Device for treatment of degenerative retinal disease via electrical stimulation of surface stuctures of the eyeball

ES 2 385 809 T3

DESCRIPTION

Device to treat degenerative diseases of the retina by electrical stimulation of superficial structures of the eyeball

FIELD OF THE INVENTION

The present invention relates to the treatment of degenerative diseases of the retina and, in particular, to devices for their treatment based on external electrical stimulation.

BACKGROUND

Many diseases of the human retina cause loss of vision due to a partial or complete destruction of the vascular layers of the eye, including the choroid and choriocapillaris, which nourish both the external anatomical retina and a part of the internal anatomical retina of the eye.

Many other diseases of the retina cause loss of vision due to a partial or complete degeneration of one or both anatomical retinal layers directly, due to abnormalities inherent in these layers. Components of the retinal layers include Bruch's membrane and retinal pigment epithelium, which consist of the outer anatomic retinal layer, as well as the outer and inner photosensitive segments, and the outer nuclear, outer plexiform, inner nuclear, inner plexiform layers. , of amacrine cells, ganglion cells and nerve fibers, which consist of the internal anatomical retinal layer, also known as the neuroretin. The outer part of the neuroretin consists of the outer and inner photosensitive segments and the outer nuclear layer (photoreceptor cell bodies) and is also known as the outer retina, which must be distinguished from the outer anatomical retinal layer as defined above . Loss of function of the outer retina is generally the result of a dysfunction of the outer anatomical retinal layer, which provides nutrition to the outer retina, and / or directly from defects in the outer resin itself. However, the common end result is dysfunction of the outer retina that contains the light-sensitive cells, the photoreceptors. Some of these diseases of the outer retina include age-related macular degeneration, retinitis pigmentosa, choroidal disease, delayed retinal detachment, diabetic retinopathies, Stargardt's disease, choroideremia, Best's disease, and the rupture of the choroid. However, the inner part of the neuroretin is often quite intact from a functional and anatomical point of view and can be activated by appropriate stimuli.

Although some investigators have reported attempts to restore visual function in humans by transplanting various retinal cells and retinal layers from donors into the subretinal space of recipients, the medical community has not widely recognized any continuous visual improvement in such recipients.

Multiple methods and devices are already known to produce prosthetic artificial vision based on structured electrical stimulation of the neuroretin in contact with, or very close to, the source of electrical stimulation. Typically, these devices employ arrays of photodiode- or micro-photodiode-actuated stimulating electrodes arranged on the epiretinal side (the surface of the retina that faces the vitreous cavity) on the subretinal side (the lower side) of the neuroretin. For example, Chow et al. described various designs for implants to be inserted into the subretinal space, that is, the space created between the internal and external retinal layers, in US patents No. 5,016,633; 5,024,223; 5,397,350; 5,556,423; 5,895,415; 6,230,057; 6,389,317 and 6,427,087. As a general rule, the implants described in these patents are brought into contact with the photosensitive layer of the inner retina in such a way that the electrodes found in the implants can supply stimulation currents, derived from the photovoltaic conversion of the incident light, to the inner retina. In several of these patents, for example US patents No. 5,016,633; 5,024,223 and 6,389,317, techniques and devices for inserting such implants into the subretinal space are further described.

Cellular electrical signals also play an important developmental role, allowing nerve cells to develop and function properly. For example, nerve cells undergo constant remodeling or arborization related to electrical signals during development. An extensive preliminary network is first formed, which is then pruned and refined by mechanisms including cell death, selective growth, loss of neurites (axonal and dendritic extensions), and stabilization and removal of synapses (Neely and Nicholls, 1995). If the transduction of normal electrical activity during arborization has been inhibited or no longer occurs in a neuron, the axons no longer retract branches that have grown to inappropriate positions.

The application of electrical currents to organ systems other than the eye is known to promote and maintain certain cellular functions, including bone growth, spinal cord growth, and preservation of ganglion cells of the cochlear coil (Acheson et al., 1991; Dooley et al., 1978; Evans et al., 2001; Kane, 1988; Koyama et al., 1997; Lagey et al., 1986; Leake et al., 1991; Leake et al., 1999; Politis and Zanakis, 1988a; Politis and Zanakis, 1988b; Politis and Zanakis, 1989; Politis et al., 1988a; Politis et al., 1988b).

