Sonic Effect on Aqueous Outflow

Malik Y. Kahook

The treatment of glaucoma typically follows the same sequence of topical drops, followed by laser trabeculoplasty (LT) and incisional surgery. There are advantages and disadvantages to each of these approaches. Topical therapy is very safe but patients demonstrate poor adherence. More invasive approaches, such as trabeculectomy and glaucoma drainage device implantation, are more effective at lowering the intraocular pressure (IOP) but entail a higher rate of complications. LT, often used as a bridge treatment between medication and invasive therapy, has been shown to be moderately effective and safe. However, the IOP lowering that results post-LT wanes over time, and repeat treatments are not as effective as the primary therapy. In an effort to enhance adherence and IOP lowering outcomes, there have been multiple attempts to innovate new treatment modalities that can bridge the gap between using topical drops and the more invasive therapies while also allowing for repeatable treatments over the lifetime of the patient.

Deep wave trabeculoplasty (DWT) is an investigational therapy intended to reduce IOP in patients with open-angle glaucoma and ocular hypertension. The DWT device (Fig. 8.1) applies focal mechanical oscillation (low amplitude, sonic frequency) to the surface of the eye proximate to the limbal region and anterior to the trabecular meshwork (TM). In healthy eyes, IOP homeostasis is in part regulated by a pressure-induced stretch of conventional outflow cells, resulting in release of adenosine triphosphate (ATP) and downstream effects on TM cell contractility, extracellular matrix turnover, and the barrier function of Schlemm’s canal. External scleral deflection with the DWT device is thought to stretch conventional outflow tissues, triggering ATP release and signaling cascades that increase outflow facility and lower IOP. Preclinical studies (Table 8.1 and Fig. 8.2) and a first-in-human study have demonstrated that DWT has a very favorable safety and efficacy profile.

In a first-in-humans clinical trial, 30 patients with primary open-angle glaucoma (baseline washed-out IOP of 22 to 36) were enrolled and followed for 3 months. In each subject, one eye was randomized to DWT treatment (single unilateral treatment) and the fellow eye served as control. Medication was washed out for 1 month prior to treatment. At follow-up visits, rescue medical therapy for elevated IOP could be administered in either eye at the discretion of the investigator. Prior to treatment and at all follow-up visits, IOP was measured, and routine slit-lamp exams were performed. The treated eyes had a statistically significant reduction of IOP at each of the follow-up visits compared with baseline, with a mean IOP reduction of 26% at the 3-month visit (Fig. 8.3). Dependence on medication also decreased significantly from a mean baseline of two medications to mean of 0.6 medications at last follow-up. The control eyes required restarting of medications at a higher rate and earlier timeline due to the lack of IOP control. These results illustrate the IOP-lowering and medication-reducing capabilities of this treatment modality. However, longer follow-up and a head-to-head trial compared with an active control (such as laser trabeculoplasty) are needed to reach definitive conclusions.