CN116829109A

CN116829109A - Apparatus and method for novel retinal irradiance distribution modification to improve and restore vision without producing corneal vitrification

Info

Publication number: CN116829109A
Application number: CN202080108398.4A
Authority: CN
Inventors: O·N·塞尔达雷维奇
Original assignee: Aperture Sports Co ltd
Current assignee: Aperture Sports Co ltd
Priority date: 2020-12-11
Filing date: 2020-12-11
Publication date: 2023-09-29
Also published as: JP2024504245A; AU2020480841A1; AU2020480841A9; CA3200780A1; EP4259054A1; WO2022125116A1

Abstract

Methods and apparatus are described herein for improving or restoring vision by causing a restart of the eye's visual system by utilizing visual search, sampling, and stimulation that modify preferred retinal gaze sites away from the eye to enhance neural integration and perception of visual information from within the field of view. Some embodiments cause ambient light to be redirected instantaneously, reversibly, or repeatedly away from the preferred retinal gaze site of the eye to a plurality of retinal locations that are not the preferred retinal gaze site. Some embodiments reduce exposure of ambient light at the preferred retinal gaze site of the eye for a determinable interval at a determinable rate. Some embodiments cause ambient light to defocus at the preferred retinal gaze site in an eye suffering from a vision disorder or loss.

Description

Apparatus and method for novel retinal irradiance distribution modification to improve and restore vision without producing corneal vitrification

Cross reference to related applications

The present application is a partial continuation of U.S. application Ser. No. 17/071,106, 10/month 15 of 2020, U.S. application Ser. No. 17/071,106 being a continuation of U.S. application Ser. No. 16/593,269 (now U.S. patent No. 10,835,417) and claiming priority from U.S. application Ser. No. 16/593,269, U.S. application Ser. No. 16/593,269 being a division of U.S. application Ser. No. 15/693,208 and claiming priority from U.S. application Ser. No. 15/693,208, 31 of 2017. The disclosure of each of these applications is incorporated herein by reference in its entirety.

Technical Field

The disclosed exemplary embodiments relate to a novel retinal Irradiance Distribution Modifying (IDM) device and method for improving, stabilizing, or restoring vision. The disclosed exemplary embodiments also relate to devices and methods for reducing vision loss caused by diseases, injuries and conditions involving damaged and/or dysfunctional and/or sensorineural retinal cells. Applications of the exemplary retinal IDM devices and methods described herein include, but are not limited to, the treatment of macular degeneration, diabetic retinopathy, and glaucoma. The therapies provided by one or more of the exemplary retinal IDM devices and methods described herein may also be used in combination with other therapies, including but not limited to pharmacology, retinal laser, gene, and stem cell therapies.

Background

Conventional devices and methods provide suboptimal solutions for improving vision and/or restoring vision to reduce vision loss caused by diseases, injuries and conditions involving damaged and/or dysfunctional and/or sensorineural retinal cells. Vision loss results from diseases, injuries and conditions including, but not limited to: age-related macular degeneration (AMD), stargardt disease, best (Best) vitelliform macular dystrophy, light-induced retinal damage, cone cytodystrophy, inverse retinitis, myopia macular degeneration, macular scars, diabetic Retinopathy (DR), macular edema, macular holes, macular degeneration, macular puckers, vascular retinal disorders including, but not limited to, retinal vein occlusion and koz (coatings) disease, retinitis pigmentosa, glaucoma or other neural retinal or ganglion cell disorders, and amblyopia (caused by ametropia, medial turbidity or blockage or an eye movement condition, or any combination thereof). AMD, DR and other retinal diseases and conditions are the leading causes of global vision disorders including blindness. There is a great unmet need for solutions that provide meaningful vision and vision-related quality of life improvement for patients suffering from vision loss caused by retinal problems. Conventional devices and methods provide only sub-optimal improvement or compensation of some of the symptoms of vision loss caused by such diseases, injuries and conditions.

Conventional devices and methods for improving or compensating for symptoms of vision loss, such as telescopic (handheld, in electronics, in eyeglasses, in contact lenses, in intraocular lenses, or in the cornea) or annular multifocal corneal laser treatments, only magnify images within a small field of view. Devices and methods for improving or compensating for symptoms of vision loss using prismatic or prismatic effects (in eyeglasses, in contact lenses, or in intraocular lenses) angle deviate only the image from objects within the field of view onto a small area of the retina. Hand-held and electronic telescopes require the patient to remain stationary, and these telescopes magnify a small area of the patient's field of view. Telescope in eyeglasses, contact lenses and intraocular devices requires vision training for periods of weeks to months, creates tunnel vision, prevents binocular vision, and results in poor dynamic vision. Telescope or prism in intraocular devices involves the risk of serious intraoperative and postoperative complications and adverse events in the surgery. The eye movement training of eccentric gaze requires training over a period of weeks to months, with reduced effectiveness over time and abnormal head positioning, with little or no improvement in reading speed, and with little or no improvement in visual acuity. The prisms in eyeglasses, contact lenses, or intraocular lenses are poorly tolerated and can cause multiple vision. All optical devices on the lens or contact lens cannot maintain a constant immediate vision correction as the eye moves, preventing the overall effect of neural adaptation. Retinal prostheses (e.g., glasses-mounted cameras that wirelessly transmit to microelectrode arrays implanted in or on the retina of a patient) do not provide high resolution vision and provide only blurred motion detection and shape recognition. Intraocular implants with telescope, prism or microelectrode arrays involve surgery with the risk of serious intraoperative and postoperative complications and adverse events, including death, vision loss and complete blindness.

Conventional vision aids provide improvement or compensation for symptoms of vision loss, but do not provide restorative benefits, including (but not limited to) repair of damaged retinal cells or improvement of retinal cell function.

Conventional pharmacotherapies, including but not limited to anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular AMD, diabetic macular edema, and other neovascular retinal disorders, and prostaglandin analogs for glaucoma, prevent further progression of vision loss, but do not provide significant vision recovery for most patients. Conventional device therapies including, but not limited to, retinal laser photocoagulation, photodynamic laser therapy, radiation therapy, photobiometry, subthreshold micropulse laser therapy, glaucoma laser therapy, and glaucoma surgery with or without shunt implantation do not significantly improve vision. Patients with dry AMD, characterized by retinal dysfunction with drusen formation and eventually retinal atrophy, have no effective treatment options other than changing lifestyle, using glasses to block uv or blue light throughout the field of view, and using vitamins and other supplements.

Disclosure of Invention

In some examples, the IDM devices and methods may permanently, temporarily optically modify, or temporally variably modify the spatial, temporal, spatiotemporal, color, achromatic, and contrast information distribution of ambient light from the ocular field of view in at least three retinal regions including the retinal gaze region by simultaneously redirecting light from the retinal gaze region to at least two other spatially separated retinal regions (hereinafter: "IDM devices and methods"). The devices and methods described herein produce novel retinal Irradiance Distribution Modifications (IDMs) to improve vision. One or more of the exemplary IDM devices and methods described herein also provide vision improvement, vision stabilization, and/or vision recovery benefits to patients having or suffering from vision loss caused by diseases, injuries, and conditions including, but not limited to, eye damage and/or dysfunction and/or sensory deficit retinal cells. One or more of the exemplary IDM devices and methods described herein also include, but are not limited to, retinal IDM devices and methods for vision improvement and/or vision restoration to overcome vision loss caused by diseases, injuries and conditions including, but not limited to, age-related macular degeneration (AMD), stargardt disease, best (Best) vitelliform macular dystrophy, light-induced retinal damage, cone cell dystrophy, retinitis retroactive, myopia macular degeneration, macular scarring, diabetic Retinopathy (DR), macular edema, macular holes, macular detachment, macular puckers, vascular retinal disorders including, but not limited to, retinal vein occlusion and kots disease, retinitis pigmentosa, nutritional retinal disorders, glaucoma or other neural retinal or ganglion cell disorders, and amblyopia (caused by ametropia, medial or blocking or eye conditions, or any combination thereof. The IDM devices and methods described herein also provide better vision and/or quality of life results, fewer and less severe complications or adverse effects, and greater patient convenience and comfort to patients treated with retinal IDMs without the need for eye movement or consciousness training, as compared to conventional devices and methods.

Exemplary embodiments of retinal IDM devices described herein include (but are not limited to): retinal IDM lasers and other light sources to produce photoablation, photodisruption, photoionization, photochemistry, and/or photothermal keratoplasty, but not corneal vitrification; retinal IDM corneal crosslinking device; retinal IDM radio frequency transmitting means; retinal IDM contact lenses; retinal IDM glasses; retinal IDM corneal inlay; and retinal IDM intraocular lenses, all of which are configured to produce retinal IDMs for vision improvement, with or without vision recovery benefits, including, but not limited to, retinal cell repair and/or retinal regeneration.

In some examples, retinal IDM devices and methods are combined with non-retinal IDM therapies, including, but not limited to, pharmacological agents, including, but not limited to, vascular endothelial growth factor antagonists, retinal lasers, ionizing radiation, photobiomodulation, stem cells, genetic, epigenetic, and optogenetic therapies.

While the description herein shows, describes, and indicates novel features as applied to the various embodiments, it should be understood that various omissions, substitutions, and changes in the form and details of the device or method illustrated may be made without departing from the spirit of the disclosure. As will be recognized, some of the exemplary embodiments described herein may be embodied within a form that does not provide all of the features and benefits set forth herein, as some features may be used or practiced separately from others. All changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Drawings

Fig. 1 is a cross-sectional view of an eye showing the primary ocular structure.

Fig. 2 is a diagram of an eye near the macula showing retinal structure and size.

Fig. 3 is a schematic diagram of retinal microstructure and vision transduction.

Fig. 4 is a simplified visual pathway schematic.

Fig. 5 is a schematic diagram of the retina showing the fovea (right circle), optic disc (left circle), and retinal blood vessels (wavy lines extending to the optic disc).

Fig. 6 is a graph of visual acuity versus retinal eccentricity using the foveal center as a zero eccentricity reference.

Fig. 7 is a schematic view of an eye with two rays incident on the paracentral cornea at points 1 and 2.

Fig. 8 is a schematic diagram of a retina showing fovea a with a central dysfunctional retinal area B.

Fig. 9 is a schematic diagram of the retina showing the four-quadrant retinal irradiance distribution from the central region to quadrants I-IV.

Fig. 10 is a schematic diagram showing a retina with non-central dysfunctional retinal areas B, C and D and fovea a of candidate functional retinal area E, where retinal IDM can increase retinal irradiance into candidate functional retinal area E by directing irradiance away from B, C and D.

Fig. 11A is a corneal map showing the local radius of curvature after IDM treatment. Fig. 11B shows an enlarged central region of fig. 11A.

Fig. 12 shows a schematic anterior surface radius of curvature (ROC) profile of the retinal IDM.

Fig. 13 shows a cross section through a schematic retinal irradiance distribution.

Fig. 14 shows a cross section of the cornea after undergoing femtosecond laser treatment to produce a change in the radius of curvature (ROC) of the anterior surface of the cornea of the retinal IDM.

Fig. 15 is an IDM intraocular lens map with modifications in the paracentral region.

Fig. 16 is an IDM intraocular lens diagram with two prism sectors.

Fig. 17 is a schematic cross-section of an IDM contact lens having a paracentral abrupt region.

Fig. 18 is a schematic cross-section of an IDM corneal inlay implanted within the cornea.

Fig. 19 is a diagram of an exemplary device for improving or restoring vision in accordance with some exemplary embodiments.

FIG. 20 is a diagram of an exemplary device for improving or restoring vision in accordance with some exemplary embodiments.

Fig. 21 is a cross section of a cornea showing an acellular layer and a collagen layer.

FIG. 22 is an anisotropy map of the cornea, where 0 corresponds to isotropy and a value > 2 corresponds to high anisotropy.

FIG. 21 is a diagram of an exemplary device for improving or restoring vision in accordance with some exemplary embodiments.

Detailed Description

Exemplary retinal Irradiance Distribution Modification (IDM) devices and methods described herein include retinal IDM devices and methods that permanently, temporarily, optically modify, or variably modify over time, spatial, temporal, color, achromatic, and contrast information distribution of ambient light from an ocular field of view in at least three retinal regions including a retinal viewing zone by simultaneously redirecting light from the retinal viewing zone to at least two other spatially separated retinal regions. Retinal IDM devices and methods find application in vision improvement or stabilization and/or vision restoration and/or improvement and/or compensation of visual symptoms caused by ophthalmic conditions, diseases, injuries and disorders, including, but not limited to, in eyes with vision loss due to diseases, injuries and disorders involving damaged and/or dysfunctional and/or sensorineural retinal cells. IDM devices and methods reduce vision loss caused by diseases, injuries and conditions including, but not limited to: age-related macular degeneration (AMD), stargardt disease, best (Best) vitelliform macular dystrophy, light-induced retinal damage, cone dystrophy, inverse retinitis, myopia macular degeneration, macular scars, diabetic Retinopathy (DR), macular edema, macular holes, macular degeneration, macular puckers, vascular retinal disorders including, but not limited to, retinal vein occlusion and koz (coatings) disease, retinitis pigmentosa, trophic retinal disorders, glaucoma or other neural retinal or ganglion cell disorders, and amblyopia (caused by ametropia, medial turbidity or blockage, or an eye movement condition, or any combination thereof).

Vision management involves the interaction of the eyes with the brain through a network of neurons, receptors, and other specialized cells. The first step in this sensory process involves stimulating photoreceptors in the retina, converting the light stimulus into neural signals, processing these neural signals through many kinds of retinal interneurons, and transmitting electrical signals containing spatial, temporal, spatiotemporal, and color visual information from each eye to the brain. The processing by the retinal interneurons involves chemical and electrical messages sent among retinal cell types, including the feed-forward pathway from photoreceptors to bipolar cells and up to ganglion cells and interactions of these cell types with and among horizontal cells and non-long process cells. This information is further processed in the brain. Functional vision is created when the brain integrates retinal information across space, time, and skip views.

Retinal irradiance is the amount of optical power per unit area incident on the retina. Radiation deviceIlluminance in W/m ² Measurements are made in units, where W is the optical power in watts and m is a measure of length. Eyes with retinal disorders may have reduced retinal sensitivity to irradiance of light in the retinal region of varying magnitude. Reduced retinal sensitivity can be demonstrated by diagnostic tests, including but not limited to micro-field assays. There is incorrect and/or fair visual treatment of light within the field of view of the environment in the retinal region where retinal sensitivity is reduced. After retinal IDM treatment by one or more of the exemplary retinal IDM devices and methods described herein, the distribution of visual information in the ambient field of view of the eye is modified by redirecting light rays multiple times and spatially separated onto multiple retinal regions, including regions with better retinal sensitivity. Thus, retinal IDM is distinct from and may or may not include a modification to the total irradiance onto the entire retina. Retinal spectral irradiance is the amount of optical power per unit area per unit wavelength incident on the retina. The detection of light by the retina is different for different wavelengths of light and for photopic, meta-and scotopic illumination conditions. IDM devices and methods are useful in all lighting conditions, including but not limited to diurnal and night vision lighting conditions. Unless otherwise specified in the present disclosure, retinal irradiance is always considered for visible light having a spectral distribution, including but not limited to sunlight or light having a Color Rendering Index (CRI) similar to sunlight (i.e., CRI 80, where the maximum is 100-the spectral distribution perfectly matches sunlight) and for open view lighting conditions, including but not limited to sunlight.

It should be understood that retinal irradiance and retinal irradiance distribution of both the model and the ex vivo eye may be measured by using photometric instruments known to those of skill in the art, including but not limited to, photodiode arrays, charge Coupled Device (CCD) sensors, and Complementary Metal Oxide Semiconductor (CMOS) sensors. Those skilled in the art will also appreciate that retinal irradiance and retinal irradiance distribution may be predicted using ray-tracing calculations for model eyes.

The retinal irradiance distribution along with its spatiotemporal, color, achromatic, and contrast information can be specified on various spatial and temporal scales. Spatial dimensions include (but are not limited to): a) A receptive field of the retinal cell domain, including but not limited to, down to the spatial scale of the individual photoreceptors and including both the center and the periphery of each cell receptive field; b) The whole central recess; c) The entire macula; d) An overall central field of view extending to an eccentricity of about 20 °; and E) the entire field of view. The position on the retina relative to the center of the fovea can be specified in terms of polar coordinates r, θ or r ', θ, where r is the distance in mm, or r' is the distance in terms of retinal eccentricity in degrees, and θ is the angular coordinate.

Time scales include (but are not limited to): a) The real-time timescale, which may be as short as 10 milliseconds, during which irradiance and contrast may be modified according to: i) A change in emissivity of an object in visual space, ii) movement of the eye, including both gaze movement and skip of a spatial region that causes light (from a different object in visual space) to illuminate the retina, or iii) any combination of i and ii; b) An intermediate time scale that extends to a duration of a few minutes during which the retinal adaptation process occurs; c) A long time scale, which ranges from days to years in duration, during which the total irradiance on the spatial region of the retina can affect the health of retinal cells; and D) a second long time scale in the range of days to years of duration during which the neuromodulation process occurs.

Contrast refers to irradiance variation across the spatial and temporal scales described above. Contrast may also refer to irradiance changes on a time scale that match the dynamics of the light response in the retinal cells. Contrast may also refer to irradiance changes on a spatiotemporal scale that match the dynamics of motion sensitive cells in the retina. Contrast may also refer to spectral irradiance changes that match the chromaticity sensitivity of retinal cells.

The retina of the eye is illustrated on the cross-sectional view of the eye shown in fig. 1. The major ocular structures are cornea, iris (defining pupil aperture), lens and retina, which contains fovea, macula, optic disc and blood vessels. The area of the retina near the macula is shown in fig. 2, where the fovea and other retinal areas are identified, as well as their size. A schematic of retinal microstructure and vision transduction is shown in fig. 3, in which light generated by the IDM device and method illuminates the retina, producing an electrical signal from photoreceptor (cone and rod) cells; these electrical signals are pre-treated by specialized retinal (horizontal, bipolar, amacrine and ganglion) cells, producing action potentials (electrical "spikes") that propagate through the optic nerve (and ultimately to the visual cortex) via axons (nerve fibers) emanating from retinal ganglion cells. The choroid contains capillaries that provide nutrition to retinal cells and transport waste from the retina.

