NEWS BRIEF

Argus II Retinal Prosthesis System for peripheral retinal degeneration

June 2011
The ArgusTM II Retinal Prosthesis System is an artificial vision restoration system designed for patients with severe sight impairment due to peripheral retinal degeneration, such as in retinitis pigmentosa. It includes an implant designed to sit on the surface of the retina and stimulate the healthy cells of the retina. The implant receives information from a patient-worn video processing unit, which in turn receives signals from a miniature video camera housed in a pair of glasses. By learning how to interpret these signals, patients may potentially be able to continue using visual cues to guide their activities and maintain independent living for longer.

Second Sight Medical Products Inc.

Background
Peripheral retinal degeneration is present in many retinal diseases, by far the most common of which is retinitis pigmentosa, a group of degenerative diseases usually caused by a wide variety of genetic mutations1. These diseases all affect the layer of the retina containing cells called photoreceptors, which convert the light entering the eye into electrical signals that are sent to the brain2. These cells are lost (leaving behind dark pigment deposits) as the disease progresses. The cells in the peripheral (outer) retina are usually affected before, and more severely than, those in the centre2. Early in the disease, patients usually experience difficulties seeing in lowlight conditions, have sensitivity to light and difficulty adjusting between different light levels. Later in life, most people experience loss of peripheral vision. Much later, some people experience loss of central vision in daylight conditions2. In most cases the disease takes several decades to progress to profound loss of sight, though this can vary greatly between individuals. The loss of peripheral vision can greatly diminish an individuals ability to live independently as walking or driving safely can be very difficult and the later stages of retinitis pigmentosa often leave patients with only a very narrow field of vision2. Complications include cataracts (clouding of the lens) and macular oedema (excess fluid and protein in the central retina)2. In 2030% of patients retinitis pigmentosa may be part of a syndrome which includes other symptoms such as deafness and renal disease3. There are an estimated 20-25 people with retinitis pigmentosa per 100,000 individuals in England and Wales, which equates to 11,000-13,750 people2,4. In a study of 1,000 retinitis pigmentosa patients over the age of 45, 25% had a visual acuity of 2/200 or worse, 12% had a visual acuity of count fingers or worse and 0.5% had no light perception at all in both eyes5. One commercial estimate is that there will be approximately 1,000 patients with severe sight impairment (2 patients per 100,000 individuals) in England who would be eligible for a retinal implant such as the one described here6.
1

This news brief is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information.

Current Practice
There is currently no treatment for retinitis pigmentosa, retinal degeneration or for severe sight impairment, though sometimes attempts are made to slow down the degeneration process through the use of dark glasses and vitamin A and E supplements2. To manage light sensitivity, the use of yellow-orange glasses and lateral protection of the eyes from light is sometimes used2. Treatment of complications such as cataracts, macular oedema and inflammation may offer some improvement in quality of life, as may learning Braille, improving social support, the use of guide dogs or a white cane2. The ArgusTM II Retinal Prosthesis System is the first commercially available retinal device for this condition, although others are in development7.

New Technology
The ArgusTM II Retinal Prosthesis System by Second Sight Medical Products Inc is designed for the treatment of severe sight impairment in patients with peripheral retinal degeneration and the implant component is implanted surgically in the back of the eye. It is intended for adults 25 years and over with some residual light perception or ability to respond to electrical stimulation of the retina; with functioning optic nerves and visual cortex (the part of the brain that processes visual information) and with a previous history of useful vision. A miniature video camera housed within a pair of special glasses captures images which are sent to a small video processing unit that is worn by the patient. The video is converted into signals which are sent back to the glasses via a cable and transmitted wirelessly to a receiver in an implant sitting on the surface of the retina. The signals are then sent to a 60 electrode array which emits small pulses of electricity to stimulate the healthy photoreceptor cells in the retina. These stimulate the optic nerve to the brain, causing the perception of patterns of light which patients may learn to interpret and use in their daily lives. The ArgusTM II Retinal Prosthesis System was CE marked in February 2011 and the company anticipate launch in two UK centres in late 2011-early 20126. The cost of the device is estimated to be 66,000 excluding VAT. Additional costs estimated by the company include 6,200 for surgery and 3,600 for clinical follow-up6.

Clinical Studies and Research Questions

A prospective, open-label study of 26 retinitis pigmentosa patients and 1 patient with choroideremia (published results to date) using the ArgusTM II Retinal Prosthesis System is in progress. Results have been presented in a journal article8, a conference paper9 and several conference abstracts11-16. Patients who had bare-light vision and no recordable visual acuity (worse than 20/15887) prior to implantation of the device, were asked to perform a task locating a square on a screen8. Feedback enabled the patients to improve their performance of this task. Of 27 patients, 26 showed significantly better improvement task completion with the device switched on, than with it switched off (and the glasses removed) (p<0.05). Results from other tasks performed by the first 17 patients who had been implanted with this device (6 months prior to testing) were also published9. In a task locating a door in a room, the proportion of times any part of the door was located was 59% with the device switched on and 32% with it switched off. When walking along a
2