ES 2 385 809 T3

In other studies, the application of growth and neurotrophic factors was found to promote and maintain certain retinal cell functions. For example, neurotrophic factor obtained from the brain (BDNF), neurotrophin-4 (NT-4), neurotrophin-5 (NT-5), fibroblast growth factor (FGF) and neurotrophic factor obtained from glial cell line (GDNF) enhance the neuritic extension of retinal ganglion cells and increase their survival in cell culture. GDNF has been shown to preserve rod photoreceptors in the rd / rd mouse, an animal model of retinal degeneration. Nerve growth factor (NGF) injected into the intraocular area of ​​the C3H mouse, also a model of retinal degeneration, results in a significant increase in surviving photosensitive cells compared to controls (Bosco and Linden, 1999; Caleo et al. ., 1999; Carmignoto et al., 1989; Cui et al., 1998; Frasson et al., 1999; Lambíase and Aloe, 1996; Reh et al., 1996). However, no methods or devices are known to improve the general inherent visual function of damaged retinal cells distant from a source of electrical stimulation, through the use of chronic electrical stimulation applied to the neuroretin, either from within the eye or indirectly, to through contact with superficial structures of the eye.

Other examples of known devices for the treatment of degenerative retinal diseases are described in US Patent No. 5,109,846 A and US Patent Application Publication No. 2003/014089 A1. Other similar devices are described in European Patent Application Publication No. EP 1 723 984 and International Patent Application Publication No. WO 2004/067088, both published after the present application.

BRIEF SUMMARY OF THE INVENTION

The present invention provides devices for the preventive or therapeutic treatment of degenerative retinal diseases by applying electrical stimulation. In particular, the present invention concerns the use for such treatment of electrical stimulation applied to surface structures of an eyeball. In general, this is accomplished with a device comprising a source of an electrical stimulation signal coupled to a first electrode, configured for contact with a first internal surface structure of an eyeball, and a second electrode configured for contact with a second surface structure of the eyeball, said second surface structure being external or internal. The superficial structures of the eyeball can be classified either as external superficial structures (for example the conjunctiva and cornea) or as internal surface structures (for example the sclera, episclera, intramuscular septum, Tenon's capsule, muscles or tendons extraocular, etc.). The source of the electrical stimulation signal can be implemented internally in a patient's body, externally to the body, or by a combined internal / external approach. According to various embodiments of the present invention, the electrodes can be arranged in one or more annular formations, including interleaved electrodes. The electrodes are preferably arranged such that a circuit formed by the source, the electrodes, and the intervening biological tissue provides transretinal electrical stimulation to effect treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGURE 1 is a cross-sectional top view of a human eye.

FIGURE 2 is a cross section through a human eye, according to the detail of Figure 1, in which the layers of the external and internal anatomical retina are indicated.

FIGURE 3 is a schematic block diagram of a prior art for indirect electrical stimulation.

FIGURE 4 is a schematic block diagram of another prior art for indirect electrical stimulation.

FIGURE 5 is a schematic block diagram of yet another prior art for indirect electrical stimulation.

FIGURE 6 is a schematic block diagram of a technique for indirect electrical stimulation in accordance with the present invention.

FIGURE 7 is a schematic block diagram of another technique for indirect electrical stimulation in accordance with the present invention.

FIGURE 8 is a partial cross-sectional side view of a human eye and surrounding structures.

FIGURE 9 is an enlarged partial cross-sectional view of an area of ​​the eye illustrated in FIGURE 8.

FIGURE 10 is a side view of a human eye, illustrating the application of a corneal electrode in accordance with one embodiment of the present invention.

FIGURE 11 is a side view of a human eye, illustrating the application of an epiconjunctival electrode in accordance with one embodiment of the present invention.

ES 2 385 809 T3

FIGURE 12 is a side view of a human eye, illustrating the application of a fiber electrode to a conjunctival fornix in accordance with one embodiment of the present invention.

FIGURE 13 is a side view of a human eye, illustrating the application of a plurality of electrode arrays applied to an internal surface structure in accordance with one embodiment of the present invention.

FIGURE 14 is a side view of a human eye, illustrating the application of a series of electrodes to an internal surface structure in accordance with one embodiment of the present invention.

FIGURE 15 is a schematic block diagram of an internal surface structure / internal surface structure technique for indirect electrical stimulation in accordance with the present invention.