Fig. 4 shows a schematic simplified path for cortical processing of visual information. Retinal ganglion cell axons attach to the lateral knee nucleus (LGN) and other subcortical structures, including but not limited to the upper hill, which is not shown. LGN relay cells attach to the primary visual cortex (region V1). The primary visual cortex is in turn connected to a plurality of cortical visual areas, including but not limited to, the ventral and dorsal streams, which process information to provide visual results, including but not limited to spatial vision, motion perception, depth perception, form perception, and color perception. The visual cortex interacts with the thalamus via the circulatory loop to produce an integrated visual perception. The visual cortical areas also interact with subcortical structures including, but not limited to, basal ganglia, thalamus, cerebellum, upper hilles, and brainstem to control eye movements. Subcortical visual treatments include, but are not limited to, eye and head movements, pupil size, and circadian rhythms. It should be understood that vision improvement, including but not limited to neural adaptation, involves complex interactions of neural processing between and among all phases of the visual pathway.

A schematic diagram of the retina is shown in fig. 5. The fovea is shown as a circle on the right side of fig. 5, with 0 ° to 180 ° (temporal-nasal) and 90 ° to 270 ° (superior-inferior) meridians dividing the retinal region into four quadrants: i (superior-temporal), II (superior-nasal), III (inferior-nasal), and IV (inferior-temporal). The foveal polar coordinates r, θ specify a location on the retina referenced to the foveal center "X". The radius of the fovea is approximately 0.75mm (2.5 degree eccentricity); which contains the highest density photoreceptors (cones) of highest visual spatial resolution. The optic disc is shown as a circle on the left side of fig. 3, with retinal blood vessels represented as wavy lines.

Fig. 6 shows the change in visual acuity as a function of retinal eccentricity (both in log mar and Snellen (Snellen)). Fig. 6 is a repainting of fig. 3 according to the cone spacing and visual resolution limits (Cone spacing and the visual resolution limit) of williams DR (Williams DR) and clatta NJ (Coletta NJ) in the united states journal of optics (J Am Opt Soc a (1987)). Measurements were for two subjects (circle and square symbols); an average value of 0.907logMAR (20/162 ston) was also measured at 20℃retinal eccentricity. A quadratic fit of the measurements is shown. Conversion from retinal eccentricity: 1 ° retinal eccentricity = approximately 0.3mm. The fovea extends to a retinal eccentricity of about 2.5 °. Maximum visual acuity of light focused on the foveal center of the full-function retina can be obtained. Both defocus and lack of complete retinal functionality reduce visual acuity. Conventional vision aids, including but not limited to, glasses and contact lenses, can improve focus but not retinal functionality. Although useful vision may be based on using large areas of the retina outside the fovea (i.e., outside approximately 2.5 ° retinal eccentricity) -see fig. 6-if higher spatial resolution visual information from the fovea is preferentially weighted in the visual cortex, these areas outside the fovea may be underutilized.

Exemplary retinal Irradiance Distribution Modification (IDM) devices and methods described herein include retinal IDM devices and methods that permanently, temporarily, optically modify, or variably modify over time, spatial, temporal, color, achromatic, and contrast information distributions of ambient light from an ocular field of view in at least three retinal regions including a fovea or another retinal viewing area by redirecting light from the fovea or another retinal viewing area to at least two other spatially separated retinal regions. The retinal regions are defined by a range of polar coordinates, wherein the spatially separated retinal regions are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping and partially overlapping regions, and wherein the amount and location of retinal IDMs are for a predetermined spatial distribution with or without a predetermined temporal distribution. Retinal irradiance distribution modifications include information including, but not limited to, spatial, temporal, spatiotemporal, color, achromatic, and contrast information, or any combination thereof.

The exemplary retinal IDM devices and methods described herein have application as described herein for both vision improvement and vision recovery of diseased eyes: a-for vision and quality of life improvement, and B-for vision recovery benefits including, but not limited to, retinal cell repair and/or retinal regeneration. It is understood that in some embodiments, vision improvement may be obtained by retinal IDM treatment using the retinal IDM devices and methods described herein without vision restoration benefits, as some areas of the retina may remain partially or fully dysfunctional after retinal IDM treatment, or may even become less functional over time. It will be appreciated that in some other embodiments, vision improvement and beneficial vision restoration effects may be obtained as a result of retinal ID treatment, including increased functionality of some areas of the retina that are partially or fully dysfunctional prior to retinal IDM treatment.

In some exemplary embodiments described herein that aim to improve vision, retinal IDM devices and methods are configured to optically redirect light of one or more partially or fully dysfunctional retinal regions, and redirect the light, in whole or in part, onto two or more retinal regions, including one or more functional retinal regions, wherein the dysfunctional retinal regions include (but are not limited to) at least one of: one region of a dysfunctional foveal photoreceptor, a plurality of regions of a dysfunctional foveal photoreceptor, one dysfunctional Preferred Retinal Locus (PRL), a plurality of dysfunctional PRLs, a plurality of spatially separated dysfunctional retinal regions of photoreceptors, or any combination thereof, wherein the functional retinal regions include (but are not limited to) at least one of: one retinal region of the functional photoreceptor, a plurality of retinal regions of the functional photoreceptor, and a plurality of spatially separated functional retinal regions of the photoreceptor, wherein all of the functional retinal regions of the photoreceptor send functional signaling to the functional ganglion cells.

In some exemplary embodiments described herein, the functional retinal region includes (but is not limited to): a. at least two spatially separated regions in at least two different quadrants (see FIG. 5); at least one spatially separated region in each of the four retinal quadrants (see fig. 5).

The retinal region is defined by a range of polar coordinates, wherein the spatially separated retinal region is a non-overlapping region, a partially overlapping region, or any combination of non-overlapping and partially overlapping regions, wherein the amount and location of retinal IDMs is for a predetermined spatial distribution with or without a predetermined temporal distribution, and wherein the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, color, achromatic, and contrast information, or any combination thereof.

In some exemplary embodiments described herein, the spatially separated retinal regions include multiple regions in each of the four retinal quadrants in order to increase the likelihood of redirecting light onto: a. one or several functional areas in the eye with many areas of dysfunction; b. a plurality of functional areas to be used for different visual tasks; multiple functional areas that can be used if or as retinal disease progresses.

In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM alters the instantaneous pattern of irradiance of light from edges and objects to increase the relative irradiance difference (i.e., increase contrast) on nearby photoreceptors.

In some embodiments of the exemplary retinal IDM devices and methods described herein, pattern of retinal Irradiance Distribution Modification (IDM): (i) Improved neural calculation by integrating additional and/or more accurately encoded retinal information from macula and peripheral retinal cells, including but not limited to photoreceptors, bipolar cells, amanita cells, horizontal cells, muller glia cells, ganglion cells, or any combination of retinal cells, to enable treatment of more complex stimulation patterns; and/or improving the function of the retinal circuit, including connectivity functions involving photoreceptors, ganglion cells, amacrine cells, bipolar cells, horizontal cells, and mueller cells, or any combination thereof, in the visual treatment; and/or (iii) trigger neural adaptation processes including, but not limited to, the use of alternative, potential and/or new visual pathways in the retina and brain, including, but not limited to: a. rerouting visual information encoded by peripheral regions of the retina to neurons at the high layers of the visual cortex, where receptive fields are generally responsible for encoding objects at the center of gaze, thereby permitting beneficial changes in crowding properties, with reduced critical spacing in those peripheral regions; changing the destination of the skip eye movement (herein referred to as "gaze") to a new retinal locus; advantageously changing the amplitude and/or speed of eye movement within the eye gaze; advantageously altering the interaction of the skip-view concomitant discharge circuit with the remainder of the visual cortex; more efficient and spontaneous searching is generated by a search mechanism to achieve more efficient integration of larger amounts of more correct visual information, including but not limited to spontaneous generation of motion learning in eye movement strategies to both collect information from a larger area of the visual scene and to use more functional retinal cells to improve visual information.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDMs reroute central vision information (typically, but not limited to, information at the gaze center) through alternative retinal pathways, thereby restoring transmission of high resolution spatial information from these areas of visual space to the remainder of the brain, including but not limited to, the cerebral cortex, basal ganglia, thalamus, upper colliculus, and other brainstem nuclei, thereby enhancing global vision processing mechanisms, including but not limited to: a. enhancing global pooling of profile information; and/or b.improve shape discrimination; and/or c.improve the motion process; and/or d. improving color processing; improving the behavior of visual guidance; or any combination thereof.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDMs trigger a neuromodulation process in the central brain circuit, including but not limited to the visual cortex and/or visual thalamus and/or upper hill or any combination thereof, including but not limited to structural and synaptic plasticity, including but not limited to:

a. for regions of visual space corresponding to damaged areas of the retina that produce little or no visual perception prior to treatment (i.e., are blind spots), restoring visual perception by inducing neurons in the central brain circuit to develop spatial receptive fields that cover these previous blind spots; and/or

b. By incorporating these new spatial receptive fields into the local spatial map and by reorganizing them into a continuous undistorted map of visual space (i.e., counteracting inaccurate perceptual filling), distortion of the field of view around blind spots in the visual space region is reduced and/or eliminated.

In some embodiments of the exemplary retinal IDM devices and methods described herein, visually perceived retinal IDM improvement occurs by forming new visual pathways from functional areas of the retina that encode high fidelity information about regions of visual space within blind spots prior to treatment. For example, distortion of the field of view perceived by a patient suffering from macular degeneration may be caused by incorrect remapping of the spatial receptive field of neurons in the central brain. In this remapping, the receptive field of neurons covering the dysfunctional area of the retina expands and shifts to encompass the region of visual space corresponding to the functional area of the retina. This causes neurons farther away to remap in a similar manner, and so on. In general, these processes induce global distortions in receptive field mapping, where clinical symptoms of straight-line objects such as letters, telephone lines bars and logos become wavy, also known as vision deformity. After treatment by some embodiments of the exemplary retinal IDM devices and methods described herein, newly formed receptive fields covering the regions of visual space within the blind spot prior to treatment become incorporated into the spatial map within each visual region. This incorporation induces a reorganization process that inverts the distortion caused by macular degeneration and thereby restores a continuous undistorted mapping of the visual space within each visual region. The wavy letters, bars and logos straighten again.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDMs achieve beneficial cortical reorganization, including but not limited to altered crowding properties, with smaller critical intervals in the retinal periphery, where the retinal IDMs direct attention to new eccentric preferred sites or other retinal viewing areas. The altered crowding properties include, but are not limited to, loss of radial tangential anisotropy in crowded areas. Because of cortical plasticity, retinal IDMs permit a reduction in the size of the new PRL or PRLs and/or crowded areas surrounding the retinal viewing area following spontaneous repeated use of the new preferred retinal location ("PRL") and/or PRLs and/or retinal viewing area. Plasticity causes the spatial properties at the PRL/PRLs/retinal viewing areas to become more foveal. Both the magnitude and extent of congestion are reduced to the amount typically found around the fovea. The reduced crowding along the major axis helps reduce the elliptical shape of crowded areas at the PRL/PRLs/retinal viewing areas, which reduces the deleterious effects of crowding, thereby improving visual acuity and visual function.

Unlike conventional devices and methods, some embodiments of the exemplary retinal IDM devices and methods described herein improve vision by waking up the residual functional vision pathway without eye movement or perception training, thereby enabling the patient to discover and use the resulting vision immediately or within days or weeks and to additionally improve within months.

In some embodiments of the exemplary retinal IDM devices and methods described herein, vision improvement is significantly enhanced by having a retinal IDM pattern that stabilizes in time as the eye views natural movements.

Some exemplary embodiments described herein create natural awareness and natural sensorimotor learning of one or more alternative functional visual pathways in a treated subject without the need for perception or eye movement training, without causing tunnel vision, visual-physical-display multiple or binocular vision in the treated subject.

Some exemplary embodiments of the retinal IDM devices and methods described herein stabilize vision and/or reduce the rate of vision loss and/or improve vision after vision loss due to a disease, injury, or condition involving retinal cell damage, retinal cell dysfunction, retinal cell sensory loss, or any combination thereof, as compared to untreated control groups. Vision improvement includes, but is not limited to, visual acuity (including both uncorrected and best eyeglass corrected visual acuity for far, intermediate, and near visual acuity), hypersensitivity, stereo acuity, vernier acuity, contrast sensitivity, depth of focus, color vision, peripheral vision, night vision, facial recognition, light adaptation, dark adaptation, vision-related quality of life, or any combination thereof.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDM achieves sustained and/or transient attention. When spatial concealment attention is directed to a target location, continued attention strictly enhances sensitivity via contrast gain, while brief attention involves a mix of both contrast gain and response gain.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDMs improve visual function, including but not limited to connectivity functions in visual processing of retinal third network cells, including but not limited to ganglion cells, amacrine cells, bipolar cells, muller cells, or any combination thereof.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDMs improve visual field defects of visual field assays and/or micro-visual field assay examinations and/or preferential hypersensitivity visual field assays, and/or recover Electroretinogram (ERG) amplitude and/or visual evoked potentials.

Some embodiments of the exemplary retinal IDM devices and methods described herein enable repositioning of a preferred retinal site or sites to a more functional location or locations on a continuous basis and for different binocular vision tasks.

Unlike conventional devices and methods, some embodiments of the exemplary retinal IDM devices and methods described herein: (i) Achieving unilateral or bilateral treatment of patients suffering from vision loss caused by damage to retinal cells and/or a disorder of reduced retinal cell function and/or loss of retinal cell sensory; and/or (ii) provide rapid vision improvement for months and years through additional sensory and/or ocular neuromodulation without the need for sensory or ocular control training.

Unlike conventional devices and methods having life-threatening or vision threatening complications or adverse events, some embodiments of the exemplary retinal IDM devices and methods described herein provide vision improvement after loss due to retinal disorders without complications or adverse events, including (but not limited to): clinically significant changes in intraocular pressure, central corneal thickness, corneal endothelial cell density; corneal decompensation, loss of corneal epithelial cells, infection, or loss of visual function including, but not limited to, optimally correcting presbyopic visual acuity, optimally correcting near visual acuity, contrast sensitivity, and stereoscopic vision.

In some embodiments of the exemplary retinal IDM devices and methods described herein that are intended for visual recovery effects, including, but not limited to, retinal cell repair and/or retinal regeneration, the retinal IDM devices and methods are configured to:

a. The retinal irradiance from the field of view is reduced by at least 0.1% over spatially separated retinal areas (including partially or fully dysfunctional retinal areas), wherein the reduction continues over a defined long time scale, and the retinal irradiance from the field of view is increased by at least 0.1% over spatially separated (including more functional retinal areas) retinal areas other than those in a., wherein the increase continues over a defined long time scale, wherein it is understood that the retinal irradiance and retinal irradiance distribution of both model and ex vivo eyes can be measured by using photometric instruments known to those of skill in the art, including, but not limited to, photodiode arrays, charge Coupled Device (CCD) sensors, and Complementary Metal Oxide Semiconductor (CMOS) sensors.

After loss due to damage to retinal cells and/or conditions of reduced retinal cell function and/or loss of retinal cell sensation, some embodiments of the exemplary retinal IDM devices and methods described herein improve vision by a comfortable and painless single quick treatment without requiring drug treatment after treatment and without requiring retreatment. By comparison, conventional devices and methods have numerous drawbacks and therapeutic burdens, including (but not limited to) at least one of: inconvenience to the patient, requiring the patient to remain stationary for use, limited to use with only one eye or use with only one eye at a time, limited to treatment of only one eye (or sequential treatment if the method is performed in both eyes), need for long-term and/or painful surgery, need for post-operative medication, need for continuous uncomfortable or difficult insertion, need for stimulating retinal inflammation, and need for multiple/repeated surgery.

Some embodiments of the exemplary retinal IDM devices and methods described herein repair and/or restore retinal cells and/or increase retinal cell function and/or reduce progressive damage to retinal cells, further significantly improve vision and rapidly improve nerve computation and beneficial neural adaptation for long-term duration (i.e., over a period of days to years after treatment).

Some embodiments of the exemplary retinal IDM devices and methods described herein compensate for retinal degeneration caused by photoreceptor or other retinal cell damage, with or without repair of retinal cells and/or triggering visual system repair processes, including but not limited to beneficial modulation of trophic factors and bioremediation processes. Bioremediation processes include, but are not limited to, re-growth of photoreceptor outer segments, reprogramming of mueller cells, regeneration of retinal cells, and reduction of drusen volume in subjects with diseased photoreceptors, retinal pigment epithelial cells, and/or Bruch's membranes.

Some embodiments of the exemplary retinal IDM devices and methods described herein repair and/or restore retinal cells and/or increase retinal cell function with fewer adverse effects and greater patient convenience. One or more of the exemplary retinal IDM devices and methods described herein overcome the shortcomings and drawbacks of the prior art, including conventional devices and methods of repairing retinal cells or improving retinal cell function or reducing progressive retinal cell damage, by targeting different mechanisms with novel retinal IDMs to more comfortably and more conveniently produce better therapeutic results with fewer systemic and ocular adverse reactions. In some exemplary embodiments described herein, retinal IDMs improve vision not only by altering neural calculation and neural adaptation, but also by repairing and/or restoring retinal cells. In some embodiments described herein, retinal IDM also triggers visual system repair processes, including bioremediation processes, including (but not limited to) re-growth of photoreceptor outer segments, reprogramming of muller cells, regeneration of retinal cells, and drusen volume reduction, wherein retinal IDM

a. Reducing retinal irradiance from a field of view of spatially separated retinal regions within at least one of a foveal region, another PRL, a plurality of PRLs, a non-PRL retinal region, a plurality of non-PRL retinal regions, or any combination thereof by at least 0.1%, wherein the reduction persists on a long-time scale as previously defined, wherein the reduced retinal irradiance reduces deleterious processes including (but not limited to) photo-oxidative stress, metabolic stress, or any combination thereof within living retinal cells, wherein reducing such deleterious processes includes (but is not limited to) retaining photoreceptors, slowing the progression of photoreceptor loss, reducing drusen volume, or any combination thereof; a kind of electronic device with high-pressure air-conditioning system

b. Increasing retinal irradiance from a field of view on a retinal area (other than a.) (included on an area with viable retinal cells) by at least 0.1%, wherein the increase persists on a previously defined long-time scale, wherein increasing retinal irradiance increases activation of viable cells of at least one of cell repair, cell regeneration, or a combination thereof within at least one of damaged retinal cells or retinal areas with non-functional cells; a kind of electronic device with high-pressure air-conditioning system

c. The spatial, temporal, spatiotemporal, color, achromatic, and contrast information contained in the irradiance distribution is redirected from one or more dysfunctional areas of the retina to one or more functional areas.

In some exemplary embodiments described herein, retinal IDM improves retinal sensitivity, wherein improved retinal sensitivity includes, but is not limited to, improving sensitivity of live cone photoreceptors, live rod photoreceptors, live ganglion cells, amacrine cells, live bipolar cells, and/or partially or fully regenerated retinal cells. It should be understood that retinal sensitivity can be measured by those skilled in the art using diagnostic instruments, including but not limited to micro-field measurement instruments. In some exemplary embodiments described herein, over a period of months or years, retinal IDMs produce at least one of the following in a treated eye with a retinal disorder, including (but not limited to) macular degeneration: a. retinal sensitivity in the retinal region increases; b. a decrease in retinal sensitivity loss rate compared to untreated control groups; c. a decrease in photoreceptor loss rate compared to untreated control group; d. the photoreceptor loss area is reduced; e. the drusen volume is reduced; f. retinal cell regeneration; or g. any combination thereof.

