EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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April 2013 Highlights continued from page 61 Mae Gordon, PhD, evaluated the importance of IOP variability as a risk factor for the progression from ocular hypertension to open-angle glaucoma in the OHTS data set. "Long-term IOP variability was found to be a risk factor for POAG only among the patients randomized to treatment," she said. She pointed to both patient-specific biologic variability and medication effects on IOP as potential contributing factors. Target IOP EL CONQUISTADOR a Waldorf Astoria Property The Premier Innovative Educational Retreat for Anterior Segment Surgeons and Administrators Make your advance reservation today. www.WinterUpdate.org A symposium on target IOP featured a panel of experts weighing the pros and cons of defining therapeutic goals for glaucoma. Paul F. Palmberg, MD, University of Miami, coined the term several decades ago and continues to advocate for its clinical relevance. "The data are clear. Progression rates in clinical trials that implemented a target IOP are consistently lower than in clinical trials that did not use a target IOP." He pointed to the Early Manifest Glaucoma Trial, in which all treated patients received argon laser trabeculoplasty and a selective beta-blocker and were then followed at whatever IOP resulted from this treatment, where the fiveyear progression rate was 45%. In contrast, the Collaborative Initial Glaucoma Treatment Study (CIGTS) required that patients be treated in stepped fashion until a predetermined target IOP was achieved. "In this study, mean visual field scores remained essentially stable throughout five years of follow-up," said Dr. Palmberg. Kuldev Singh, MD, Stanford University, Stanford, Calif., suggested that target IOP was not a useful clinical concept. Among the limitations of target IOP, he said, is the challenge of knowing at what IOP a given patient is likely to remain stable over time. Another limitation is that we can only accurately measure IOP to within 2-3 mm Hg using the clinical standard Goldmann tonometer. In addition, patients' risk progression profile changes over time, so target IOP becomes a moving target. Drug developments A recent dose-ranging study compared the safety and IOP-lowering efficacy of commercially available latanoprost to a new nitric oxidedonating latanoprost formulation. Nitric oxide is thought to play a role in IOP regulation, and its mechanism of action suggests that it does so by restoring trabecular outflow. A combination drug featuring both nitric oxide and latanoprost—which lowers IOP primarily by enhancing non-trabecular uveoscleral outflow— would in theory offer a combined mechanism of action addressing both trabecular and non-trabecular outflow. In this phase 2 study, 413 glaucoma patients received either latanoprost or one of four doses of BOL-303259-X, the nitric-oxide donating latanoprost formulation. "After 28 days of therapy, the mean IOP reduction in the highest dose group was greater than in the latanoprost group," said Robert N. Weinreb, MD, University of California-San Diego (8.9 mm Hg versus 7.8 mm Hg, respectively). Phase 3 trials are currently underway. Drug delivery remains an issue in glaucoma, as adherence with daily eye drop therapy is suboptimal. Shamira Perera, MD, Singapore, presented the results of a study in which a punctual plug system was used to deliver travoprost for up to 60 days at a time. The plugs resemble the devices commonly used to treat tear deficiency and were designed to deliver a steady-state dose of travoprost for 30 or 60 days. Glaucoma patients with untreated IOP between 23-33 mm Hg received either the 30-day or 60-day plugs. After 30 days, average IOP reduction was greater than 5 mm Hg at 8 a.m., 10 a.m., and 4 p.m. At 60 days, mean IOP was reduced by more than 7 mm Hg. These were small studies with fewer than 50 patients total, but they demonstrate proof of concept that a punctual plug-based delivery system may allow us to move away from daily drop therapy. EW Contact information Gordon: mae@vrcc.wustl.edu Katz: ljkatz@willseye.org Palmberg: ppalmberg@med.miami.edu Perera: shamiraperera@hotmail.com Seibold: leonard.seibold@ucdenver.edu Singh: kuldev.singh@stanford.edu Weinreb: Weinreb@eyecenter.ucsd.edu Zangwill: lzangwill@ucsd.edu Mark your calendars: The 24th AGS meeting will be held February 27March 2, 2014, in Washington, D.C.