Intraoperative OCT was used to verify reintal flattening and the air was exchanged with a tamponade agent, either silicone oil or gas. In three of the five patients that underwent implantation, the agent was removed under local anesthesia one month later.
In the other two patients, the air was exchanged with gas hexafluoroethane in patient 4 and sulfur hexafluoride in patient 5. The 2. Post-surgically, patients were prescribed routine postoperative topical treatment of dexamethasone and tobramycin eye drops three times daily for 4 weeks.
The two patients 4 and 5 who received air-gas exchange also received mg of acetazolamide at 1 and 6 hours postoperatively and assumed prone positioning for 12 hours after surgery. Patients also underwent visual field testing Octopus ; Haag-Streit, Koniz, Switzerland at 6 and 12 months, with all 5 reporting light perception in the atrophic zone, elicited by the implant when the system was on, with no perception reported when the system was off.
In the forced-choice bar orientation test vertical, horizontal, and 2 diagonals in opposing directions , patients 2, 3, 4, and 5 achieved The population average prosthetic LogMAR acuity was 1. Patient 2 was tasked to recognize letters 2. Letter recognition did not involve head scanning, only eye scanning of the image. Electrical impulses are transferred to the retina by 25, micrometer diameter electrodes arrayed in a hexagonal pattern coated in a thin film of iridium oxide and affixed to the end of a via a 40 mm long, 3 mm wide polyimide foil micro-cable which connects the electrodes to a receiver module implanted within the lens capsule.
The receiver module consists of a receiver coil that wirelessly obtains transmitted data, a receiver chip that processes that data, and a stimulation chip that generates and sends impulse activation patterns to the micro-electrode array. The entire implant is coated with parylene C for biocompatibility. Data and power originate from a portable computer system worn or carried by the user.
Prior to EPIRET3 implantation, removal of natural or artificial intraocular lenses and vitreous must be performed and the posterior chamber filled with perfluorcarbon. A complete gauge vitrectomy via the pars plana may accomplish this.
Additionally, following phacoemulsification of the lens, an excentric posterior capsulotomy is created for passage of internal components. To begin implantation, the receiver module is inserted into the lens capsule via an 11 mm corneoscleral incision and secured by two trans-scleral sutures. From there, the polyimide foil cable and array are led through the defect in the posterior capsule into the vitreous chamber.
The micro-electrode array is positioned within the macular region by progressively removing the perfluorcarbon cushion. Two titanium retinal tacks are used to affix the stimulator array onto the surface of the posterior pole of the retina. Before closure, the eye is filled with saline solution. Surgery reported to take less than 2 hours. Successful experimental implantation and explantation of the EPIRET3 system in 6 subjects was reported in by Roessler and colleagues.
No severe adverse events were reported in any of the subjects. However, one patient developed culture-negative hypopyon on post-implantation day 3 which was treated and cleared by day 5.
During explantation, a different subject developed a macular hole which was filled with silicone oil. Although minor gliosis was visible on angiography near tack sites, visual acuity was stable at long-term follow-up for all patients. During the implantation period, the implant was turned on for visual function and stimulation testing only on days 7, 14, and 27, and the results from these tests remain unpublished.
All subjects in the study completed the National Eye Institute Visual Functioning Questionnaire - 25 [37] 1 or 2 days before implantation, 3 weeks after implantation, 6 months after implantation, and months after implantation except for one subject who was deceased at the time of long-term follow-up.
Mean composite scores did not significantly differ between any of the time-points which was expected since the device was not used continuously by subjects during the implantation period. Detailed description of surgical techniques used to implant the IRIS system are currently unavailable.
The IMI retinal implant system upon which the first version of the IRIS Bionic Vision Restoration System is based was implanted for at least 1 year in 4 patients with retinitis pigmentosa and visual acuities ranging from no light perception to hand movement. Similar results were shown in a one-time, acute stimulation study wherein 19 out of 20 subjects with retinitis pigmentosa experienced visual perceptions when micro-electrodes provided stimulation.
Multi-center clinical trials were begun in for the IRIS version 1 and at the beginning of for IRIS version 2 with estimated enrollments of 20 and 10 subjects and estimated primary completion dates of and , respectively clinicaltrials.