In some exemplary embodiments described herein, retinal IDMs increase retinal absorption of photons in some retinal areas to improve vision and vision processing of retinal image quality while reducing cumulative light absorption and light damage in other retinal areas, including, but not limited to, foveal areas, other fixation areas, other macular areas, peripheral areas, and any combination of retinal areas that should reduce cumulative light absorption and light damage.

In some exemplary embodiments described herein, retinal IDMs selectively reduce irradiance of light, including but not limited to, on the fovea, on other fixation areas (preferably retinal loci), on other macular areas, on peripheral retinal areas, and on any combination of retinal areas, to selectively reduce oxidative stress and/or phototoxicity of retinal structures, including but not limited to photoreceptors, retinal pigment epithelial cells, bruch's membrane, and choroidal capillaries, and/or to selectively reduce cumulative photodamage by including but not limited to reducing oxidative stress and/or phototoxicity in the fovea, in other fixation areas (preferably retinal loci), in other macular areas, in peripheral retinal areas, or in any combination of retinal areas.

In some exemplary embodiments described herein, retinal IDMs provide beneficial effects, including, but not limited to, selectively preventing photoreceptor loss, selectively reducing the rate of progression of photoreceptor loss, and reducing photoreceptor loss, including, but not limited to, apoptosis and/or necrosis and/or pyrosis and/or autophagy.

In some exemplary embodiments described herein, retinal IDMs selectively reduce photoinduced oxidative stress and reactive oxygen species in retinal areas where irradiance is reduced to produce beneficial effects, including, but not limited to, protecting photoreceptor DNA, promoting DNA repair, reducing pathophysiologic by-inflammation, reducing inflammatory body activation, reducing unwanted autophagy, including, but not limited to, chaperone-mediated autophagy (also known as microalbuming), reducing retinal cell death via apoptosis, reducing activation of pro-inflammatory and pro-angiogenic pathways, reducing other unwanted processes associated with oxidative stress and its resulting hyper-reactive oxygen species.

In some exemplary embodiments described herein, retinal IDM selectively reduces photooxidation of retinoid A2E in the outer photoreceptor segments. In some exemplary embodiments described herein, retinal IDMs selectively reduce A2E formation and/or promote A2E reduction in the photoreceptor outer segment without the occurrence of adverse ocular events such as night blindness, color vision disorders, blurred vision, and photophobia associated with delayed dark adaptation of current research drugs that reduce A2E information.

In some exemplary embodiments described herein, retinal IDMs selectively reduce retinal irradiance and/or cumulative retinal irradiance in a retinal region to reduce oxidative phosphorylation in the retinal region to reduce reactive oxygen species, thereby preventing mitochondrial dysfunction and/or reversing mitochondrial dysfunction. In some exemplary embodiments described herein, retinal IDMs reduce metabolic and/or oxidative stress and/or metabolic instability of retinal structures, including but not limited to retinal cells, including but not limited to photoreceptors, retinal pigment cells, muller glial cells, and ganglion cells, and bruch's membranes in some retinal areas, to produce beneficial effects, including but not limited to reducing damage and/or repairing and/or regenerating damaged retinal structures, including but not limited to retinal cells, including but not limited to photoreceptors, retinal pigment cells, muller glial cells, and ganglion cells, and bruch's membranes in some retinal areas.

In some exemplary embodiments described herein, retinal IDMs selectively reduce retinal irradiance and/or accumulate retinal irradiance in some retinal areas and/or reduce oxidative stress to produce beneficial effects, including, but not limited to, photoreceptor cell protection and/or regeneration with muller glial cells and/or increase muller glial cell differentiation and/or reduce muller glial proliferation and/or prevent deleterious retinal remodeling and/or preserve glutamine synthetase expression in the muller cells and/or enable the retinal microenvironment surrounding the muller cells to support cone function.

In some exemplary embodiments described herein, retinal IDMs selectively reduce retinal irradiance and/or cumulative retinal irradiance in some retinal areas, thereby causing a reduction in drusen volume (i.e., the number and/or size of drusen).

In some exemplary embodiments described herein, retinal IDMs selectively reduce retinal irradiance and/or accumulate retinal irradiance in some retinal regions to produce beneficial effects, including, but not limited to, beneficial modulation of trophic factors and regeneration and/or rescue of retinal structures, including, but not limited to, retinal cells, including, but not limited to, photoreceptors, retinal pigment epithelial cells, muller glial cells, and ganglion cells, and bruch's membrane and external limiting membrane.

Exemplary embodiments described herein include retinal IDM devices and methods based on: light sources, including but not limited to continuous wave and pulsed lasers, including but not limited to lasers for corneal photodisruption, intra-lens photodisruption, corneal photoionization, corneal photodisruption, corneal photoablation, thermokeratoplasty, and photowelding, corneal crosslinking systems, corneal radio frequency emitters, lenses, contact lenses, corneal inlays, intraocular lenses for insertion into crystalline, aphakic, or pseudomorphic eyes, and combinations thereof, configured to generate a pattern of retinal irradiance distribution in many areas of the retina or within the entire retina using the design, materials, and optics of IDM to stabilize vision, improve vision, restore vision, or reduce vision loss rate after vision loss caused by conditions involving damaged and/or dysfunctional retinal cells and/or sensory loss compared to untreated control groups; wherein the retinal IDM device and method are configured to permanently, temporarily optically modify, or temporally variably modify spatial, temporal, spatiotemporal, colored, achromatic, and contrast information distribution of ambient light from an ocular field of view in at least three retinal regions including a fovea or another retinal gaze region by means of redirecting light from the fovea or another retinal gaze region simultaneously to at least two other spatially separated retinal regions, wherein the retinal regions are defined by polar coordinate ranges, wherein the spatially separated retinal regions are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping regions and partially overlapping regions, and wherein the amount and location of retinal IDMs are for a predetermined spatial distribution with or without a predetermined temporal distribution, and wherein the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, colored, achromatic, and contrast information, or any combination thereof. In some embodiments of the retinal IDM devices and methods described herein, the retinal device generates a retinal IDM to simultaneously and optically redirect light from a partially or fully dysfunctional retinal region and to redirect the light, either entirely or partially, onto one or more functional retinal regions, wherein the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, color, achromatic, and contrast information, or any combination thereof. In some exemplary embodiments of the retinal IDM devices and methods described herein, the retinal device generates a retinal IDM, wherein the amount and location of retinal IDMs are for spatially separated retinal regions that are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping and partially overlapping regions; the amount and location of the retinal IDM is for a predetermined spatial distribution with or without a predetermined temporal distribution; wherein the amount and location of retinal IDMs have a pattern and symmetry that is different from the pattern and symmetry caused by self-generated image modification, including (but not limited to): i) Eye movement that causes a single translation of the entire field of view on the retina, ii) lens accommodation that causes a change in focus of the entire field of view on the retina; and iii) pupil dilation/constriction that causes the entire field of view to quickly lighten/darken on the retina, as this prevents the central brain from being able to compensate and thus partially eliminate the effects of retinal IDM; wherein the retinal IDM inhibits at least one visual pathway for gaze and stimulates at least one alternative functional visual pathway for gaze in the eye without the need for eye movement and/or perception training; wherein the retinal IDM creates awareness of at least one or more alternative functional visual pathways in the treated subject without the need for eye movement and/or perception training; wherein retinal IDM may also have beneficial effects, including, but not limited to, reducing damage and/or repairing and/or regenerating damaged retinal structures, including, but not limited to, retinal cells (including, but not limited to, photoreceptors, retinal pigment cells, muller glia cells, and ganglion cells) and bruch's membrane in some retinal areas; and wherein retinal IDM improves vision following vision loss caused by one or more of a disease, injury, or condition involving one or more of retinal cell injury, retinal cell dysfunction, retinal cell sensory loss, or any combination thereof, wherein the improved vision is configured to result in an improvement in vision-related results, including, but not limited to, visual acuity (including both uncorrected and best spectacle corrected visual acuity for far, intermediate, and near visual acuity), hypersensitivity, depth of focus, color vision, peripheral vision, contrast sensitivity, stereo acuity, vernier acuity, light adaptation, dark adaptation, vision-related quality of life, or any combination thereof.

Some of the exemplary retinal IDM devices and methods described herein alter the cornea of an eye. In some corneal embodiments, a laser retinal IDM device is used to modify the radius of curvature of the cornea (ROC), as schematically shown in fig. 7. In the unmodified cornea, the light rays incident on points 1 and 2 are focused on the fovea, as shown by the solid line in fig. 7. The ROC (not shown in fig. 7) at points 1 and 2 is reduced to change the direction of the light illuminating the locations L1 and L2 outside the fovea. In fig. 7, the modified ROC at point 2 is reduced by a greater amount than the modified ROC at point 1, both of which are reduced relative to the unmodified radius of curvature; in this case, the reduction in radius of curvature at point 2 causes more light to be redirected than at illumination location L1 to illuminate location L2 that is separated from the fovea by a greater distance. Light repositioning at any point on the cornea may be produced by corneal modification, including, but not limited to, modification of the radius of curvature of the cornea, the refractive index of the cornea, the diffraction rate of the cornea, the scattering rate of the cornea, and any combination of corneal modifications thereof. It should be understood that the sample rays shown in fig. 7 represent only the entire set of rays that map from object space to image space on the retina. In some exemplary embodiments described herein, retinal IDM includes light repositioning resulting from corneal modification within two or more corneal zones, including but not limited to a central to lateral central sector extending to 7mm or a larger optical zone, with alternating steeper and flatter sectors over a full 360 ° angular range on the cornea.

Fig. 8 is a schematic diagram of a retina showing fovea a with central dysfunctional area B. In this case, retinal IDM devices, including but not limited to devices that modify the cornea, should be designed to utilize spatiotemporal, contrast, color, and achromatic information to redirect light away from the central dysfunctional region B to functional retinal regions, including but not limited to functional regions outside of foveal region B. Fig. 9 is a retinal schematic diagram illustrating a four-quadrant retinal IDM that can be generated for retinal IDMs from the central dysfunctional retinal region to the four functional retinal regions by using a retinal IDM device.

Fig. 10 shows a functional imbalance and functional retinal area on the retina with various shapes and locations. It should be understood by those of skill in the art that any retinal IDM device should be configured to generate retinal IDMs remote from and onto the area of the retina of the dysfunction (B, C and D in the example of fig. 10); in the case of fig. 10, functional retinal region E is a candidate region in which retinal IDM can be used to improve vision and vision function.

Some embodiments of retinal IDM devices and methods produce the treatment pattern of the radius of curvature of the cornea (ROC) shown in fig. 11A and the enlarged portion of fig. 11A shown in fig. 11B. FIG. 11B shows a 0.1mm delta boundary for a radius of curvature; the actual ROC continuously changes from one delta boundary to another. Fig. 12 shows a continuous ROC profile that approximates a 30 ° to 210 ° meridian ROC profile along the treatment pattern shown in fig. 11A. The ROC may be symmetrical, as shown in fig. 12, or asymmetrical, having a variable shape. The location of the minimum ROC may be centered or eccentric with respect to the pupil center (or another center reference). As an example, if the untreated cornea has a ROC of approximately 7.6mm in the central optical zone (diameter within 3 mm); within the same zone, the treated cornea may have a ROC in the range of 7.2 to 7.8 mm. Some embodiments of IDM treatment also produce significant ROC changes throughout the cornea, extending to the peripheral cornea at the 7mm optical zone. As shown in fig. 11A, the resulting IDM treatment change may be approximately described as four sets of alternating steeper/flatter sectors within a central (3 mm diameter) optical zone surrounded by four sets of flatter zones in the paracentral cornea between about 5 to 7mm optical zones. The change in ROC causes redirection of light from the four aspherically extended "lenslets" that redirect retinal irradiance to functional retinal areas similar to that illustrated in fig. 9, as well as light from other areas of the cornea. The ROC mode shown in fig. 11A and 11B results from a retinal IDM device that causes IDM treatment of four small volumes of corneal stromal tissue positioned below the surface treatment region (e.g., small white circles on fig. 11A). Due to the biomechanical nature of the cornea, highly localized treatments in four small volumes of corneal stromal tissue produce non-localized effects extending from each treated volume to the center of the cornea, with peak effects approximately midway between the treated volume and the center of the cornea. Some embodiments of IDM treatment produce a non-localized ROC change throughout the cornea extending from the center of the cornea to an optical zone of at least 7 mm.

In some exemplary embodiments described herein, the means for retinal IDM produces corneal modifications, including but not limited to, modifications to the radius of corneal curvature, the refractive index of the cornea, and any combination of corneal modifications made throughout the cornea using various modes, including but not limited to four circular non-central volume treatments. In corneal radius of curvature modification, IDM treatment induces various non-central locations and magnitudes of severe depressions and/or ridges in the anterior surface of the cornea, which result in an increase and/or decrease in the anterior corneal radius of curvature throughout the cornea.

In some exemplary embodiments described herein, the retinal IDM produces a change in radius of curvature that changes the irradiance distribution in all four quadrants of the retina, wherein the retinal IDM causes irradiance and/or contrast on the retinal region and/or micro-region to decrease or increase, wherein the rate of change of the bright and dark edges of the viewing object changes the irradiance contrast. In some embodiments, the exemplary pattern of retinal IDMs is centered about the Pupil Center (PC) or Corneal Vertex (CV) or coaxial corneal glint (CSCLR). In some embodiments, the pattern of retinal IDM is eccentric relative to PC, CV, or CSCLR.

In some exemplary embodiments described herein, retinal IDMs do not produce deleterious retinal effects, including but not limited to retinal inflammation and retinal wound healing. In contrast to conventional devices and methods of retinal laser therapy, including but not limited to laser retinal photocoagulation, laser retinal photodynamic therapy, and subthreshold micropulse diode laser therapy, and photobiomodulation therapy, some embodiments of IDM devices and methods do not use laser or Light Emitting Diode (LED) light to illuminate the retina; some IDM embodiments only illuminate the retina with natural ambient light, and thus are not affected by deleterious retinal effects associated with exposure of the retina to lasers and other non-natural non-ambient light. In some embodiments of IDM treatment, only the cornea is illuminated with an "eye-safe" lamp; the "eye-safe" light is fully absorbed by the cornea and other pre-retinal ocular structures, thereby preventing direct illumination of the retina.

In some exemplary embodiments described herein, retinal IDMs continue to compensate for sustained impairment or reduction of retinal cell function caused by the underlying disease process for months and years after treatment. In some embodiments, the sustained change in retinal IDM produced by one or more of the exemplary methods described herein facilitates sustained neural compensation for sustained damage to retinal cells or reduced retinal cell function caused by a potential disease process, e.g., which enables changes in anterior corneal surface depressions and/or elevations over days, weeks, months, or years. Some of the curvature of the anterior cornea gradually changes throughout the cornea over days, weeks, months or years to continue to compensate for the sustained damage or reduced function of retinal cells.

In some exemplary embodiments described herein, the amplitude of the change in corneal ROC from IDM treatment disappears over time. In some exemplary embodiments described herein, the IDM treatment may be modified by changing the mode of treatment and/or the treatment energy density delivered to the cornea so that the IDM change in the cornea ROC is temporary over different time periods. The transient IDM-induced ROC changes are particularly useful for treating amblyopia in children, adolescents and young adults. IDM treatment of both eyes of a subject suffering from amblyopia can prevent vision disorders and single eye loss resulting from conventional amblyopia treatment. IDM treatment of both eyes of a subject suffering from amblyopia may improve binocular vision during normal daily functioning, as compared to conventional monocular methods. Binocular vision is hindered by treatment of the monocular deficit for amblyopia and is not improved during normal daily function when conventional binocular vision training is performed with or without video games. IDM treatment of both eyes of a subject cannot prevent the use of peripheral vision of both eyes. Peripheral vision in subjects with amblyopia is generally normal, may be affected by obstructive therapy, and may contribute to improvement of central vision in the amblyopia after IDM treatment.

In the application of some embodiments of retinal IDM devices, IDM treatment of eyes with age-related macular degeneration (AMD) using a treatment pattern similar to that of fig. 11A produces significant retinal IDM vision improvement in terms of average best spectacle far and near visual acuity (CDVA and CNVA), contrast sensitivity and other visual functions, and vision-related quality of life. The far and near versions of the ETDRS chart may be used to measure far and near visual acuity, respectively. ETDRS measurements are reported in a number of ways: based on the stonelen value, logMAR value, decimal value and/or the number of letters correctly read (starting with 0 letters for the stonelen value 20/1000). Improvement in visual acuity is typically reported in terms of letters obtained and/or rows obtained on ETDRS charts; there are 5 letters per row on the chart.

Those of skill in the art will appreciate that individual customized retinal IDM treatments may be performed by one or more of the exemplary retinal IDM devices and methods described herein. These individually tailored retinal IDM treatments may be based on diagnostic information including, but not limited to, individual optical coherence tomography, micro-vision measurements, high definition vision measurements, and fundus autofluorescence.

In some embodiments described herein, retinal IDM treatment patterns may be configured based on the extent of macular damage and visual field loss to improve vision in glaucoma patients. Glaucoma damage to the macula occurs early in the disease process and is more common in the upper visual field, where local and deep arch defects may occur near fixation. Early glaucoma damage results in a significant reduction in binocular contrast sensitivity scores and depth perception, which can be improved by bilateral retinal IDMs.

Fig. 13 shows unmodified and modified retinal irradiance distributions, in which the effect of the central dysfunctional retinal region (shadow grey) is schematically illustrated. In the unmodified retinal irradiance distribution (upper panel), only a small fraction (4.3%) of the light illuminates functional retinal areas outside of the dysfunctional retinal area. The useful retinal irradiance is increased to 30% by conventional modifications such as 2 x magnification produced by IMT implantation (bottom left panel), outside the dysfunctional retinal area and inside the functional retinal area. The optimization modification described herein (lower right plot) produces a retinal IDM similar to that shown in fig. 7, increasing useful retinal irradiance to 83%, outside and thus inside the functional retinal area of the dysfunction. Conventional modifications by magnification are fundamental to IMT and intraocular-like telescopic devices, and have always limited effectiveness in improving vision in eyes with central vision loss. In addition, IMT devices result in "tunnel vision" due to the limited field of view of the telescope optics. Cornea treatment by some of the exemplary embodiments described herein more effectively improves vision of eyes with central vision loss, and also improves peripheral vision without causing "tunnel vision.

