17Winter 2011

Optoelectronics and Retinal ProsthesisThe Revival of Vision

Andrew ZureiCk ‘13

engineering

What was once mere fantasy has evolved into a biotechnologi-cal revolution. Groundbreak-

ing research in the field of vision resto-ration has brought hope to those who are unable to see. While vision impair-ment—caused by a wide range of condi-tions including cataracts, degenerative diseases, and accidents—impacts quali-ty of life, research in optoelectronics and retinal prostheses continues to prog-ress in a quest for restoring eyesight.

The Human Eye: How Do We See?

Light passes through many layers during the transmission of an image to the brain for visualization (Fig. 1). The cornea is a thin layer on the surface of the eye that protects the pupil and iris, the iris uses two muscles to regu-late the size of the pupil, and the pu-pil controls how much light passes (1). The lens behind the pupil focuses light into a narrow beam onto the back of the eye, the retina. The retina is composed of ten distinct layers of cells, includ-ing photoreceptors (rods and cones), ganglion cells, bipolar cells, and nerve fibers. cones, primarily found in the center of the retina (the “fovea”), are essential for color vision and high reso-lution vision, while rods, distributed along a much wider range in the retina, are essential for scotopic (dark-adapt-ed) vision and peripheral vision (2). At the very back of the eye is the optic nerve, which connects the retina to the brain via a series of electrical impulses.

Some Causes of Vision ImpairmentCataracts

The lens of the eye often becomes cloudier with age. Because the lens is essential for focusing light, one will perceive a blurry image as a result. This condition, known as a cataract, not

only results from aging but also from other eye problems, injuries, radia-tion, or may even exist from birth (3).

Macular DegenerationThere is an increased risk of de-

generative diseases that affect the retinal cells with increasing age. Age-related macular degeneration (ARMD), the loss of cells in the macula—near the center of the retina—affects mil-lions of people; symptoms start with loss of fine vision, but can lead to de-clining central vision and ultimately legal blindness in many cases (4).

Retinitis PigmentosaA genetic disorder that primar-

ily affects photoreceptors in the retina, retinitis pigmentosa (RP) leads to in-curable blindness. Symptoms include decreased night vision, decreased pe-ripheral vision, and in more severe stages, decreased central vision (5). Randomized trials have shown that in-creased Vitamin A intake helps to slow symptoms of photoreceptor degenera-tion, meaning the cells undergo apop-tosis or necrosis, but too much Vitamin A may result in liver damage (6, 7).

Image retrieved from http://www.aao.org/theeyeshaveit/anatomy/section-retina.cfm (Accessed 27 Jan 2011).

Fig. 1: Structure of the eye, with a cross section of the retina

Artificial EyesIn some severe cases, an eye

must be removed because of either a retinoblastoma—cancerous tumor in the eye—or other significant damages. in the past, an artificial eye could be put in place of the enucleated eye, but this would simply be a non-functional placeholder. This practice dates back as early as ancient Egypt, when eyes were replaced with “precious stones, bronze, copper, or gold,” as confirmed by findings in tombs (8). this practice evolved during the 16th and 17th centu-ries, and eyes needing to be removed were replaced with glass. In more re-cent times, prosthetics have governed appropriate replacements. These are commonly made with either acrylic or cryolite glass; care is given to make the product look similar to the existing eye, specifically with regard to the iris pig-ment (9). While this is indeed a solu-tion as far as aesthetics are concerned, the more beneficial procedure is not just an optical prosthesis but also a vi-sual prosthesis, both replacing an eye and restoring vision. Retinal stimula-tion by electrodes helps restore partial vision in cases where photoreceptors or other parts of the retina are damaged, as will be explored in the next section.

OptoelectronicsElectrical stimulation of the reti-

na and other technological approaches have become increasingly researched areas of restoring vision. It is pos-sible to use a series of energized elec-trodes that can transmit information to the brain through neurons in the eye. These multielectrode devices tar-get the retina, which communicates with the visual cortex; arrays ranging from only 16 electrodes to over 1000 electrodes have been studied, and in these cases the retina perceives not an image but rather a series of dots (10,11). As shown in Fig. 2, the micro-electrode array is routed to a video

Dartmouth unDergraDuate Journal of Science18

Image retrieved from (17), which was adapted with permission from the Department of Energy newsletter, 5 January 2008. Originally printed in IEEE Engineering in Medicine

and Biology, 24:15 (2005).

Fig. 2: A schematic representation of a microelectrode array in a sub-retinal implant.

Image retrieved from J. J. van Rheede, C. Kennard, S. L. Hicks, J. Vision. 1, 1–15 (2010).