20ft line, 44% of patients finished the task on the line with the device switched on (26% with it switched off). Adverse event data from the product insert10 is detailed below and data from a subset of these patients have been published previously9,13. Of 30 patients followed up for 6-32 months (average 18 months), 4 experienced erosion of the conjunctiva, or a reopening of the surgical cut, requiring explantation of the device in one case, surgical intervention in one case and stitches in two cases. Surgery was required for three cases of hypotony (lowered eye pressure) and two cases of retinal detachment. Two patients required the device to be reattached with a stitch and five patients underwent elective revision surgery. One small retinal tear required laser treatment and there were three cases of endophthalmitis (inflammation of the main cavity of the eye) or undefined severe inflammation which required antibiotics or steroids. Ten patients had conjunctival congestion, one required medication. The company also reports a wide range of non-serious adverse events in up to 25% of patients. There were more adverse events reported in those enrolled earlier in the trial and the company states that surgical techniques and design of the device were improved as the trial progressed. Other tests of vision for the same group of patients were reported in abstracts at conference11-16. Trials of an earlier, 16 electrode array version of the device (Argus16 Retinal Prosthesis System) are also available17. More data on the effectiveness of this device, including on independent mobility, falls and accidents are needed to determine the extent of benefits for patients. Longerterm collection of adverse event data is awaited.

Potential Impact
The ArgusTM II Retinal Prosthesis System may offer benefits to patients with peripheral retinal degeneration, who currently have no treatment options. If the device proves to be safe and effective, it may provide a way for patients to maintain their independence, employment and mobility for longer. The cost to the NHS of the device plus surgery exceeds 75,000. Additional costs will include the training needed for surgeons to implant this device, probably in specialist centres. Healthcare professionals may also require support to train the patient in its use. Major benefits are likely to be societal, with public sector savings largely among social care and support services.

References
1. Foundation for Genomics and Population Health. Genetic ophthalmology in focus: a needs assessment & review of specialist services for genetic eye disorders. Cambridge:PHG Foundation;April 2008. Hamel C. Retinitis pigmentosa. Orphanet Journal of Rare Diseases 2006;1:40-52. Hartong DT, Berson EL and Dryja TP. Retinitis pigmentosa. The Lancet 2006;368:1795-1809. Bundey S and Crews S. A Study of retinitis pigmentosa in the city of Birmingham. I Prevalence. Journal of Medical Genetics 1984;21:417-420. Grover S, Fishman GA, Anderson RJ et al. Visual acuity impairment in patients with retinitis pigmentosa at age 45 years or older. Opthalmology 1999;106:1780-1785.

2. 3. 4.

5.

6. 7.

Company Communication 24th March 2011. Hossain P, Seetho IW, Browning AC et al. Artificial means for restoring vision. British Medical Journal 2005;330:30-33. Ahuja AK, Dorn JD, Caspi A et al. Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. British Journal of Ophthalmology 2011;95:539-543. Humayun MS, Dorn JD, Ahuja AK et al. Preliminary results from the ArgusTM II epiretinal prosthesis feasibility study. Conference Proceedings of the IEEE Engineering in Medicine and Biology Society 2009; 2009:4566-4568.

8.

9.

10. Argus II Retinal Prosthesis System Product Insert. Second Sight Medical Products Inc. 11. Ahuja AK, Dorn JD, Caspi A et al. The Argus II retinal prosthesis enables blind subjects to identify the direction of motion. Investigative Ophthalmology and Visual Science 2009;50:E-Abstract 4590. 12. McMahon MJ, Dorn JD, Ahuja AK et al. The Argus II retinal prosthesis enables blind subjects to localize objects. Investigative Ophthalmology and Visual Science 2009;50:E-Abstract 4589. 13. Humayun MS. Preliminary results from Argus II feasibility study: a 60 electrode epiretinal prosthesis. Investigative Ophthalmology and Visual Science 2009;50:E-Abstract 4744. 14. da Cruz L, Coley B, Chistopher P et al. Patients blinded by outer retinal dystrophies are able to identify letters using the ArgusTM II retinal prosthesis system. Investigative Ophthalmology and Visual Science 2010;51:E-Abstract 2023. 15. Barale PO, Mohand Said S, Ayello-Scheer S et al. ArgusTM II epiretinal prosthesis: Paris experience and an improved surgical technique. Investigative Ophthalmology and Visual Science 2010;51:EAbstract 3048. 16. Arsiero M, da Cruz L, Merlini F et al. Subjects blinded by outer retinal dystrophies are able to recognise shapes using the Argus II retinal prosthesis system. Investigative Ophthalmology and Visual Science 2011;52:E-Abstract 4951. 17. Caspi A, Dorn JD, McClure KH et al. Feasibility study of a retinal prosthesis. Archives of Ophthalmology 2009;127:398-401.

The National Institute for Health Research (NIHR) National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are not necessarily those of the National Health Service, the NIHR or the Department of Health. The National Horizon Scanning Centre, University of Birmingham, United Kingdom nhscadmin@contacts.bham.ac.uk www.nhsc-healthhorizons.org.uk 4