Some exemplary embodiments described herein relate to IDM devices and methods configured to generate corneal modifications, including, but not limited to, corneal radius of curvature, corneal refractive index, corneal diffraction rate, modification of corneal scattering rate, and any combination of corneal modifications, for redirecting light away from the fovea or another retinal see of the retinal IDM to at least two other retinal regions. These embodiments include, but are not limited to, corneal devices and methods for corneal photodisruption, corneal photoionization, corneal dissociation, corneal photoablation, photothermal keratoplasty (LTK), corneal photowelding, corneal Crosslinking (CXL), conductive Keratoplasty (CK), and corneal inlays, all of which are configured for retinal IDM. For optimal retinal IDM, the radius of curvature and/or the change in refractive index should be outside the area of the dysfunctional retina and as much as possible produce retinal IDM within the area of the functional retina. The IDM treatment devices and methods may be configured to produce a corneal radius of curvature (ROC) change for a corneal anterior surface ROC change of the retinal IDM, including, but not limited to, the corneal ROC changes shown in fig. 11 and 12. IDM treatments and devices may be configured to produce a lensed radius of curvature or refractive index modification to the natural lens of the retinal IDM using devices including, but not limited to, femtosecond lasers for photodisruption. It should be appreciated that the modification of the cornea may be performed initially (first modification) and at a later time (subsequent modification).

In some exemplary embodiments described herein, a Femtosecond (FS) laser or nanosecond lessor may be used to generate intrastromal photodisruption or photoionization or photodissociation of retinal IDMs, or any combination thereof, by means of corneal modification. Fig. 14 illustrates a schematic cross-section through a cornea receiving a Femtosecond (FS) laser treatment (Tx) mode configured to generate a retinal IDM. In the example shown, intrastromal FS laser irradiation is configured to ablate intrastromal corneal volumes that result in depressions (exaggerated in depth in fig. 14) and thus in a change in anterior corneal surface radius of curvature (ROC); as an alternative, FS laser irradiation may be configured to produce other corneal modifications, including, but not limited to, intrastromal refractive index modifications, intrastromal diffraction modifications, and intrastromal scattering modifications of the retinal IDM; any combination of cornea modification changes may be used for retinal IDM. The FS laser mode for corneal tissue ablation or refractive index change may be spherical, as shown in fig. 14, or may have any volumetric shape. The FS treated volume may be positioned at any depth within the corneal stroma. The volumes of two or more FS treatments may be generated centrally (within the 3mm optical zone), paracentrally (within the 3 to 6mm optical zone), or peripherally (at >6mm optical zone), with the treatment pattern centered or decentered with respect to the pupil center or another central reference. The volumes of treatment may be equal or unequal in shape and/or depth to produce a customized effect. Unlike FS annular intrastromal treatments previously used for other applications (e.g., presbyopia correction), FS laser modification is not a 360 degree annular volume and therefore does not induce corneal dilation.

In some exemplary embodiments described herein, laser tissue ablation procedures including, but not limited to, laser photodisruption, photoionization or photodisruption, and/or laser photoablation devices and methods, including, but not limited to, small incision microlens extraction (SMILE), laser in situ keratomileusis (LASIK), and photorefractive keratectomy (PRK) devices and methods, can be used to produce corneal modifications useful for retinal IDM. Fig. 12 shows a cross-section through a cornea having an anterior surface ROC profile configured to be usable with retinal IDM. Laser tissue ablation procedures, including but not limited to femtosecond laser treatments to form a corneal lens for SMILE treatment, and laser photoablation of a stromal bed for LASIK treatment and PRK treatment, should be configured to produce a corneal modification sufficient to provide retinal IDM

In some exemplary examples described herein, corneal crosslinking devices, including but not limited to ultraviolet a (UVA) light emitting devices, LTK devices, and other devices that can be combined with photosensitizers, including but not limited to riboflavin, or other photoactivating systems with photoactivators, including but not limited to glyceraldehyde, glutaraldehyde, genipin (genipin), nitroalcohol, or formaldehyde releasing agents, for corneal Crosslinking (CXL) surgery are configured to create crosslinked focal regions (FCXL). In some embodiments of FCXL IDM surgery, in two or more spatially separated treatment areas of the cornea, the areas of the cornea not to be treated are shielded from UVA light or other light or photoactivating agents for application of retinal IDM. FCXL can be performed with complete or partial removal of the corneal epithelium to enhance penetration of the photosensitizer into the corneal stroma, including, but not limited to, application of a photosensitizer (including, but not limited to, riboflavin) to the cornea followed by UVA or other light irradiation. FXCL can also be produced by CXL using combination laser thermokeratoplasty plus the use of photosensitizers, including but not limited to those produced by high irradiance (10W/cm) ² Or higher irradiance) of riboflavin activated by visible or UVA light sources including, but not limited to, gaN diode lasers and Diode Pumped Solid State (DPSS) lasers operating in the 360 to 460nm wavelength region. The FXCL IDM devices and methods are configured to produce corneal modifications, including but not limited to corneal radius of curvature modifications using various modes of treatment shown in fig. 11 and 12, including but not limited to two or more non-central treatments to induce various positions and magnitudes of corneal modifications to redirect light away from the fovea to the other two retinal areas. Within each treatment mode, FCXL is configured to produce a diameter of at least 0.1mm and is positioned either side-centered (within the 3-6 mm optical zone) or peripheral (at>At the 6mm optical zone) Wherein the treatment pattern is centered or decentered with respect to the pupil center or another center reference.

In some exemplary embodiments described herein, conventional corneal shape changing procedures and devices, including but not limited to Conductive Keratoplasty (CK) and devices, including but not limited to radio frequency transmission devices, are configured to produce corneal modifications in two or more spatially separated treatment areas of the cornea for retinal IDM. CK-generated corneal modifications include, but are not limited to, corneal radius of curvature modifications shown in fig. 11 and 12 using various treatment modes, including, but not limited to, two or more non-central treatments to induce various locations and magnitudes of ROC modifications. Within each treatment mode, CK is configured to produce a treatment volume that is at least 0.1mm in diameter and is positioned paracentrally (within a 3-6 mm optical zone) or peripherally (at >6mm optical zone), with the treatment mode being centered or decentered with respect to the pupil center or another center reference.

In some exemplary embodiments described herein, the retinal IDM is produced by inserting an intraocular lens (IOL) and/or intraocular lens attachment device (IOLAD) configured to modify the retinal IDM. IOLAD includes, but is not limited to, light redirecting structures including, but not limited to, refractive structures, diffractive structures, or any combination thereof that work in conjunction with an IOL to modify retinal IDM. IOLs and iolds of phakic, aphakic or pseudophakic eyes include, but are not limited to, IOLs and iolds positioned in the sulcus or capsular bag, anterior chamber IOLs and iolds, iris fixated IOLs and iolds, and transscleral sutured IOLs and iolds. Fig. 15 illustrates an IOL modification suitable for use in retinal IDM, including four lateral central regions with IOL modifications, including, but not limited to, IOL radius of curvature, IOL refractive index, IOL diffraction rate, modifications of IOL scattering rate, and any combination of IOL modifications thereof, as compared to other regions of the IOL. In the case of IOL diffractive modifications, the exemplary modifications described herein are different from annular (annular pattern centered about the center of the IOL) modifications used in diffractive multifocal IOLs; for example, FIG. 15 illustrates four separate lateral central zones, one or more of which incorporate modifications to IOL diffraction. Additional IOL modifications include, but are not limited to, including light redirecting structures (including, but not limited to, any combination of one or more reflectors, one or more optical fibers, one or more prisms, or light redirecting structures) within at least one paracentral region of the IOL. It will be appreciated that two, three or more central, paracentral or peripheral regions that are spatially separated, with or without overlapping regions, may be used to create IOL modifications in any or all regions for redirecting light away from the fovea or another retinal viewing area to two or more retinal regions. It should also be appreciated that IOL and IOLAD modifications may be configured in the IOL and IOLAD before and/or after insertion of the IOL and IOLAD; after insertion, the FS laser, another light source, and/or electronics can be used to create in situ modifications to the IOL and IOLAD to create adjustments to the radius of curvature of the IOL and IOLAD, the refractive index of the IOL and IOLAD, the light redirecting structures of the IOL and IOLAD, the diffraction of the IOL and IOLAD, the scattering of the IOL and IOLAD, and any combination thereof.

Fig. 16 illustrates an IOL modification suitable for retinal IDM that includes two or more prisms that directly impinge on the functional area of the retina. In addition, the IOL may be configured to include a combination of at least two central, paracentral, or peripheral regions that are spatially separated (with or without regions overlapping) to modify the radius of curvature and/or refractive index in any or all regions, and two or more prisms may be used for retinal IDM. The change in radius of curvature, refractive index, prismatic effect, or any combination thereof should produce as much retinal IDM as possible outside and within the functional retinal region for an eye having a functional retinal region.

Some exemplary embodiments described herein relate to retinal IDMs produced by eyeglasses, contact lenses, or any combination thereof, wherein modifications include, but are not limited to, radius of curvature, refractive index, diffraction rate, modification of scattering rate, and any combination of modifications thereof, for redirecting light away from the fovea or another retinal see to at least two other retinal regions configured to produce a retinal IDM. Figure 17 shows a cross section of a modified contact lens (CL; dimensions: diameter 8mm, thickness 0.2mm, radius of curvature of anterior-posterior 7.8 mm) including a lateral central abrupt region designed to redirect retinal irradiance from a dysfunctional retinal region to a functional retinal region. CL dimensions may be different from those shown, including smaller or larger diameters, thicknesses, and radii of curvature. Spectacle lenses can also be designed for retinal IDM. The Spectacle Lenses (SL) and CL may be made of a single or multiple materials. The CL may be cornea, sclera, or a combination thereof. The modified SL and CL regions may have different or the same radius of curvature, different or the same refractive index, different or the same diffraction, different or the same scattering, or any combination thereof. Additional eyeglass modifications include, but are not limited to, including light turning structures, including, but not limited to, at least one reflector and at least one fiber array within one or both eyeglass lenses. Within the CL diameter and/or SL shape, there may be 1, 2, or more than 2 modified regions located centrally, paracentric, or peripherally. SL and CL may be used for one eye, both eyes, or in any combination of SL and CL. All SL and CL characteristics, dimensions and modifications are designed to direct light into the optimal retinal irradiance distribution required for the patient's retinal IDM. SL and CL may be statically or actively configured, wherein the static configuration is accomplished prior to incorporation into the ocular system, and wherein the active configuration is accomplished one or more times after incorporation into the optical system by means of adjustments, including, but not limited to, electronic and/or photonic adjustments to any combination of corneal radius of curvature changes, refractive index changes, diffraction changes, scattering changes, and changes thereof.

Some additional exemplary embodiments described herein relate to the use of "test" ophthalmic lenses (SL), "test" Contact Lenses (CL), or any combination thereof, for screening and/or customization. In screening applications, a "test" lens may help determine whether a patient's eye is capable of achieving vision and visual function improvement through retinal IDM devices and methods. In custom applications, the characteristics of the "test" lenses may be varied to determine the optimal retinal IDM configuration. In both screening and custom applications, the patient may wish to use "test" lenses for extended periods of days or weeks to obtain neuromodulation benefits.

Some exemplary embodiments described herein relate to retinal IDMs produced by Corneal Inlays (CIs). FIG. 18 shows a Corneal Inlay (CI) implanted into the cornea; the length of the illustrated corneal section is about 1.8mm with a central thickness of 0.55mm, but the length of the corneal section may extend to about 11mm. Two lenses are shown on the insert; these lenses may have the same or different modifications, including, but not limited to, modifications of radius of curvature, refractive index, diffraction rate, scattering rate, and any combination of modifications thereof. The CI shape may be circular or non-circular. CI dimensions include, but are not limited to, a length of 1 to 8mm, a width of 1 to 8mm, a diameter of 3 to 8mm, and a uniform or variable thickness in the range of 0.01 to 0.5 mm. There may be one, two or more inserts, each of which may have 0, 1, 2 or more lenses. The insert may be centrally located as shown in fig. 18, or may be eccentrically located. The insert may be implanted at a depth from the anterior corneal surface, including but not limited to a depth of 0.05 to 0.5 mm. The lens on each of the corner film inserts may be positioned at any location on each insert. The CI is composed of materials including hydrogels, biocompatible materials, and other materials known to those skilled in the art. The corneal inlay may be statically or actively configured, wherein the static configuration is accomplished prior to intracorneal implantation, and wherein the active configuration is accomplished one or more times after intracorneal implantation by means of adjustment, including but not limited to electronic and/or photonic adjustment of any combination of corneal curvature changes, refractive index changes, diffraction changes, scattering changes, and changes thereof.

In some exemplary embodiments described herein, retinal IDM devices and methods combine retinal IDM teachings with prior art retinal therapies, including pharmacology and/or retinal laser and/or radiation and/or stem cell transplantation and/or epigenetic and/or genetic and/or other therapies (hereinafter, other therapies) to improve the treatment of macular degeneration and/or diabetic retinopathy and/or glaucoma and/or other neovascular and/or atrophy and/or inflammation and/or genetic and/or nutritional and/or senile retinal diseases (hereinafter, "retinal diseases"). The exemplary retinal IDM devices and methods described herein overcome the shortcomings and drawbacks of the prior art by introducing different mechanisms for vision and/or retinal pathology and/or repair processes associated with retinal diseases. The exemplary retinal IDM devices and methods described herein overcome the shortcomings and drawbacks of prior art therapies by synergistically combining prior art therapies and retinal IDMs with other therapies to improve vision and/or anatomical results, which also improves patient compliance with prior art therapies. The combination therapy may be administered at the same patient visit, or may be administered sequentially at different times. In some embodiments of the combination therapy, retinal IDM treatment is administered at a time prior to the non-retinal IDM therapy or at a time after initiation of the non-retinal IDM therapy. In some embodiments of the combination therapy, more than one retinal IDM treatment is administered at a separate time prior to other therapies or at a variable time after initiation of non-retinal IDM therapy.

In some exemplary embodiments described herein, retinal IDM treatment is combined with other therapies for retinal disease, including but not limited to retinal laser therapy, including but not limited to photo-bioregulation, laser photocoagulation, laser photodynamic therapy, subthreshold micropulse laser therapy, glaucoma laser therapy, including but not limited to laser trabeculoplasty and cyclophotocoagulation, glaucoma filtration surgery, including but not limited to trabeculectomy, endo-or exogenously shunt implantation, suprachoroidal shunt implantation, stem cell transplantation, and radiation therapy, including but not limited to focal intraocular strontium 90 beta radiation.

In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDM treatment is combined with other therapies for retinal diseases, including but not limited to genetic, epigenetic, and optogenetic therapies.

In some exemplary embodiments described herein, retinal IDM treatment is administered in combination with pharmacological treatment of retinal disease, including pharmacological agents, including nutritional supplements, orally, topically to the cornea, via subconjunctival injection, via intravitreal injection, intraretinal, via implants, and via iontophoresis.

In some exemplary embodiments described herein, retinal IDM treatment is combined with anti-angiogenic drug therapy.

In some exemplary embodiments described herein, retinal IDMs provide a method of improving or treating an ocular disorder, including, but not limited to, macular degeneration, choroidal neovascularization, or diabetic retinopathy in a subject, comprising administering by retinal IDMs in combination a therapeutically effective amount of any Vascular Endothelial Growth Factor (VEGF) antagonist, including, but not limited to, ranibizumab, bevacizumab, bucuzumab (broucizumab), and aflibercept, in combination with any PDGF antagonist, including, but not limited to, fu Luoxi mab (volociximab) and P200, or in combination with any combination of the above. As used herein, the term "modifying" or "treating" or "compensating" means that clinical signs and/or symptoms associated with an ocular disorder (e.g., macular degeneration) are reduced as a result of the action performed. The sign or symptom to be monitored will be a characteristic of the ocular disorder, and the sign or symptom and methods for monitoring the sign, symptom and condition will be well known to practitioners in the art.

In some exemplary embodiments described herein, retinal IDMs provide a method of modifying or treating an ocular disorder including, but not limited to, macular degeneration, choroidal neovascularization, or diabetic retinopathy in a subject, comprising administering a therapeutically effective amount of vitamin a with or panopanib (pazopanib) or any other tyrosine kinase inhibitor or any other VEGF and PDGF receptor phosphorylation inhibitor in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating an ocular disorder in a subject comprising administering a therapeutically effective amount of an inhibitor of VEGF activity in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder in a subject, the method comprising administering a therapeutically effective amount of an inhibitor of α5β1 integrin activity in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, neovascular ocular disease and/or wet macular degeneration and/or diabetic retinopathy in a subject, comprising administering a therapeutically effective amount of an inhibitor of PDGF activity in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, neovascular ocular disease and/or wet macular degeneration and/or diabetic retinopathy in a subject, comprising administering a therapeutically effective amount of an inhibitor of tyrosine kinase activity in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease, including, but not limited to, neovascular ocular disease and/or wet macular degeneration and/or diabetic retinopathy in a subject, comprising administering a therapeutically effective amount of an mTOR inhibitor (sirolimus) in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including, but not limited to, neovascular ocular disorder and/or wet macular degeneration and/or diabetic retinopathy in a subject, comprising administering a therapeutically effective amount of fluocinolone acetonide (fluocinolone acetonide) or any other anti-inflammatory agent by retinal IDM in combination, wherein the anti-inflammatory agent is administered by intravitreal injection or by intraocular implant.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of a complement inhibitor (including, but not limited to, an inhibitor of complement 3 or 5 activity) in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDM provides a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of avermectin Xin Kapu taedpolyethylene glycol (avacincaptad pegol), LEG3l6,eculizumab (eculizumab), JPE-1375, ARC1905 or any other complement inhibitor.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of doxycycline (doxycycline) in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of glatiramer acetate (glatiramer acetate) or other T-helper 2 inducer or immunomodulator in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of OT551 or protein complex nuclear factor in combination with retinal IDMsAny other over-expressed downregulator of (c) or any other antioxidant or combination of antioxidants for treatmentOr antioxidant combinations including, but not limited to, vitamin C, vitamin E, beta-carotene or lutein and zeaxanthin and omega-3 fatty acids as in, for example, the senile eye disease study (AREDS) and the AREDS2 study. />

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease, including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of Nicotinamide Adenine Dinucleotide (NAD) or any NAD precursor, including, but not limited to, nicotinamide riboside (nicotinamide riboside) or nicotinamide mononucleotide (nicotinamide mononucleotide), in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease, including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of a trophic factor, including, but not limited to, pigment Epithelium Derived Factor (PEDF), fibroblast Growth Factor (FGF), and Lens Epithelium Derived Growth Factor (LEDGF), in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising administering a therapeutically effective amount of ciliary neurotrophic factor (CNTF) or any other neurotrophic factor or any other photoreceptor apoptosis inhibitor in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease, including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising the combined administration of a therapeutically effective amount of a neuroprotective agent, including, but not limited to, bromo Mo Dining (brimod ine), by retinal IDM.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disease, including, but not limited to, geographic atrophy and/or dry macular degeneration in a subject, comprising the combined administration of a therapeutically effective amount of Fas inhibitor or other agent designed to protect retinal cells from cell death by retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including, but not limited to, geographic atrophy and/or dry macular degeneration and/or neovascular macular degeneration and/or glaucoma in a subject, comprising administering a therapeutically effective amount of a statin, including, but not limited to, atorvastatin, lovastatin, rosuvastatin, fluvastatin or simvastatin, in combination with retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including (but not limited to) glaucoma or ocular hypertension in a subject, comprising administering a therapeutically effective amount of an intraocular pressure (IOP) lowering agent (including (but not limited to) miotics, alpha or alpha/beta adrenergic agonists, beta blockers, ca2+ channel blockers, carbonic anhydrase inhibitors, cholinesterase inhibitors, prostaglandin agonists, prostaglandins, prostamides, cannabinoids, and combinations thereof) in combination with the retinal IDM.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including (but not limited to) glaucoma in a subject, comprising administering a therapeutically effective amount of a pharmacological agent that reduces retinal ganglion cell dysfunction and/or pathology associated with ischemia or excitotoxicity in combination with the retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including, but not limited to, glaucoma in a subject, the method comprising the combined administration of a therapeutically effective amount of a pharmacological agent (including, but not limited to, a glutamate antagonist and/or any combination of a glutamate antagonist and at least one IOL-lowering agent) that reduces hyperexcitability amino acid (EAA) stimulation (EAA permits bipolar and non-long process cells to communicate with ganglion cells) by retinal IDMs.

