Creating the Bionic Eye: Implanting the Argus II

A primer on patient selection through postop rehabilitation

NINEL Z. GREGORI, MD • LISA C. OLMOS DE KOO, MD, MBA • PAUL HAHN, MD, PhD • JANET L. DAVIS, MD

Retinitis pigmentosa (RP) is a group of genetically heterogeneous inherited retinal degenerative disorders characterized by early rod dysfunction with progressive rod and cone dysfunction and photoreceptor death.

Mutations in more than 45 genes cause RP.¹ The mode of inheritance can be autosomal-dominant, autosomal-recessive, or X-linked; however, approximately 50% are sporadic cases without family histories of RP.

The manifestations of RP are highly variable, but patients typically report difficulty with night vision, peripheral vision, and eventually also loss of central vision. Most patients progress to legal blindness by age 40 because of severely constricted visual fields despite preserved central vision. However, some patients lose central vision relatively early in the disease process.

Currently, there are no treatments available to reverse the progression of RP. However, multiple clinical trials, including gene therapy (RPE65), ciliary neurotrophic factor, and stem cell transplantation, are under way.¹

It has been shown that supplementation with 15,000 IU of oral vitamin A palmitate every day may reduce the rate of electroretinographic (ERG) and visual field decline in some RP patients.¹ Once all vision is lost to the point of bare light perception, artificial vision may now be considered.

FDA APPROVAL OF THE ARGUS II RETINAL PROSTHESIS

After more than two decades of research and development, on February 14, 2013, the Food and Drug Administration approved the Argus II Retinal Prosthesis, codeveloped by Second Sight Medical Products, Inc. (Sylmar, CA), with Mark S. Humayun, MD, PhD, and others at the USC Eye Institute of the University of Southern California’s Keck School of Medicine in Los Angeles, to treat patients in the end stages of RP.

The FDA approved the Argus II as a Humanitarian Use Device, ie, a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.²

The US Department of Energy, the National Eye Institute at the National Institutes of Health, and the National Science Foundation collaborated to provide grant funding of more than $100 million to support the development of the Argus II.

ARGUS II APPROVED INDICATIONS

The Argus II is intended to deliver electrical stimulation of the retina to induce visual perception in patients with severe RP who meet the following criteria: ≥ 25 years of age; bare light or no light perception in both eyes (if the patient has no residual light perception, evidence of intact inner retina function must be confirmed); a previous history of a useful form of vision; and the ability to receive the recommended postimplant clinical follow-up, device fitting, and visual rehabilitation.

The Argus II Prosthesis is intended to be implanted in a single eye, typically the worse-seeing eye.

DEVICE DESCRIPTION

The Argus II system includes external equipment worn by the patient along with internal electronics surgically implanted in and around the eye. The external hardware consists of glasses equipped with a miniature video camera on the nasal bridge that transmits images through a wire to the battery-powered video processing unit (VPU), which the patient wears on his or her belt.

The VPU has multiple user-adjustable settings that transform the video images into electrical stimulation, delivered to a transmitting coil located on the side of the glasses, which is subsequently sent wirelessly to a receiving coil sutured to the sclera. In addition to wireless communication, the external equipment also wirelessly powers the internal implant.

The surgically implanted component consists of a receiving coil and an electronics case, which are secured to the sclera circumferentially in a scleral buckle fashion. The wirelessly delivered electrical signal is received by the coil, processed by the electronics case, and sent via a cable through a sclerotomy into the eye, terminating at an epiretinal 60-electrode array secured to the retina-choroid-sclera with a retinal tack (Figures 1 and 2).

Figure 1. Argus II Retinal Prosthesis.

Figure 2. Schematic of Argus II implantation showing the array cable entering the eye through a sclerotomy located in the superotemporal quadrant and the placement of the array over the macula.

Data sent from the VPU wirelessly stimulate the array to emit small pulses of electricity that excite the remaining viable inner retinal cells, including the ganglion cells. These artificially stimulated retinal ganglion cells transmit signals through their axons via a functioning optic nerve and tract to the lateral geniculate nucleus, optic radiations, and onto the occipital cortex, which perceives patterns of pixelated light that the patient learns to process into formed vision.

SURGICAL IMPLANTATION

Argus II implantation surgery has been progressively refined to incorporate skills familiar to the trained vitreoretinal surgeon. Following peritomy and rectus muscle isolation, the surgeon secures an encircling band to the sclera with the receiving coil located under the lateral rectus and the electronics case in the superotemporal quadrant. Suture tabs secure the electronics package and coil at precise locations posterior to the limbus, which are predetermined based on the axial length of the eye.

Next, the surgeon performs a complete vitrectomy with crystalline lens removal and membrane peeling as needed. The array is then inserted through a 5.2-mm sclerotomy and is secured to the center of the macula using a retinal tack inserted through the posterior ocular coats (retina-choroid-sclera) (Figures 3 and 4).

