A 58-year-old man is diagnosed with primary open-angle glaucoma (POAG) on routine eye examination. Intraocular pressure (IOP) is 28 mmHg in both eyes, and optic disc cupping is 0.6. He has no contraindications to any class of antiglaucoma drugs. What is the drug of choice for initiating monotherapy in this patient?

Explanation

## First-Line Monotherapy in POAG **Key Point:** Prostaglandin analogues (PGAs) are the gold-standard first-line agents for POAG due to superior IOP-lowering efficacy and once-daily dosing. ### Why Prostaglandin Analogues? | Feature | PGA | Beta-blocker | CAI | Cholinergic | |---------|-----|--------------|-----|-------------| | **IOP reduction** | 25–32% | 20–25% | 15–20% | 15–20% | | **Dosing frequency** | Once daily (evening) | Twice daily | Twice daily | 3–4 times daily | | **Systemic side effects** | Minimal | Significant (bradycardia, bronchospasm) | Metabolic (myopia, hyperchloremic acidosis) | Miosis, accommodation issues | | **Local side effects** | Iris pigmentation, hypertrichosis | Minimal | Minimal | Miosis, accommodation, cataract risk | | **First-line status** | ✓ Yes | Alternative | Reserve | Rarely used | **High-Yield:** PGAs (latanoprost, travoprost, bimatoprost) work by increasing uveoscleral outflow of aqueous humor and are superior to all other monotherapy options in terms of efficacy and tolerability. ### Mechanism of Action Prostaglandin analogues bind to prostaglandin F (FP) receptors on ciliary muscle and increase unconventional (uveoscleral) outflow of aqueous humor, reducing IOP by 25–32%. **Clinical Pearl:** Evening dosing of PGAs is preferred because IOP naturally peaks in the morning; evening administration provides better 24-hour coverage. ### Why Other Options Are Not First-Line - **Pilocarpine** (cholinergic): Outdated; causes miosis, accommodation problems, and requires frequent dosing. Reserved only for acute angle closure or when other agents fail. - **Timolol** (beta-blocker): Good efficacy but requires twice-daily dosing and carries systemic risks (bradycardia, bronchospasm, fatigue). Used as second-line or adjunct. - **Acetazolamide** (CAI): Causes metabolic acidosis, myopia, and electrolyte disturbances. Reserved for acute glaucoma or when topical agents insufficient. **Warning:** Do not confuse PGA efficacy with beta-blockers; timolol was once considered first-line but has been superseded by PGAs in modern practice.