appropriate in patients with difficulties tolerating treatment or in whom treatment risks outweigh potential benefits.9

Reduction of IOP can currently be achieved through pharmacotherapy, laser therapy (trabeculoplasty), and/or surgery (trabeculotomy). These methods can be used alone or in combination. Both pharmacotherapy and laser therapy are considered first-line treatment options by the American Academy of Ophthalmology, with pharmacotherapy most chosen as initial treatment.3,9 The choice between these two is patient specific, calling for collaborative decision making between patient and doctor. Laser therapy does not carry the burden of daily medication use but may be daunting to individuals averse to medical procedures. Medication may be perceived as a less invasive option but requires a greater commitment to daily administration in order to achieve the desired results. Surgical treatment options are typically reserved for severe cases or performed after failure of pharmacologic or laser therapy.5


When pharmacotherapy is chosen as the initial treatment, monotherapy with a single agent is preferred.9 Currently available pharmacotherapeutic options generally decrease IOP by increasing fluid outflow and/or decreasing fluid production. Prostaglandin analogs are the most frequently prescribed class due to their efficacy, tolerability, and once-daily administration frequency.9

A 3-to-4-week initial trial of medication in just one eye (monocular therapy) can help determine how effective a medication is by allowing the untreated eye to be used as a baseline control. If this initial treatment proves effective, therapy in both eyes (binocular therapy) may be initiated.9 When the IOP is not adequately reduced with monotherapy and good patient adherence, a change to or addition of an alternative agent should be considered.9

Prostaglandin analogs such as bimatoprost, latanoprost, latanoprostene, tafluprost, and travoprost are recommended by the American Academy of Ophthalmology Preferred Practice Pattern guidelines as the initial medication therapy for both POAG and ocular hypertension due to their good efficacy, tolerability, and once-daily administration.3,5,9 These medications work by increasing outflow through both the uveoscleral pathway and the trabecular meshwork.5,9 Possible adverse effects include hyperemia, ocular irritation, an increase in the number and length of eyelashes, and changes in pigmentation of the iris and lashes.5 Latanoprost is associated with lower rates of hyperemia than bimatoprost or travoprost.3 Prostaglandin analogs are contraindicated in patients with macular edema, active uveitis, or a history of herpetic keratitis.9

Beta-blockers such as carteolol, levobunolol, metipranolol, timolol, or betaxolol are thought to decrease IOP by reducing aqueous production. These products may be selected due to their lower cost but carry a higher risk of side effects and are often dosed twice daily.9 They are contraindicated in patients with chronic obstructive pulmonary disease, asthma, congestive heart failure, bradycardia, hypotension, or heart block greater than first-degree.9 If dosed too close to bedtime, beta-blockers may contribute to a “dipping” phenomenon, where systemic blood pressure drops too low at night. Extreme decreases in systolic and diastolic blood pressure at night are associated with further visual field losses.12 Because of this phenomenon, consider recommending that twice-daily topical beta-blockers be administered in the morning and the afternoon.

Alpha-2-adrenergic agonists or sympathomimetic agents such as apraclonidine and brimonidine have three mechanisms of action. They are thought to decrease IOP by decreasing both aqueous production and episcleral venous pressure as well increasing uveoscleral outflow.9 This class of medication is primarily indicated as add-on therapy for patients on maximally tolerated medical therapy rather than as an initial treatment option.5 They must be dosed more frequently, typically three times daily, and may lead to ocular itching, allergic conjunctivitis, and hyperemia.9 Tachyphylaxis, or a diminished therapeutic effect, can occur with apraclonidine, so therapeutic response to this medication requires close monitoring over time. Both apraclonidine and brimonidine are contraindicated in patients on concurrent monoamine oxidase inhibitor therapy, and brimonidine is contraindicated in infants and children aged 2 years and younger.13

