INVITED PAPER 1 Visual Prosthesis 2 Microelectronic implants that provide identification of simple objects and motion 3 detection for blind patients have been tested and evaluated; further development is 4 needed for face recognition and reading implants. 5 By James D. Weiland and Mark S. Humayun 6 ABSTRACT | Electronic visual prostheses have demonstrated requirements for a parallel neural interface and power 37 7 the ability to restore a rudimentary sense of vision to blind efficiency that make certain engineering challenges impor- 38 8 individuals. This review paper will highlight past and recent tant to all visual implants. This paper will review the causes 39 9 progress in this field as well as some technical challenges to of blindness, the microelectronic approaches to treating 40 10 further advancement. Retinal implants have now been tested in blindness, and technology needs to enable future implants. 41 11 humans by four independent groups. Optic nerve and cortical 12 implants have been also been evaluated in humans. The first 42 13 implants have achieved remarkable results, including detection II. CAUSES OF BLINDNESS 14 of motion and distinguishing objects from a set. To improve on Blindness can result from damage to the optical pathway 43 15 these results, a number of research groups have performed (cornea, aqueous humor, crystalline lens, and vitreous 44 16 simulations that predict up to 1000 individual pixels may be Fig. 3) that focuses light on the retina or damage to the 45 17 needed to restore significant functions such as face recognition visual neurons that sense light and send visual information 46 18 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 47 19 visual system in this many locations, issues of power con- worth noting that cataracts (opacities in the crystalline lens) 48 1 20 sumption and electronic packaging must be resolved. are a major cause of blindness worldwide. An excellent 49 2 review of the retina and vision can be found online. 50 21 KEYWORDS | Electrical stimulation; implantable medical pack- Blindness has a significant impact on the economy. 51 22 aging; medical implants; neural prosthesis; retinal prosthesis Recent studies have found that only 29% of severely 52 visually impaired persons are gainfully employed, com- 53 pared with a national average of 84% [1]. Persons with 54 23 I. INTRODUCTION severe visual impairment earn 37% per year less than their 55 24 Photoreceptors are the specialized neurons in the eye that able bodied counterparts [2]. The total economic impact 56 25 convert photons into a neural signal (Fig. 1). The of vision loss in the United States is estimated at nearly 57 3 26 photoreceptors are part of the retina, a multilayer neural $68 billion annually. 58 27 structure about 200 m thick that lines the backIEEE of the eye. The two most common retinal degenerative diseases that 59 28 Other cells in the retina process the signal from the result in blindness secondary to photoreceptor loss are age- 60 29 photoreceptors. Retinal ganglion cells send the processed related macular degeneration (AMD) and retinitis pigmen- 61 30 signal from the retina to the brain via the optic nerve. tosa (RP). RP is generally more severe, and its symptoms 62 31 Blindness can result when any part of this visual pathway is appear earlier in life, but AMD is more prevalent. In the 63 32 damaged by injury or disease. Electronic visual prostheses United States, there are approximately 700 000 new AMD 64 33 are being developed that can be implanted in different patients; each year, 70 000 of these patients will become 65 34 anatomical locations along the visual pathway (Fig. 2). While legally blind,Proof with many more suffering significant vision 66 35 the final implementation of the implant will depend on the loss [3]. AMD results from a slow degeneration of the 67 36 anatomy of the targeted area, visual prostheses have common photoreceptor cells of the retina, ultimately culminating in 68 photoreceptor cell death. This is sometimes accompanied by 69 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. 0018-9219/$25.00 Ó2008 IEEE Vol. 96, No. 7, July 2008 | Proceedings of the IEEE 1 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 processing 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.) IEEE Proof 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.) 2 Proceedings of the IEEE | Vol. 96, No. 7, July 2008 Weiland and Humayun: Visual Prosthesis lating electrode array. Implants in humans have been 102 tested in the retina, visual cortex, and optic nerve. 103 Recent clinical trials of retinal implants have included 104 epiretinal implants [7]–[10], a passive subretinal device [11], 105 and an active subretinal device [12] (see Fig. 3). Passive 106 devices rely on incident light for power, whereas active 107 devices have an external power source. All of the devices 108 currently being tested are manufactured by companies, 109 which have the required quality systems and manufacturing 110 skills to produce robust, medical-grade implants. The trials 111 reviewed below will be referred to by the company that 112 produced the implant. 113 The first clinical trial of a permanently implanted 114 retinal prosthesis was initiated by Optobionics, Inc., in 115 2000. The device was a passive microphotodiode array 116 with 3500 elements. Subjects in the passive subretinal trial 117 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 118 and lens on the retina. The retina lines the posterior of the eye. photodiode were acting as a photoreceptor [11]. However, 119 (Image from http://www.nei.nih.gov/health/cataract/ some of the subjects have reported improved visual 120 cataract_facts.asp.) function away from the implant site, suggesting that the 121 presence of the implant alone, or coupled with low-level 122 electrical stimulation, induced a Bneurotrophic effect[ 123 70 the formation of new blood vessels. Individuals afflicted that improved the health of the retina and consequently 124 71 with AMD will start to have distorted central vision and improved visual function. 125 72 eventually will lose most vision in the central 30 of visual A prototype epiretinal implant with 16 electrodes is 126 73 field, rendering them legally blind (less than 20/200 vision). beingtestedbySecondSightMedicalProducts,Inc. 127 74 RP is a collective name for a number of genetic defects that (Sylmar, CA). This trial began in 2002 and has enrolled 128 75 also result in photoreceptor loss [4]. More than 100 genetic six individuals with bare light perception secondary to RP. 129 76 defects have been identified that cause the different forms of Test subjects can use spatial information from the 130 77 RP. The overall incidence of RP is 1 in 3500 live births. In stimulator to detect motion and locate objects [9]. 131 78 general, RP strikes the rod photoreceptor cells first, Subjects demonstrated their ability to distinguish between 132 79 resulting in poor night vision and loss of peripheral vision. three common objects (plate, cup, and knife) at levels 133 80 Eventually, cone photoreceptors, which mediate color and statistically above chance. Subjects have also demonstrat- 134 81 daytime vision, are lost, leading to complete blindness. ed that they can discern the direction of motion of a bar 135 82 Neither AMD nor RP is presently curable through surgery passed in front of the camera. Recent reports involve 136 83 or treatment, but there are some treatments that can slow detection of the orientation of a black and white grating 137 84 the progression of AMD [5]. pattern [13]. A subject was able to detect these gratings at 138 85 Diseases that damage the optic nerve include diabetic 4 increasing spatial frequency up to the theoretical limit 139 86 retinopathy and glaucoma. In diabetic retinopathy, retinal predicted by the electrode spacing on the retina. 140 87 blood vessel abnormalities can prevent nourishment from Perceptual thresholds are in general low, compared to 141 88 reaching neural cells in the retina, leading to ganglion cell IEEEthe earlier short-term implants [8]. Some subjects have 142 89 and optic nerve damage. Glaucoma often includes high shown a majority of electrodes with a perceptual 143 90 intraocular pressure as a symptom. In the past, it was thought threshold below 50 A (1 ms pulse), with a range of 144 91 that high eye pressure was damaging to the retina and led to 24–702 A (1 ms pulse) reported across three subjects. A 145 92 ganglion cell and optic nerve loss, but more recently it has second clinical trial of an epiretinal implant, built by 146 93 been found that even individuals with normal eye pressure Intelligent Medical Implants AG (Zurich, Switzerland), 147 94 can have optic nerve damage from glaucoma [6].