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Editors Selection IGR 11-2

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Comment by Christopher Girkin on:

27800 A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study, Krupin T; Liebmann JM; Greenfield DS et al., American Journal of Ophthalmology, 2011; 151: 671-681

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Patients with primary open-angle glaucoma in whom visual damage occurred at intraocular pressures (IOP) less than 21 mmHg were randomized to twice daily brimonidine 0.2% (99 patients) or timolol 0.5% (79 patients) eye drops, and were followed for a mean of 30 months. Primary outcome measure was carefully defined visual field progression in either eye, assessed by pointwise linear regression; secondary outcome measures were progression based on glaucoma change probability maps and the 3-omitting method for pointwise linear regression.

The baseline, untreated IOP in patients was just over 15 and the mean IOP under treatment during the study was around 14 – i.e., there was minimal IOP lowering in either group

Even though IOP reduction was about the same in both groups over the follow-up period, the difference in rate of detected visual field loss progression between the two groups was startling: by pointwise linear regression, 9.1% of the brimonidine group versus 39.2% of the timolol users (P = 0.001); similar differences were observed for the secondary outcome measures.

Because of drug-related adverse events, 28.3% of brimonidine instillers discontinued compared with 11.4% in the timolol group (P = 0.008). As anticipated, the most common reason for discontinuation was drug allergy: after one year, 20.2% for the brimonidine users versus 3.8% for those on timolol.

The authors concluded: “Low-pressure glaucoma patients with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%.” In the laboratory, alpha-2 agonists show neuroprotection: they improve chances of vision retention beyond IOP reduction. They are thought to promote retinal ganglion cell survival in the hostile environment created by glaucoma. Questions have included lack of randomized controlled clinical trials to demonstrate this property prospectively and scepticism that instilled brimonidine would reach retinal receptors in sufficient concentration to duplicate laboratory results in humans. This study set out to answer those questions.

Now we face the question: how come the differences observed for these two drugs are so large, and in so short a time?

How come the differences observed for these two drugs are so large, and in so short a time?

Most clinicians would not note progressive field loss in more than a third of patients on timolol in 30 months. Is there something different about this group of patients? Even though another group of patients will need to show similar results to validate the findings in this LoGTS, this data deserves careful consideration by clinicians treating glaucoma.

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