Recruitment criteria include confirmed diagnosis of retinitis pigmentosa, choroideremia, or cone-rod dystrophy and a visual acuity of logMAR 2. The current iteration improves upon a first-generation design in three significant ways: 1 an increase in power and data telemetry transfer capabilities due to a larger internal receiver coil, 2 a more resilient hermetic, titanium casing of internal circuitry, and 3 a longer cable connecting the micro-electrode array to other internal components to allow for easier implantation.
External components of the system include a computer controller with an interface which allows users to adjust parameters of retinal electrical stimulation such as strength, duration, and spatial distribution. Using power amplifiers, this computer sends power and data signals to internal components wirelessly via near-field inductive coupling. These signals are received by internal coils that sit just under the conjunctiva of the anterior eye and passed along to the internal processor which is housed in a hermetic, titanium casing and attached to the sclera in the superior nasal quadrant of the eye.
Internal processors decode data signals and send stimulating impulses via a serpentine, polyimide foil to the micro-electrode array which enters the sclera and choroid in the supero-temporal quadrant and is implanted subretinally. The 16 micro-electrodes on the array are each micrometers in diameter and made from sputtered iron oxide film.
Each is controlled independently by corresponding internal processor channels. The following implantation techniques were used to implant devices in two minipigs weighing approximately 20 kg. Conjunctiva is dissected and a 6 mm x 2 mm scleral flap is created in the supero-temporal quadrant. After partial vitrectomy, a needle is used to raise a retinal bleb, a separation of the choroid and retinal pigment epithelium from the retina, from the front.
Receiver coils and the casing containing the internal processors are secured to the sclera anteriorly and in the superior nasal quadrant, respectively. Next, an incision is made in the choroid under the scleral flap to insert the micro-electrode array. The array is positioned so that it rests in the subretinal space created by the bleb. Once the array is positioned, the serpentine, polyimide foil connecting it to the other internal components is secured to the sclera with sutures and the scleral flap is sutured close.
Finally, the conjunctiva is sutured back down over the implanted receiver coils. Joseph Rizzo, the principal investigator of the Boston Retina Implant Project, has stated that his team will forego human trials until development of a device capable of or more, independently controlled micro-electrodes is completed.
Though these measurements showed sustained function, the devices were explanted at 3 and 5. Since then, the shape of the coils has been altered for future long-term implantation studies. Bionic Vision Australia is a research consortium based in Australia currently developing suprachoroidal retinal prosthesis implants.
A 24 channel prototype with 20 stimulating electrodes was implanted in three volunteers as a phase I human clinical trial, but the consortium is now focusing efforts on similar 44 and 98 channel versions. The 24 channel implant contained an array of 33, micrometer platinum stimulating micro-electrodes set 50 micrometers from the surface of a silicone substrate measuring 19 mm x 8 mm.
Of the 33, 20 functioned as independent stimulating electrodes. This array was designed to be implanted between the sclera and the choroid behind the retina. Unlike other implant systems, this one did not use wireless transfer of energy and data. The titanium connector piece is attached to the temporal bone with self-tapping screws after making a curved scalp incision, an incision through the posterior temporalis muscle, and dissection of the temporal periosteum.
An additional incision is made in the scalp flap to allow the connector to protrude from the skin. A tunnel between the connector and the lateral orbital rim is made by dissecting under temporalis fascia, and a lateral canthotomy is performed to expose the lateral orbital margin.
After incision through the periosteum, 10 mm burrs were used to perform a lateral orbitotomy below the zygomaticofrontal suture for securement of the connecting wire with custom made silicone grommet. A temporal peritomy is performed to expose and disinsert the lateral rectus muscle under which a scleral incision is made and marked with diathermy approximately mm posterior to the limbus depending on axial globe length.
After full thickness incision of the sclera with a 15 degree blade, the suprachoroidal space is dissected with a crescent blade and lens glide. To allow for micro-electrode array positioning and wire exit, an incision extending the superior wound edge posteriorly is made. After positioning of the array, visualized using indirect ophthalmoscopy during surgery, in the suprachoroidal space under the macula the wound is closed and a Dacron patch is sutured to the sclera over it. Then, the lateral rectus is reattached, the conjunctiva closed, and the connecting wire secured in the orbitotomy with the grommet.