In some exemplary embodiments described herein, retinal IDMs provide a method of treating or ameliorating an ocular disorder, including, but not limited to, glaucoma in a subject, comprising administering a therapeutically effective amount of a pharmacological agent (including, but not limited to, a rho-kinase (ROCK) inhibitor or an adenosine receptor agonist) that provides neuroprotection and/or nerve regeneration of retinal ganglion cells in combination with the retinal IDMs.

The retinal location of the eye for attempting to fixate on a visual target is referred to as the preferred retinal gaze site (e.g., "PRL"). The PRL of an eye may be determined by gaze, e.g., eye gaze on light. PRL can also be determined by visual field measurement or micro-visual field measurement. For example, the PRL may correspond to the center of gravity of the gaze point cloud on the micro-vision measurement. In some examples, the retinal position of the PRL may be described with respect to the foveal center of the eye or with respect to the estimated center of the fovea, and may be specified in terms of polar coordinates r, θ, or r ', where r is distance in mm, or r' is distance in degrees in terms of retinal eccentricity, and θ is angular coordinate.

The PRL of a normal vision eye is located in the fovea, but not always in the center of the fovea. Furthermore, in normal vision eyes, the PRL is typically located within the foveal region. The fovea covers only a viewing angle of 1, which corresponds to a field of view of less than 0.1%. In some examples, the PRL may be shifted from the position of highest foveal cone density by an average of about 10 degrees in a normal vision eye. Furthermore, in some examples, there may be no correlation with the offset value of the PRL and the corresponding foveal professional measurement, including, but not limited to, pit volume, FAZ area, and peak cone density.

In eyes with central retinal damage or loss, the PRL is located either within the fovea or eccentric to the fovea. The vision system includes eye and brain elements that capture and process visual information, as illustrated in fig. 3 and 4. The spatial and temporal nature of the neural processing within the visual system is a factor affecting the preferred retinal gaze site location. Furthermore, minimum gaze eye movement is known to have a magnitude of between about 0.01 ° and about 0.1 °.

In some examples described herein, methods and devices may cause ambient light to be redirected away from the PRL of the eye to multiple retinal locations that are not PRLs. One or more of these exemplary methods and apparatus may cause safe and efficient redirection of ambient light from within the eye's field of view away from the PRL of the eye and toward multiple retinal locations that are not PRL. In some examples, one or more of these exemplary methods and apparatus may cause redirection that shifts the center of gravity of the eye gaze point cloud by at least 0.01 °, e.g., as measured by a micro-field of view assay. In some examples, one or more of these exemplary methods and apparatus may cause redirection that shifts the center of gravity of the eye gaze point cloud by at least 0.1 °, e.g., as measured by a micro-field of view assay.

Moreover, in some examples, one or more of the exemplary methods and apparatus described herein may cause light to be redirected away from the PRL of the eye to multiple retinal locations that are not PRLs, and may modify visual searches, retinal sampling and stimulation of retinal and brain cells to enhance neural integration and perception of visual information in the field of view, and facilitate sustained neural adaptation, such as to "restart" the visual system including the eye and brain.

One or more of the exemplary methods and apparatus described herein may also restart the vision system to safely and effectively improve and/or restore vision. Vision may include, but is not limited to, discrimination of spatial details, visual acuity (including both uncorrected and/or best eyeglass corrected visual acuity for far, intermediate, and/or near visual acuity), hypersensitivity, stereo acuity, vernier acuity, contrast sensitivity, depth of focus, color vision, peripheral vision, night vision, facial recognition, light adaptation, dark adaptation, vision and/or vision-related quality of life, or any combination thereof.

Moreover, one or more of the exemplary methods and apparatus may restart the vision system. The restarting of the vision system may include, but is not limited to, any one or any combination of the following: (i) Improved neural calculation by integrating additional and/or more accurately encoded retinal information from macula and peripheral retinal cells, including but not limited to photoreceptors, bipolar cells, amanita cells, horizontal cells, muller glia cells, ganglion cells, or any combination of retinal cells, to enable treatment of more complete stimulation patterns; (ii) Improving the function of the retinal circuit, including connective functions involving photoreceptors, ganglion cells, amacrine cells, bipolar cells, horizontal cells, and mueller cells, or any combination thereof, in visual processing; and/or (iii) trigger neural adaptation processes including, but not limited to, the use of alternative, potential and/or new visual pathways in the retina and brain, including, but not limited to: rerouting visual information encoded by peripheral regions of the retina to neurons at the higher layers of the visual cortex, where receptive fields are generally responsible for encoding objects at the center of gaze, thereby permitting beneficial changes in crowding properties with reduced critical spacing in those peripheral regions; changing the destination of gaze eye movement; advantageously changing the magnitude and/or speed of eye movement; beneficially altering the interaction of the skip-view concomitant discharge circuit with the remainder of the visual cortex; and/or more efficient and spontaneous searching through search mechanisms, including but not limited to spontaneous generation of motion learning in eye movement strategies, to both collect information from a larger area of the field of view and use of more retinal cells for visual perception of the field of view, to achieve more efficient integration of larger amounts of more correct visual information. In addition, one or more of the exemplary methods and apparatus described herein that cause light to be redirected away from the PRL of the eye to multiple retinal locations that are not PRLs enhance beneficial steady-state plasticity mechanisms that facilitate cellular signaling and visual function.

In some examples, one or more of the exemplary methods and apparatus described herein may cause a restart of the ocular vision system by reducing exposure of ambient light from within the eye's field of view to the PRL. One or more of the exemplary methods and apparatus described herein may cause a restart of the ocular vision system by reducing exposure of ambient light from within the eye's field of view to the PRL by at least 10%, i.e., by any amount or cumulative amount equal to or greater than 10%. The exposure to ambient light may be reduced at the PRL to force the vision system, including the eye and brain, to discover and use alternative, potential, and/or new vision pathways created by retinal locations other than the PRL.

One or more of the exemplary methods and apparatus described herein may cause a restart of the ocular vision system by weighting exposure from ambient light within the eye's field of view to reduce exposure to the PRL of the eye by at least 10% over a determinable interval. Intervals may be defined in units of milliseconds, seconds, minutes, hours, days, weeks, months, and/or years, and may be determined at any time prior to or after initial use. The determinable interval may be determined by a number of factors including, but not limited to, individual patient response, type of disease or disorder of the eye, progression or regression of disease or disorder of the eye, pre-treatment visual data, and/or post-treatment visual data. One or more of the exemplary methods and apparatus described herein may cause weighting of exposure from ambient light within the eye's field of view to reduce exposure to the PRL of the eye by at least 10% over a determinable interval. In some examples, ambient light within the field of view may be exposed to the retina at a determinable rate of up to 50 kilohertz, which may cause a restart of the processing of ambient light from within the field of view of the eye.

In some examples, the determinable rate may be any rate not greater than 50 kilohertz, which may be determined by a number of factors including, but not limited to, individual patient response, type of disease or disorder of the eye, progression or regression of the eye disease or disorder, pre-treatment vision data, and/or post-treatment vision data. Some of the exemplary methods and apparatus described herein may achieve exposure rates of any rate up to 50 kilohertz to enable modulation of light capture from within the entire field of view by retinal photoreceptors, causing temporal neural integration changes in the eye and brain prior to perception. One or more of the exemplary methods and apparatus described herein may cause temporal-lateral neuro-integration changes within the eye and brain to achieve stable and seamless perception after neural processing while causing at least a 10% reduction in exposure of ambient light from within the field of view to the eye PRL over a determinable interval. Moreover, some of the exemplary methods and apparatus described herein may cause weighting of exposure to ambient light from within the eye's field of view to reduce exposure to the eye PRL by at least 10%, at least 25%, at least 50%, at least 75%, at least 90%, or any amount over a determinable interval to cause a restart of the treatment of ambient light from within the eye's field of view. Some exemplary embodiments cause weighting of exposure from ambient light within the eye's field of view to reduce exposure to the eye's PRL by at least 10% over a determinable interval, thereby causing vision improvement or vision recovery.

Some of the exemplary methods and apparatus described herein may be configured to cause weighting of exposure from ambient light within the eye's field of view to increase exposure to more than one retinal location that is not the preferred retinal central site of the eye by at least 10% over a determinable interval, resulting in vision improvement or vision recovery. One or more of the exemplary methods and apparatus described herein may also cause weighting of exposure from ambient light within the eye's field of view to increase exposure to a plurality of retinal locations other than the PRL by at least 10% over a determinable interval to cause vision improvement or vision recovery. Some of the exemplary methods and apparatus described herein may also achieve exposure rates of any rate up to 50 kilohertz to achieve modulation of light capture from within the entire field of view by retinal photoreceptors to achieve a stable and seamless perception after neural processing while causing exposure of ambient light from within the field of view to the PRL of the eye to multiple retinal locations other than the PRL to increase by at least 10% over a determinable interval than at the PRL.

Furthermore, some of the exemplary methods and apparatus described herein may cause a restart of the ocular vision system by causing ambient light from within the eye's field of view to defocus at the PRL of the eye. Ambient light from within the eye's field of view may be defocused at the PRL to force the vision system, including the eye and brain, to find and use alternative, potential and/or new vision pathways created by retinal locations other than the PRL. Some of the exemplary methods and apparatus described herein may cause a restart of the visual system including the eye and brain by causing focus at numerous and discrete retinal locations that are not PRLs of the eye. Furthermore, one or more of the exemplary methods and apparatus described herein may also cause a restart of the eye vision system by causing ambient light from within the eye's field of view to defocus at the PRL of the eye and/or focus at a plurality of discrete retinal locations that are not the PRL of the eye to cause vision improvement and/or vision restoration in an eye having central and/or peripheral vision impairment and/or loss.

Some of the exemplary methods and apparatus described herein may improve vision of an eye with central vision impairment or loss by defocusing ambient light from within the eye's field of view at the PRL for a determinable distance. Some of the exemplary methods and apparatus described herein may defocus images of objects located within the field of view of the eye at a particular or different distance from the eye at the PRL. Moreover, one or more of the exemplary methods and apparatus described herein may cause ambient light from within the eye field of view to defocus at the PRL without determining optical errors or image quality at the PRL. Some of the exemplary methods and apparatus described herein may focus images of objects positioned within the field of view of the eye at specific or different distances from the eye at numerous and discrete retinal locations that are not PRLs. Some of the exemplary methods and apparatus described herein may cause a restart of the visual system of an eye by causing focus at multiple and discrete retinal locations that are not PRLs of the eye without determining optical errors or image quality at discrete retinal locations that are not PRLs.

Some of the exemplary methods and apparatus described herein may also cause a restart of the ocular vision system by causing focusing at numerous and discrete retinal locations that are not PRLs of the eye. For example, these exemplary methods and apparatus may achieve random or non-random focusing at numerous and discrete retinal locations by modifying the range of optical and/or mechanical parameters.

Some of the exemplary methods and apparatus described herein may cause light to be redirected away from the PRL of the eye to multiple retinal locations that are not PRLs to immediately restart the vision system after light redirection. For such immediate restart, some of the exemplary methods and apparatus described herein may cause a reduction in the instantaneous redirection and/or number of redirection and/or a reduction in redirection size over time of light to improve efficacy and safety. Some of the exemplary methods and apparatus described herein may include deformable components and/or structural deformable changes that cause the eye or insertion within the eye to increase the safety and effectiveness of redirecting light away from the PRL of the eye to multiple retinal locations that are not PRLs. Some of the exemplary methods and apparatus described herein may cause an increase or decrease in the number of redirects and/or an increase or decrease in the redirect size and/or a change in the portion of the retina to which ambient light is redirected to improve restarting the vision system for initial and/or reuse, either continuously or intermittently or repeatedly, within any determinable time interval after light redirection. Some of the exemplary methods and apparatus described herein may cause light to be redirected immediately and/or continuously and/or intermittently and/or repeatedly away from the PRL of the eye to a plurality of discrete retinal locations that are not PRLs to immediately and/or continuously and/or intermittently and/or repeatedly restart the vision system for initial and/or repeated use within any determinable time interval after light redirection. The determinable interval of initial and/or repeated use may be determined by a number of factors including, but not limited to, individual patient response, type of eye disease or disorder, progression or regression of eye disease or disorder, pre-treatment vision data, and/or post-treatment vision data. Some of the exemplary methods described herein may be reversible to improve safety and/or efficacy and/or permit another redirection at determinable intervals and/or facilitate other therapies. Some of the exemplary methods and apparatus described herein may cause a reversible redirection of light and/or a reversible change in ocular tissue and/or a reversible change in at least one component of the apparatus.

Some of the exemplary methods and apparatus described herein may cause light to be redirected away from the PRL of the eye to a plurality of retinal locations disposed within a normal portion of the retina, a damaged portion of the retina, a retinopathy portion, a retinal gene changing portion, a retinal epigenetic changing portion, a neurodegenerative changing portion of the retina, or a portion of the retina including retinal transplants, implanted retinal cells (including but not limited to retinal epithelial cells, photoreceptors, ganglion cells, retinal progenitor cells), implanted stem cells, or implanted prostheses.

Some of the exemplary methods and apparatus described herein may cause weighting of exposure from ambient light within the eye's field of view to reduce exposure to the PRL of the eye by at least 10% over a determinable interval. In some examples, the ambient light within the field of view may be exposed to the retina at a determinable rate of up to 50 kilohertz, and the ambient light within the field of view may be exposed to a genetically altered portion of the retina, an epigenetic altered portion of the retina, a neurodegenerative altered portion of the retina, or a portion of the retina comprising at least one of a retinal transplant, an implanted retinal cell, an implanted stem cell, or an implanted prosthesis.

Some of the exemplary methods and apparatus described herein may improve vision of an eye having central vision impairment and cause ambient light from within the eye's field of view to defocus at the PRL of the eye and ambient light to focus within at least one of a genetically altered portion of the retina, an epigenetic altered portion of the retina, or a neurodegenerative altered portion of the retina. Some of the exemplary methods and apparatus described herein may cause ambient light from within the field of view of the eye to defocus at the PRL of the eye and the ambient light to focus within portions of the retina including at least one of retinal transplantation, implantation of retinal cells, implantation of stem cells, or implantation of prostheses.

Some of the exemplary apparatus described herein may include deformable components, or may be configured to cause deformable modification of one or several eye structures placed within an eye to cause instantaneous or reversible or repeatable redirection of ambient light away from the PRL to multiple retinal locations in an eye with progressive retinal disease or degeneration that are not PRL. Some of the exemplary apparatus described herein may also include deformable components, or may be configured to cause deformable modification of one or several ocular structures placed within an eye to cause weighting of exposure from ambient light within the eye's field of view, reducing exposure to the eye's PRL by at least 10% over determinable intervals in an eye with progressive retinal disease or degeneration. Some of the exemplary apparatus described herein may also include deformable components, or may be configured to cause deformable modification of one or several eye structures placed within the eye to cause ambient light from within the eye's field of view to defocus at the PRL of the eye and/or focus at numerous and discrete retinal locations that are not PRL in an eye with progressive retinal disease or degeneration. Some of these exemplary devices and methods may permit repeated restarting of the visual system after progressive damage to photoreceptors, ganglion cells, or other retinal tissue has occurred. Some of these exemplary apparatus and methods may also permit safe and effective restarting of the vision system to improve vision and/or enhance retinal repair and/or myelination.

Some of the exemplary methods and apparatus described herein may promote safe and effective increase and/or stimulation of the metabolic processes and/or repair mechanisms of living retinal cells by the activity of a plurality of retinal cells. Furthermore, some of the exemplary methods and apparatus described herein may facilitate safely and effectively reducing cumulative focused light exposure or cumulative oxidative stress in individual retinal cells in some portions of the retina, and/or slowing the progression of macular and/or peripheral retinal degeneration in hereditary and acquired diseases and disorders. For example, unlike treatments for slowing the progression of macular degeneration, such as selective pyrolysis, photo-bioregulation, or intravitreal photovoltaic stimulation, which are currently proposed and studied but not yet approved, that can damage and/or overstimulate retinal cells and/or cause a detrimental amount of complement activation and/or cause premature retinal atrophy, some of the exemplary methods and apparatus described herein delay macular and/or peripheral degeneration without overstimulating and/or damaging retinal tissue.

Some of the exemplary apparatus described herein may include deformable components, or may be configured to cause deformable changes in one or several ocular structures placed within the eye to cause transient or reversible redirection of ambient light away from the PRL to multiple retinal locations in genetically or epigenetically altered portions that are not PRL. Some of the exemplary devices described herein may cause weighting of exposure of ambient light from within the eye's field of view in the genetically altered portion of the retina or the epigenetic altered portion of the retina. One or more of the exemplary apparatus and methods described herein may permit repeated restarting of the vision system of the eye by: redirecting ambient light away from the PRL to multiple other retinal locations in the gene-altered portion, or weighting the exposure of ambient light, or reducing focusing at the PRL while focusing on the gene-altered portion, increases the number of retinal locations, which achieves adequate tissue transduction and trans-gene expression and can aid in neural integration and perception.