FIGURE 16 is a schematic block diagram of an internal surface structure / external surface structure technique for indirect electrical stimulation in accordance with the present invention.

FIGURE 17 is a top view of a human eye, illustrating an example implementation of the embodiment of FIGURE 15.

FIGURE 18 is a top view of a human eye, illustrating a first example implementation of the embodiment of FIGURE 16.

FIGURE 19 is a top view of a human eye, illustrating a second implementation example of the embodiment of FIGURE 16.

DETAILED DESCRIPTION OF CURRENTLY PREFERRED EMBODIMENTS

In the course of trials relating to the safety and efficacy of retinal implants in blind humans as a result of retinitis pigmentosa, something unexpected and surprising was observed: even though the implants were placed in a specific place in the subretinal space (functioning as a prosthesis ), vision improved not only in those specific locations, as expected, but also in distant locations on the retina. Thus, chronic electrical stimulation at specific sites improved retinal cell function throughout the eye. This halo effect can be used to improve vision in individuals suffering from diseases, conditions and trauma that have damaged the outer retinal layer leaving the inner retinal layer at least partially intact. Although electrical prosthetic devices designed to replace damaged or missing retinal cells have been used to treat vision loss caused by degeneration of the outer retina, electrical stimulation aimed at improving large areas of retinal cellular visual function is new. As a non-limiting explanation, the promotion of improved retinal cellular visual function by chronic electrical stimulation can be explained by the stimulation of the production and release of growth factors, more specifically neurotrophic-type growth factors, by stimulated retinas. The synthesis and / or secretion of neurotrophic factors would then improve retinal cell function and survival under conditions in which these activities would be lost.

Accordingly, the present invention provides new devices for electrical stimulation of the retina in order to improve large areas of retinal visual function and to protect the retina against degeneration. As described in more detail below, the devices disclosed herein can be broadly classified as indirect. Direct techniques involve stimulation of a retina in which the stimulus passes through essentially non-intermediate biological structures. Conversely, indirect techniques involve stimulation of a retina in which the stimulus must pass through one or more intermediate biological structures.

Subject / patient

A subject (patient) can be a human or a non-human animal, but preferably a human. Typically, the individual has suffered some type of retinal damage and / or retinal degeneration that results in some degree of visual loss and / or has a condition that will result in retinal damage and / or retinal degeneration. . A normal (healthy) subject does not have any condition that will result in retinal damage and / or retinal degeneration, nor has he suffered any retinal damage and / or retinal degeneration.

Improved visual function

Visual function improvement refers to the improvement of a targeted eye function, selected by the practitioner, and includes improvement of some or all of the following capabilities of the eye, retina, and visual system: perception of luminosity in the presence of light, perception of darkness in the absence of light, perceptions of contrast, color, shape, resolution, movement and size of the visual field.

Primary visual degradation means a loss of visual function due to malfunction, damage, or degeneration of localized structures in the eye. Secondary visual impairment means a loss of visual function due to secondary damage, usually due to the lack of use of parts of the brain associated with vision. The

ES 2 385 809 T3 improvement of visual function means to improve the visual function of primary visual impairment, secondary visual impairment or both.

Eye / eyeball

The eye (or eyeball) has the usual definition in the art. The term eye includes all interior and exterior surfaces, components, contents, and cavities of the eye. The term eye does not include the eyelid or the optic nerve.

The retina of the eye can be divided into sectors, as is commonly accepted in the art. Such sectors are described by the use of the terms temporal, nasal, superior, inferior, by designation of clock time, and by the number of degrees of separation from the macula. For example, the temporal sector of the retina is the temporal retina with respect to a perpendicular plane that passes through the retina from the 12 o'clock position to the 6 o'clock position and through the macula. In another example, the superior sector is the superior retina with respect to a perpendicular plane that passes through the 9 o'clock position to the 3 o'clock position and through the macula. In yet another example, the temporal-superior sector is the intersection of these two sectors, a pie-shaped area traced from the 9 o'clock position of the peripheral retina to the macula and then clockwise. of the clock to the 12 o'clock position. More specific locations on the retina can be indicated by the degrees of separation from the macula and the place as clock time: for example 20 degrees of separation from the macula and the 3 o'clock position (nasal) . The number of degrees of separation from the macula is in degrees of optical axes. These axes all pass through the lens.

