Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007

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capturing image data, (2) implanted microelectronic for converting image data into a stimulus pattern, and (3) a microelectrode array interface for delivering the stimulus current to the retina. The implementation of these functions is system dependent; however, the potential for harmful interaction between the device and the eye is considerable in all cases. The following issues must be considered for any of these implants.

•Toxicity: The device should either be made of (or hermetically coated with) materials that are not toxic to the retina or any other ocular tissue.

•Degradation: Even if the outer coating is not toxic, over time, the degradation of the device coating can expose the retina to toxic materials which are part of the implant electronics.

•Mechanical damage: The electrode array should also properly fit over the area of the retina that is being implanted. The retina is a delicate neural tissue, and rigid electrodes and microelectronic chips can easily cut the retina, without careful mechanical design. Additionally, limited space in the eye and orbit will constrain the device size and shape.

•Electrical damage: An electrical stimulus beyond safe limits may damage the retina.

•Thermal damage: The retinal prosthesis electronics produce heat which can be damaging to the retina and other ocular structures, if beyond a given threshold.

•Reversibility: Extreme measures in fabricating a robust prosthesis and preoperative testing of the device reduce the chance of its becoming dysfunctional; however, despite best efforts, some prostheses may break down, and it is important to be able to remove the faulty device.

Background

Anatomy and Physiology of the Eye

The eyeball is classically divided into two segments: the anterior segment, composed of the cornea, iris, lens, and ciliary body; and the posterior segment, composed of the sclera, choroid, retina, vitreous, and optic nerve (Figure 1.1).

The eyeball is located within a bony socket called the orbit (Figure 1.2). In addition to housing the eyeball, the orbital cavity contains extraocular muscles, vessels, nerves, connective tissue, and orbital fat.

Although it may be possible to insert a prosthetic device around the eyeball, the device size and shape are important limiting factors. For instance, a poorly shaped, rigid object inside the orbital cavity may damage vessels and nerves, interfere with eye movement, and directly damage the eyeball. On the other hand, a bulky device may displace the eyeball, jeopardize the blood supply to the eye, or raise the intraocular pressure (IOP), thereby resulting in nerve fiber layer damage. These constraints will obviously limit the capability of an electronic device because of necessary size restrictions.

chamber

Vitreous

Cornea

Fovea

Iris

Lens

Optic nerve

Figure 1.1. Schematic cross section of the eyeball as viewed from the side.

Anterior Segment

The iris divides the anterior segment into anterior and posterior chambers and gives the eye its color (Figure 1.3). The opening in the center of the iris is the pupil (Figure 1.3). The pupil regulates light entry to the back of the eye by dilatation or constriction.

Figure 1.2. The bony orbit that accommodates the eyeball, and all surrounding structures (adapted with permission from http://anatome.ncl.ac.uk/tutorials/clinical/eye/page3.html).

The rate at which aqueous is produced and drained determines IOP; the overproduction or more often outflow obstruction will result in raised IOP, which may in turn lead to retinal nerve fiber layer damage and loss of peripheral vision – a common eye disease known as glaucoma. Thus, a retinal prosthesis, which has components in the anterior chamber, risks disrupting the fluid flow in the eye.

The lens is surrounded by a very thin capsule and is kept in place by zonules, tiny fibers which attach the capsule to the ciliary body. The lens is normally clear, but may become opaque following injury secondary to trauma or intraocular surgery. The opaque lens is known as cataract and more commonly occurs with age. During cataract surgery, the lens is removed from the capsule and replaced by an artificial lens made of silicone, PMMA, acrylic, etc. (Figure 1.5). If necessary, the capsular bag can also be used to accommodate some parts of the retinal prosthesis.

Posterior Segment

The sclera, or outermost layer of the eye, merges with the cornea and conjunctiva at the limbus (Figures 1.1 and 1.4). Unlike the cornea which is clear, the sclera is white and blocks most light from entering the posterior chamber. The conjunctiva is a partially transparent membrane that contains vessels and covers anterior part of the sclera (Figure 1.4). The sclera and cornea give the eye its shape.

The choroid is a highly vascular tissue located underneath the sclera, and merges anteriorly with the ciliary body. This structure supplies nutrients to the outer third of the retina, including the photoreceptor outer segments which are particularly metabolically demanding. The inner retina is perfused by a separate circulatory pathway, retinal vessels (Figure 1.6). The vitreous, which fills the space between the lens and the retina, is jelly-like in consistency and helps to keep the retina attached to the underlying layer.

Retina

The retina is positioned as the innermost layer of the posterior segment of the eye and functions as both the sensory detector and the early processing for the

Artificial lens

Posterior capsule

Figure 1.5. Schematic cross section of the anterior segment after cataract surgery, showing an artificial intraocular lens inside the capsular bag.

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Macula

Fovea

Optic disc

Figure 1.6. The fundus as viewed through the pupil; retinal arteries are shown in red and retinal veins in blue.

visual system. After the initial processing of a given image, the retina sends coded signals to the brain via the optic nerve.

