Why are prostaglandin analogues the preferred first-line treatment for glaucoma?

Prostaglandin analogues (latanoprost, travoprost, bimatoprost) provide the greatest IOP reduction of any single topical agent (20-35%), require only once-daily dosing (improving compliance), have minimal systemic side effects (negligible cardiovascular or pulmonary effects), and are well tolerated ocularly. These properties make them more effective and safer for most patients than beta-blockers, which were the traditional first choice.

Why are beta-blocker eye drops contraindicated in patients with asthma?

Nonselective beta-blockers (like timolol) block both beta-1 receptors (in the heart) and beta-2 receptors (in the lungs). Blocking beta-2 receptors causes bronchial smooth muscle contraction, which can trigger severe bronchospasm in patients with asthma or COPD. Even though the drop is applied to the eye, enough drug is absorbed through the nasolacrimal mucosa to produce systemic beta-2 blockade. Betaxolol is a cardioselective beta-1 blocker with less bronchospastic risk, but even it should be used cautiously in reactive airway disease.

What side effects should a patient starting a prostaglandin analogue be warned about?

Key side effects to discuss before starting a prostaglandin analogue: (1) iris darkening -- permanent increase in iris pigmentation in light-colored irides, not harmful but irreversible; (2) periocular skin darkening -- the skin around the eye may darken; (3) eyelash changes -- lashes may grow longer, thicker, and darker (hypertrichosis); and (4) conjunctival redness (usually mild). Patients applying the drops to only one eye will notice more dramatic changes in the treated eye.

What is the significance of sulfa allergy for carbonic anhydrase inhibitors?

Topical and oral carbonic anhydrase inhibitors (dorzolamide, brinzolamide, acetazolamide) are sulfonamide-based compounds and have structural similarity to sulfa drugs. Patients with sulfa drug allergies may have cross-reactions to CAIs, including skin reactions and, rarely, more serious hypersensitivity responses. CAIs (especially systemic acetazolamide) are contraindicated in patients with a documented sulfa allergy. Always check sulfa allergy status before prescribing or assisting with CAI therapy.

What is netarsudil (Rhopressa) and how does it differ from other glaucoma drops?

Netarsudil is a Rho-kinase (ROCK) inhibitor -- the newest class of topical glaucoma medication. It lowers IOP primarily by relaxing the trabecular meshwork and Schlemm's canal, improving conventional outflow. It also has mild effects on reducing aqueous production. Unlike prostaglandins, beta-blockers, and alpha-agonists, it acts directly on the trabecular outflow pathway (which accounts for the majority of normal aqueous drainage). Side effects include significant conjunctival redness and corneal verticillata (whorled deposits in the epithelium that are usually asymptomatic).

Glaucoma Medications for the CPOA Exam

Why Glaucoma Is Managed Medically

Glaucoma management centers on reducing intraocular pressure (IOP) to a target level that halts or slows optic nerve damage and visual field loss. The first line of treatment for most patients is topical eye drops that lower IOP through one of two mechanisms: decreasing aqueous production or increasing aqueous outflow. As a CPOA, you will encounter patients on these medications daily and need to understand their classes, actions, and common side effects.

Major Glaucoma Drug Classes

Prostaglandin Analogues (PGAs)

First-line therapy for most patients. They lower IOP by increasing uveoscleral outflow (the secondary outflow pathway for aqueous humor). They are dosed once daily (at night), have the greatest IOP-lowering effect of any single agent (20-35%), and have minimal systemic side effects.

Examples: latanoprost (Xalatan), travoprost (Travatan Z), bimatoprost (Lumigan), tafluprost (Zioptan), latanoprostene bunod (Vyzulta)

Key side effects: iris darkening (increased iris pigmentation, permanent in susceptible patients), periocular skin darkening, eyelash growth (hypertrichosis, longer/thicker/darker lashes), conjunctival hyperemia, and rarely cystoid macular edema.

💡 Clinical Tip: Warn patients starting prostaglandins (especially those with light-colored irides) that the iris can permanently darken over months to years. This is a cosmetic change, not harmful, but patients should know it is expected and cannot be reversed by stopping the drop.

Beta-Blockers

Lower IOP by decreasing aqueous production by the ciliary body. Dosed twice daily (or once for long-acting formulations). IOP reduction: 20-25%.

Examples: timolol (Timoptic), betaxolol (Betoptic), levobunolol (Betagan)

Key side effects: bradycardia (slow heart rate), bronchospasm (dangerous in asthma and COPD patients -- timolol is a nonselective beta-blocker and is contraindicated in patients with reactive airway disease), depression, fatigue. Betaxolol is cardioselective and relatively safer in lung disease.

Alpha-2 Adrenergic Agonists

Lower IOP by both decreasing aqueous production and increasing uveoscleral outflow. Dosed 2-3 times daily.

Examples: brimonidine (Alphagan P), apraclonidine (Iopidine)

Key side effects: ocular allergy (contact allergy with follicular conjunctivitis occurs in 10-15% of long-term users), dry mouth, fatigue, CNS depression in infants and young children (brimonidine is contraindicated in neonates and infants due to risk of apnea and hypotension).

Carbonic Anhydrase Inhibitors (CAIs)

Lower IOP by inhibiting carbonic anhydrase in the ciliary body, reducing aqueous production. Available as topical drops (dorzolamide, brinzolamide) or systemic oral agents (acetazolamide, methazolamide).

Examples: dorzolamide (Trusopt), brinzolamide (Azopt), acetazolamide (Diamox)

Key side effects (topical): bitter taste, burning/stinging, corneal edema in patients with borderline corneal endothelium. Key side effects (oral): diuresis, hypokalemia, paresthesias (tingling in fingers and toes), metabolic acidosis, sulfa cross-reactivity (contraindicated in sulfa allergy).

Miotics (Cholinergic Agents)

Pilocarpine increases trabecular outflow by contracting the ciliary muscle and widening the trabecular spaces. Dosed 3-4 times daily (short duration). Rarely used today as primary therapy but still used for acute angle closure and as adjunctive therapy.

Side effects: brow ache, miosis (dim vision, especially at night), myopia, and accommodative spasm in younger patients.

Rho-Kinase (ROCK) Inhibitors

The newest class. Netarsudil (Rhopressa) lowers IOP by increasing trabecular outflow and reducing aqueous production. Once-daily dosing. Side effects include conjunctival hyperemia and corneal verticillata (whorled deposits in the corneal epithelium -- usually visually insignificant).

Combination Drops

Many patients use combination drops that contain two agents in one bottle for improved convenience and compliance. Common combinations:

Cosopt = dorzolamide + timolol
Combigan = brimonidine + timolol
Rocklatan = netarsudil + latanoprost

⚠️ Common Mistake: Forgetting that topical beta-blockers (timolol) can cause systemic side effects even as eyedrops, because they are absorbed through the nasolacrimal mucosa into the systemic circulation. A patient who presents with bradycardia or shortness of breath should be asked about all eye drop medications, not just oral medications.

Key Takeaways

Prostaglandin analogues: first-line, once daily, greatest IOP reduction; side effects include iris darkening and lash growth.
Beta-blockers: twice daily, decrease aqueous; contraindicated in asthma/COPD.
Alpha-2 agonists: decrease aqueous + increase uveoscleral outflow; allergy common long-term; contraindicated in infants.
Carbonic anhydrase inhibitors: decrease aqueous; oral CAIs contraindicated in sulfa allergy.
Miotics (pilocarpine): increase trabecular outflow; used for angle closure; cause miosis and brow ache.
ROCK inhibitors (netarsudil): increase trabecular outflow; cause conjunctival redness and corneal deposits.