Some of the exemplary apparatus described herein may include deformable components or may be configured to cause deformable modification of one or several ocular structures placed within the eye to cause instantaneous or reversible or repeatable redirection of ambient light away from the PRL to multiple retinal locations in the retina (including retinal transplants, implanted retinal cells, implanted stem cells, or implanted prostheses) that are not PRL. Some of the exemplary apparatus described herein may cause weighting of portions of the retina (including retinal transplants, implanted retinal cells, implanted stem cells, or implanted prostheses) that are exposed to ambient light from within the eye's field of view. Current diagnostic techniques often fail to provide a reliable assessment of the visual function of individual retinal cells or areas and/or prostheses. Some of the exemplary apparatus and methods described herein may permit safe and effective repeatable restarting of the vision system in the retina (including retinal transplants, implanted retinal cells, implanted stem cells, or implanted prostheses) so that more retinal areas where ambient light is focused or where light has been redirected or exposed can contribute to neural integration and perception under weighting.

Some of the exemplary methods and apparatus described herein may safely and effectively restart a vision system in conjunction with natural vision processing. Some of the exemplary methods and apparatus described herein may restart the vision system without the need for perception or eye-movement training. Some of the exemplary methods and apparatus described herein may also restart the vision apparatus without compromising retinal structure or natural vision processing mechanisms. As an example of these advantages, and unlike some currently studied (but not yet approved) strategies for vision loss, such as retinal prosthesis implantation that irreversibly disrupt retinal structure and natural vision processing, some of the exemplary methods and apparatus described herein do not damage or replace any ocular tissue, and do not disrupt natural vision processing. As another example of some advantages, and unlike currently studied (but not yet approved) strategies for central vision loss, such as electronic retinal remapping that replaces real visual information from the field of view with simulated and distorted information in the lateral central region of the field of view and does not transmit all images within the field of view, some exemplary methods and devices described herein may transmit actual and complete fields or views and do not distort visual information within the field of view.

Some of the exemplary methods and apparatus described herein may facilitate optical, mechanical, or both optical and mechanical redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not PRLs. Some of the exemplary methods and apparatus described herein may facilitate simple, safe, effective, efficient, and/or timely optical, mechanical, or optomechanical weighting of exposure to ambient light from within the eye's field of view to reduce exposure to the eye's PRL by at least 10% over determinable intervals. In some examples, ambient light within the field of view may be exposed to the retina at a determinable rate of up to 50 kilohertz, the determinable interval may include milliseconds, seconds, minutes, hours, days, weeks, or years, and the exemplary methods and apparatus described herein may determine the determinable interval based on the user's visual response, equipment configuration, progression of ocular disease/disorder and/or vision disorder, vision loss, and/or ocular disease/disorder. Some of the exemplary apparatus described herein may include optical components and/or mechanical components.

Some of the exemplary methods described herein may be implemented by or may utilize an apparatus, and may cause ambient light from within the eye's field of view to defocus at the PRL, and may modify the optical properties or behavior of portions outside the optical region of structures positioned in front of the retina. Some of the exemplary methods described herein may be implemented by or may utilize an apparatus, and may cause ambient light from within the eye's field of view to defocus at the PRL of the eye, and may modify mechanical properties or behavior of portions located outside the optical region of structures in front of the retina. Some of these exemplary methods may improve and/or restore vision of an eye having central and/or peripheral vision impairment and/or loss.

Some of the exemplary methods described herein may be implemented by or with an apparatus positioned in front of the retina of an eye. In some examples, positioning the device "in front of the retina" may include positioning the device outside the eye, positioning the device on a surface of the eye, positioning the device within the cornea, and/or positioning the device within the eye. Some of the exemplary apparatus described herein may include eyeglasses and other eye-mountable devices, contact lenses, corneal inlays, intraocular lenses (IOLs), and other intraocular devices.

Some of the exemplary apparatus described herein may be configured to programmable instantaneous, reversible, and/or repeatable redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not PRLs. In some examples, an exemplary apparatus may include a control unit (e.g., a controller) coupled to a source of electrical energy (e.g., a power source), and the control unit may include one or more processors that, upon execution of software instructions (e.g., stored locally by the control unit or apparatus within a tangible, non-transitory memory or contained within a received signal), cause the exemplary apparatus to generate a programmable instantaneous, reversible, and/or repeatable redirection of ambient light.

Moreover, some of the exemplary methods or apparatus described herein may cause the ambient light to be instantaneously, reversibly, and/or repeatedly redirected away from the PRL to multiple retinal locations that are not PRL by mechanically, electromechanically, optically, or optomechanically directing the ambient light away from the PRL of the eye to multiple retinal locations. Additionally, one or more of the exemplary apparatus described herein may be configured to redirect ambient light away from the PRL of the eye to a plurality of retinal areas that are not PRLs, and may include one or more transparent components disposed in front of the retina of the eye and coupled to the controller. As described herein, the controller may be coupled to a power source, and the controller may be configured to generate and route control signals to the transparent component (e.g., based on software instructions executed by one or more processors, etc.), which may cause the transparent component to redirect ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRLs.

In some examples, one or more of these exemplary apparatuses may include one or more transparent components, one or more optomechanical components disposed on or within a surface of the one or more transparent components, and a controller electrically coupled to the one or more optomechanical components via a conductive layer. As described herein, the controller may be configured to generate and route control signals (e.g., based on software instructions executed by the one or more processors, etc.) to the one or more optomechanical components, and upon receipt of the control signals, the one or more optomechanical components may cause ambient light to be redirected away from the PRL of the eye to a plurality of retinal locations that are not PRLs.

Some of the exemplary apparatus described herein that may be configured to redirect ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRLs may include one or more transparent components disposed in front of the retina of the eye and a controller coupled to the one or more transparent components via conductive components. The controller may perform any of the exemplary operations described herein to generate and route control signals to the transparent component via the conductive component. For example, an exemplary apparatus may include one or more components disposed on or within a surface of one or more transparent components, and upon receipt of a control signal, the one or more components cause ambient light to be redirected away from the PRL to a plurality of retinal locations that are not PRL. In some examples, the one or more components may include a refractive component, a diffractive component, or a combination of diffractive and refractive components, and the control signal may cause modification of the refractive component, the diffractive component, or the combination of diffractive and refractive components to redirect ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRLs. Furthermore, one or more of the exemplary apparatus described herein may also include at least one lens for correcting refractive errors of the eye.

Some of the exemplary apparatus described herein may include at least one control unit (e.g., a controller), and may be configured (e.g., based on control signals generated by the controller) to generate programmable weights from exposure of ambient light within the eye field of view to reduce exposure to the PRL of the eye by at least 10% over a determinable interval. Some of the exemplary apparatus described herein may include at least one control unit (e.g., a controller), and may be configured (e.g., based on control signals generated by the controller) to generate programmable weights of exposure from ambient light within the eye field of view to reduce exposure to the PRL by at least 10% or to increase exposure to retinal locations other than the PRL by 10% over determinable intervals at a determinable rate from 0 to 50 kilohertz. Some of the exemplary methods and apparatus described herein may cause light to be instantaneously, reversibly, and/or repeatedly redirected away from the PRL to multiple retinal locations that are not PRL by mechanically, electromechanically, optically, and/or optomechanically directing ambient light away from the PRL of the eye to multiple retinal locations. Moreover, some of the exemplary methods and apparatus may include or may be mechanically, electromechanically, optically, and/or optomechanically operated that produces a weighting of exposure to ambient light from within the eye's field of view to reduce exposure to the PRL by at least 10% or to increase exposure to multiple retinal locations other than the PRL by 10% over a determinable time interval at a determinable rate from 0 to 50 kilohertz.

Fig. 19 illustrates an exemplary apparatus 1900 for improving or restoring vision. In some examples, the apparatus 1900 may include one or more transparent components 1902 positioned in front of the retina 1901A of the eye 1901 (which also includes the fovea 1901B and the optic nerve 1901C), one or more deformable components 1904 disposed on or within a surface of one or more of the transparent components 1902, and a controller 1906 coupled to the deformable components 1904 via conductive components 1908. Further, the controller 1906 may also be coupled to a source of electrical energy, such as a power supply 1910, and may be configured to generate a control signal 1912 and route the control signal 1912 to the deformable component 1904 (e.g., based on electrical energy received from the power supply 1910).

As illustrated in fig. 19, the controller 1906 may receive one or more elements of the input data 1905 and may be configured to process the received elements of the input data 1905 and generate and route control signals 1912 to the deformable component 1904. In some examples, the elements of the input data 1905 may include, but are not limited to, the position of the PRL 1918 of the eye 1901, information characterizing component deformation modes that direct ambient light to cause a determinable distance of defocusing of the ambient light at the PRL 1918, and determinable rates (e.g., ranging from 0 to 50 kHz). In some examples, the controller 1906 may include one or more processors that, upon execution of software instructions (e.g., stored locally by the controller within a tangible, non-transitory memory or included within a received signal), cause the controller to generate the control signal 1912 and transmit the control signal 1912 to the deformable component 1904.

In some examples, and after receiving control signal 1912, one or more of deformable components 1904 may reorganize at least one mode of steering of ambient light 1914 to retina 1901A at a determinable rate up to 50 kilohertz. The at least one mode of ambient light directing may cause the processing of ambient light 1914 to be restarted by the vision system of eye 1901. For example, the at least one mode may cause defocus at a PRL of the eye 1901 (e.g., PRL 1918 of fig. 19) and/or focus at numerous and discontinuous retinal locations that are not PRLs (e.g., location 1920). Further, in some examples, the at least one mode does not produce an aperture.

In some examples, the signal for generating the pattern that causes the focusing or defocusing of the ambient light may last any number of milliseconds, seconds, minutes, hours, days, months, or years (e.g., using any of the exemplary processes described herein by the controller 1906) to cause and/or maintain and/or repeat the restarting of the processing of the ambient light 1914 by the vision system. Further, although not illustrated in fig. 19, some of the exemplary apparatus described herein (e.g., apparatus 1900) may include at least one lens, such as, but not limited to, at least one lens for correcting at least one refractive error.

In some examples, deformable component 1904 may include at least one of an optically effective component, an opto-mechanical component, an electromechanical component, or a projection component. Moreover, some of the exemplary apparatus described herein may also include at least one component having at least one of isotropic properties and isotropic behavior. For example, at least one of the deformable components 1904 may include a deformable component having at least one of isotropic properties and isotropic behavior. In some examples and in response to control signal 1912, deformable component 1904 may reorganize at least one mode of steering of ambient light 1914 to retina 1901A at a determinable rate up to 50 kilohertz. By way of example, deformable component 1904 may reorganize the guided mode of ambient light 1914 to retina 1901A by at least isotropic modification.

Further, and by way of example, deformable component 1904 may include one or more deformable components having isotropic properties or behavior, such as optically isotropic liquid crystals. In some examples, the optically isotropic liquid crystal may provide faster switching times and wider viewing angles than the anisotropic liquid crystal in response to the control signal 1912. For example, in the case of an in-plane switching electrode generating a horizontal electric field, the liquid crystal may exhibit optical isotropy with the voltage off, resulting in a dark state, and the refractive index profile may become anisotropic with the voltage on, resulting in transmission.

In some examples not illustrated in fig. 19, deformable component 1904 may be combined with a fixed focus single focal lens. For example, deformable component 1904 may be combined with a lens of glass or plastic or any determinable material having a curved surface. Further, deformable components 1904 may be arranged in a pattern to produce approximately isotropic behavior. For example, in some embodiments, deformable component 1904 may include an optically isotropic polymer layer having a reverse lens shape on a first surface and a lens portion where a surface of the optically isotropic polymer layer is filled with liquid crystal polymer. The deformable component 1904 may also include electro-optic components including, but not limited to, liquid crystals and polymer gels.

Additionally, not illustrated in fig. 19, apparatus 1900 may include ultra-thin planar lenses such as, but not limited to, lenses composed of periodic sub-wavelength dielectrics or metal structures and liquid crystal lenses. In some examples, device 1900 may also include a panama-Bei Li (panharatnam-Berry) phase lens with spatially separated focal points shifted out of the PRL axis. Furthermore, in some examples, the deformable component 1904 of apparatus 1900 may include an electrically tunable liquid crystal lens, such as, but not limited to, diffractive, refractive, and gradient index lenses. For example, the apparatus 1900 may vary pixel arrangement and/or refractive index and/or optical axis orientation. Further, and in response to control signals 1912, one or more of deformable components 1904 may control the length of a focused light path generated at spatial points comprised of numerous and discrete retinal locations that are not PRL 1918. Furthermore, the exemplary apparatus 1900 may also include a photo-orientation component and/or a photo-patterning component.

In some examples, and based on control signals 1912 generated by controller 1906 and provided to deformable component 1904, apparatus 1900 may perform exemplary processes including, but not limited to, light polarization rotation, voltage controllable diffraction, or fast switching of LC refractive index. Furthermore, in some examples, the apparatus 1900 may incorporate or utilize electro-optic technology, such as, for example, local refractive indices at any given location within the active region of the electro-optic component, determined by voltage waveforms applied across the electro-optic component at that location and controlled by circuitry coupled to the electrodes for recombination modes. Design features related to refractive index, voltage, and electroactive material of the deformable element may be determined based on the location of the device, the needs of the manufacturer, and the needs of the user.

In some examples, although not illustrated in fig. 19, the apparatus 1900 may include an actuation component configured to independently control the position of a corresponding one of the optomechanically deformable components 1904, such as a micromirror (e.g., based on control signals generated by the controller 1906). Independent control of each of the micromirrors may, for example, modify the focal length and/or optical axis of the lens to cause defocusing at PRL 1918 and focusing at numerous and discontinuous retinal locations that are not PRL, such as location 1920. In some examples, modification of one or more of the focal lengths may be controlled by translation and/or rotation of a corresponding one of the micromirrors. Furthermore, the focal length may be modified by the device 1900 without determining the optical error or image quality at the PRL 1918 and/or discontinuous retinal locations that are not PRL (e.g., location 1920).

Some of the exemplary methods described herein may transiently, reversibly, or repeatedly transform the refractive index, radius of curvature, and/or diffraction of one or more refractive or diffractive components within at least one of the apparatus or the eye to cause safe and efficient redirection of ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRL. In some examples, some of the exemplary apparatus described herein may include one or more deformable components configured (e.g., via control signals generated by corresponding controllers) to produce instantaneous, reversible, and/or repeatable changes in refractive index and/or radius of curvature and/or diffraction within the apparatus or eye. Moreover, some exemplary apparatus described herein may include one or more lenses and/or tunable lenses.

Some of the exemplary apparatus described herein may include one or more deformable components positioned in front of the retina of the eye and a controller coupled to the one or more deformable components via a conductive component. In some examples, the controller may be configured to generate and route control signals to one or more deformable components (e.g., based on executing software instructions, etc.). Based on receipt of the control signal by the one or more deformable components, the apparatus may be configured to cause weighting of exposure of ambient light from within the eye field of view, which may reduce exposure of ambient light from the eye field of view to the PRL of the eye by at least 10% over a determinable interval. In some examples, ambient light within the field of view may be exposed to the retina at a determinable rate of up to 50 kilohertz.

Moreover, some of the exemplary methods and apparatus described herein may transiently, reversibly, repeatably, or continuously transform the refractive index, radius of curvature, and/or diffraction of one or more refractive or diffractive components within at least one of an ophthalmic device and an eye to cause weighting of exposure of ambient light from within the eye's field of view to reduce exposure to PRL by at least 10% at a determinable rate from 0 to 50 kilohertz over determinable intervals. Some of the exemplary apparatus described herein may include one or more deformable components that, in response to receiving control signals generated by corresponding controllers, may generate instantaneous, reversible, and/or repeatable changes in refractive index, radius of curvature, and/or diffraction within the apparatus or eye that cause weighting of exposure to ambient light from within the eye field of view to reduce exposure to the PRL by at least 10% at a determinable rate from 0 to 50 kilohertz over a determinable time interval. In some examples, one or more of the exemplary apparatus described herein may include a deformable component. For example, these deformable components may include, but are not limited to, electro-optic components such as, but not limited to, liquid crystals and polymer gels, and/or optomechanical components. In additional or alternative examples, the deformable component may include, but is not limited to, a photo-alignment component and/or a photo-patterning component. Some of the exemplary methods described herein that utilize deformable components may include, but are not limited to, light polarization rotation processes, voltage controllable diffraction processes, and/or processes for rapidly switching the LC index of refraction.

In some examples, a controller coupled to the power supply and circuitry may be configured to control the voltage applied to the excitation electrode to shift the optical axis of the lens (e.g., based on execution of software instructions by one or more processes as described herein, etc.). In some exemplary methods described herein, the controller may receive input data, including but not limited to PRL location and/or axis of the eye. The controller may perform any of the exemplary processes described herein to process the input data and based on the process input data, generate and apply control voltages to the excitation electrodes, as well as control the size and/or position of the initial shift of the optical axis. By controlling the size and/or position of the initial shift of the optical axis, certain exemplary methods described herein may cause the vision system to restart by defocusing at the PRL, focusing at discrete locations other than the PRL, and/or weighting the exposure to ambient light from within the eye's field of view to reduce the exposure to the PRL by at least 10% at a determinable rate from 0 to 50 kilohertz over a determinable time interval. Although diagnostic methods like micro-field assays can determine the location of PRL, clinically useful micro-field assay tests have not been able to accurately detect all areas of reduced or increased retinal sensitivity in diseased or damaged retina. Furthermore, clinically available diagnostic tests have not been able to accurately predict which retinal locations contain the best functioning photoreceptors linked to the best functioning ganglion cells, and have not been able to measure the integrated and pooled potential of multiple regions of functional retinal cells. If the amount of vision improvement after an initial restart is unsatisfactory, certain exemplary apparatus described herein may use any of the exemplary operations described herein to modify the initial light defocus at the PRL, the initial light focus at the non-PRL location, and/or the initial weighting of the reduced exposure at the PRL for repeated restarts.

Some of the exemplary methods and apparatus described herein may transiently, reversibly, or repeatably transform the refractive index, radius of curvature, and/or diffraction of one or more refractive or diffractive components within at least one of the apparatus and the eye to cause safe and efficient redirection of ambient light. In some examples, one or more of the exemplary methods or devices described herein may cause modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements within the device or eye. Some of the exemplary methods or devices described herein may cause modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements within the device or eye, and the modification may vary over time. Some of the exemplary methods or devices described herein may cause modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements within the device or eye, which may be controlled at any time before, during, or after restarting by the device, healthcare provider, or user of the device.

In some examples, one or more of the exemplary apparatus described herein may determine the PRL location and/or axis prior to use or insertion of the apparatus. In other examples, one or more of the exemplary apparatus described herein may determine the PRL location and/or the axis may be determined during use of the apparatus or after insertion of the apparatus. Furthermore, in some examples, PRL location and/or axis may be determined by a healthcare provider or user using existing clinical procedures, including but not limited to gaze or micro-vision measurements.

