Neuroprotective Effect of Brimonidine in Glaucoma
The evidence for brimonidine's neuroprotective effect in glaucoma remains inconclusive and of very low certainty, preventing any definitive recommendation for its use specifically as a neuroprotective agent in clinical practice. 1, 2
Current Evidence Status
The only high-quality clinical trial examining brimonidine's neuroprotective properties (the Low-pressure Glaucoma Treatment Study) found less visual field progression in brimonidine-treated patients compared to timolol after 4 years, but this evidence is of such low certainty that no firm conclusions can be drawn. 1, 2 The study suffered from:
- High attrition bias with 55% dropout in the brimonidine group versus 29% in the timolol group 2
- Potential selective outcome reporting that undermines confidence in the findings 2
- Similar IOP reduction between groups, making it difficult to attribute benefits solely to neuroprotection rather than IOP-lowering effects 2
FDA-Approved Indication
Brimonidine is FDA-approved solely for lowering intraocular pressure in open-angle glaucoma and ocular hypertension, not for neuroprotection. 3 The drug works through a dual mechanism: reducing aqueous humor production and increasing uveoscleral outflow, with IOP reductions of approximately 4-6 mmHg. 3
Preclinical Evidence vs. Clinical Reality
While preclinical studies suggest potential neuroprotective mechanisms—including Erk1/2 phosphorylation promoting axon regeneration 4, suppression of NMDA receptor phosphorylation 5, and stimulation of neurotrophic factor production from Müller glia 5—these laboratory findings have not translated into conclusive clinical evidence. 2, 6
Clinical Practice Implications
- Use brimonidine for its proven IOP-lowering effect, which remains the primary evidence-based treatment for slowing glaucoma progression 7
- Do not prescribe brimonidine specifically for neuroprotection given the lack of high-certainty clinical evidence 1, 2
- Monitor for ocular allergy, the most common adverse effect, which occurs significantly more frequently with brimonidine than other agents (5-fold increased risk versus timolol) 2
- Be aware of tachyphylaxis: brimonidine's IOP-lowering efficacy diminishes over time in some patients, requiring close monitoring 3
Common Pitfall
The most significant pitfall is prescribing brimonidine based on its theoretical neuroprotective properties rather than its established IOP-lowering effect. 2, 6 Despite off-label use of various agents for neuroprotection in glaucoma practice, lack of compelling clinical evidence should guide conservative prescribing. 6