DWT shows promise for reducing IOP

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Deep wave trabeculoplasty reduced IOP by 26% in an initial clinical investigation and is being compared with sham and selective laser trabeculoplasty in a second clinical trial.

By Cheryl Guttman Krader; Reviewed by Malik Y. Kahook, MD

Aurora, CO-Deep wave trabeculoplasty (DWT) (Ocutherix)-a novel non-invasive approach designed to lower IOP by enhancing aqueous outflow through the trabecular meshwork-has demonstrated promising efficacy and safety in both pre-clinical studies and an initial clinical trial.

Based on the encouraging results, a second clinical study is now under way.

DWT was invented by Malik Y. Kahook, MD, The Slater Family Endowed Chair in Ophthalmology and Professor of Ophthalmology, University of Colorado, Aurora, and inspired by evidence that IOP-lowering following phacoemulsification surgery occurs secondary to ultrasound activation of a stress response in trabecular meshwork cells accompanied by the release of cytokines able to modulate outflow.

DWT aims to trigger that tissue response using externally applied non-invasive mechanical energy, but at a much lower (sonic) frequency than phaco to avoid tissue trauma. In DWT, mechanical oscillations are delivered to the trabecular meshwork using a handheld instrument positioned along the limbal region that overlies the trabecular meshwork.

Results from pre-clinical testing performed in two animal models showed DWT lowered IOP 24% from baseline. In the clinical trial, DWT was associated with a 26% reduction in IOP from a mean of 24.27 mm Hg at baseline to 17.87 mm Hg at 3 months.

There were no remarkable safety findings in the pre-clinical studies, including no histological evidence of thermal or other tissue damage.

In clinical testing where DWT was performed under topical anesthesia, the procedure was well tolerated and caused no serious complications.

“DWT would negate the issue of adherence to glaucoma medications and we anticipate it may be a more cost-effective option than topical drops,” Dr. Kahook said. “The initial ‘first in human’ study showed promising IOP lowering in the majority of treated patients. The current clinical trial will allow us to learn more about the efficacy and reproducibility of the decrease in IOP compared [with] selective laser trabeculoplasty.”

The University of Colorado holds the patent for DWT under Dr. Kahook’s name and has licensed the technology to Ocutherix for commercial development.

DWT offers some very attractive attributes, explained Robert Atkinson, chief executive officer, Ocutherix,

“DWT would not require any capital equipment and could be offered as an efficient, in-office procedure that might successfully defer the use of other more invasive treatments for glaucoma without limiting their use as downstream options,” Atkinson said.

The first human study of DWT included patients with primary open-angle glaucoma whose IOP was >23 mm Hg after a 1-month washout of existing medications. Participating patients underwent DWT in one eye-the procedure took about 5 minutes to complete-and the fellow untreated eye served as a control.

A significant decrease from baseline IOP was first observed at 2 weeks post-DWT and persisted throughout the 3-month follow-up period. About 30% of DWT eyes were started on rescue IOP-lowering medication compared with 100% of the control eyes.

Safety evaluations showed no evidence of anterior chamber inflammation.

Second study

The second clinical trial is randomly assigning patients to treatment with DWT, sham, or selective laser trabeculoplasty, with primary endpoints at 6 months and long-term follow-up out to 2 years.

“This second study is designed to give us stronger evidence about the efficacy of DWT and further insight on the durability of its IOP-lowering effect,” Atkinson said. “It is known that IOP reductions after phacoemulsification can be maintained for 1-2 years or even longer, and we believe DWT may have a similar benefit, but that has yet to be demonstrated.”

Mechanistic proof

In the pre-clinical investigations, measurements of changes in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs provided surrogate evidence that DWT increased outflow facility.

However, in order to obtain more definitive evidence, W. Daniel Stamer, MD, Duke University, is planning studies to evaluate outflow function in human cadaveric eyes treated with DWT.

Malik Y. Kahook, MD

E: Malik.kahook@ucdenver.edu

Deep wave trabeculoplasty was invented by Dr. Kahook.

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