Coverage Policy Manual
Policy #: 2005027
Category: Surgery
Initiated: July 2005
Last Review: December 2018
  Subconjunctival Retinal Prosthesis

Description:
A retinal prosthesis is a device that replaces lost photoreceptor function by transmitting external images to an array of electrodes placed in the epiretinal or subretinal space.
 
Background
There is ongoing research interest in developing an artificial retina that could potentially restore sight to patients with blindness secondary to retinal diseases, such as retinitis pigmentosa, hereditary retinal degeneration, and some forms of age-related macular degeneration. Two different approaches are being developed. The first is implantation of electrode arrays in the epiretinal or subretinal space in order to stimulate retinal ganglion cells. A second approach is the implantation in the subretinal space of light-sensitive multiphotodiode arrays which stimulate the remaining photoreceptors in the inner retina. Use of a multiphotodiode array does not require external image processing. The latter approach is being evaluated for degenerative retinal diseases such as retinitis pigmentosa, in which outer retinal cells deteriorate, but inner retinal cells remain intact for years.
 
Research in the U.S. has begun with a first generation, 16-electrode device (e.g., the ArgusTM 16, Second Sight Medical Products), which is expected to permit the distinction between the presence and absence of light, and the second generation (e.g., ArgusTM II), which has 60 electrodes. The Argus artificial retina consists of a small external video camera, held on eyeglass frames, that captures images that are then processed by an externally worn microcomputer. These signals are transmitted to a coil on the globe, an electronics package in the superior temporal quadrant and an electrode array implanted in the back of the eye, which in turn stimulates the optic nerve. It is hoped that further generation devices, containing more than 1,000 electrodes, will provide more detailed vision. Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding, support for material design and other basic research for the project.
 
Other devices in development include:
 
Learning Retinal Implant (Intelligent Medical Implants AG) uses an external camera on the frame of a pair of glasses and wireless data and power transfer. Receiver electronics connect via a scleral tunnel to an epiretinal implant. A retinal encoder with 100 to 1000 tunable spatiotemporal filters simulates the filtering operations performed by the ganglion cell and allows individual calibration to improve each patient’s visual perception
 
EPIRET3 retinal implant (Philipps-University Marburg, Marburg, Germany) is a wireless system that consists of a semiconductor camera in glasses frames and a transmitter coil outside the eye which sends electromagnetic signals to a receiver coil in the anterior vitreous (similar to an intraocular lens), which passes them on to a receiver microchip. A stimulator chip then generates the stimulation pulses and activates a selection of 25 electrodes placed on the epiretinal surface via a connecting microcable. A second generation wireless implant is being developed with a greater number of electrodes.
 
Microelectrode-STS (suprachoroidal-transretinal stimulation) system (Osaka University Graduate School of Medicine, Osaka, Japan) places the 9 electrode retinal prosthesis in a scleral pocket with a reference electrode in the vitreous cavity. A video camera is used to detect a visual object. Because the electrodes are at a greater distance from the retina, the resolution of the image may be lower than other devices. A proposed advantage of the STS prosthesis over epi- or subretinal prostheses is the safety of the surgical procedure, since the electrodes do not touch the retina.
 
alpha-IMS was developed at the University of Tubingen, Tubingen, Germany with the electronic chip design provided by the Institute for Microelectronics, Stuttgart (IMS) Germany. The second-generation Alpha-IMS device has wireless power and signal transmission and is produced by Retina Implant AG (Germany). The microchip is implanted subretinally and receives input from a multiphotodiode array with, 1500 elements, that moves with the eye, senses incident light, and applies a constant-voltage signal at the respective 1500 electrodes. The multiphotodiode array transforms visual scenes into corresponding spatial patterns (38 x 40 pixels) of light intensity-dependent electric stimulation pulses with a maximum visual field of 15.
 
