A 62-year-old woman with POAG is intolerant to prostaglandin analogues due to iris pigmentation and hypertrichosis. Her IOP remains 24 mmHg despite lifestyle modifications. What is the preferred alternative monotherapy?

Explanation

## Second-Line Monotherapy When PGAs Are Contraindicated **Key Point:** When prostaglandin analogues are contraindicated or poorly tolerated, beta-blockers (timolol) are the preferred second-line monotherapy for POAG. ### Hierarchy of Antiglaucoma Agents ```mermaid flowchart TD A[POAG Diagnosed]:::outcome --> B{PGA Tolerated?}:::decision B -->|Yes| C[PGA Monotherapy]:::action B -->|No| D{Contraindications to Beta-blocker?}:::decision D -->|No| E[Beta-blocker Monotherapy]:::action D -->|Yes| F{Contraindications to CAI?}:::decision F -->|No| G[CAI Monotherapy]:::action F -->|Yes| H[Alpha-2 agonist or Combination]:::action ``` **High-Yield:** When PGAs fail or are contraindicated, the second-line preference is **beta-blockers** (timolol), followed by carbonic anhydrase inhibitors (CAI), then alpha-2 agonists. ### Comparison of Second-Line Options | Agent | Class | IOP Reduction | Dosing | Systemic SE | Local SE | Second-line Rank | |-------|-------|---------------|--------|-------------|----------|------------------| | **Timolol** | Beta-blocker | 20–25% | BID | Bradycardia, bronchospasm, fatigue | Minimal | **1st choice** | | **Dorzolamide** | CAI (topical) | 15–20% | TID | Minimal (topical) | Stinging, bitter taste | 2nd choice | | **Brimonidine** | Alpha-2 agonist | 15–20% | TID | Minimal | Allergic conjunctivitis (10–15%) | 3rd choice | | **Pilocarpine** | Cholinergic | 15–20% | QID | Minimal | Miosis, accommodation, cataract | Rarely used | **Clinical Pearl:** Timolol is preferred over dorzolamide as second-line because it has slightly better efficacy and requires only twice-daily dosing (vs. three times daily for dorzolamide). ### Why Timolol Is Preferred Over Alternatives 1. **Better efficacy** (20–25% IOP reduction) than CAI or alpha-2 agonists 2. **Fewer local side effects** than dorzolamide (no stinging, bitter taste) or brimonidine (no allergic conjunctivitis) 3. **Twice-daily dosing** is more convenient than three-times-daily CAI 4. **Minimal local ocular toxicity** compared to cholinergics **Warning:** Do not confuse second-line with third-line agents. Timolol is second-line; dorzolamide and brimonidine are third-line. Pilocarpine is rarely used in modern practice.