Modern visual implants
FirstVDS company blog, Habr
The visual analyzer is the main tool for obtaining information about the environment. Vision for animals is a danger detector, a signal about the presence of prey, a means of orientation in space, and for humans it is the main way of communication and learning. The more terrible it is for a modern person to lose his sight.
But we live in an age of extensive knowledge in biology and medicine and advanced technologies in the field of microelectronics. Why not combine all this? Is it possible to help people who have lost their sight by transmitting a video signal directly to the brain? And are there already similar technologies that have gone beyond prototypes and experiments?
Blindness
There are various criteria for blindness, for example, in the USA this concept is applied to people with visual acuity worse than 20/200. This means that a person with such vision is forced to approach a distance of 20 feet (6.1 m) to an object that a person with normal vision sees from a distance of 200 feet (61 m). WHO defines this limit at 20/400. The quality of vision worse than this is equated to complete blindness – the absence of light perception as such.
In order to understand how to help a person, you need to know exactly how he went blind. In the modern world, most cases are the result of age-related degenerative diseases of the eye tissues: cataracts (about half of cases), glaucoma (less than 10%), macular degeneration (5%). But if we consider only people of working age, then pathologies that are not heard by the layman come to the fore: congenital (up to 20% of cases) and diabetic (15%) retinopathy.
Diabetic retinopathy, as the name implies, is one of the complications of diabetes mellitus of vascular origin. Due to chronic endothelial damage, atherosclerotic changes, loss of elasticity and impaired vascular permeability, the function of all vascularized tissues is disrupted. But this type of retinopathy is managed – usually as successfully as insulin therapy for diabetes is carried out carefully in a particular patient.
The situation is quite different with patients with so-called retinitis pigmentosa. This is a general term for a group of hereditary diseases with various inheritance variants, which correspond to more than 250 currently detected genetic mutations. The pathogenesis of the disease lies in the fact that, starting from a young age, people have a gradual degeneration of the cells of the pigment epithelium or other layers of the retina. Degeneration can develop on the periphery, concentrically narrowing the field of vision, or vice versa, affect the central zone, forcing the patient to look sideways. Eventually, all photoreceptor cells of the visual field undergo degeneration. Unlike opacities and injuries of the lens, cornea, where it is possible to increase transparency or replace tissue surgically, with retinitis pigmentosa, it is not the "optics" that suffers, but the "matrix", and it is impossible to stop this process. More than 1.5 million people are affected by this condition in the world.
Prosthetics
Thus, it is people with retinitis pigmentosa who are the subjects for the introduction of experimental technologies for prosthetics of vision. The irreversibility of blindness, which does not occur in old age, but in the most socially active and able-bodied age, creates a strong demand for such technologies. In addition, in many cases, retinitis pigmentosa is a failure of only the system of the pigment and photoreceptor layers, when mutations of the visual pigment rhodopsin occur, or the phagocytic system of its spent fragments is disrupted. At the same time, the remaining layers of the retina involved in the transformation of the photoreceptor signal into nerve impulses remain weakly or practically unaffected (up to 30% of ganglion cells and up to 80% of the cells of the inner nuclear layer remain even in the severely affected retina), which makes it possible to create the "first echelon" of prosthetics – special retinal implants.
Photo (left) and enlarged CT image (right) of the Argus retinal implant on the retina of the eye
The idea of retinal prosthetics is to excite retinal neuronal cells bypassing the photoreception mechanism by acting on the membrane potential of neurons with electrical impulses. This approach has a number of technical, surgical and physiological limitations, but it is quite feasible. The result of the operation is the introduction into the retina of a small matrix of stimulating electrodes, which actually returns the eye to the state of a primitive photoreceptor system. One of the disadvantages is the need for serious surgical intervention in the eyeball, including the removal of the vitreous body.
Irritation of almost all parts of the visual system leads to the appearance of so–called phosphenes - flashes, visual artifacts that occur when high-energy particles hit the retina of astronauts, and with external electrical stimulation of the visual cortex, and with the usual friction of closed eyes. This property can be used to fine-tune local irritation of individual areas of neuronal cells on the retina, and then calibrate the resulting image.