As described herein, some of the exemplary apparatus described herein may include one or more deformable components coupled to a controller via corresponding conductive components. The one or more deformable components include, for example, liquid Crystal (LC), supertwist liquid crystal, ferroelectric liquid crystal, surface stabilized ferroelectric liquid crystal (SSFLF), bistable liquid crystal, polymer Light Emitting Diode (PLED), bistable liquid crystal, transparent and color tunable Organic Light Emitting Diode (OLED), or any other suitable material. The one or more deformable components may be disposed on the surface of or within one or more transparent components that are flat or curved and are composed of glass, plastic, polymer, or any other suitable material, such as, but not limited to, polysulfone, polyetherimide, and/or other thermoplastic materials.

As described herein, one or more of the exemplary methods may incorporate diffraction, and apparatus with components including, but not limited to, at least one of lenses, diffraction gratings, electroactive materials, deformable polymers, actuators, and any determinable diffraction component may be utilized. Furthermore, one or more of the exemplary apparatus described herein may also include optomechanical components such as, but not limited to, polarizers, digital micromirror devices, micromirror arrays, deformable mirrors, and/or lenses.

Some of the exemplary apparatus described herein may include at least one control unit (e.g., a controller), and may be configured (e.g., based on control signals generated by the controller) to generate programmable weights of exposure from ambient light within the eye field of view to reduce exposure to the PRL by at least 10% at a determinable rate from 0 to 50 kilohertz, or to increase exposure to retinal locations other than the PRL by 10% over a determinable interval. In some examples, one or more of these exemplary apparatuses may include one or more transparent components, one or more deformable components disposed on or within a surface of the one or more transparent components, and a controller electrically coupled to the one or more deformable components via a conductive layer. As described herein, the controller may be configured to generate and route (e.g., based on software instructions executed by the one or more processors, etc.) the control signals to the one or more deformable components, and upon receipt of the control signals, the one or more deformable components may cause weighting of exposure from ambient light within the eye's field of view. In some examples, an exemplary apparatus for improving and/or restoring vision (e.g., apparatus 2000 of fig. 20) may include one or more transparent components 2002 positioned in front of a retina 2001A of an eye 2001 (which also includes a fovea 2001B and an optic nerve 2001C), one or more deformable components 2004 disposed on or within a surface of the transparent components 2002, a controller 2006 coupled to the one or more deformable components 2004 via a conductive component 2008. Further, the controller 2006 may also be coupled to a source of electrical energy, such as the power supply 2010, and may be configured to generate and route control signals 2012 (e.g., based on the electrical energy received from the power supply 2010) to the deformable components 2004.

The controller 2006 may include one or more processors that, upon execution of software instructions (e.g., stored locally by the controller within a tangible, non-transitory memory or contained within a received signal), cause the controller to generate a control signal 2012 and transmit the control signal 2012 to the deformable component 2004. As illustrated in fig. 20, the controller 2006 may receive one or more elements of the input data 2005 and may be configured to process the received elements of the input data 2005 and generate and route control signals 2012 to the deformable components 2004. In some examples, elements of input data 2005 may include, but are not limited to, a location of PRL 2018 of eye 2001, information characterizing component deformation modes that reduce ambient light exposure at PRL 2018, weighted intervals, and determinable rates (e.g., ranging from 0 to 50 kHz).

In some examples, and upon receipt of control signal 2012, the one or more deformable components 2004 may reorganize at least one exposure pattern of ambient light at the non-PRL location 2020 from within the field of view of the eye 2001 to the retina 2001A at a determinable rate of up to 50 kilohertz within a determinable interval. Further, in some examples, at least one mode does not include an aperture. Further, in some examples, determinable intervals in milliseconds, seconds, minutes, hours, days, weeks, months, and/or years may be continuous or intermittent.

Further, and by way of example, the pattern reorganization may cause weighting of the exposure to ambient light to reduce the exposure to the PRL 2018 by at least 10% at a determinable rate ranging from 0 to 50 kilohertz over determinable intervals. Weighting the exposure of ambient light to reduce the exposure to PRL 2018 may cause the treatment of ambient light 2014 to be restarted by the vision system of eye 2001. Although not illustrated in fig. 20, the apparatus 2002 may also include at least one lens. Further, in some examples, the exemplary apparatus 2000 may perform any of the operations described herein to reorganize at least one mode of exposure of the ambient light 2014 to the retina 2001A based at least on a deformation of an optomechanical component of the apparatus 2000. The optomechanical components may include, but are not limited to, polarizers, digital micromirror devices, micromirror arrays, deformable mirrors, and/or lenses.

In some examples, the deformable component 2004 may include one or more micromirrors or lenses. For example, one or more micromirrors within the deformable component 2004 may be arranged in a determinable array of determinable shapes, and one or more lenses within the deformable component 2004 may have determinable shapes, sizes, and positions. Further, although not illustrated in fig. 20, the apparatus 2000 may integrate one or more of the deformable components 2004 (e.g., one or more of the micromirrors or lenses) with microelectronic circuitry and/or corresponding micromirror technology. For example, although not illustrated in fig. 20, the apparatus 2000 may include actuation components configured to independently control the position of a corresponding one of the micromirrors (e.g., based on control signals generated by the controller 2006).

Some of the exemplary methods and apparatus described herein may cause a visual system of an eye (e.g., eye 1901 of fig. 19 or eye 2001 of fig. 20) to restart and may cause focusing at numerous and discontinuous retinal locations that are not PRLs (e.g., PRL 1918 of fig. 19 or PRL 2018 of fig. 20). In some examples, focusing may be achieved randomly or non-randomly by modifying the focal length and/or optical axis range at different retinal locations. In additional examples, some of the exemplary methods and apparatus described herein may cause defocus at the PRL of the eye (e.g., PRL 1918 of eye 1901 in fig. 19, PRL 2018 of eye 2001 in fig. 20, etc.) by determining the optical axis of the PRL and modifying the optical axis of the lens.

Some of the exemplary methods and apparatus described herein may cause a restart of the vision system to improve or restore vision of the eye by performing one or more projection methods. By way of example, one or more of the exemplary apparatus described herein may include one or more projection components, such as a projector, functionally coupled to a controller. The controller may include one or more processors that, upon execution of software instructions (e.g., stored locally by the controller in a tangible, non-transitory memory or included in a received signal), cause the controller to generate and transmit control signals to the projector. Based on the received control signals, the projector may selectively redirect ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRLs. Based on the received control signal, the projector may weight the exposure to ambient light to reduce the exposure at the PRL by at least 10%. In some examples, the exemplary apparatus may include a projection component and a waveguide, and the exemplary apparatus may be configured to redirect ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRLs, or weight the exposure of ambient light to reduce the exposure at the PRL by at least 10%.

Some of the exemplary aspects and apparatus described herein may improve vision by causing redirection of ambient light away from the PRL of the eye into a sufficient number of retinal locations that are not PRL in a sufficient number of retinal quadrants. Some of the exemplary methods and apparatus described herein that cause ambient light to be redirected away from the PRL of the eye to multiple retinal locations that are not PRLs may require the location and/or axis of the PRL to be determined prior to use or insertion in the eye. PRL location and/or axis may be determined by methods including, but not limited to, gaze or micro-vision measurements. In low vision eyes, certain exemplary processes described herein that redirect ambient light to multiple locations away from the PRL may restart the vision system and achieve visual attention through other non-PRL retinal locations.

Although diagnostic methods like micro-field assays can determine the location of PRL, clinically useful tests (including micro-field assays) cannot detect all areas of reduced or increased retinal sensitivity in diseased or damaged retina. Furthermore, clinically available diagnostic tests have not been able to predict which retinal locations contain photoreceptors and ganglion cells that most effectively process visual information for integration, aggregation, and perception. Thus, current clinical procedures do not accurately locate a particular retinal location to improve vision. Certain exemplary methods and apparatus described herein that cause redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not PRLs and that are reversible and/or safely repeatable to achieve multiple redirection to improve vision may be implemented in addition to or as an alternative to current clinical procedures that lack reversibility and/or repeatability.

In some examples, one or more of the exemplary apparatus described herein may include one or more light directing components positioned in front of the retina of the eye. Further, and in addition to the light directing component, one or more of these exemplary devices may also include a light source positioned in front of the retina. The light source does not cause corneal vitrification. For example, some of the exemplary apparatus described herein may include one or more components that direct light from a light source (e.g., at least one of a laser light source and a non-laser light source) to multiple discrete portions of at least one structure in front of the retina to cause a restart of the processing of ambient light by the vision system by causing the ambient light to be redirected away from the PRL to multiple retinal locations that are not the PRL or reducing exposure of ambient light at the PRL or defocusing ambient light at the PRL and focusing light at multiple discrete and non-PRL retinal locations during specified intervals, or any combination thereof.

Structures to which light is directed from a laser or non-laser light source include, but are not limited to, acellular structures with or without cells and/or collagen structures in front of the retina within the eye. As defined herein, the phrase "intra-ocular" may include, but is not limited to, intra-ocular cornea (e.g., as illustrated in fig. 21), intra-ocular anterior chamber, intra-ocular lens, and intra-ocular posterior chamber. Furthermore, as defined herein, non-cellular structures within the eye may include structures inherent to the eye and non-inherent structures placed within or on the eye. Examples of non-cellular structures inherent to the non-eye but within the eye include, but are not limited to, intraocular lenses, donor non-cellular corneal microlenses, and biosynthetic collagen inserts. Further, examples of non-cellular structures inherent to the eye include, but are not limited to, the non-cellular portions of the cell-free corneal layer and the lens.

In some examples, one or more of the exemplary methods and apparatus described herein that direct light from a light source to non-cellular or substantially non-cellular structures, rather than to cellular structures within the eye, may improve safety and efficacy by reducing potential wound healing effects, potentially deleterious effects caused by targeted cellular structures, or potentially reduced efficacy. Collagen structures are collagen-containing structures and include structures inherent to the eye as well as structures inserted into or onto the eye, such as, but not limited to, structures having cells, including, but not limited to, biosynthetic collagen, corneal stroma, scleral portions, and lens portions.

The goal of some of the exemplary methods and apparatus described herein is to laser and non-laser treat (both of which may alter the biomechanical and optical behavior of the structure) structures based on their collagen fibril tangles and collagen fibril dispersions. In some examples, targeting structures or portions of structures with increased fibril entanglement and fibril dispersion may increase the efficacy and efficiency of surgery that causes ambient light to be redirected away from the PRL of the eye to multiple locations other than the PRL. For example, in the cornea, individual collagen fibrils are most densely interwoven together in the anterior acellular layer between the epithelium and stroma. Dense interconnections make those portions of the cornea stiffer and more mechanically active. Atomic force microscopy has demonstrated that the anterior acellular layer has a maximum elastic modulus in the cornea, for example, approximately three times greater (less than 20 μm deep) than that of the anterior stroma. In addition, many pre-matrix fibrils are inserted into the pre-acellular layer, which can be demonstrated using second harmonic imaging confocal microscopy. Under the anterior acellular layer, the fibrils in the anterior matrix also interweave together, but are not as dense as in the anterior acellular layer. From anterior to posterior of the cornea, the density of fibril branches and fibril inclinations from aligned positions decreases exponentially with depth, and at all depths, the average collagen inclination is predominantly parallel to the tissue surface. However, in the central cornea, the spread of the tilt angle is greatest in the anterior-most stroma (reflecting the increased lamellar entanglement in this region), and decreases with tissue depth. The foremost part of the matrix (less than 20 μm from the anterior acellular layer) may be characterized by the maximum modulus of elasticity within the matrix. For example, the first third of the matrix has a hardness three times that of the second third.

In addition to imaging by second harmonic generation, fibril dispersion can be measured by X-ray diffraction and scattering studies. The fibrils are more dispersed in the pre-acellular layer than in the underlying matrix. Collagen fibrils are proportionally less dispersed and more aligned in the latter two thirds of the cornea, whereas in the first third of the central cornea and paracentral cornea (and especially in the first sixth with the greatest dispersion nearest to the anterior acellular layer), collagen fibrils are arranged in many directions. In addition, fibril dispersion exhibited spatial variation on the corneal surface, with fibers extremely aligned along the nasal-temporal and superior-inferior meridians, and more dispersed in the transition zones within the four quadrants of the corneal surface, with the greatest fibril dispersion in the central section of each quadrant. The amount of collagen fibers dispersed in the transition zone may vary from cornea to cornea. In addition, X-ray diffraction also showed that there was a difference in the proportion of fibrils oriented in the 45 ° sectors of the nasal-temporal and superior-inferior meridians between the corneas of different healthy persons.

The spatial distribution of fibril dispersion may also vary between healthy and diseased corneas. The most fully dispersed regions of fibrils are nearly isotropic (i.e., arranged in all directions), and the nearly isotropic portion with nearly fully dispersed fibrils exhibits nearly isotropic biomechanical and/or optical properties or behavior (i.e., nearly equivalent isotropic biomechanical and/or optical properties or behavior in all directions). When the value differs from the value obtained along a different meridian after testing along one radial meridian of the cornea, the corneal properties (e.g., elastic modulus or other properties) are anisotropic. For example, brillouin (Brillouin) microscopy measures corneal anisotropy in vivo and ex vivo, and clinical measurements using frontal Brillouin corneal mapping can be used to determine the region of maximum isotropy.

In some examples, a greater amount of surface deformation, corneal mechanical behavior, may occur in the central zone in each quadrant of the cornea than in the nasal-temporal and superior-inferior zones due to the increased degree of fibril dispersion. Some of the exemplary methods and apparatus described herein modify the corneal portion with fibril dispersion and/or modify fibril dispersion in the corneal portion. For example, the more compliant a portion of the cornea, the more easily it is deformed. Modifying the portion of the interwoven collagen fiber region may also change the stiffness of the anterior stroma, change the corneal curvature, change the refraction of light, change the vision of the eye, or any combination thereof. Some of the exemplary methods and apparatus described herein modify the corneal portion with interwoven fibrils/fibers and/or modify interwoven fibrils/fibers in the corneal portion. Compliance measurements of the corneal layer or portion may be accomplished by, for example, corneal indentation, young's modulus estimation based on a fluid-filled spherical shell model with Semholtz (Scheimpflug) imaging, and surface acoustic wave elastography.

Although clinical techniques for measuring corneal biomechanical responses have been available about 15 years ago, these clinical techniques have not been able to measure local biochemical behavior until recently. Although ex vivo analysis of corneal surfaces has been in existence for decades, methods for studying corneal biomechanics in vivo have not been developed until recently. Furthermore, although clinical measurements of corneal biomechanical responses have been used for the diagnosis of glaucoma, cone keratomes and other corneal distension disorders, to date, local biomechanical criteria have not been used to program ophthalmic surgery unrelated to abnormal corneal distension. The exemplary methods and apparatus described herein may receive, process, and utilize inputs from corneal compliance and/or inputs from a local corneal compliance map and/or outputs from a corneal anisotropy/isotropy map, as illustrated in the corneal anisotropy map in fig. 22. For example, in fig. 22, 0 corresponds to an isotropic cornea portion, and a value >2 corresponds to a highly anisotropic cornea portion.

In some examples, some of the exemplary methods and apparatus described herein may safely and effectively restart the vision system of the eye by virtue of: the properties or behavior of structures on or in the eye that are intrinsic or extrinsic to the eye are transformed by transformation of an approximately isotropic part of the structure in the eye, by transformation of at least one part of the structure on or in the eye into an approximately isotropic structure and/or a structure that exhibits at least one property and/or behavior in all directions, by transformation of isotropy of at least one part of the structure on or in the eye, or by transformation of at least one part of the structure on or in the eye that is based on isotropy or anisotropy of at least one part.

Moreover, some of the exemplary methods and apparatus described herein may safely and effectively restart the visual system of the eye through a transformation of the mechanical properties of the structures within the eye. For example, mechanical properties may be effectively and safely transformed by removing and/or mechanically enhancing a determinable small number of mechanically active structures or portions of structures in determinable locations on or within the eye. Additionally, in some examples, mechanical properties may be effectively and safely transformed by removing and/or mechanically enhancing determinable small amounts of near-mechanically isotropic structures or portions of structures in determinable locations on or within the eye.

Some of the exemplary methods and apparatus described herein may safely and effectively restart the vision system of an eye through a transformation of optical properties of structures on or within the eye. In some examples, refractive properties may be efficiently and safely transformed by modifying portions of structures or structures that may determine a small amount of anisotropy and/or near isotropy. For example, the parameter κ (ρ, θ) represents a continuous distribution of collagen fibrils over the cornea of an eye, and exhibits a minimum value of zero if the fibrils are perfectly aligned along their preferential orientation, and a maximum value of 1/3 if the fibrils are perfectly dispersed and the cornea appears almost isotropic. Because (i) the fibrils in the cornea are not all oriented isotropically, but in precise locations, (ii) about 60% of the fibrils are uniformly dispersed, resulting in isotropic behavior, and (iii) about 40% of the fibrils are oriented anisotropically in different amounts (as illustrated in fig. 22), some of the exemplary methods and apparatus described herein can effectively, efficiently, and safely restart the vision system by directing laser or non-laser light to portions of the cornea based on their isotropic or anisotropic behavior or properties and/or modifying the isotropy of the portions of the cornea.

Some of the exemplary methods and apparatus described herein for restarting the vision system and/or improving or restoring vision may include at least one of a light source and one or more components that direct light from the light source to at least a plurality of discrete portions of the cornea of the eye. In addition or alternative examples, some of the exemplary methods and apparatus described herein to restart the vision system and/or improve or restore vision may also include one or more components that direct light from a light source to at least a plurality of discontinuous portions of at least the anterior non-cellular layer overlying the anterior cornea portion, which may be selected based on a degree of isotropy or anisotropy of the cornea portion underlying the anterior non-cellular layer. For example, light from a light source may be directed to a near-isotropic portion of the cornea. The light source may include at least one of a laser or a non-laser light source.

By way of example, and as illustrated in fig. 23, an exemplary apparatus 2300 for improving or restoring vision includes at least one of a light source 2302 and a light directing component 2304, the light directing component 2304 directing light 2306 from the light source 2302 to at least a plurality of discontinuous portions, generally shown as discontinuous portions 2310A and 2310B, of a cornea 2308A of an eye 2308. In some examples, the cornea may be an aged cornea. The light source 2302 may include at least one of a laser or a non-laser light source, and the light source 2302 does not produce corneal vitrification. Further, the discontinuous portions including discontinuous portions 2310A and 2310B may be positioned outside the central optical zone and may include at least an acellular layer of the cornea (e.g., cornea 2308A). In some examples, and by redirecting light 2306 from light source 2302 to at least a plurality of discontinuities of cornea 2308A, device 2300 can modify the isotropy of the cornea outside the central optical zone.