The outermost layer of the retina is the retinal pigment epithelium (RPE), a monocellular layer firmly attached to the underlying choroid (Figure 1.7). The remainder of the retina is composed of several layers that collectively form the neurosensory retina. Although the RPE is often considered a part of the retina, the term “retina,” in practice and in literature, implies neurosensory retina; in this chapter, retina also implies the neurosensory retina unless stated otherwise.

The retina is generally firmly attached to the RPE but, in a number of pathological conditions, detachment can occur (Figure 1.8). Trauma, age, and disease processes can all lead to separation, often with ensuing photoreceptor cell death.

The integrity of RPE cells is vital for the viability of the photoreceptors. In addition to absorbing stray light, RPE cells also supply nutrients and oxygen to photoreceptors, remove and digest discs shed by photoreceptors, and have a regulatory role in ion and metabolite transport. Photoreceptors detect light and are divided into two main classes, based on wavelength sensitivity and their location in the retina: the cones are highly concentrated at the central part of the retina (macula) and are responsible for both fine and color vision, whereas rods are more prevalent in the periphery and mainly function in peripheral vision, movement detection, and night vision. Color vision is due to the presence of three types of cones: blue, green, and red. Each type is sensitive to a different spectrum of light, but there is a considerable overlapping amongst them. The nuclei of photoreceptors are located within the outer nuclear layer (ONL). Another major group of cells are bipolar cells, located within the inner nuclear layer (INL). Bipolar cells are involved in the processing and transferring of visual signals from the photoreceptors to the ganglion cells. Other cells within the INL include amacrine and horizontal cells, which modify the neural response as it passes through the retina. The bipolar cells connect to ganglion cells; the axons of the ganglion cells form the nerve fiber layer. These axons converge at the optic disc to form the optic nerve; the axons travel via the optic nerve and make

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Choroid

Retinal tear

Detached retina

Vitreous cavity

Figure 1.8. Schematic diagram of a retinal detachment showing separation of the retina from the underlying RPE and choroid (RPE and choroid are shown as a single layer).

connections with the central visual pathways. The outer plexiform layer contains the contacts between photoreceptors and bipolar cells, and the inner plexiform layer contains the contacts between bipolar cells and ganglion cells. Each of the retinal layers are transparent, and light can easily reach the photoreceptors. Muller cells are glia which extend through virtually the entire thickness of the retina and are thought to have a supporting metabolic role. Other retinal glial cells include astrocytes and microglia.

Retinal neurons do not simply transfer signals to a higher level. Indeed, there is a very complex system of signal processing in both the retina and the brain which involves many regulatory cells. Of note, even within one class of neurons (for instance bipolar cells), there may be different reactions to a given stimulus.

Average Ocular Dimensions in Human

•Weight: 7.5 g [1]

•Volume: 6.5 ml [1]

•Axial length (from cornea to retina): approximately 24 mm (between 21 and 26 mm) [1]

•Transverse and vertical diameters of the eye: approximately 24 mm (between 23 and 26 mm) [1]

•The distance between insertion of ocular muscle to limbus: between 5.5 and

7.7mm [1]

•Cornea [2]:

•Diameter: 11.7 mm horizontal, 10.6 mm vertical

•Radius of curvature: 7.8 mm

•Thickness: 520 in the center, 670 at the periphery

•Depth of anterior chamber: 2.6 mm [2]

•Lens [1]:

•Weight: from 130 to 25 mg

•Anteroposterior diameter: from 3.5 to 5 mm

•Equatorial diameter: 9 mm (after removal of the lens, the capsule can stretch to accommodate objects with larger diameters)

•Radius of curvature: anterior 10 mm; posterior 6 mm

•Sclera [1]:

•Diameter: 22 mm

•Thickness: 800 near limbus; 300 just behind the muscle insertions; 1000 around the optic nerve

•Diameter of optic disc: 1 86 mm × 1 75 mm [3]

•Normal field of vision in each eye: vertical 120 ; horizontal 150

•Diameter of macular area: 5 mm

• Retinal thickness: 150 at center of fovea (thinnest part); 400 at foveal rim [6]; 249 mean retinal thickness; 109 mean nerve fiber layer thickness [7]

Common Methods of Evaluating Retinal Anatomy

and Function

Retinal prosthesis implantation is an experimental procedure. New devices that become available will require extensive biological testing before they can be declared safe to test in humans. The following diagnostics are standard in ophthalmology and can be used with either human or animals implanted with retinal prosthesis:

Fundus Photo

The fundus (or interior of the back of the eye) can be seen using an ophthalmoscope; it is also possible to photograph it with a fundus camera which reverses the optics of the eye (Figure 1.9).

Fluorescein Angiogram

Fluorescent dye (fluorescein) can be used to assess the integrity of the vessels of the retina and choroid. Within a few seconds after systemic intravenous injection of fluorescein, the dye reaches the retinal vessels where they can be seen and photographed with a fundus camera (Figure 1.10). Fluorescein angiogram (FA) is a useful test for the diagnosis of many retinal conditions, especially those which affect the vessels or RPE.