Bill Holton
For most of us our experience of medical ultrasound is limited to sonagrams of a new baby or diagnostic evaluations of the heart and other internal organs. Here in this article we will present two exciting new uses for medical ultrasound: the possibility of restoring sight with a non-surgical retinal bypass, and the latest innovation in the treatment of glaucoma.
Bypassing the retina with sound waves
If you’ve ever poked yourself in the eye, or, like so many cartoon characters, walked underneath a falling piano, safe or anvil, you are likely familiar with the expression “seeing stars.” It happens even in pitch dark—pressure-induced flashes of light called Phosphenes that originate from inside the eye rather than from an outside light source. But what if you could control this phenomenon and use it to transmit patterns, shapes, even the scene ahead of you? Around the world Retinal degenerative diseases are one of the leading causes of blindness, affecting tens of millions of people worldwide. However in many cases while the light-sensitive rods and cones are no longer functioning the underlying neural circuitries connecting them to the brain are relatively intact. And if, like Phosphenes, we could pressure stimulate those neural pathways directly… That was the thinking of a USC research group co-led by Drs. Qifa Zhou, Professor of Biomedical Engineering and Ophthalmology, and Mark S. Humayun, Professor of Ophthalmology and Biomedical Engineering, and one of the inventors of Argus II. Happily, you don’t need a poke in the eye or a falling anvil to stimulate retinal nerves. “You can do it with ultrasound,” says Zhou. And whereas current retinal stimulators and bypass solutions require invasive eye and/or brain surgery, "Using ultrasound could lead to a non-invasive retinal prosthesis that works without retinal or brain implants. Special glasses with a camera and an ultrasound transducer could be all that is required to restore at least partial vision.” To test this hypothesis the team stimulated blind rats’ eyes with ultrasound waves, sound with a frequency far above what a human can hear. “These high-frequency sounds can be well-manipulated and tightly focused on a desired area of the retina. This approach made it possible to physically stimulate extremely small groups of neurons in the rat's eye, just like light signals can activate a normal eye. The team then measured the visual activities directly from the superior colliculus, a midbrain structure that plays a central role in visual information processing and to which the optic nerve is directly connected. Using a multi-electrode array the team was able to record a matching retinal activation. “When the ultrasound was projected as a pattern on the retina--for example, a circular point, or the letter ‘C’--it was possible to measure corresponding activities in the superior colliculus,” says Zhou. As mentioned, the research is in its infancy. There are two major hurdles to overcome: resolution and frame rate. “To be useful an ultrasound retinal stimulator would have to provide images at a fairly high resolution containing as many individual points as possible. “The camera attached to the system may be able to handle this, but whether the sound waves are capable of transmitting such small details to the retinal neurons without merging into each other is still an open question,” says Zhou. In the test rats the ultrasound beam stimulated a circular area of the retina with a diameter of about 600 millionth of a meter, while individual neurons that are only a few millionths of a millimeter in size are packed together in the retina. “To achieve better resolution we need to experiment with higher-frequency ultrasound beams with even shorter wave lengths.” In the tested rats the neurons gave off the strongest signal when they were activated about five times per second. But human brains have a much higher calculation speed, so at that speed they may see each image separately. Film and video game makers are aware that images can be smooth only at a frame rate higher than 24 frames per second. Unfortunately, when the team tested rats at this frame rate the images failed to process. “But we are hopeful that using even higher frequencies will solve this problem, as our work has shown that the higher the frequency of the ultrasound the stronger the retina reacts. We’re optimistic this will enable us to at least double the current frame rate.” There is a pending patent on this new ultrasound stimulation system. A Texas-based company and Zhou is looking forward to initiating human testing sometime in the next three to five years.
Afive-minute blast of ultrasound can cure glaucoma
Glaucoma is the leading cause of irreversible blindness, affecting more than 70 million people around the world. The disease progresses slowly, often showing no symptoms until after it has already caused permanent damage—which is why medical professionals recommend regular glaucoma screenings. Glaucoma is usually associated with increased ocular pressure. This is caused mostly by an excess of aqueous humor, due to the drainage channels becoming blocked or otherwise non-functioning,” says Luís Abegão Pinto, M.D., PhD., Assistant Professor of Ophthalmology Medicine at Lisbon University. “The hydraulic pressure increases, putting pressure on the optic nerve and leading to irreversible vision loss.”
Currently the standard treatment for glaucoma uses eyedrops to decrease the amount of aqueous humor produced or increase the drainage. The drops must be taken regularly and indefinitely, however people often forget to take the drops, especially since they have no visible symptoms to remind them. For some however, even diligent use of drops will not sufficiently reduce the intraocular pressure. For these patients surgery or laser treatments may be required to physically open the blocked drainage tubes, create new channels or reduce the production of aqueous humor. “Each of these options have their risks, involve cutting, stitching and/or burning away tissue, and may not be effective,” says Pinto. Recently, Pinto and other European researchers have begun work on a new, less invasive glaucoma treatment called ultrasound cyclo plasty. The procedure uses high-intensity, focused blasts of ultrasound to reduce production of aqueous humor. The ultrasound device, known as the EyeOP1 and developed by France’s Eye Tech Care, resembles a tiny telescope with a ring probe that contains 6 piezoelectric transducers delivering ultrasound at 6 different places at different times. The patient’s eye is numbed with anesthetic drops or anesthetic block, then the device is positioned over the eye. The device aims and fires pulses of ultrasound on to the ciliary body, the area of the eye that pumps out the aqueous humor. In the weeks following the treatment the pressure reduces as less aqueous humor is produced —although enough is made to keep the eye healthy. The post operative is mostly painless, and the procedure can be repeated if necessary.
As part of a two-year study by ophthalmologists at Genoa University and other centers in Italy, 66 patients were treated with the device. The results, reported in the journal Scientific Reports, showed that in 68 percent of patients the treatment was a success, with their need for eye drops cut in half. Ten per cent of patients were classed as a complete success, with eye pressure below 21 mmHg.
Ultrasound cyclo plasty is not yet FDA approved in the US, but so far over 10,000 glaucoma patients have been treated with the procedure. “The procedure could be done in a clinic—even a mobile clinic, which would be especially useful in areas where medical specialists are not readily available,” says Pinto.
Of course the best treatment is always preventative. According to one study of 6,000 men and women aged 40 or over who reported what they ate each day, those with glaucoma had a ‘significantly lower’ daily niacin intake compared with those who didn’t. One theory is that the vitamin, found in liver and chicken breast as well as in supplements, may have a protective effect on optic nerve cells.
This article is made possible in part by generous funding from the James H. and Alice Teubert Charitable Trust, Huntington, West Virginia.