The sectors of the visual field correspond in the opposite way to the sectors of the retina, as is commonly understood in the art. For example, the temporal-superior sector of the retina corresponds to the nasal-inferior part of the visual field.

Peripheral

Being peripheral with respect to an object, device or other point of reference includes all the surrounding parts, but not the object, device or point of reference, that is to say that the object, device or point of reference and the peripheral part together constitute the whole .

Light

The term light not only refers to the electromagnetic spectrum that humans can easily perceive visually (approximately 400 nm to 750 nm), but also includes ultraviolet light (<400 nm wavelength), as well as infrared light ( > 750 nm wavelength).

Indications

The invention can be used to improve visual function in subjects where the retina is damaged by disease, degeneration, condition, or trauma and / or to delay or stop the progression of damage from disease, degeneration, condition, or trauma. Common diseases, conditions, degenerations, or trauma that are particularly curable by this treatment include age-related macular degeneration, retinitis pigmentosa, Leber's congenital amaurosis, Stargardt's disease, Best's disease, and retinopathy. diabetes, late retinal detachment and choroidal damage.

Structure of the eye

Referring to the drawings, FIGURE 1 illustrates a section through the eyeball. Neuroretin 150 comprises multiple layers of cells and structures (see FIGURE 2). The photosensitive components of the retina are found within the neuroretina that covers the inner posterior cavity of the eye, ending anteriorly in the ora serrata 167. The ciliary body 168 and the iris 162 are covered by extensions of the retina that lack components. photosensitive. The outermost layers of the eye consist of the sclera 164 and cornea 158. The sclera is traversed by the emerging optic nerve 166. The lens 160 and the vitreous cavity 154 are also indicated. The macula 169 of the retina is generally an oval region 3 mm by 5 mm, in the center of which is the fovea 170.

FIGURE 2 shows the following layers of the eye in the posterior pole from inside to outside: inner limiting membrane 40, nerve fiber layer 42, ganglion cell layer 44, inner plexiform 46, inner nuclear layer 48, outer plexiform 50, Outer nuclear cell layer 52 and outer and inner photosensitive segment layer 54, all of which make up the inner anatomical retinal layer, also known as the neuroretina 56. The retinal pigment epithelium 58 and Bruch's membrane 60 make up the outer retinal layer 62. The choriocapillary 64 and choroid 66 make up the choroidal vasculature 68. The outer layer of the eye is the sclera 70. Light 156 enters the retina as sample.

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Indirect stimulation

Previous applications disclosed embodiments that had the common feature that the electrical stimulus was delivered directly to the neuroretin, ie that there were essentially no intermediate biological structures. In accordance with the present invention, the electrical stimulus can be applied to the neuroretin in an indirect manner, ie through one or more intermediate biological structures.

Various methods for indirect stimulation are already known, as this term is defined here. FIGURES 3-5 are schematic illustrations of such prior art. FIGURE 3 illustrates a technique (described in US Pat. No. 5,147,284, issued to Fedorov et al .; hereinafter Fedorov) in which electrical stimulation is applied to an eye 204 of a patient 202 via a pair of surgically implanted electrodes 210, 212 applied to surfaces of eye 204 and optic nerve 206. A source of electrical stimulation 208 coupled to pair of electrodes 210, 212. In practice, source 208 comprises an induction coil that delivers electrical currents as a result of magnetic fields applied to the temporal region of patient 202. Although Fedorov reports improved vision in patients, the circumstances in which patients received the treatment are not known nor do they appear to have undergone peer review. Furthermore, it will be perfectly apparent to the person skilled in the art that implantation of an electrode in close proximity to the optic nerve 206 requires highly invasive and complicated surgery.

FIGURE 4 illustrates a more recent technique proposed by Chow in US Patent No. 6,427,087. Specifically, the electrode 210 'is brought into contact with tissues of the eye 204, while within the vitreous cavity 205 another electrode 212' is placed that may be in contact with the internal limiting membrane (see also the vitreous cavity 154 shown in FIGURE 1). The transretinal stimulation resulting from this configuration is believed to result in more effective stimulation.