Carbonic anhydrase inhibitors (CAIs) are available as eye drops and oral medications. Both oral and topical versions work by decreasing aqueous production.9 Currently available eye drop formulations include brinzolamide and dorzolamide. As these medications tend to be less effective than other topicals and require dosing three times daily, they are best used as a therapeutic addition. Topical CAIs are contraindicated in patients with a sulfonamide allergy or who have sickle cell disease with hyperemia.9

Oral CAIs, such as acetazolamide and methazolamide, are more efficacious but carry a greater side effect burden in comparison to their topical counterparts. Typically reserved for add-on therapy for more severe cases or for patients who prefer oral medications, these may also be used as short-term therapy prior to surgical treatment. They may also be a reasonable choice for patients with unreliable topical absorption due to scarring or severe corneal edema.14 Oral CAIs are contraindicated in patients with a sulfonamide allergy, kidney stones, aplastic anemia, thrombocytopenia, and sickle cell disease.9

Miotic or parasympathomimetic agents such as pilocarpine, echothiophate iodide, and carbachol are rarely used for POAG as they are associated with substantial adverse effects and require dosing up to four times daily.9 Broadly speaking, these medications cause contractions of the ciliary muscle, opening the trabecular meshwork and facilitating increased trabecular outflow.9,15 Miotic agents can lead to fixed pupils, conjunctival scarring, keratitis, abdominal cramps, increased salivation, visual disturbances, retinal detachment, and paradoxical angle closure.9 These agents are more commonly used for other ophthalmic conditions but may be a more affordable choice for patients with limited financial resources.

In 2017, the FDA approved a medication with a new mechanism of action for the reduction of IOP in patients with POAG or ocular hypertension. Netarsudil is a rho kinase inhibitor that is believed to increase aqueous humor outflow through the trabecular meshwork.16 It is recommended that netarsudil be administered once daily in the evening. Conjunctival hyperemia is the most com

mon side effect, with corneal verticillata, instillation-site pain, conjunctival hemorrhage, blurred vision, increased lacrimation, and eyelid erythema also occurring in 5% to 20% of patients in clinical trials.16 More experience is needed with this medication to determine its appropriate place in POAG therapy.9

Combination products of the above medication classes are also available. These may help reduce exposure to preservatives and increase patient adherence to therapy. Choice of a combination product should be considered carefully, as they may also mean suboptimal dosing intervals for drug classes that would normally have different dosing times and/or frequencies.9 (See SIDEBAR 1.)


Glaucoma may be asymptomatic, and patients may not fully understand the consequences and importance of medication therapy. Adherence to prescribed regimens is often poor.9 Community pharmacists can make a difference in patient outcomes by discussing the rationale behind medication therapy, teaching patients the best methods to administer eye drops (see SIDEBAR 2), identifying patterns of poor adherence, and talking to patients about their experiences. Be prepared to recommend alternatives for patients struggling to afford their medication, having trouble with a dosing regimen or specific bottle type, or experiencing medication side effects.


Glaucoma is a widely prevalent group of ophthalmic diseases that develop quietly but also have a dramatic impact on quality of life. Management of POAG depends on careful and consistent control of the IOP. Pharmacists are in a key position to help patients understand the role of medication therapies and effectively use their medications to slow disease progression and maximize quality of life.


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12. Hayreh SS, Podhajsky P, Zimmerman MB. Beta-blocker eyedrops and nocturnal arterial hypotension. Am J Ophthalmol. 1999;128(3):301-309.
13. Brimonidine tartrate package insert. Princeton, NJ: Sandoz; April 2015.
14. Perkins TW. Oral CAIs: still an option worth using. Rev Ophthalmol. Accessed December 11, 2021.
15. Isopto Carpine (pilocarpine hydrochloride) package insert. East Hanover, NJ: Alcon Laboratories; May 2020.
16. Rhopressa (netarsudil) package insert. Irvine, CA: Aerie Pharmaceuticals, Inc; October 2020.
17. Kahook MY. The pros and cons of preservatives. Rev Ophthalmol. Accessed December 12, 2021.
18. Schuster B. Is there a best technique for putting in eye drops? Glaucoma Research Foundation. Accessed December 12, 2021.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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