The Effect of Ultrasound on Aqueous Dynamics

7 The Effect of Ultrasound on Aqueous Dynamics

Donald Schwartz

Ultrasound has several beneficial attributes that are potentially useful in medical treatment. Most ophthalmologists are familiar with phacoemulsification, whereby ultrasound is used to create cavitation and destroy lens nucleus material. Besides its vibrational effect, ultrasound has other noteworthy effects. Ultrasound has an associated thermal effect, which as cataract surgeons are aware, must be mitigated with constant irrigation. Another possible effect found with low-frequency ultrasound is the ability to trigger intracellular activities through a stretch effect within the trabecular meshwork (TM).1

The use of ultrasound as a treatment for glaucoma began with the work of Jackson Coleman’s group at Cornell.^2,3 His device became commercialized in the 1980s as one of the first uses of ultrasound in medicine, known as the Sonocare Therapeutic Ultrasound System (Sonocare, Ridgewood, NJ). This method of treatment used high-intensity focused ultrasound (HIFU). The ultrasound was focused on the ciliary body to decrease the production of aqueous by thermal destruction of ciliary body processes. Later, it was thought that there might be an additional effect on outflow due to thinning of the scleral wall. Comorbidities of intractable uveitis, scleral wall thinning, and even phthisis resulted in the abandonment of this device.

More recently, EyeTechCare of Lyon, France, developed a more refined device to decrease aqueous production using HIFU.⁴ This device (EyeOP1) offers a more precise technique to ablate the ciliary body to treat intransigent glaucoma. It has a circular attachment ring with six piezoelectric precisely aimed transducers to titrate the amount of tissue treated, thereby decreasing the potential for significant adverse effects.

The use of a nonfocused ultrasound for its vibrational effects in clearing trabecular meshwork debris was proposed and tested by Bjorn Svedbergh in Sweden in the 1990s with some limited and temporary effect on intraocular pressure (IOP).⁵ A mechanical oscillatory device, Deep Wave Trabeculoplasty (DWP), is being developed to use a sonic (non-ultrasound) frequency applied externally to stretch the trabecular meshwork.⁶ It is in early studies.

Beginning in 2006, I began developing a low-power, low-frequency, focused ultrasound device to lower the IOP^7,8 (Fig. 7.1). This Therapeutic Ultrasound for Glaucoma (TUG; EyeSonix, Long Beach, CA) device is designed to yield a combined vibrational and mild, controlled hyperthermic effect within the trabecular meshwork. The induced hyperthermia would be mild and less than 45°C; above this temperature, tissue thermal damage and pain occur,⁹ but just below it, only a mild inflammatory response occurs. It was thought that the cytokine cascade arising by this mild thermally induced inflammation lowers the IOP,^10–12 as might also occur after phacoemulsification surgery.^13–17

This application has been developed to enhance the outflow of aqueous humor and lower the IOP in mild to moderate open-angle glaucoma (Fig. 7.2). Early clinical studies in human patients showed at least 20% IOP lowering in over 80% of those treated.⁷ This included patients with insufficiently controlled IOP by medicines, in whom the therapeutic effect lasted at least 6 months. Examinations of over 80 treated patients have revealed scant side effects, with the most common being a posttreatment inflammatory reaction on day 1 similar to that seen after selective laser trabeculoplasty (SLT). Here, mild ocular irritation typically accompanies moderate conjunctival injection and rare mild anterior chamber flare without cells on slit-lamp examination.¹⁸

Although originally thought to enhance outflow solely by its thermal effect on trabecular meshwork microanatomy,⁸ as was believed with argon laser trabeculoplasty (ALT),^19,20 recent studies indicate ultrasonically induced IOP lowering occurs by mechanisms similar to SLT (and probably its predecessor, ALT), namely by the triggering of a cytokine cascade.²¹ This cytokine cascade may lower IOP by increasing matrix metalloproteinases, inducing macrophage activity, and altering intercellular connections in the juxtacanalicular meshwork.^22–25 It may be that common cytokine pathways mediate the IOP lowering of TUG ultrasound and SLT therapies for glaucoma.