Boston Retinal Implant (Retinal Implant Research Group, Boston) uses an external camera mounted on a pair of glasses and a 100-electrode array. The image obtained by the external camera is translated into an electromagnetic signal transmitted from the external primary data coil mounted on a pair of glasses to the implanted secondary data coil attached to the cornea. Most of the volume of the implant lies outside the eye, with transscleral cables connected to a subretinal electrode array. The Retinal Implant Project is a joint effort of MIT, the Massachusetts Eye and Ear Infirmary, the VA Boston Healthcare System, and the
NanoScale Science & Technology Facility at Cornell University.
 
Intelligent Retinal Implant System (IRIS, Pixium Vision, SA) uses an external camera that is integrated with a pair of glasses and linked by wire to a pocket computer. Receiver electronics connect via a scleral tunnel to an electrode array on the surface of the retina. Pixium Vision is also developing PRIMA, which uses a subretinal implant.
 
Regulatory Status
The Argus II device received commercial approval in Europe in March 2011. In 2013, the U.S. Food and Drug Administration (FDA) approved a humanitarian use device exemption (HDE) for the Argus II retinal prosthesis by Second Sight Medical. HDE approval is limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. The Argus II system is intended for use in adults, age 25 years or older, with severe to profound retinitis pigmentosa who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation.
 
The Alpha-IMS is approved for use in Europe.
 
Intelligent Retinal Implant System (IRIS) is expected to receive CE approval in Europe in 2015

Policy/
Coverage:
Effective August 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of subconjunctival retinal prostheses (Argus II system) used to treat severe to profound retinitis meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when the following criteria are met:
 
    • The patient is age 25 years or older;  AND
    • The patient has bare light perception or no light perception in both eyes; AND
    • There is evidence of intact inner layer retina function; AND
    • Previous history of the ability to see objects, shapes and lines; AND
    • The patient is willing and able to receive the recommended post-implant follow-up, device fitting and visual rehabilitation; AND
    • The patient is NOT currently and has NOT been treated with voretigene neparvovec-rzyl within 1 year.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of subconjunctival retinal prostheses (Argus II system) for any other indications or in any other situation, including but not limited to use in both eyes does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of subconjunctival retinal prostheses (Argus II system) for any other indications or in any other situation, including but not limited to use in both eyes is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to August 2018
The use of subconjunctival retinal prostheses (Argus II system) used to treat severe to profound retinitis meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when the following criteria are met:
 
    • The patient is age 25 years or older;  AND
    • The patient has bare light perception or no light perception in both eyes; AND
    • There is evidence of intact inner layer retina function; AND
    • Previous history of the ability to see objects, shapes and lines; AND
    • The patient is willing and able to receive the recommended post-implant follow-up, device fitting and visual rehabilitation.
 
The use of subconjunctival retinal prostheses (Argus II system) for any other indications or in any other situation, including but not limited to use in both eyes does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of subconjunctival retinal prostheses (Argus II system) for any other indications or in any other situation, including but not limited to use in both eyes is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to March 2013
Subconjunctival retinal prostheses do not meet the benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, subconjunctival retinal prostheses are considered investigational.  Investigational services are a contract exclusion.

Rationale:
2007 Update
A search of the MEDLINE database for the period of February through May 2007 did not identify any published results with a retinal prosthesis in humans. No device has final U.S. Food and Drug Administration (FDA) approval.
 
Second Sight Medical Products reports that the Argus 16 was implanted in 6 subjects with retinitis pigmentosa between 2002 and 2004; the study is ongoing with 5 of 6 subjects wearing the retinal prosthesis at home. The company is currently recruiting 10 subjects for a National Institutes of Health-sponsored phase II multicenter safety and effectiveness study of the second generation Argus II Retinal Stimulation System.
 
2009 Update
A literature search for the period of August 2005 through March 2009 did not reveal any published literature that would prompt a change in the policy/coverage statement.   The Phase II study on the retinal stimulation system is ongoing and currently enrolling according to the study summary accessed on ClinicalTrials.gov.  The coverage statement remains unchanged.
 
2012 Update
The following is a summary of the literature concerning the various models of retinal prostheses currently in development.
 