Retinal prostheses
Several models of retinal implants have been clinically tested and approved for patients to date. These are Argus II from Second Sight Medical Products (USA), Alpha AMS from Retina Implants AG (Germany) and IRIS from Pixium Vision (France).
Argus II is an epiretinal (located on the surface of the retina from the center of the eyeball) implant. It is a development of the Argus I prototype, which, in turn, was made on the basis of a cochlear (auditory) implant consisting of only 16 electrodes. A square of 4x4 electrodes with a diameter of 250 and 500 micrometers with a distance of 800 microns between them after implantation to people gave valuable information about the performance and optimization possibilities of such technology. As a result, the second-generation implant approved by the FDA in 2011 already has 60 electrodes with a diameter of 225 microns and arranged in a rectangle of 6x10 pieces at a distance of 525 microns from each other, which allows you to cover the field of view in 11 ° x19°.
The assembly of stimulating electrodes is connected by a loop to an external chip fixed externally on the surface of the sclera from the upper-outer quadrant of the eyeball. There is also a receiving induction coil, which receives a signal from an external module. The external module is glasses – the second element of the system, on their bridge there is a camera that transmits a signal to the DVR attached to the belt. The video signal is then converted into a wireless signal, which is decoded by a chip on the sclera and transmitted to the electrode array inside the eye.
Left: general scheme of the Argus II system. Right: one of the patients demonstrates the ability to read and write large characters of the Korean alphabet.
What can be seen with Argus II? On the one hand, the best of all patients with this implant, the result of visual acuity was a little impressive 20/1260. On the other hand, it is difficult to expect any quality of vision at all from 60 working "pixels", this is a kind of auxiliary method of perception designed to navigate in space by silhouettes, illumination boundaries, color contrasts. In certain cases, the patient may follow a line drawn on the floor, or distinguish large figures or letters on a contrasting background.
In the study of the quality of vision conducted in patients with the implanted Argus II system, the most interesting are the results of the FLORA test, which is less dry and standardized compared to laboratory tests, but still statistically valid. FLORA (short for "functional visual abilities in and around a residential setting" – "visual function in near–home conditions") is a test for patients to perform 35 daily tasks with an activated and deactivated implant. With the active Argus II, it was much easier for patients to find doorways, navigate by room lighting, light from windows, sort white and dark underwear, notice passers-by, distinguish curbs and markings of pedestrian crossings. However, there were tasks where the included implant, on the contrary, was confusing compared to the lack of vision – for example, moving inside the house and up stairs.
Another prosthesis, IRIS, is a similar Argus epiretinal implant with an external module and 150 active electrodes. The developers made the signal transmission to the implant inside the eye using an infrared beam, which allowed to increase the transmission speed, and also made it possible to continuously change both the coordinates and the intensity of phosphenes, more accurately simulating the visual process. Otherwise, the scheme is very similar to Argus.
Alpha AMS offers a fundamentally different stimulation scheme. This is a subretinal, that is, an implant placed under the surface of the retina. It contains 1500 functional elements consisting of a photodiode connected to a stimulating electrode. This photosensitive and simultaneously stimulating retinal cells matrix does not have a control electronic chip, instead it receives light from the patient's eye, and power is supplied from an induction coil, which is controlled from the remote control by the patient himself. With the help of an external induction coil attached to the head by a magnet, the patient can amplify the signal on the implant, adjusting it depending on the illumination. The system is powered by conventional AA batteries, does not have additional electronic modules attached to the eye, does not use a video signal and an external module with glasses and a DVR, and most importantly, the patient sets the direction of vision with habitual eye movements, and not by directing the camera lens with head movements. Alpha AMS showed the maximum result of visual acuity in 20/546. Studies have shown that patients with this system are noticeably more comfortable performing actions such as walking through illuminated areas, avoiding obstacles, and also seeing some outlines and objects, from houses and the horizon line to plates and billiard balls.
Limitations
Alas, the most advanced technologies have their limitations. And in the case of such a complex organ as the eye, the creators of implants have to work on the edge of physical and physiological capabilities.