In FIGURE 5 yet another approach is shown, in which the stimulation 210 and return electrodes 212, instead of being in direct contact with the eye 204, are placed on external tissues 214, 216. In US Patent No. 5,522,864 to Wallace et al. and in US Patents Nos. 6,035,236 and 6,275,735 to Jarding et al. Examples of this approach (sometimes referred to as microcurrent stimulation) are given, particularly for the purpose of treating degenerative diseases of the retina, such as macular degeneration and retinitis pigmentosa. As a general rule, the stimulation electrode 210 '' is coupled to external tissue very close to the eye 204, for example the eyelid, and the return electrode 212 is coupled to distal external tissues, such as the occipital lobe or the arm of the eye. patient 202. Although anecdotal evidence of efficacy has been reported sporadically, no controlled peer-reviewed human studies have been performed to our knowledge and furthermore The American Academy of Ophthalmology's Task Force on Complementary Therapies concluded in September 2000 that no compelling evidence has been found to demonstrate the efficacy of microcurrent stimulation treatment for [age-related macular degeneration] compared to standard therapies.

Unlike the prior art described above, the present invention encompasses indirect stimulation techniques based on the application of one or more electrodes to surface structures of the eye rather than to peripheral structures such as the optic nerve or the eyelids. As used herein, the surface structures of the eye can be divided into two classes: internal surface structures and external surface structures, as described in more detail below. In general, the surface structures of the eye can be defined as any of several laminae (beginning internally with the sclera in the case of internal surface structures) that form and surround the eye, depending on the specific region of the eye taken into consideration.

FIGURE 6 shows a schematic illustration of an embodiment of indirect stimulation in accordance with the present invention. In this embodiment, at least one active or stimulating electrode 226 is applied to a surface structure of an eye 220. The active electrode (s) 226 are configured for chronic contact with the surface structure of eye 220. As used herein, the term chronic encompasses not only continuous periods of time, but also repeated and / or periodic intervals of time. For example, the active electrode (s) 226 may be attached or otherwise attached to the surface structure essentially permanently, or may be configured to allow repeated contact with the surface structure over a period of time. time established by a course of treatment and a subsequent repeated of said contact.

At least one return or ground electrode 228 is configured for tissue application 222 of an external surface structure of the eyeball, or to an internal surface structure of the eyeball, which is an external surface of the patient's sclera. Additionally, the return electrode (s) 228 may be configured for chronic or temporary application to tissue 222. For example, the return electrode (s) 228 may comprise one or more implantable electrodes essentially permanently attached to tissue 222 or may comprise one or more temporary skin electrodes secured with an adhesive and electrically connected through the use of a suitable conductive gel. . Placed in this way, and given the relatively low resistance of the vitreous in relation to the surface structures and surrounding tissues of the eye, the active and ground return electrodes establish a transretinal circuit such that the application of an electrical stimulation signal to the electrode active will result in beneficial transretinal currents.

ES 2 385 809 T3

In addition to electrodes 226, 228, the system illustrated in FIGURE 6 also comprises a source of the electrical stimulation signal. The particular configuration of the source depends on whether the source is implemented entirely internally or externally or internally and externally combined, relative to the patient. For example, in the case where only active electrode 226 is configured to be removably in contact with external surface structures of the eye and return electrode 228 is configured for temporary skin contact, the source may comprise one or more terminals. input 224 for applying the electrical stimulation signal to the electrodes. In this case, the electrical stimulation signal is supplied by an extraocular signal source 224 '.

Alternatively, source 224 'may be entirely internal to patient 202', as in the case of an implantable battery and, optionally, signal generating circuitry (not shown). In this case it is assumed that the return electrode (s) 228 is also chronically implanted in the patient 202 ', thus eliminating any need for input terminals 224.

The source may further be implemented as a combination of internal 224 'and external 224 (relative to the patient) components. For example, the inner component of source 224 'may comprise a subcutaneously implanted receiving induction coil and the outer component of source 224 may comprise a transmitting coil, which may be exactly aligned with the receiving induction coil. As is known in the art, such transmitter coil / receiver coil pairs can be used to transmit power and data, which can be used to deliver the electrical stimulation signal.

