INVITED PAPER Visual Prosthesis Microelectronic implants that provide identification of simple objects and motion detection for blind patients have been tested and evaluated; further development is needed for face recognition and reading implants. By James D. Weiland and Mark S. Humayun ABSTRACT | Electronic visual prostheses have demonstrated requirements for a parallel neural interface and power the ability to restore a rudimentary sense of vision to blind efficiency that make certain engineering challenges impor- individuals. This review paper will highlight past and recent tant to all visual implants. This paper will review the causes progress in this field as well as some technical challenges to of blindness, the microelectronic approaches to treating further advancement. Retinal implants have now been tested in blindness, and technology needs to enable future implants. humans by four independent groups. Optic nerve and cortical implants have been also been evaluated in humans. The first implants have achieved remarkable results, including detection II. CAUSES OF BLINDNESS of motion and distinguishing objects from a set. To improve on Blindness can result from damage to the optical pathway these results, a number of research groups have performed (cornea, aqueous humor, crystalline lens, and vitreous simulations that predict up to 1000 individual pixels may be Fig. 3) that focuses light on the retina or damage to the needed to restore significant functions such as face recognition visual neurons that sense light and send visual information and reading. In order to achieve a device that can stimulate the to the brain. We will review only the neural diseases, but it is visual system in this many locations, issues of power con- worth noting that cataracts (opacities in the crystalline lens) sumption and electronic packaging must be resolved. are a major cause of blindness worldwide.1 An excellent review of the retina and vision can be found online.2 KEYWORDS | Electrical stimulation; implantable medical pack- Blindness has a significant impact on the economy. aging; medical implants; neural prosthesis; retinal prosthesis Recent studies have found that only 29% of severely visually impaired persons are gainfully employed, com- pared with a national average of 84% [1]. Persons with I. INTRODUCTION severe visual impairment earn 37% per year less than their Photoreceptors are the specialized neurons in the eye that able bodied counterparts [2]. The total economic impact convert photons into a neural signal (Fig. 1). The of vision loss in the United States is estimated at nearly photoreceptors are part of the retina, a multilayer neural $68 billion annually.3 structure about 200 m thick that lines the back of the eye. The two most common retinal degenerative diseases that Other cells in the retina process the signal from the result in blindness secondary to photoreceptor loss are age- photoreceptors. Retinal ganglion cells send the processed related macular degeneration (AMD) and retinitis pigmen- signal from the retina to the brain via the optic nerve. tosa (RP). RP is generally more severe, and its symptoms Blindness can result when any part of this visual pathway is appear earlier in life, but AMD is more prevalent. In the damaged by injury or disease. Electronic visual prostheses United States, there are approximately 700 000 new AMD are being developed that can be implanted in different patients; each year, 70 000 of these patients will become anatomical locations along the visual pathway (Fig. 2). While legally blind, with many more suffering significant vision the final implementation of the implant will depend on the loss [3]. AMD results from a slow degeneration of the anatomy of the targeted area, visual prostheses have common photoreceptor cells of the retina, ultimately culminating in photoreceptor cell death. This is sometimes accompanied by Manuscript received August 14, 2007; revised January 14, 2008. 1See World Health Organization, www.who.int/mediacentre/ The authors are with Doheny Eye Institute, University of Southern California, factsheets/fs282/en/. Los Angeles, CA 90033 USA (e-mail: [email protected]; [email protected]). 2www.webvision.med.utah.edu/. 3 Digital Object Identifier: 10.1109/JPROC.2008.922589 See http://www.silverbook.org/visionloss. 