First of all, it would seem that it is possible to increase the area of the implant. But surgical restrictions work against this. The incision through which vitrectomy is performed (removal of the vitreous body), and then the insertion of the implant, should not exceed 5 mm in length due to the risk of complications, which immediately limits one of the measurements of the implanted electrode assembly in size. In principle, this is not particularly necessary: all accurate color vision is created in the area of the central fovea (fovea) of the retina with a diameter of up to 0.5 mm. The rest of the area contains mostly sticks and serves for peripheral vision. Theoretically, it would be possible to "get" the field of view with a composite or folding implant covering a large area. According to psychophysiological experiments, people with normal vision need at least 27°-30° of the field of view for comfortable orientation in space, while Argus II gives less than 20°. But first of all, it does not provide at least some significant visual acuity either.
Then is it logical to increase the density of the electrodes? For purely stimulating electrodes, this is difficult due to the presence of wiring to each electrode. In the case of Alpha AMS, this is possible, since the signal to the neuronal layer of the retina is not supplied via a loop from the outside, but comes from photocells located on the same substrate, and only power goes to the implant. But here another limit begins to work, which is based on the complex physical chemistry of surface phenomena.
A neuron is not a wire, but a living cell that is electrically excited, changing the ionic composition inside by the work of complex molecular structures – ion channels and pumps, and due to this it changes the amount of charge on the surface of its membrane from the outside and from the inside. For proper stimulation of the neuron membrane, it is necessary to carefully and reversibly affect the double electrical layer on its surface. If the required potential is exceeded, the Faraday current can go on the electrode. This means that the electrode will be corroded due to a chemical reaction with surrounding substances - salt ions and organic molecules in the cell membranes. In addition to spoiling the electrode, the products of such reactions can also be harmful to cells. And with a decrease in the size of the electrodes, the threshold of the charge density required to affect the membrane sharply increases, which dangerously brings us closer to the area of undesirable electrochemical reactions. Further, in animal experiments, a nonlinear increase in the perceptual resolution of the retina was shown with a decrease in the size of the electrodes, which negates the gain in increasing their number and density. And this is not all of the known subtle effects of the interaction of electrodes with the living retina. Even the banal removal of heat from the components can be a problem for the body, which is undesirable to overheat anywhere above 37 ° C.
The fate of projects
Although these projects have been approved as medical devices after successful clinical trials, their fate is far from rosy.
Alpha AMS, with all the apparent advancement of technology, caused complications in patients. Due to the invasive procedure of retinal detachment to accommodate chips, as well as the displacement over time of almost all implants (some - outside the central fossa of the retina) by an average of 0.6 mm, most patients expressed dissatisfaction with the procedure. As a result, after 27 installed IMS prototypes and 8 approved AMS products, the project was completely phased out in 2019, and Retina Implants AG collapsed.
Serious problems have befallen the company Second Sight. In 2019, with a client base of 350 patients with Argus series products, they announced the next ambitious project – the Orion brain implant for visual cortex stimulation. However, in 2020, the company began to dramatically lose money, employees, and was on the verge of bankruptcy. Having resumed her ambitions by the end of the year, she, nevertheless, could not support her patients, who were faced with a choice: to carry a system doomed to breakage, or to have an operation to remove it. Recently, Second Sight held merger talks with Nano Precision Medical, which, of course, do not give predictions about whether they will deal with the Orion project and other inherited problems.
Things are going more or less well with Pixium Vision, which also developed the PRIMA subretinal implant.
Prospects?
As it is clear from the above, a retinal implant cannot be used if the eyeball is severely damaged or destroyed. But perhaps it is possible to connect stimulating electrodes in other parts of the visual pathway? Yes, it is.
Firstly, it is possible to stimulate the optic nerve itself, as well as the lateral geniculate nucleus, a zone of the brain where the correspondence of its layers with the areas of the retina is precisely known. These are hard-to-reach areas, in the skull under the brain itself, but they can also be used if it is impossible to affect the retina.
Secondly, some groups of scientists are studying the stimulation of the visual cortex, for example, Monash University in Melbourne, or the European CORTIVIS collaboration from Alicante in Spain. Maybe he coughs and a stalled Second Sight will start. So far they have no talk of releasing a finished product for people, but the concept itself looks promising. Despite the fact that the intervention in the brain seems to be a very serious operation, a number of limitations, such as inaccessibility, liquid intraocular medium, small size of the implant, the risk of complete retinal detachment in this version of the operation are absent. In the near future, we may witness new non-trivial tasks on the way to developing a visual system, and maybe serious success in this area.
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