Finally, periosteum, subcutaneous tissue, and skin are closed. Surgical time is hours. Three subjects with light perception visual acuity due to outer retinal degenerative diseases 2 with rod-cone dystrophy, 1 with syndromic retinitis pigmentosa were implanted with suprachoroidal retinal prosthesis devices and percutaneous connectors.
One year of follow-up data was published in by Ayton and colleagues and will be summarized here. Otherwise, post-surgical hemorrhage in the subretinal and suprachoroidal spaces was noted in all subjects, but in each case spontaneously resolved without further complications.
Device stability and integrity was measured regularly using fundus photography, infrared imaging, OCT, and impedance studies. Imaging showed no movements of the device, but distance from the device to the RPE markedly increased over the course of the year in two subjects. In one, the distance increased from roughly micrometers to micrometers and in the other from roughly micrometers to micrometers as measured by OCT.
In these, OCT showed a hyper-reflective band which authors could not explain develop between the choroid and the retina. Impedance studies showed significantly decreased micro-electrode impedance in one subject over time which was thought to be due to changes in the electrode-tissue interface.
For visual function testing, a head-mounted video camera and a reconstruction filter processing algorithm were used to send electrical stimulation data to the micro-electrode array.
Data for the Landolt-C task was reported for one subject whose visual acuity was estimated to be logMAR 2. With the device off, the same subject was unable to see any Landolt-C optotypes. Similar to the BVA system, this prosthesis implant requires a temporalis incision and tunneled connection between a visual decoder, an internal coil and a stimulating electrode array and return electrode. The implanted internal components of the system consists of a secondary coil for receiving signals from the external coil and a decoder which generates biphasic pulses to deliver to individual electrodes sequentially.
The size of the electrode array itself is 5. The center-to-center separation distance of a pair of electrodes is 0. Power for the system is provided via an external portable battery pack carried by the patient.
To determine optimal site placement of the internal STS array, the lateral rectus is first dissected at its insertion under local anesthesia. Next, transscleral monopolar stimuli are delivered to determine the sleral area that is consistently evoking low-threshold phosphenes.
Incision is made in the skin overlying the left temporal bone to insert the internal coil and decoder. A second skin incision is made over the left zygomatic bone to fix the cable in its appropriate positioning.
Before the electrode array can be implanted in the scleral pocket, the bone of the lateral orbital wall is drilled and the return electrode and cable are passed into the periocular space using a trocar catheter. The cable with its protective layer is then fixed by a titanium plate underneath the site of the second incision over the zygomatic bone. The electrode array and cable are then circled around the equator of the eye passing underneath the four recti muscles.
A scleral pocket measuring 6x5mm is created at the temporal to lower-temporal scleral region where the low-threshold phosphenes were successfully elicited.
The electrode array is then placed inside of the scleral pocket and secured with sutures which pass through the protective silicone cover surrounding the connection junction of the electrode array and cable. The return electrode is inserted into the vitreous cavity through the upper nasal pars plana region.
In a pilot study of two patients using a prototype 9-electrode implant, it was demonstrated that phosphenes could be reproducibly elicited in the area of the visual field corresponding to the implant during direct stimulation. Using a headband-mounted camera with the patients eyes covered with a mask, they were tasked with following a visual object.
While the safety profile of the device was reassuring, with no SAEs requiring further surgery at 1 year, the tests of function were less consistent. One subject could localize a square better with the device on during all of the follow-up, while two subjects were able to walk along a white line and recognize an everyday object better than chance, but not reproducibly at separate time points.
Results suggest that the subject could reach more accurately using a combination of natural and artificial vision than with residual natural vision alone. Despite numerous advances in retinal prosthetic device understanding, design, and implementation over the last few decades, there remain significant questions to answer and hurdles to overcome in the work to develop a stable, long-term, useful prosthesis. Perhaps the most critical of these pertain to our lack of understanding of retinas affected by degenerative changes.
Their findings have just been published in Communication Materials. Field of vision and resolution Two parameters are used to measure vision: field of vision and resolution. The engineers therefore used these same two parameters to evaluate their system.
The retinal implants they developed contain 10, electrodes, with each one serving to generate a dot of light. We had to find just the right number so that the reproduced image doesn't become too hard to make out. The dots have to be far enough apart that patients can distinguish two of them close to each other, but there has to be enough of them to provide sufficient image resolution," says Ghezzi. The engineers also had to make sure that each electrode could reliably produce a dot of light.
