Carbonic anhydrase inhibitor added to fixed-combination protocol may further reduce IOP

Brinzolamide increased IOP reduction in eyes with primary open-angle glaucoma and ocular hypertension, study shows.

Issue: April 25, 2012

Ivan Goldberg

A fixed-combination prostaglandin and non-selective beta-blocker with an adjunctive topical carbonic anhydrase inhibitor reduced IOP in patients with ocular hypertension or primary open-angle glaucoma, a study found.

Ivan Goldberg, AM, MBBS, FRANZCO, FRACS, and colleagues analyzed the addition of Azopt (brinzolamide, Alcon) or placebo to DuoTrav (travoprost 0.004%/timolol 0.5%, Alcon).

“The significance of the study was that, in a controlled and prospective fashion, it demonstrated something to reassure clinicians: adding a third drug can be beneficial,” Dr. Goldberg, OSN APAO Edition Board Member, said in an interview with Ocular Surgery News.

Decreasing aqueous inflow and increasing outflow reduce IOP. Prostaglandins increase outflow. Both beta-blockers and carbonic anhydrase inhibitors decrease inflow but through different mechanisms, Dr. Goldberg said.

The study was published in the Journal of Glaucoma.

Patients and protocols

The prospective, randomized study enrolled 163 patients with a minimum age of 18 years and a clinical diagnosis of ocular hypertension, primary open-angle glaucoma, exfoliation or pigment dispersion glaucoma in at least one eye.

Patients underwent treatment with travoprost alone or travoprost combined with timolol before being switched to a daily travoprost/timolol fixed-combination protocol for 4 weeks.

Patients who had IOP of 19 mm Hg to 32 mm Hg at 8 a.m. underwent subsequent measurements at 12 p.m. and 4 p.m. and were randomized to receive brinzolamide or placebo twice daily in conjunction with the travoprost/timolol fixed combination. The final analysis included 75 patients in the brinzolamide arm and 78 patients in the placebo arm.

“We wanted to look at patients who were relatively uncontrolled on a combination of two medications to see whether in that group adding a third medication was going to be helpful,” Dr. Goldberg said.

IOP measurements were repeated at 12 weeks. Diurnal IOP was calculated as the average of measurements taken at 8 a.m., 12 p.m. and 4 p.m.

Results

Study results showed that brinzolamide and placebo significantly reduced mean diurnal IOP and IOP at the three time points from baseline (P = .005).

Brinzolamide reduced mean diurnal IOP from 20.3 mm Hg to 17.5 mm Hg. Placebo reduced IOP from 20.9 mm Hg to 19.4 mm Hg.

Reduction of mean diurnal IOP and IOP at 8 a.m. and 4 p.m. was significantly greater in the brinzolamide group than in the placebo group (P = .014). The between-group difference in IOP at 12 p.m. was insignificant.

“We actually showed that the pressure was reduced significantly both in the morning and in the afternoon. In other words, the effect was throughout the times that we tested,” Dr. Goldberg said. “The 8 a.m. test was, in fact, a trough effect because that was before the medications went in that day. So, we were seeing the medications at their weakest effect.”

Results showed 30 adverse events in the placebo group and 24 adverse events in the brinzolamide group; this difference was insignificant. – by Matt Hasson

Reference:

Goldberg I, Crowston JG, Jasek MC, Stewart JA, Stewart WC; ADAPT Study Investigator Group. Intraocular pressure-lowering efficacy of brinzolamide when added to travoprost/timolol fixed combination as adjunctive therapy. J Glaucoma. 2012;21(1):55-59.

For more information:

Ivan Goldberg, AM, MBBS, FRANZCO, FRACS, can be reached at 187 Macquarie St. Park House, Floor 4, Suite 2, Sydney NSW 2000, Australia; 61-2-9247-9972; fax: 61-2-9232-3086; email: eyegoldberg@gmail.com.
Disclosure: Dr. Goldberg serves on advisory boards for Alcon, Allergan, Merck and Pfizer.