1076 Proceedings of the IEEE | Vol. 96, No. 7, July 2008 0018-9219/$25.00 Ó2008 IEEE Weiland and Humayun: Visual Prosthesis Fig. 1. Cross-section of the retina. The photoreceptors (rods and cones) convert photons into neurochemical energy, which is relayed through the retina. The different layers of the retina process the image signal. The output of the retina comes from the retinal ganglion cells, whose axons gather at the optic disc to form the optic nerve. In retinitis pigmentosa and age-related macular degeneration, the photoreceptors are degenerated but the other layers of the retina remain. (Image courtesy of Webvision, webvision.med.utah.edu.) Fig. 2. Human visual system. The optic nerve transmits retinal information to the lateral geniculate, which relays the information to the primary visual cortex (striate cortex or V1). (Image courtesy of Webvision, webvision.med.utah.edu.) Vol. 96, No. 7, July 2008 | Proceedings of the IEEE 1077 Weiland and Humayun: Visual Prosthesis lating electrode array. Implants in humans have been tested in the retina, visual cortex, and optic nerve. Recent clinical trials of retinal implants have included epiretinal implants [7]–[10], a passive subretinal device [11], and an active subretinal device [12] (see Fig. 4). Passive devices rely on incident light for power, whereas active devices have an external power source. All of the devices currently being tested are manufactured by companies, which have the required quality systems and manufacturing skills to produce robust, medical-grade implants. The trials reviewed below will be referred to by the company that produced the implant. The first clinical trial of a permanently implanted retinal prosthesis was initiated by Optobionics, Inc., in 2000.Thedevicewasapassivemicrophotodiodearray with 3500 elements. Subjects in the passive subretinal trial Fig. 3. Cross-section of a human eye. Light is focused by the cornea do not report pixelized vision, as might be expected if each and lens on the retina. The retina lines the posterior of the eye. photodiode were acting as a photoreceptor [11]. However, (Image from http://www.nei.nih.gov/health/cataract/ some of the subjects have reported improved visual cataract_facts.asp.) function away from the implant site, suggesting that the presence of the implant alone, or coupled with low-level electrical stimulation, induced a Bneurotrophic effect[ the formation of new blood vessels. Individuals afflicted that improved the health of the retina and consequently with AMD will start to have distorted central vision and improved visual function. eventually will lose most vision in the central 30 of visual A prototype epiretinal implant with 16 electrodes is field, rendering them legally blind (less than 20/200 vision). beingtestedbySecondSightMedicalProducts,Inc. RP is a collective name for a number of genetic defects that (Sylmar, CA). This trial began in 2002 and has enrolled also result in photoreceptor loss [4]. More than 100 genetic six individuals with bare light perception secondary to RP. defects have been identified that cause the different forms of Test subjects can use spatial information from the RP. The overall incidence of RP is 1 in 3500 live births. In stimulator to detect motion and locate objects [9]. general, RP strikes the rod photoreceptor cells first, Subjects demonstrated their ability to distinguish between resulting in poor night vision and loss of peripheral vision. three common objects (plate, cup, and knife) at levels Eventually, cone photoreceptors, which mediate color and statistically above chance. Subjects have also demonstrat- daytime vision, are lost, leading to complete blindness. ed that they can discern the direction of motion of a bar Neither AMD nor RP is presently curable through surgery passed in front of the camera. Recent reports involve or treatment, but there are some treatments that can slow detection of the orientation of a black and white grating the progression of AMD [5]. pattern [13]. A subject was able to detect these gratings at Diseases that damage the optic nerve include diabetic 4 increasing spatial frequency up to the theoretical limit retinopathy and glaucoma. In diabetic retinopathy, retinal predicted by the electrode spacing on the retina. blood vessel abnormalities can prevent nourishment from Perceptual thresholds are in general low, compared to reaching neural cells in the retina, leading to ganglion cell the earlier short-term implants [8]. Some subjects have and optic nerve damage. Glaucoma often includes high shown a majority of electrodes with a perceptual intraocular pressure as a symptom. In the past, it was thought threshold below 50 A (1 ms pulse), with a range of that high eye pressure was damaging to the retina and led to 24–702 A(1mspulse)reportedacrossthreesubjects.A ganglion cell and optic nerve loss, but more recently it has second clinical trial of an epiretinal implant, built by been found that even individuals with normal eye pressure Intelligent Medical Implants AG (Zurich, Switzerland), can have optic nerve damage from glaucoma [6]. has recently begun. This implant features a microfabri- A. Visual Prostheses cated electrode array of 49 platinum electrodes on a polyimide