Argus I and Argus II
Literature searches of the MEDLINE database through November 2011 have identified 2 publications with the Argus™ II (60 electrode) device, one of which was a conference proceeding (Humayan, 2009) (Ahuja, 2011).  Preliminary 6-month results in 17 subjects showed improvement in high-contrast localization and orientation (Humayun, 2009). For example, the success rate of reaching a door improved from 32% with the system off to 59% with the system on. The average success rates of following a white line on a dark floor improved from 26% to 44%, respectively. Localization of a high-contrast target on a computer monitor was also found to improve with the Argus™ II in 27 subjects implanted with the device (Ahuja, 2011).  
 
In a 2009 summary of their work to date, Chader et al. reported that the 60-electrode device is currently in a Phase II/III clinical trial (registered at the online site www.clinicaltrials.gov as NCT00407602), a 250-electrode unit is “on the drawing board,” and functional vision with a 1,000-electrode prosthesis could potentially be achieved within 5-10 years (Chader, 2009). The Argus II is reported to be the closest to becoming commercially available (Ong, 2011).  
 
Learning Retina Implant
An acute trial began in 2003 with 20 patients who underwent electrical stimulation lasting 45 minutes (Ong, 2011). Nineteen of the subjects described sensations of phosphenes (small spots of light) during stimulation. Chronic studies in human subjects began in 2005, and a multicenter clinical trial is proposed in Europe. (registered at online site www.clinicaltrials.gov as NCT00427180)
 
EPIRET3
Initial results from the EPIRET3 were reported in 6 legally blind subjects with retinitis pigmentosa in 2011 (Klauke, 2011). The device was activated on 3 occasions to record visual sensations and then removed at day 28, per the study protocol. During the 1-hour sessions the current amplitude, pulse duration, pulse frequency, number of pulses per stimulus, and stimulated electrodes were varied. Although the same stimulation patterns were used, they elicited different sensations in the 6 subjects. Most visual sensations were described as bright colors such as red, green, blue and yellow, but some subjects also reported seeing dark or black patterns. Some of the subjects reported seeing geometric patterns that corresponded to different stimulation patterns and/or could discriminate the stimulus orientation.
 
STS [Suprachoroidal-Transretinal Stimulation] System
In 2011, functional testing of the STS system was reported in 2 subjects with retinitis pigmentosa (Fujikado, 2011). Visual acuity consisted of light perception; an eye mask was placed over both eyes during the testing. Both subjects performed better than chance for object detection and object discrimination using a video camera. One patient scored better than chance in detecting the direction of motion of an object and grasping objects. The device was removed 5-7 weeks after implantation.
 
Tubingen Subretinal Implant
The ability to recognize complex spatial percepts with subretinal implantation of a microchip was reported in 3 subjects with hereditary retinal dystrophy (retinitis pigmentosa and choroideraemia) in 2011 (Zrenner, 2011). The subjects, who previously had only limited light perception, were able to locate bright objects on a dark table. One subject was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit, and to read large simplified letters. The authors concluded that while this study provides proof-of-concept, further development is needed to provide long-term stability, improve contrast and spatial resolution, and increase field size through implantation of multiple chips. A follow-up study with the next-generation system (Alpha IMS) is ongoing (registered at online site www.clinicaltrials.gov as NCT01024803).
 
Summary
Several models of retinal prostheses are in development in the U.S., Europe, and Asia. At this time, testing of visual function has been performed with first generation designs in a small number of subjects; most have included only short-term testing. These pilot studies include only limited outcomes, such as detection of contrast and/or identification of common objects, and report some improvement on these crude measures. Testing of the second generation devices is ongoing. No device has final U.S. Food and Drug Administration (FDA) approval.
 
2014 Update
One study was identified assessing letter and word reading and long-term function in patients with profound vision loss with Argus II implanted. Twenty-one subjects were tested for letter and word reading at an average 19.9-month follow-up (range, 8.6-34.8) (da Cruz, 2013). Correct letter reading ranged from 51.7% to 72.3% with the device on, compared with 15.3% to 17.7% with the device off. The average time for correctly identified letters ranged from 47.7 seconds to 68.6 seconds. Subjects who successfully completed the letter identification task proceeded to the next task. Six subjects were able to consistently read letters of reduced size. The smallest letter identified was 0.9 cm for 1 subject, but preferred letter size was as much as 22.6 cm. Four subjects were able to correctly identify 2-, 3-, and 4-letter words.
 