In practice, the electrical stimulation signal supplied by the source can comprise practically any type of waveform that shows a beneficial effect. For example, the electrical stimulation signal may consist of an anodic or cathodic DC signal or a time-varying waveform, such as a square, sinusoidal, triangular, sawtooth signal, or any other similar waveform. . The electrical stimulation signal preferably comprises a biphasic waveform that is compensated in the sense that a net zero charge is applied to the retina over a period of time. By way of non-exhaustive examples, this can be achieved by using a signal comprising a continuous train of biphasic pulses of equal duration; biphasic pulses of equal duration separated by periods of inactivity; load compensated biphasic pulses of variable duration and amplitude; combinations of the above, etc. The frequencies of the pulses can have any value between 10 KHz and 0.001 Hz or, in an extreme case, even a continuous monophasic waveform, that is 0 Hz. The person skilled in the art will understand that the particular type of stimulation signal used is a matter of design choice and is selected so as to have the maximum beneficial effect.

A schematic illustration of another embodiment of indirect stimulation in accordance with the present invention is shown in FIGURE 7. In this embodiment, the active electrode (s) 226 are applied to a first surface structure of the eye 220 and the return electrode (s) 228 are applied to a second surface structure of the eye 220. In practice, the first and second surface structures they can be the same or different surface structures. In this embodiment, the source 224, 224 ', 224 of the electrical stimulation signal may consist of any of the alternatives described above in connection with FIG. 6. The indirect stimulation embodiment illustrated in FIGURE 7 is expected to provide high retinal stimulation, given the relative proximity of the electrodes to the retina. The various surface structures applicable to the present invention are described below with reference to FIGURES 8 and 9.

Referring now to FIGURE 8, an eye and surrounding structures are shown. The ocular orbit is defined by bony structures 230, 231. Within the orbit, a layer of extraconal fat 233 and intraconal fat 235 surrounds the eyeball. The fat layers 233, 235 are separated from each other by a cone defined by the upper 236, lower 238 and lateral 240 extraocular muscles, as well as by an intermuscular septum 242 connecting the muscles. The optic nerve 166 exits the orbit posteriorly, while the anterior part of the eyeball is made up of a portion of the sclera and the cornea 158. The so-called Tenon's capsule 244 (partially shown) separates the globe eyeball from orbital fat and forms a socket within which the eyeball moves. The upper and lower lids 246, 247 enclose and protect the anterior part of the eyeball. The conjunctiva comprises the bulbar conjunctiva 159 ', which lines the anterior part of the sclera, and the palpebral conjunctiva 159, which lines the inner surface of the upper and lower eyelids 246, 247. The fold between the bulbar conjunctiva 159' and the conjunctiva palpebral 159 gives rise to a conjunctival fornix 250. In the context of the present invention, the external surface structures comprise the surface structures that are accessible through the palpebral fissure defined by the eyelids, i.e. the cornea 158 and the conjunctiva 159. The internal surface structures are defined as the superficial structures posterior to the bulbar conjunctiva 159 'and comprise the various laminae that begin with the sclera and the structures that cover it, the latter depending on the specific region of the eyeball taken into consideration.

FIGURE 9 schematically illustrates the various surface structures present in the region indicated by way of example in FIGURE 8. Dimensions shown are not to scale. The sclera 164 forms the innermost surface structure. Continuing outward from the sclera 164, the episclera 260 is a thin loose layer of connective tissue that forms the outer surface of the sclera 164. Above episclera 260 is intermuscular septum 242 and above intermuscular septum 242 is Tenon's capsule 244. For the purposes of the present invention, each of the layers shown in FIGURE 14 comprises a surface structure.

ES 2 385 809 T3 separate to which an electrode can be applied. The person skilled in the art will understand that other regions of the eyeball may have layers of surface structure other than those shown in FIGURE 9.

FIGURES 10-14 schematically show various implementation examples of the embodiments of FIGURES 6 and 7. For reference, each of FIGURES 10-12 shows the upper 236, lower 238 and lateral 240 extraocular muscles. , the upper and lower lids 246, 247, and the cornea 158. FIGURE 10 illustrates an embodiment in which a contact lens body 265 carries one or more corneal electrodes 266. The average person skilled in the art is already familiar with various materials to manufacture the support body 265 and the corneal electrode (s) 266. The corneal electrode 266 is used as a return electrode (this is also valid for the other embodiments illustrated in FIGURES 11 and FIGS. 12). The corneal electrode (s) 266 may comprise a plurality of separate electrodes arranged, for example, in an annular array attached near the periphery of the support body 265, or may comprise a single annular electrode also attached to the support body 265. Alternatively , the corneal electrode (s) 266 may be disposed closer to the central region of the cornea. It should be noted that, for clarity, neither FIGURES 10-12 show the complementary electrode nor FIGURES 10-14 show the electrical connections between the electrodes and the source of the electrical stimulation signal, with the average technician being able to It is easy to conceive such connections, this being a matter of design choice.

