What is the recommended first‑line eye‑drop treatment and dosing for primary open‑angle glaucoma, including follow‑up and alternatives if beta‑blockers are contraindicated?

First-Line Eye Drop Treatment for Primary Open-Angle Glaucoma

Start with a prostaglandin analog—specifically latanoprost 0.005%, bimatoprost 0.03%, or travoprost 0.004%—administered once daily in the evening. 1

Initial Drug Selection

Prostaglandin analogs are the definitive first-line therapy because they achieve the greatest IOP reduction (25-35%, approximately 7-8 mmHg), require only once-daily dosing, and lack systemic side effects. 1 Network meta-analysis demonstrates that bimatoprost, latanoprost, and travoprost rank as the three most efficacious medications, reducing IOP by 4.83-5.61 mmHg at 3 months compared to placebo. 2

• Latanoprost 0.005% reduces diurnal IOP by 22-39% over 1-12 months and maintains efficacy for up to 2 years. 3
• Bimatoprost 0.03% achieves the highest mean IOP reduction (5.61 mmHg) among all glaucoma medications. 2
• Travoprost 0.004% demonstrates equivalent efficacy to bimatoprost (4.83 mmHg reduction). 2

The within-class differences between these three prostaglandins are small and likely not clinically meaningful, so selection can be based on cost, availability, and patient tolerance. 2

Dosing and Administration

• Administer one drop once daily in the evening for all prostaglandin analogs. 1, 3
• Instruct patients on eyelid closure or nasolacrimal occlusion after instillation to reduce systemic absorption. 4

Target IOP and Follow-Up

Reduce IOP by 20-30% below baseline as the initial treatment goal, adjusting based on disease severity and progression. 4, 1

• Check IOP response within 2-4 weeks of initiating therapy to confirm adequate pressure reduction. 1, 5
• Perform multiple baseline IOP measurements in the same eye rather than monocular trials, as the two eyes may respond differently to the same medication. 4
• Monitor for progression using visual field testing and optic nerve/RNFL imaging at intervals determined by disease severity. 4

Alternatives When Beta-Blockers Are Contraindicated

If prostaglandin analogs fail or are not tolerated, timolol 0.5% twice daily or timolol 0.1% gel once daily is the next best option. 1, 5

• Timolol achieves IOP reductions of approximately 7-9 mmHg, making it the most effective beta-blocker. 1, 6
• Avoid nighttime dosing of beta-blockers, as this provides limited efficacy and may worsen visual field progression through nocturnal blood pressure reduction. 1

When Beta-Blockers Are Contraindicated

If the patient has respiratory disease (asthma, COPD), cardiac conduction abnormalities, or bradycardia, proceed to third-line agents:

• Alpha-2 agonists (brimonidine): Reduce IOP by 3.59 mmHg but are less effective than prostaglandins. 2
• Topical carbonic anhydrase inhibitors (dorzolamide, brinzolamide): Achieve 15-20% IOP reduction (2.42-2.49 mmHg). 1, 2
• Rho kinase inhibitors (netarsudil): Provide 10-20% IOP reduction through increased trabecular outflow. 1

Combination Therapy

If monotherapy fails to achieve target IOP:

• Add a second medication rather than switching, unless the first agent is ineffective or poorly tolerated. 4
• Fixed combination of latanoprost plus timolol provides superior IOP reduction compared to either agent alone and is more effective than dorzolamide-timolol combinations. 1, 3
• Wait at least 5 minutes between different eye drops to prevent washout and ensure proper absorption. 1, 5

Critical Pitfalls to Avoid

• Do not use unoprostone as first-line therapy—it was the least effective prostaglandin in network meta-analyses, reducing IOP by only 1.91 mmHg. 2, 1
• Do not rely on monocular trials to assess medication efficacy, as they poorly predict long-term effectiveness due to asymmetric responses and contralateral effects. 4
• Avoid oral carbonic anhydrase inhibitors (acetazolamide) except for acute IOP emergencies, as they carry significant risks including Stevens-Johnson syndrome, renal calculi, and blood dyscrasias. 1, 7

Common Side Effects

• Prostaglandin analogs: Conjunctival hyperemia (3-15%) and permanent iris color change (2-9%), though these rarely require discontinuation. 3
• Beta-blockers: Bronchospasm in patients with respiratory disease, bradycardia, and fatigue. 6
• Carbonic anhydrase inhibitors: Ocular stinging and metallic taste. 1

Adherence Strategies

Nearly 45% of glaucoma patients take fewer than 75% of prescribed doses even with free medication and once-daily dosing. 4

• Prefer once-daily medications (prostaglandin analogs, timolol gel) over twice-daily regimens. 1
• Use fixed combinations when multiple medications are needed to reduce pill burden. 4
• Provide repeated instruction on proper drop instillation technique, as many patients—especially elderly—cannot correctly administer eye drops. 4
• Consider smartphone reminders and follow-up telephone calls to improve adherence. 4