Eyeworld

MAR 2012

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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106 EW GLAUCOMA February 2011 March 2012 Is brimonidine neuroprotective in normal pressure glaucoma? by Tony Realini, M.D., M.P.H. "This study is remarkable for having been conceived, conducted, and completed at all," said Dr. Fechtner. "The very concept of look- ing for a visual function endpoint by point-wise linear regression is a daunting task. The recruitment of a sufficient sample size of low-pressure glaucoma patients meeting the eligi- bility criteria must have been a chal- lenge. The IOP-lowering effects of the two treatment arms were modest at best. Yet the difference in out- comes is striking." "This study is not without its Source: Larry Gatz/The Image Bank/Getty Images Results of the Low- Pressure Glaucoma Treatment Study N ormal pressure glaucoma remains a clinical chal- lenge for many physi- cians. The Collaborative Normal Tension Glau- coma Study demonstrated over a decade ago that reduction of IOP is beneficial even in eyes having dam- age with IOP in the normal range. Nevertheless, there remains a need for therapy that impacts the disease process independently of IOP. Neuroprotection, the holy grail of glaucoma therapy, has proven to be elusive, with the failure of the ex- pensive memantine trials having dampened enthusiasm for further neuroprotection trials in glaucoma. A new study has stimulated in- terest and discussion about the po- tential role of neuroprotection in the management of low pressure glaucoma. The Low-Pressure Glau- coma Treatment Study was begun over a decade ago, and the results have been published in the peer-re- viewed literature. EyeWorld revisits the results presented at the March 2011 meeting of the American Glau- coma Society in Dana Point, Calif. Study design "The Low-Pressure Glaucoma Treat- ment Study compared the long-term stability of visual fields in patients with normal pressure glaucoma treated either with timolol or brimonidine twice daily," said Theodore Krupin, M.D., professor of ophthalmology, Northwestern University Feinberg School of Medi- cine, Chicago, and the principal in- vestigator and chief architect of the study. Overall, 190 subjects were re- cruited from 13 clinical sites around the U.S. and in the United Kingdom. Subjects had normal pressure glau- coma, at least two abnormal visual fields, and IOP consistently below 21 mm Hg on diurnal testing, he said. Subjects were randomized to receive either timolol 0.5% (Timoptic, Merck, Whitehouse Station, N.J.) or brimonidine 0.2% (Alphagan, Allergan, Irvine, Calif.) each dosed twice daily. "These medications have equiv- alent lowering of IOP," he pointed out, "so that any outcome differ- ences between groups should be at- tributable to non-IOP mechanisms." Subjects were treated and fol- lowed with serial visual field testing for up to 4 years. Glaucoma progres- sion was declared if any of three pre-specified visual field changes appeared on three consecutive tests after baseline. Study findings "After a mean follow-up period of 30 months," said Dr. Krupin, "33% of eyes in the timolol group, compared with only 10% of eyes in the brimonidine group, reached a visual field endpoint." The results were the same re- gardless of which of the three visual field endpoints was considered, he said. "When we looked at eyes that met all three endpoints, the results were also similar, with 18 timolol eyes and five brimonidine eyes meeting all three field endpoints." On average, IOP was reduced by approximately 12.5% in both groups. "Importantly, there was no difference in IOP reduction between groups, ruling out differential IOP reduction as an explanation for the differential outcomes," said Dr. Krupin. Interestingly, the IOP reduction in eyes that did and did not progress was also similar, he said, which fur- ther suggests that IOP was not re- lated to progression in these eyes. Clinical implications "The study demonstrated that there was a significantly reduced 4-year rate of visual field progression in low-pressure glaucoma eyes treated with brimonidine compared to timolol," Dr. Krupin said. What do these findings mean for patients with glaucoma? It is important to consider the study carefully when drawing con- clusions for clinical practice, said Robert Fechtner, M.D., director, Glaucoma Division, University of Medicine and Dentistry of New Jersey, Newark. problems," Dr. Fechtner cautioned. "The discontinuation rate in the brimonidine cohort was 28.3%, compared to a timolol discontinua- tion rate of 11.4%. This certainly complicates the analysis." He also pointed out that the bri- monidine marketplace has changed significantly since the last patient completed the initial 4-year follow- up nearly 7 years ago. "The brimoni- dine used was 0.2% twice daily. The label for brimonidine indicates three-times daily use, so the study used an off-label dosing regimen. Also, brimonidine 0.2% is now a generic formulation. It is not clear that these results can be generalized to other formulations or to other populations." But overall, Dr. Fechtner was heartened by the implications of the Low-Pressure Glaucoma Treatment Study. "The most striking aspect of this study beyond the reported results is the proof of concept that it is possi- ble to investigate the effects of glau- coma treatments that might impact the disease through mechanisms be- yond simply IOP-lowering effects. The design and analysis aspects of this study should be thoughtfully considered for future efforts to in- vestigate neuroprotective strategies for the treatment of glaucoma and other ophthalmic diseases," he said. EW Editors' note: Drs. Fechtner and Krupin have no financial interests related to this article. Contact information Fechtner: fechtner@umdnj.edu Krupin: krupin@northwestern.edu

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