A 52-year-old Indian woman with newly diagnosed POAG is counseled about first-line pharmacological management. Her IOP is 28 mmHg bilaterally, and she has no contraindications to any drug class. Which of the following is NOT recommended as a first-line monotherapy agent for POAG according to current guidelines?

## First-Line Monotherapy Agents in POAG **Key Point:** Prostaglandin analogues, beta-blockers, and topical carbonic anhydrase inhibitors are all acceptable first-line monotherapy options for POAG. Alpha-2 agonists (brimonidine) are reserved for adjunctive therapy or when other agents are contraindicated, not recommended as initial monotherapy. ### First-Line vs. Adjunctive Agents | Agent Class | IOP Reduction | First-Line? | Role | |---|---|---|---| | Prostaglandin analogues (latanoprost, travoprost, bimatoprost) | 25–35% | **YES** | Preferred initial choice; once-daily dosing | | Beta-blockers (timolol, betaxolol) | 20–25% | **YES** | Excellent efficacy; systemic side effects limit use | | Topical CAIs (dorzolamide, brinzolamide) | 15–20% | **YES** | Good efficacy; safe profile; useful in combination | | Alpha-2 agonists (brimonidine, apraclonidine) | 15–20% | **NO** | Adjunctive only; tachyphylaxis common; reserve for add-on | | Rho kinase inhibitors (netarsudil) | 20–25% | Emerging | Newer agent; increasingly used as monotherapy | **High-Yield:** Current AAO and NICE guidelines recommend prostaglandin analogues as first-line due to superior efficacy and once-daily dosing. Beta-blockers and CAIs are equally valid alternatives. Alpha-2 agonists are NOT recommended for monotherapy initiation. **Mnemonic:** **PBCA** = Prostaglandins, Beta-blockers, CAIs = **First-line**. **Alpha-2 agonists** = **Adjunctive only**. ### Why Alpha-2 Agonists Are Not First-Line 1. **Tachyphylaxis:** Brimonidine loses efficacy over 6–12 months in 20–30% of patients 2. **Moderate IOP reduction:** Only 15–20% reduction; inferior to other classes 3. **Systemic side effects:** Dry mouth, fatigue, drowsiness limit tolerability 4. **Allergy risk:** Higher incidence of contact dermatitis with chronic use 5. **Guideline consensus:** AAO, NICE, and Indian Glaucoma Society all recommend alpha-2 agonists as adjunctive agents only **Clinical Pearl:** Brimonidine is valuable in combination therapy (e.g., with prostaglandin analogue) but should not be chosen as the sole initial agent. Reserve it for patients who cannot tolerate or have contraindications to first-line drugs.