FIGURE 11 illustrates another embodiment in which an annular support body 270 provides support for at least one epiconjunctival electrode 271. Once again, various materials are known to the person skilled in the art for making support body 270 and the support body (s). epiconjunctival electrodes 271. As in the embodiment of FIGURE 10, the epiconjunctival electrode (s) 271 may comprise a plurality of individually selectable electrodes or a single annular electrode, this being a matter of design choice. In the example shown in FIGURE 11, the epiconjunctival electrode (s) 271 is in contact with the bulbar conjunctiva 159 'in close proximity to the cornea 158. However, additionally or alternatively, the epiconjunctival electrode (s) 271 may be positioned more distal to the cornea 158, still in contact with the bulbar conjunctiva 159 '.

FIGURE 12 illustrates yet another embodiment in which an electrode 275 is placed in epiconjunctival contact within conjunctival fornix 250. In practice, electrode 275 may comprise a fibrous or filamentary electrode, such as a DTL electrode. DTL electrodes are particularly advantageous, because they are known to be well tolerated by patients given their relatively thin dimensions. Although a single electrode is shown in the lower conjunctival fornix 250, it is also possible that there is an electrode placed in the upper conjunctival fornix as an alternative or in addition to the lower electrode. In addition, more than one electrode can be placed at the same time in any of the fornices.

All FIGURES 10-12 illustrate embodiments in which second electrodes are placed in contact with external surface structures of the eye. FIGURE 13 schematically illustrates an embodiment in which the electrodes are applied to internal surface structures. In particular, one or more support rings 281-283 are implanted in contact with internal surface structures. It should be noted that, although the third ring 283 is placed in contact with an essentially anterior part of the eye, it is implanted below the bulbar conjunctiva 159 '. However, a hybrid internal / external surface structure technique would be possible if the third ring 283 were positioned above the bulbar conjunctiva 159 ', similarly to that shown in FIGURE 11 (such hybrid arrangements are further described below. detailed with reference to FIGURES 16, 18 and 19). Techniques for introducing such rings into the orbit and fastening them to the eye are already known in the current state of the art, in particular through the use of so-called scleral buckles. For example, each ring can be sutured into position in accordance with such techniques. It should be noted that the first and second rings 281, 282 are preferably positioned below the extraocular muscles 236, 238, 240 according to known techniques.

Each ring comprises at least one electrode 285 and in a preferred embodiment each ring comprises a plurality of electrodes. The average person skilled in the art is already familiar with suitable materials for making the support rings and the electrodes. It is preferable that each electrode can be selected individually. Additionally, each individual electrode can be electrically configured to act as an active electrode or a return electrode. Thus, each ring 281-283 can comprise both active electrodes and return electrodes. In such an embodiment, it may be preferable to intersperse active and return electrodes and furthermore arrange the active and return electrodes so that they are opposite each other. The arrangement of opposing electrodes will result in a transretinal current path essentially perpendicular to the retinal surface. Furthermore, by being individually selectable, each electrode of a pair of electrodes opposed to each other can be periodically switched between active and return operation. And furthermore, the inter-ring electrodes could be activated as stimulation pairs, for example an electrode of a first ring 281 could be operated as an active electrode and an electrode of a second ring 282 could be operated as a return electrode, and vice versa. Although a specific number of support rings 281-283 positioned in essentially vertical orientations is shown in FIGURE 13, it is understood that it is possible to employ a greater or lesser number of such rings and, furthermore, that the orientation of such rings has no why limit yourself to an essentially vertical orientation. Taken to the extreme, support rings 281-283 could be eliminated, each electrode 285 may instead comprise a

ES 2 385 809 T3 separate and independent support element such that it is possible to implant individual electrodes at specific locations on specific internal surface structures.