Figure 3. Fundus photograph showing the array tacked over the macula.

Figure 4. OCT showing placement of the array in close proximity of the retina.

To close the eye, the surgeon first places Tutoplast (IOP Ophthalmics, Inc., Costa Mesa, CA) or corneal patch grafts to cover the electronics case and coil tabs and then closes the conjunctiva and Tenon’s capsules. The median surgical duration is approximately four hours, and the surgery is performed under general anesthesia.³

Special Surgical Considerations

Certain steps must be completed very cautiously to ensure smooth implantation. The surgeon must undertake special precautions to avoid damage to the delicate electronics, which are tested throughout the surgical procedure for integrity. The surgeon must fixate the external portions of the device precisely, according to a normogram developed by Second Sight because the extraocular location influences the positioning of the array over the macula. The axial length must be between 20.5 and 26.0 mm for the eye to be Argus II-eligible.

The vitrectomy portion of the procedure must be thorough, particularly when trimming the vitreous base in the quadrant of array insertion, to avoid device capture within residual vitreous gel. Staining the vitreous with steroid and the use of chandelier illumination are particularly helpful.

The sclerotomy for the array and cable should be made perpendicular to the sclera and should be full-thickness. If the array becomes caught on the sclerotomy edge, choroidal detachment can occur.

One of the most unique features of the surgery is tack placement, which is done with a 19-gauge specialized instrument. Before engaging the tack, it is critical to ensure that the array will be positioned over that macular center and that there is no twist in the array cable, to ensure optimal functionality.

At the Bascom Palmer Eye Institute, a bimanual technique to position and tack the array was found to increase the ease and precision of this critical surgical step (Video). Meticulous closure of all wounds is critical.

SELECTING AN IDEAL PATIENT

The degree of visual impairment in RP is highly variable, and only patients with profound visual loss are currently good candidates for the Argus II. Early clinical trials data have shown that there appears to be some degree of variability in patient acceptance of the device after it is implanted.³

Patient Screening

The surgeon must ensure that the patient meets all of the eligibility criteria contained in the product label, there are no contraindications to device placement, the patient’s level of residual vision contributes to a favorable risk/benefit profile, and the patient’s motivations, expectations, cognitive and communication skills, and physical abilities are likely to contribute to receiving benefit from the device. Screening typically involves a standardized survey, patient interview, and complete eye exam with biometry.

The vision must be bare light or no light perception in both eyes. If there is no light perception, photoflash testing or electrically evoked response must be used to confirm the function of the nerve fiber layer and optic nerve. Patients with profound amblyopia may not benefit due to a lack of development of the visual cortex.

Prospective patients should understand that diligence and a firm commitment to learning to use the device are required to obtain the best results. It may be helpful to explain that learning to use the Argus II is similar to learning a new language.

Contraindications

Contraindications to the Argus II include ocular diseases or conditions that could prevent the system from working (optic nerve disease, central retinal artery or vein occlusion, history of retinal detachment, trauma, severe strabismus, profound amblyopia) or that could prevent successful implantation (extremely thin conjunctiva, axial length <20.5 mm or >26.0 mm, choroidal neovascularization in the area of the intended tack location, corneal opacity). Cataract is not a problem, because any cataracts should be removed at the time of surgery.

Patients with the inability to tolerate general anesthesia or the recommended antibiotic and steroid regimen should be excluded. Metallic or active implantable devices in the head, such as cochlear implants, may interfere with device functionality and should be avoided.

Any disease or condition that prevents understanding or communication of informed consent, fitting of the Argus II system, or postoperative follow-up is a contraindication, such as developmental disability or dementia. A preoperative psychological evaluation may be recommended. A predisposition to eye rubbing can lead to postoperative device exposure, and should be addressed preoperatively.

Finally, a critical but intangible aspect of patient selection is establishing realistic patient expectations about device functionality, as described below.

MANAGING PATIENT EXPECTATIONS

The screening physician should directly ask the patient what he or she hopes to gain with the system. The answer may involve seeing a loved one’s face, driving a car, or reading a book. However, at the present time, none of these visual tasks are realistic expectations after implantation.

The physician should explain to the patient that the artificial vision generated by the device and the vision the patient had prior to sight loss are quite different. Artificial vision generated by the Argus II typically consists of light and dark spots or patterns, often shimmering, which the patient must learn to interpret as objects. This process takes time and patience, and it is analogous to learning a foreign language. Color vision is not currently possible.

Another critical aspect to convey is that any residual vision could decline in the implanted eye. It is helpful to ask the patient whether he or she has any useful residual vision. Can the patient locate objects at home, such as windows and lamps? Can the patient follow the lines of a crosswalk or detect obstacles when walking? Can the patient use his or her vision to participate in sports or hobbies? If the answer to any of these question is “yes,” the patient is not likely to benefit from the system.

