What is the role of acetazolamide in managing glaucoma?

Role of Acetazolamide in Glaucoma Management

Acetazolamide is an oral carbonic anhydrase inhibitor that serves primarily as a second-line or adjunctive therapy in glaucoma management, providing significant IOP reduction (20-30%) but with notable systemic side effects that limit its long-term use. 1, 2

Mechanism of Action

• Acetazolamide inhibits the enzyme carbonic anhydrase, which catalyzes the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid
• In the eye, this inhibitory action decreases aqueous humor secretion, resulting in reduced intraocular pressure 2
• The IOP-lowering effect occurs through decreased aqueous humor formation rather than increased outflow 3

Clinical Applications in Different Types of Glaucoma

Acute Angle-Closure Glaucoma

• Primary role: Emergency management to rapidly reduce IOP before definitive treatment with laser peripheral iridotomy
• Provides rapid IOP reduction in acute situations when topical medications alone may be insufficient 4
• Used alongside other medications (topical beta-blockers, alpha-agonists, prostaglandin analogs) in the initial management of acute angle-closure attacks 4

Open-Angle Glaucoma and Ocular Hypertension

• Secondary role: Adjunctive therapy when target IOP is not achieved with topical medications
• Not considered first-line therapy due to systemic side effects 1
• Prostaglandin analogs are the preferred first-line agents for open-angle glaucoma due to better efficacy, tolerability, and once-daily dosing 1

Dosing and Administration

• Standard dosing: 250mg tablets four times daily or 500mg sustained-release capsules twice daily 5
• Alternative dosing: 500mg sustained-release capsule once daily provides substantial pressure-lowering effect lasting at least 23 hours, though with less magnitude than higher doses 5
• Once-daily dosing may improve tolerability for some patients 5
• Therapeutic serum concentration range: 15-20 μg/mL 5

Efficacy

• Reduces IOP by approximately 20-30% from baseline 1, 2
• Achieves approximately 45% reduction in outflow pressure at therapeutic serum concentrations 5
• Effect begins within 1-2 hours and can last up to 12 hours (standard tablets) or 24 hours (sustained-release formulation) 5

Important Clinical Considerations

Combination Therapy

• No additive effect when combined with topical carbonic anhydrase inhibitors (e.g., dorzolamide, brinzolamide) 3
• Either oral acetazolamide or topical carbonic anhydrase inhibitors alone result in maximum reduction in IOP and aqueous humor formation 3
• Concomitant therapy with both topical and systemic carbonic anhydrase inhibitors is not warranted 3

Contraindications

• Hypersensitivity to acetazolamide or other sulfonamide derivatives
• Depressed sodium and/or potassium blood serum levels
• Marked kidney or liver disease/dysfunction
• Suprarenal gland failure
• Hyperchloremic acidosis
• Cirrhosis (risk of hepatic encephalopathy)
• Long-term use is contraindicated in chronic non-congestive angle-closure glaucoma as it may mask worsening glaucoma while permitting organic angle closure 2

Adverse Effects

• Systemic side effects limit long-term use:
  • Stevens-Johnson syndrome (rare but serious)
  • Malaise, anorexia, depression
  • Serum electrolyte imbalances
  • Renal calculi
  • Blood dyscrasias (aplastic anemia, thrombocytopenia)
  • Metallic taste
  • Paresthesia
  • Gastrointestinal symptoms (diarrhea, abdominal cramps) 1

Emerging Developments

• Novel formulations such as cubosome-based systems for topical delivery of acetazolamide show promise in experimental settings 6
• Topical formulation could potentially provide the benefits of acetazolamide while avoiding systemic side effects 6
• Research shows cubosome-based acetazolamide formulations may achieve superior IOP reduction compared to commercial topical carbonic anhydrase inhibitors 6

Clinical Decision Algorithm

1. For acute angle-closure glaucoma:

   • Use acetazolamide 500mg IV or PO immediately as part of emergency management
   • Follow with definitive treatment (laser peripheral iridotomy) as soon as possible 4

2. For open-angle glaucoma:

   • Start with prostaglandin analogs as first-line therapy 1
   • If target IOP not achieved, add topical beta-blockers, alpha-agonists, or topical carbonic anhydrase inhibitors
   • Consider acetazolamide only when multiple topical medications fail to achieve target IOP
   • Limit duration of acetazolamide use due to side effect profile
   • Monitor for electrolyte imbalances and other systemic effects during treatment 7

Monitoring

• Regular measurement of IOP to assess efficacy
• Periodic electrolyte monitoring, especially in long-term use
• Coordination with primary care physician for monitoring of systemic effects 7