Yet another embodiment is shown in FIGURE 14 that provides contact with internal surface structures. In this embodiment, one or more support sheaths 290 comprising a plurality of electrodes 292 are positioned and secured in contact with internal surface structures of the eye. The above explained with respect to the individually selectable and mutually opposed electrodes in relation to FIGURE 13 is equally applicable to the arrangement of FIGURE 14. To accommodate the presence of various ocular structures, such as the connections between the various muscles 236, 238, 240 and the sclera, openings 294 may be provided. In the example illustrated in FIGURE 14 a plurality of sheaths 290 are provided in such a way that each sheath 290 covers the surfaces between adjacent muscles, thus forming the openings 294 to be adjacent to the sheaths 290 upon implantation. If a single shell 290 surrounds at least one of the muscles, the anterior portion of the aperture 294 can be fabricated in such a way as to create a unitary body (shown in dotted lines), while the aperture at the rear of the aperture 294 allows the wrap 290 to be bent to place it under the muscle. And furthermore, rather than attempting to maneuver the wraps 290 around the muscles, holes could be provided within the otherwise continuous wraps 290. In this case, it would be necessary to first cut the muscles to allow placement of the wraps and then fix them again in positions corresponding to the holes. Regardless of the particular configuration, the embodiment illustrated in FIGURE 14 allows for the placement of multiple electrodes in contact with internal surface structures of the eye to facilitate indirect stimulation of the retina.

The embodiments of FIGURES 13 and 14 are concrete examples of the scheme shown in FIGURE 15. Similar to the schemes shown in FIGURES 6 and 7, the scheme of FIGURE 15 comprises a source 224, 224 ', 224 coupled to electrodes 226, 228 in contact with an eye 220. However, in this scheme the electrodes are both in contact with internal surface structures 300, 302 of the eye. In a presently preferred embodiment, the electrodes 226, 228, configured for contact with internal surface structures, are preferably configured for chronic implantation, for example composed of materials exhibiting very good bio-durability, biocompatibility, etc.

In FIGURE 16 another scheme is shown (generalizing the hybrid embodiment mentioned above in relation to FIGURE 13). The scheme of FIGURE 16 differs from that of FIGURE 15 in that a second electrode 228 is configured for contact with an external surface structure 304, while the other electrode 226 is configured for contact with an internal surface structure 300. Once again, electrodes 226 configured for contact with internal surface structures are preferably configured for chronic implantation. Instead, the second electrodes 228, configured for contact with external surface structures, can be configured for chronic or acute (ie, removable) contact. In the embodiments illustrated in FIGS. 15 and 16, as well as in all previous embodiments, the electrodes 226, 228 may each consist of a plurality of separately selectable electrodes, each of which may be alternated between electrode functionality. stimulation and return electrode. FIGURES 17-19 show specific embodiments of the schemes in FIGURES 15 and 16. For reference, each of FIGURES 17-19 shows a top view of an eyeball comprising a cornea 158, a conjunctiva 159, a sclera 164 and, in hidden view, a neuroretin 150, a macula 169 and a optic nerve 166.

Referring now to FIGURE 17, an example of embodiment of the scheme of FIGURE 15 is shown. In particular, FIGURE 17 illustrates the placement of a first electrode 310 (in this case a plurality of electrodes) placed in a first internal surface structure and a second electrode 320 arranged in a second internal surface structure. Connections to an electrical source 324 are shown schematically. In this embodiment, the first and second internal surface structures may comprise, for example, separate regions of scleral tissue. As can be seen, the plurality of electrodes 310 that make up the first electrode are supported by a body element 322 in the form of a scleral band or ring, as described above in relation to FIGURE 13. Although shown as an electrode single, second electrode 320 may comprise a plurality of electrodes. In either case, the second electrode 320 may include a body support member (not shown) to facilitate placement and fixation of the second electrode. Application of an electrical stimulation signal through the first and second electrodes will result in transretinal currents that stimulate the retina. To maximize the effects of the transretinal current, the second electrode 320 is preferably configured for an internal surface structure corresponding to (ie aligned with) and positioned over the macula 169 of the eye.

Referring now to FIGURES 18 and 19, embodiments not forming part of the invention are shown. FIGURE 18 illustrates the placement of a second electrode 320 (as described above in connection with FIGURE 17) on an internal surface structure of the eye. However, in this embodiment, the first electrode 330 is configured for epiconjunctival placement, that is, in contact with an external surface structure. As can be seen, the first electrode may comprise a supporting body element 332, as described above in connection with FIGURE 11. FIGURE 19 illustrates yet another embodiment of internal / external surface structure, combining the implementation of a annular scleral electrode 310 and the implementation of an epiconjunctival electrode 330.