Fig. 3: A simulation of the image seen by a subject using a retinal prosthesis device

camera on the outside that senses light. Two different varieties of retinal

implants are currently in the stage of clinical trials to determine their safety and effectiveness: subretinal implants and epiretinal implants (12-15). Both cases rely on the fact that—even dur-ing degeneration of cells in ARMD or RP—the neural network of the retina stays intact. In other words, the light sensing photoreceptors do not func-tion, but the rest of the visual system still can function (16). For the first type of retinal prosthesis, subretinal, the implant is placed beneath the retina to essentially “replace” photoreceteptors (13). In the second type, the implant is placed on the surface of the retina and functions with healthy nerve (ganglion and bipolar) cells. A small video cam-era captures a light signal and converts the data into an electric signal through a microprocessor, which is transduced across these nerve cells, through the op-tic nerve, and ultimately to the brain for the creation of an image (14-15, 17). At the same time, this device must be en-gineered in such a way that it must not disturb the rest of the tissue in the eye, and exist stably in the saline environ-ment of the vitreous (18). The US Food and Drug Administration has not yet approved these devices and methods, but clinical trials still continue to test how well they will potentially function.

Fig. 3, adapted from an article in the Journal of Vision, shows a simu-lation of the creation of an electron-array image. In short, the electrodes tap enough nerve cells in the eye such that certain Fig.s can be outlined, and the clarity of the image reflects how optimum of a device it is. The device worn by the subject is connected to a computer, which processes the im-age; each phosphene, or spot of light

produced by electrical stimulation, is rendered into the software (7).

People who have tried using this technology find it extremely useful. Though there are only a small number of electrodes compared to the millions of photoreceptors, people can make out a general sense of their surroundings. “They can differentiate a cup from a plate, they know where the door is in their home, and they can tell where the tables are,” according to Dr. Mark Hum-ayun of the Doheny Eye Institute at the University of Southern California (18). Furthermore, the brain can take over and fill in some of the missing pieces of information especially when mem-ory is taken into consideration (19).

ConclusionVision, an essential element in

the quality of life, brings color to the world and adds multiple dimensions to everything that surrounds us. We have many different surgical proce-dures for curing different ocular dis-eases, including cataracts, glaucoma, and myopia (nearsightedness), so why not have ways of restoring the retina? Only further research and clinical trials

will determine, with a greater certainty, whether these methods prove effective.

References

1. M. Bear, B. Connors, M. Paradiso, Neuroscience: Exploring the Brain (Lippincott Williams & Wilkins, ed. 3, 2007).2. Neuroscience for Kids- Retina, Available at http://faculty.washington.edu/chudler/retina.html (15 January 2011).3. Facts about Cataracts, National Eye Institute (2010). Available at http://www.nei.nih.gov/health/cataract/cataract_facts.asp#1a (15 January 2011)4. Macular Degeneration: MedlinePlus (2010). Available at http://www.nlm.nih.gov/medlineplus/maculardegeneration.html (15 January 2011)5. Retinitis Pigmentosa: Medline Plus Medical Encyclopedia (2010). Available at http://www.nlm.nih.gov/medlineplus/ency/article/001029.htm (15 January 2011).6. National Eye Institute, Update on Vitamin A as a Treatment for Retinitis Pigmentosa (2008). Available at http://www.nei.nih.gov/news/statements/pigmentosa.asp (15 January 2011).7. Drug-induced liver disease symptoms, causes, and treatments (2011). Available at http://www.medicinenet.com/drug_induced_liver_disease/page8.htm (15 January 2011)8. B. S. Deacon, J. Ophthalmol. Med. Tech. 4:2 pages (2008) “Orbital Implants and Ocular Prostheses: A comprehensive review”9. I. I. Artopoulou, P. C. Montgomery, P. J. Wesley, and J. C. Lemon, J. Prosthet. Dent. 95, 327-30 (2006).10. J. J. van Rheede, C. Kennard, S. L. Hicks, J. Vision. 1, 1–15 (2010).11. E. Zrenner, “Restoring neuroretinal function by subretinal microphotodiode arrays” (2007). Speech delivered at ARVO, Fort Lauderdale, USA.12. H. G. Sachs, V. Gabel, Graef. Arch. Clin. Exp. 242, 717–723 (2004).13. S. Klauke et al., Invest Ophthal Vis Sci. In press (2010).14. G. Roessler et al., Invest Ophthal Vis Sci. 50, 3003-8 (2009).15. H. Benav, “Restoration of Useful Vision up to Letter Recognition Capabilities Using Subretinal Microphotodiodes” (2010). Speech Delivered at the 32nd Annual International Conference of the IEEE EMBS Buenos Aires, Argentina, 31 Aug 2010.16. The Dept. of Energy Artificial Retina project, Available at http://www.youtube.com/watch?v=iUz1ScDKslk (14 January 2011).17. G. J. Chader, J. Weiland, M. S. Humayun, “Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis” (2009). Available at http://www.thecaliforniaproject.org/pdf/chader/Artificial%20vision.pdf (15 January 2011).18. V. Kandagor, “Spatial Characterization of Electric Potentials Generated by Pulsed Microelectrode Arrays” (2010). Speech Delivered at the 32nd Annual International Conference of the IEEE EMBS Buenos Aires, Argentina, 31 Aug 2010.19. M. Lipner, Setting sights on artificial vision (2010). Available at http://www.eyeworld.org/article.php?sid=4742&strict=&morphologic=&query=retina (15 January 2011).