Also, in 2013, short-term outcomes with the next-generation alpha-IMS system were reported from 9 subjects with subfoveal placement and from 12 subjects with parafoveal placement (registered at online site www.ClinicalTrials.gov as NCT01024803 and NCT00515814, respectively) (Stingl, 2013a; Stingl, 2013b). Preoperatively, 8 of 9 subjects with subfoveal implantation had light perception without localization and 1 had complete blindness (Stingl, 2013a).
 
2015 Update
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Argus I and Argus II
Six subjects from one of the study sites were tested for reaching and grasping after a period of at least years (Kotecha, 2014). The test consisted of picking up a white cube from a table covered with black felt, and was conducted with the electrode array on, array off, and array with scattered input, in a randomized order. Also randomized was the location of the object, which could be placed in one of 4 positions.
Repeatability of performance was assessed after 4 to 6 weeks. The percentage of successful grasps was higher with the device on (69%) compared to device off (0%). With the signal scrambled, success rates were 59% on the first visit and 28% on the second visit. There were no significant differences between “on” or “scrambled” conditions for movement onset, time to object contact, or deviation of the movement trajectory from a straight route between the start and object contact. As noted by the authors, future studies should evaluate the use of the prosthesis for every-day tasks.
 
Ongoing and Unpublished Clinical Trials
  • IRIS-1 (NCT01864486) is a study to evaluate the safety and effectiveness of the Intelligent Retinal Implant System (IRIS V1) in 20 patients with retinal dystrophy. Study completion with 18  month follow-up is expected January 2015.
 
2016 Update
A literature search conducted through January 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Argus II
A prospective multicenter clinical trial evaluating the Argus II Retinal Prosthesis System was conducted and data were submitted to the FDA prior to device approval. The Argus II Study Group has published numerous articles on various findings of this study.
 
Functional outcomes at 3 years were reported by Geruschat and colleagues (Geruschat, 2016). Functional ability was assessed using the Functional Low-Vision Observer Rated Assessment (FLORA) instrument, which is an observer-rated assessment of the ability to complete common activities. The instrument assesses 35 tasks in 4 domains (Visual Orientation, Mobility, Daily Life, and Interaction With Others). Tasks were performed with the device in the on and off positions. Twenty-six (87%) of the 30 enrolled patients were included in the analysis at a mean of 36 months (range, 18-44 months) after device implantation. Twenty-four (69%) of tasks had significantly better scores with the device turned on than off. Two (6%) tasks were significantly worse with the device turned on, and the remaining 9 (26%) tasks showed no significant difference with the device on or off.
 
Long-term safety results in 29 of the 30 patients included in the Argus II study were reported by Ho and colleagues (Ho, 2015).  At 3 years postimplantation, 23 serious adverse events (SAEs) were reported in 11 patients. The most common SAEs were conjunctival erosion (n=4), hypotony (n=4), conjunctival dehiscence (n=3), and presumed endophthalmitis (n=3).
 
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below:
 
Ongoing
(NCT01024803) an industry-sponsored or cosponsored trial. Safety and Efficacy of Subretinal Implants for Partial Restoration of Vision in Blind Patients: A Prospective Multicenter Clinical Study Based on Randomized Intra-individual Implant Activation in Patients With Degenerative Retinal Diseases; planned enrollment 45; completion date April 2017.
 
(NCT00407602) an industry-sponsored or cosponsored trial. Argus® II Retinal Stimulation System Feasibility Protocol; planned enrollment 30; completion date August 2019.
 
(NCT02303288) an industry-sponsored or cosponsored trial. Post-Market Study of the Argus® II Retinal Prosthesis System – France; planned enrollment 18; completion date November 2018.
 
(NCT01860092) an industry-sponsored or cosponsored trial. New Enrollment Post-Approval Study of the Argus® II Retinal Prosthesis System; planned enrollment 53; completion date Audust 2018.
 
