Ophthalmic electro-neural Iinterfaces: from photovoltaic restoration of sight to dry eye therapy

Neurons mediate majority of the body functions, from sensory input, to secretion, cognition, and muscle control. Electrical control of neural signaling can help restore damaged organs and body functions. I will review two examples of electro-neural interfaces in applications to treatment of ocular diseases: retinal degeneration and dry eye syndrome.

Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image-processing” inner retinal layers are relatively well preserved. Information can be reintroduced into the visual system using electrical stimulation of the surviving inner retinal neurons. Some electronic retinal prosthetic systems have been already approved for clinical use, but they provide low resolution and involve very difficult implantation procedures. 

We developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the nearby inner retinal neurons. Visual information is projected onto the retina by video goggles using pulsed near-infrared (~880nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity. Optical activation of the photovoltaic pixels allows scaling the implants to thousands of electrodes, and multiple modules can be tiled under the retina to expand the visual field.

We found that similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies (>20 Hz), adaptation to static images, antagonistic center-surround organization and non-linear summation of subunits in the receptive fields, providing high spatial resolution. Photovoltaic arrays with 70?m pixels restored visual acuity up to a single pixel pitch, which is only two times lower than natural acuity in rats. If these results translate to human retina, such implants could restore visual acuity up to 20/250. Higher resolution arrays (40?m pixels), which are currently being tested, may provide acuity up to 20/140. Ease of implantation and tiling of these wireless modules to cover a large visual field, combined with high resolution opens the door to highly functional restoration of sight.

Tear film maintains a clear optical path and smooth refractive surface, protects the eye against environmental conditions, infections, facilitates nutrient transport, and carries away cellular debris. Decreased aqueous or lipid secretion lead to dry eye and ocular surface disease, which may result in a significant loss of vision.

Electrical stimulation of the efferent fibers controlling the lacrimal gland can enhance aqueous secretion by about 50%. Stimulation of the afferent nerves (anterior ethmoid nerve) activates all components of the lacrimal system, which increased tear volume by as much as 130%, resulting in reduced tear osmolarity. It also added lipid, increased the concentration of normal lacrimal gland proteins, and induced release of mucin, which is responsible for stabilization of the tear film on corneal surface. Clinical trials with intranasal neurostimulator demonstrated significant improvements in subjective symptoms and objective measures of the corneal health in patients with dry eye disease. Recent approval of this system (TrueTearTM, Allergan) for clinical use will allow exploring its efficacy in patients with various forms of dry eye disease. 
 
Bio: Daniel Palanker is a Professor in the Department of Ophthalmology and Director of the Hansen Experimental Physics Laboratory at Stanford University. He received MSc in Physics in 1984 from the Yerevan State University in Armenia, and PhD in Applied Physics in 1994 from the Hebrew University of Jerusalem, Israel. 

Dr. Palanker studies interactions of electric field with biological cells and tissues, and develops optical and electronic technologies for diagnostic, therapeutic, surgical and prosthetic applications, primarily in ophthalmology. These studies include laser-tissue interactions with applications to ocular therapy and surgery, and interferometric detection of neural signals. In the field of electro-neural interfaces, Dr. Palanker is developing retinal prosthesis for restoration of sight to the blind and implants for electronic control of secretory glands and blood vessels.

Several of his developments are in clinical practice world-wide: Pulsed Electron Avalanche Knife (PEAK PlasmaBlade, Medtronic), Patterned Scanning Laser Photocoagulator (PASCAL, Topcon), and OCT-guided Laser System for Cataract Surgery (Catalys, AMO). Several others are in clinical trials: Gene therapy of the retinal pigment epithelium (Ocular BioFactory, Adverum Biotechnologies Inc); Neural stimulation for enhanced tear secretion (TrueTear, Allergan Inc.); Smartphone-based ophthalmic diagnostics and monitoring (Paxos, DigiSight Inc.).