Reviewing these factors, particularly with an emotional patient who has high expectations from the Argus II, may be challenging, awkward, and time-consuming for the screening physician, but it is critical to establish realistic expectations early on so that patients who will not benefit are spared the significant burden of surgery, the device cost, and rehabilitation.

Patients with RP who do not qualify for the device because of useful residual vision may take comfort in knowing that future device improvements will render it helpful to those with better vision. Should their vision decline further, the Argus II represents a sort of “safety net” against the total darkness that some patients with RP experience.

POSTIMPLANTATION DEVICE PROGRAMMING AND FITTING

Approximately two weeks after surgery, the patient begins to undergo a fitting process to customize the stimulation levels for optimal performance and comfort. Electrical stimulation of the prosthesis is controlled by a laptop during three- to four-hour sessions, to adjust the camera position to compensate for array placement on the retina, to test the implant and each electrode, to create a custom program for each patient, and to adjust the video configuration file to deliver comfortable brightness of stimulation indoors and in bright outdoor settings.

VIDEO ON DEMAND

1

Download the free Actable interactive print app from the app store (available for both iOS and Android devices)

2

Launch the app and scan this entire page

3

Your video will begin

Surgical video from the Bascom Palmer Eye Institute. Surgery performed by Ninel Gregori, MD, and Janet L. Davis, MD.

VISUAL REHABILITATION

Next, the patient undergoes five to 10 rehabilitation sessions that focus on learning to interpret the artificial vision. Patients describe Argus vision as pixelated shimmering white lights and patterns corresponding to the light objects. Rehabilitation sessions are performed by an occupational therapist or low-vision optometrist in the clinic or in the patient’s home.

In addition to learning the new visual language, patients learn to move their heads, instead of the eyes, because the coil on the side of the glasses and the receiving coil on the eye must be properly aligned for the signal transmission.

Patients also work with a certified orientation and mobility specialist, who focuses on integrating Argus II into the patients’ everyday lives to improve independence. Patients learn to use the Argus with their canes and other mobility devices.

EXPECTED VISUAL GAINS WITH ARGUS II

In a pivotal study of 30 patients with follow-up of up to 2.7 years, subjects performed statistically better with the system on vs off in object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%).³

The best VA was 1.8 logMAR (20/1260) with head scanning and visual field of approximately 20º.³ At an average implant duration of 19.9 months, 21 Argus II users were able to identify letters with the system on.⁴ Six subjects were able to read letters of reduced size, the smallest measuring 0.9 cm (1.7º) at 30 cm, and four subjects correctly identified two-, three-, and four-letter words unrehearsed.⁴ In a different report, 15 of 28 subjects (54%) were able to perform a motion detection task.^5,6

The things that Argus II users have been able to do and see include the following:

• Locate doors, windows, elevators

• Follow a crosswalk across a street

• Avoid obstacles

• Find utensils on a table or when serving food

• Locate coins

• Track the motion of a napkin when cleaning

• Sort light and dark clothes

• Locate people in front of them (but not see the details of a face)

• Track a ball

• Track players on a field

• Locate an overhead light in an entrance way

• Locate the light of a candle or light bulb

• Watch fireworks

MANAGEMENT OF POTENTIAL POSTOPERATIVE COMPLICATIONS

The most common postoperative complication is hypotony, due to the large size of the sclerotomy required for the array placement and the delicacy of closure. If hypotony persists after several days despite pressure patching, a repeat visit to the OR for wound revision and closure may be required.

Conjunctival closure and coverage of the suture tabs with patch grafting material are critical to avoid exposure and the consequent risk of endophthalmitis, which is a significant risk with any conjunctival breach for the lifetime of the device, due to the open intraocular channel made by the array cable.

It is critical to carefully examine the conjunctiva at all follow-up visits and to counsel the patient to have any irritation or foreign-body sensation evaluated immediately. Endophthalmitis can be treated in the typical fashion with a tap and inject procedure or vitrectomy. If there is exposure of the device, revision surgery is indicated once the infection has cleared.

CONCLUSION

The Argus II Retinal Prosthesis is the first FDA-approved artificial vision implant and is indicated only for patients with advanced RP and vision no better than bare light perception in both eyes. The surgical procedure is performed by a trained vitreoretinal surgeon.

The patient must be carefully screened to assure realistic visual expectations and eligibility. The artificial vision provided by the Argus II is similar to shimmering light and dark spots or patterns, which the patient must learn to interpret as objects. The patient must be fully committed to undergoing postoperative visual rehabilitation. Argus II represents the first exciting step to artificial vision for blind patients. RP

REFERENCES