Ghezzi explains: "We wanted to make sure that two electrodes don't stimulate the same part of the retina. So we carried out electrophysiological tests that involved recording the activity of retinal ganglion cells. And the results confirmed that each electrode does indeed activate a different part of the retina. Using any more wouldn't deliver any real benefits to patients in terms of definition," says Ghezzi.
However, their location on the eye needs to be very precise, and you have to be much more careful not to damage the antenna and the electronics. After that is a pars plana vitrectomy. The next part is something new: we have to enlarge the sclerotomy, put the electrode array in, and then close the sclerotomy around the cable.
Although the incision in the sclera is large to get the electrode array in—closer to 5 mm—you can close it all down to sub-2 mm. The next step is to tack the electrode array, centered on the macula, to the retina. So the last 2 steps of putting in an electrode array through the sclera and then being able to tack it involve new techniques that retina surgeons can readily and easily learn.
And you end the procedure by closing the remaining sclerotomies and then closing the conjunctiva and tenons over the electronics and scleral buckle. From there, the critical step is to take the time to tack and make sure the array is very flat on the retina. Mark Humayun: I think the best way to tell that is if you get folding in the retina. So I really look for that.
If you push it too hard, you get retinal folds around the edge of the array—then you just pull back on the tack a bit.
But we spend a lot of time with any starting surgeons to be sure they understand the tacking. The FDA requires that Argus II patients be willing and able to complete the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation. Argus II has been FDA approved as a humanitarian-use device, an approval pathway limited to devices that treat or diagnose fewer than people in the US each year.
Mike Jumper: For an experienced surgeon, is this a 2-hour procedure? After a few procedures, I can complete one in just under 2 hours. For the first operation, I would obviously allow more time. You have to suture the sclerotomies so there is no leakage—ie, the eye is watertight. Mark Humayun: Thanks for bringing that up. Actually, we use a thin layer of pericardium over the cable of the electrode array where it comes out of the sclerotomy into the electronic can.
Mike Jumper: Where will the training for this new technique be available? Mark Humayun: We have developed a training program which is available from Second Sight, and they also have a mock surgery setup. Typically, the training is done at the implanting center the day prior to the first case—and it takes about 1 to 2 hours. A number of stories highlighted the case of year-old Kathy Blake, who is Dr.
The Argus II restored her sight after having been blind for 23 years. Bazell R. Gift of Sight. February 14, Benitez G. Belluck P. Device offers partial vision for the blind.
The New York Times. The FDA does require training of both the hospital staff and the surgeon prior to the first case.
In addition to the training program from Second Sight, a surgeon experienced in Argus II implantation will be present at the first case. Mike Jumper: What kind of rehab do you think the person who receives one of these commercial products will receive?
Will there be pretty intensive rehab for weeks or months? How do you see it happening? Mark Humayun: Rehab time has lessened considerably. In the latest patients in Europe, it's taken about 2 months. Today, rehab is typically performed after the device has been programmed, and most patients go through a rehab program that involves 10 to 15 sessions of about 1 hour each.
These sessions tend to be spread out over the first 3 months post-operatively. The occupational or low-vision therapist works with the patient to teach basic skills, identify important goals, and help the patient achieve them. Mike Jumper: What is the treatment regimen after the patient completes post-op rehab? Mark Humayun: Once a patient finishes post-op rehab, the sessions are once quarterly. Patients do get their settings looked at, and of course we want to look at the patients once quarterly as well.
This is not an implant you put in and then forget about it; you do need to follow the patients periodically. Mike Jumper: So is this like a model for pacemakers or cochlear implants, where the company will employ engineers for field support? Mark Humayun: In the early days post-launch, the company will provide extensive field support.
And there will always be a place for field services provided by the company for difficult or unusual cases. But as with the cochlear implant, independent specialists likely will be trained to program the devices, just as audiologists do for cochlear implants.
Mark Humayun: The device in its current format is approved only for patients with light perception or worse vision due to outer retinal degenerations; this is not the level of vision loss experienced by patients with macular degeneration. The amount of acuity that needs to be provided for macular degeneration patients depends on the stage of the disease and patient expectations.
It is not yet clear whether there needs to be an evolution in the technology to treat these patients. Second Sight hopes to address this open question by running a small pilot study in the most severely affected AMD patients to see if the Argus II provides any benefit.
0コメント