The evidence for retinal prosthesis in individuals who have blindness secondary to retinal diseases includes case series. Relevant outcomes are functional outcomes, quality of life, and treatment-related morbidity. Most series are small (ie, <10 patients), preliminary investigations, and/or do not assess functional outcomes. A prospective series with 30 patients was conducted using the Argus II system and numerous articles on this study have been published. At a mean follow-up of 36 months, with the device in the on position versus off, there was significant improvement on 69% of tasks, no change in 26% of tasks, and significantly worse performance on 6% of tasks. Additional prospective studies are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.
 
2017 Update
A literature search conducted using the MEDLINE database through February 2017 did not reveal any new information that would prompt a change in the coverage statement.
 
2018 Update
A literature search was conducted through June 2018.  There was no new information identified that would prompt a change in the coverage statement.  

CPT/HCPCS:
0100TPlacement of a subconjunctival retinal prosthesis receiver and pulse generator, and implantation of intra-ocular retinal electrode array, with vitrectomy
0472TDevice evaluation, interrogation, and initial programming of intra-ocular retinal electrode array (eg, retinal prosthesis), in person, with iterative adjustment of the implantable device to test functionality, select optimal permanent programmed values with analysis, including visual training, with review and report by a qualified health care professional
0473TDevice evaluation and interrogation of intra-ocular retinal electrode array (eg, retinal prosthesis), in person, including reprogramming and visual training, when performed, with review and report by a qualified health care professional
L8608Miscellaneous external component, supply or accessory for use with the argus ii retinal prosthesis system

References: Ahuja AK, Dorn JD, Caspi A et al.(2011) Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br J Ophthalmol 2011; 95(4):539-43.

Chader GJ, Weiland J, Humayun MS.(2009) Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis. Prog Brain Res 2009; 175:317-32.

da Cruz L, Coley BF, Dorn J et al.(2013) The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br J Ophthalmol 2013; 97(5):632- 6.

Fujikado T, Kamei M, Sakaguchi H et al.(2011) Testing of semichronically implanted retinal prosthesis by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci 2011; 52(7):4726-33.

Geruschat DR, Richards TP, Arditi A, et al.(2016) An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years. Clin Exp Optom. Jan 24 2016. PMID 26804484

Ho AC, Humayun MS, Dorn JD, et al.(2015) Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind. Ophthalmology. Aug 2015;122(8):1547-1554. PMID 26162233

Humayun MS, Dorn JD, Ahuja AK et al.(2009) Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study. Conf Proc IEEE Eng Med Biol Soc 2009; 2009:4566-8.

Klauke S, Goertz M, Rein S et al.(2011) Stimulation with a wireless intraocular epiretinal implant elicits visual percepts in blind humans. Invest Ophthalmol Vis Sci 2011; 52(1):449-55.

Kotecha A, Zhong J, Stewart D, et al.(2014) The Argus II prosthesis facilitates reaching and grasping tasks: a case series. BMC Ophthalmol. 2014;14:71. PMID 24885164

Montezuma SR, Risso JF 3rd, Ziv OR.(2004) Differential recovery of the electroretinogram, visually evoked cortical potential, and electrically evoked cortical potential following vitrectomy: implication for acute testing of an implanted retinal prosthesis. J Rehabil Res Dev 2004; 41:113-20.

Ong JM, Cruz LD.(2011) The bionic eye: a review. Clin Experiment Ophthalmol 2011.

Stingl K, Bartz-Schmidt KU, Besch D et al.(2013) Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc Biol Sci 2013a; 280(1757):20130077.

Stingl K, Bartz-Schmidt KU, Gekeler F et al.(2013) Functional outcome in subretinal electronic implants depends on foveal eccentricity. Invest Ophthalmol Vis Sci 2013b; 54(12):7658-65.

Weiland JD, Liu W, Humayun MS.(2005) Retinal prosthesis. Annu Rev Biomed Eng 2005; 7:361-401.

Zrenner E, Bartz-Schmidt KU, Benav H et al.(2011) Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc R Soc Biol Sci 2011; 278(1711):1489-97.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.