As illustrated in fig. 23, the apparatus 2300 may also include a controller 2312, the controller 2312 being electrically coupled to an electrical energy source (e.g., a power supply 2314), a light source 2302, and one or more components, such as a light directing component 2304 disposed between the light source 2302 and the cornea 2308B. Based on the power received from the power source 2314, the controller 2312 may be configured to generate and route light source control signals 2316 to the light sources 2302 and component control signals 2318 to the light directing components 2304. For example, the controller 2312 may include one or more processors that, upon execution of software instructions (e.g., stored locally by the controller in a tangible, non-transitory memory or contained within a received signal), cause the controller 2312 to generate and transmit light source control signals 2316 to the light sources 2302, and generate and route component control signals 2318 to the light directing components 2304. In some examples, upon receiving the light source control signal 2316, the light source 2302 may be configured to generate light 2306, and the light 2306 may be illuminated and incident on the light guide assembly 2304. Further, and in response to the component control signal 2318, the light-directing component 2304 may perform any of the exemplary processes described herein to direct light 2306 to at least a plurality of discrete portions of the cornea 2308A.

In some examples, the light source 2302 of the apparatus 2300 may include a laser light source, such as an ArF excimer laser emitting 193nm ultraviolet radiation (e.g., laser light), and the controller 2312 may be configured to direct laser light to a plurality of discrete portions of at least an anterior non-cellular layer of the cornea based on the input data 2320, which may include, among other things, the location of the PRL of the eye 2308, the determinable diameter of the central Optical Zone (OZ) of the cornea 2308A, and the determinable location, depth, and surface area of the discrete cornea portions, which may be based on isotropic behavior or properties of the portions. For example, the controller 2312 may be configured (e.g., by executing software instructions) to control ablation of four circular corneal sections (including at least a front acellular layer overlying the stroma of the cornea and having a diameter of 1 mm) to a depth of 20 microns (if epithelium is manually resected on the section) or 80 microns (for transepithelial ablation). In some examples, each of the four rounded cornea portions may be centered about 6mm OZ centered about PRL (by having the patient look on the light), and may overlie the most isotropic cornea portion at 1:30 o 'clock, 4:30 o' clock, 7:30 o 'clock, and 10:30 o' clock positions (as illustrated in fig. 22 and described herein).

In some examples, one or more of the exemplary processes described herein may utilize a first apparatus including a laser light source and a controller electrically coupled to the laser light source and one or more laser components in conjunction with a separate second apparatus disposed between the laser light source and the cornea to direct laser light delivered by the first apparatus to a plurality of discontinuous portions of at least an anterior acellular layer of the cornea. For example, the central optical zone may comprise a circular zone of at least 2mm in diameter of the cornea. In some examples, the central optical zone has a diameter of at least 3mm, and in other examples, the central optical zone has a diameter of at least 4mm. Some of the exemplary methods and apparatus described herein may include at least one of a light source and a component that directs light from the light source, and any of the operations described herein may be performed to cause vision improvement or vision recovery. Some of the exemplary methods and apparatus described herein may include at least one of a light source and a component that directs light from the light source, and any of the operations described herein may be performed to modify corneal isotropy. In some examples, the modification of the isotropy of the cornea outside the corneal optical zone may include modification of at least one of a mechanical property or a mechanical behavior of the cornea or a portion of the cornea in at least one direction. In addition or alternatively, the modification of the isotropy of the cornea outside the corneal optical zone may include modification of at least one of the optical properties or optical behavior of the cornea or a portion of the cornea in at least one direction.

In some examples, one or more of the exemplary apparatus described herein may include a light source (e.g., light source 2302 of apparatus 2300 in fig. 23), and the light source may include at least one of a laser and a non-laser light source. The light source may, for example, emit at least one of ultraviolet radiation or infrared radiation. Furthermore, some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may cause the corneal surface to be patterned. The corneal surface patterning may be at least one of optically tunable and approximately reversible, for example. Additionally, in some examples, one or more of the exemplary methods described herein and the exemplary apparatus described herein that includes at least one of a light source and a component that directs light from the light source may also cause mechanical enhancement of a plurality of discontinuous cornea portions to which light from the light source is directed. Moreover, some of the exemplary methods described herein and the exemplary apparatus described herein that includes at least one of a light source and a component that directs light from the light source may cause mechanical enhancement of the plurality of portions based on an isotropy/anisotropy criterion. In further examples, one or more of the exemplary methods described herein and the exemplary apparatus described herein that includes at least one of a light source and a component that directs light from the light source may also release a mechanical enhancer.

Some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may cause ambient light from within the eye's field of view to defocus at the PRL and/or focus at numerous and discontinuous retinal locations that are not PRL. Some of the exemplary methods and apparatus described herein may cause ambient light from within the eye's field of view to defocus at the PRL of the eye and focus at a plurality of discrete retinal locations that are not PRL, and do not require measurement of discrete retinal locations or optical errors at the PRL by or input into the apparatus.

Some of the exemplary methods described herein and the exemplary apparatuses described herein including at least one of a light source and a component that directs light from the light source may improve and/or restore vision of an eye having central and/or peripheral vision impairment and/or loss by causing ambient light from within the field of view to defocus at the PRL. Some of the exemplary methods and apparatus described herein may cause ambient light from within the field of view to defocus at the PRL by modifying at least portions of the cornea that are outside of the central optical zone. For example, portions of the cornea may include mechanically active portions of the cornea. Some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may cause ambient light from within the field of view to defocus at the PRL and may modify optical and/or mechanical properties or behaviors of portions outside the central optical zone of structures positioned in front of the retina. The mechanically active portion of the cornea may be selected based on its amount of mechanical activity compared to other portions of the cornea.

Some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source to cause a restart of the visual system of the eye may cause any structural surface patterning positioned on or within the eye. In some examples, the surface patterning may be at least one of light tuning and approximately reversible. Some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may cause mechanical enhancement of a plurality of discontinuities located on or within any structure on or within an eye to which light from the light source is directed. Moreover, some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may cause mechanical enhancement of portions of any structure positioned on or within the eye to which light from the light source is directed, which enhancement may be based on isotropic or anisotropic criteria. Some of the exemplary methods described herein and the exemplary apparatus described herein that include at least one of a light source and a component that directs light from the light source may release a mechanical enhancer for enhancing any structure positioned on or within the eye.

Some of the exemplary apparatus described herein and exemplary components within these apparatus that may direct light from a light source may be positioned in front of the retina of an eye, either intra-ocular, intra-corneal, or extra-ocular, and may be configured to allow for transmission from the light source (including at least one of a laser light source and a non-laser light source) to multiple discontinuities of at least one structure in front of the retina. At least one structure in front of the retina may be positioned in, or out of the eye, and may include, but is not limited to, non-cellular structures inherent to the eye (e.g., structures within the cornea or lens of the eye) or non-cellular structures inherent to the eye (e.g., contact lenses, intracorneal inserts, intraocular lenses, or donor cornea non-cellular structures) or other intraocular, intracorneal, or extraocular structures (e.g., collagen structures inherent or extrinsic to the eye, such as corneal stroma, donor corneal stroma, or biosynthetic collagen).

Some of the exemplary apparatus described herein that improve vision of an eye with central vision impairment may cause ambient light from within the eye's field of view to defocus at the PRL and/or focus at numerous and discontinuous retinal locations that are not PRL, and may direct light from a light source to multiple discontinuities of at least one structure in front of the retina. The at least one structure in front of the retina may be positioned in the eye, in the cornea, or outside the eye, and may include, but is not limited to, non-cellular structures such as contact lenses, intracorneal inserts, intraocular lenses, or another intraocular and intracorneal or extraocular non-cellular or collagenous structures. Some exemplary apparatus may include components that direct light from a light source, and the components may be placed in front of the retina of an eye. In some examples, one or more of these exemplary apparatuses may prevent light from being transmitted from a light source to at least one portion of at least one structure in front of the retina, the light source including at least one of a laser light source and a non-laser light source, and the at least one structure being positioned in front of the retina in an intraocular, intracorneal, or extraocular manner.

Some of the exemplary apparatus described herein for improving vision of an eye with central vision impairment by causing ambient light from within the eye's field of view to defocus at the PRL and/or focus at numerous and discrete retinal locations that are not PRL may direct light from a light source, may be positioned in front of the eye's retina, and may be configured to allow transmission from a light source (including at least one of a laser light source and a non-laser light source) to at least a plurality of discrete portions of non-cellular and/or collagenous structures in front of the retina. In some examples, at least one acellular and/or collagenous structure in front of the retina can be disposed within the cornea or crystalline lens of the eye. Furthermore, some of the exemplary devices described herein that direct light from a light source may be positioned in front of the retina of an eye and may prevent transmission from the light source to one or several portions of at least one acellular or collagenous structure in front of the retina. For example, the light source may include at least one of a laser light source and a non-laser light source, and the at least one non-cellular and/or collagenous structure in front of the retina may be disposed within the cornea or crystalline lens of the eye.

In some examples, one or more of the exemplary methods described herein may include utilizing a laser device or an accessory device of a laser to direct light from a light source and confine laser treatment to a plurality of discrete volumes of at least non-cellular structures (e.g., layers) of the cornea. Further, some of the exemplary devices described herein may include a laser device or an accessory device of a laser configured to direct light from a light source and limit laser treatment to a plurality of discrete volumes of at least one structure (e.g., layer or portion) of the cornea. Additionally, the exemplary apparatus described herein, or some of one or more components of such exemplary apparatus, may direct laser light from a laser light source and may be used for transepithelial laser treatment of the cornea. The exemplary apparatus described herein, or some of one or more components of such exemplary apparatus, may be used after non-laser ablation of the corneal epithelium, which may be performed manually with a spatula, diamond file, or any other instrument, and by any determinable method for corneal epithelium ablation.

Further, in some examples, one or more of the exemplary apparatus described herein or one or more components of these exemplary apparatus may direct light from a light source, and may include, but are not limited to, one or more additional components having a laser-transmissive aperture for laser treatment of multiple discrete volumes of at least the non-cellular layer of the cornea and/or the collagen layer of the cornea. The exemplary apparatus described herein, or some of one or more components of such exemplary apparatus, may direct light from a light source and may include, but is not limited to, one or more additional components including a laser-absorbable substance surrounding multiple regions without the laser-absorbable substance being positioned in discrete regions of the one or more components. The one or more components may, for example, limit laser treatment to a plurality of discrete volumes of at least an acellular layer of the cornea or a collagenous layer of the cornea. The laser-absorbable material may comprise, for example, polymethyl methacrylate for 193nm laser light. In some examples, a portion of one or more additional components having a laser-absorbable substance may surround a region corresponding to a plurality of discrete volumes to be resected, and may be attached to an underlying portion of the one or more additional components having a laser-transmissive substance, such as, for example, quartz.

Some of the exemplary methods and apparatus described herein may cause the ambient light to be instantaneously and/or safely repeatable redirected away from the PRL of the eye to multiple retinal locations that are not PRL by directing the light from the light source to multiple discontinuities in at least one of the non-cellular structure and the collagen structure. For example, the structure may be positioned in front of the retina, and the light source may include at least one of a non-laser light source and a laser light source. Some of the exemplary apparatus described herein may include a light source and components configured to treat a plurality of discontinuities that are volumes within or on the eye, including at least one of acellular structures and collagen structures, and redirect light from the light source away from the PRL to a plurality of retinal locations that are not PRL. Further, in some examples, one or more of the exemplary methods described herein may utilize an apparatus including a light source and components to treat a plurality of discontinuous portions that are volumes in an eye, including at least one of non-cellular ocular structures and collagenous ocular structures, and redirect light from the light source away from the PRL to a plurality of retinal locations that are not PRL. The light source may include at least one of a non-laser light source and a laser light source.

Some of the exemplary apparatus described herein may include lasers and components for corneal ablation configured to ablate at least an acellular layer of the cornea. Furthermore, one or more of the exemplary apparatus described herein include lasers and components for corneal ablation configured to ablate the corneal epithelium and/or corneal stroma. Examples of ablation lasers include, but are not limited to, argon fluoride excimer lasers and solid state lasers that emit extreme ultraviolet light at wavelengths including, but not limited to 193 nm. One or more of the exemplary apparatus described herein may direct light from a laser light source, including, but not limited to, a laser light source that emits infrared or ultraviolet light that produces photoablation.

Some of the exemplary apparatus described herein may include a laser light source, a controller electrically coupled to one or more laser components, and at least one component configured to ablate a portion of the cornea. For example, the at least one component may be disposed between a laser light source and a surface of a plurality of discontinuities to be ablated, and the at least one component may include a laser directing component, a laser directing control, a laser stopper, a programmable blocking microarray, and/or a laser blocking control. Some of the exemplary apparatus described herein may include laser light sources and components for corneal ablation, and examples of components include, but are not limited to, sensors, processors, controllers, cameras, eye-pieces, displays, lenses, laser beam shaping components, laser beam targeting components, laser scanning components, and/or delivery optics.

In some examples, one or more of the exemplary apparatus and methods described herein may produce ablation of microvolume of any desired volumetric shape of corneal tissue, including at least a portion of the acellular layer and/or the collagen layer. For example, the micro-volume may comprise corneal epithelium and/or corneal stromal tissue, although in other examples, the micro-volume may comprise only corneal stromal tissue. Furthermore, in some examples, one or more of the exemplary apparatus and methods described herein may produce ablation of any determinable volumetric shape microvolume of corneal tissue, including at least a portion of the rigid anterior layer and/or the anterior acellular layer. For example, the ablated micro volume may be characterized as having or not having a depth of the anterior surface transition region of any determinable depth no deeper than 200 microns, and may be characterized as having a surface area of minimum diameter no less than 0.05mm and maximum diameter no greater than 5 mm. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

Additionally, in some examples, one or more of the exemplary apparatus and methods described herein may produce ablation of any determinable volumetric-shaped micro-volume of a contact lens comprising an ablatable material, an intraocular lens comprising an ablatable material, or an intraocular lens device comprising an ablatable material. For example, the ablated micro volume may be characterized by a depth of any depth no deeper than 200 microns with or without a front surface transition region, and may be characterized by a surface area having a minimum diameter no less than 0.05mm and a maximum diameter no greater than 5 mm. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

Some of the exemplary apparatus described herein may include a laser light source and components for corneal ablation configured to ablate a plurality of discrete micro-volumes in a corneal region outside a central optical zone having a diameter greater than 2 mm. Examples of ablation concentration methods include, but are not limited to, on-axis corneal glints, and the center of the entrance pupil.

Some of the exemplary apparatus described herein may include a laser configured to ablate a portion of the cornea, and the ablation may be performed when the subject is gazing on the light target, thereby determining the PRL axis.

Some of the exemplary apparatus described herein configured to ablate portions of the cornea do not require determination of PRL location or axis prior to or during ablation, such as, for example, during ablation of multiple discrete portions outside a central optical zone of 4mm or greater.

Some of the exemplary apparatus described herein may include at least one or more components configured to direct laser light to a plurality of discrete portions of the cornea or lens in pulses of at least one of a femtosecond duration, a nanosecond duration, or a picosecond duration by causing light to be redirected away from the PRL to a plurality of retinal locations that are not PRL and/or by causing ambient light to defocus from within the eye's field of view to the PRL and/or to focus at a plurality of discrete retinal locations that are not PRR to cause a restart of the eye's vision system. Further, in some examples, one or more of the exemplary apparatus described herein may include one or more components configured to direct laser light to at least one of the corneal epithelium, the corneal acellular layer, or the corneal stroma in pulses of at least one of a femtosecond duration, a nanosecond duration, or a picosecond duration. Additionally, some of the exemplary apparatus described herein may include, but are not limited to, laser systems that produce photoablation, photodisruption, photoionization, photodissociation, photochemical effects, or any combination thereof. One or more of the exemplary apparatus described herein may include one or more laser light sources, and examples of such laser light sources include, but are not limited to, laser light sources that emit infrared, visible, or ultraviolet light. One or more of the exemplary apparatus described herein may direct light from a laser light source, including, but not limited to, a laser light source that emits infrared, visible, or ultraviolet light.

Some of the exemplary apparatus described herein may include one or more components configured to direct laser light to at least one of an acellular layer of the cornea, a corneal epithelium, or a corneal stroma in pulses of at least one of a femtosecond duration, a nanosecond duration, or a picosecond duration. For example, the one or more components may include at least one of a laser light directing component, a laser light directing control, an etch-flat stopper, a contact liquid stopper, an immersion lens, a programmable blocking microarray, a laser light blocking control, a lens, a laser beam shaping element, or a laser beam aiming element. Furthermore, one or more of the exemplary apparatus described herein may produce any determinable spot size. In some examples, one or more of the exemplary apparatus described herein may include components that generate any determinable pulse energy, pulse frequency, and/or laser pattern, such as, for example, a spiral or grating, and may utilize any determinable contact interface, such as, for example, curved or flat, or a centralized technique (mechanical or computer). By way of example, any determinable average power up to about 100W, peak power up to the level of teva, repetition rate up to 100 megahertz, pulse duration, polarization, and/or wavelength from extreme ultraviolet to mid-infrared may be used for laser-substance interactions, including ultrafast laser-substance interactions. In addition, some of the exemplary apparatus described herein may produce any ultrafast laser-substance interactions, including any pulse duration from femtoseconds to attoseconds.

Some of the exemplary apparatus described herein may be configured to cause ambient light to be instantaneously and reproducibly redirected away from the PRL of the eye to a plurality of retinal locations that are not PRLs, and include at least one component configured to direct laser light to at least one of the acellular layer of the cornea, the corneal epithelium, or the corneal stroma in pulses of at least one of a femtosecond duration, a nanosecond duration, or a picosecond duration to modify and/or ablate a plurality of discrete micro-volumes.

In some examples, one or more of the exemplary apparatus and methods described herein may modify and/or ablate the micro-volume of any determinable volumetric shape of corneal tissue. Some of the exemplary apparatus and methods described herein may also modify and/or ablate the micro-volume of any determinable volume-shaped corneal tissue. Furthermore, some of the exemplary apparatus and methods described herein may modify and/or ablate any determinable volume-shaped micro-volume in a mechanically active portion of the cornea. In some examples, one or more of the exemplary apparatus described herein may direct light to a micro-volume having any depth no deeper than 200 microns and having a surface area of a minimum diameter no less than 0.05mm and a maximum diameter no greater than 5 mm. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

Some of the exemplary apparatus described herein may include at least one component configured to direct laser light to at least one of a cornea, a natural lens, a contact lens, an intracorneal insert, an intraocular lens, an intraocular device, or any other structure positioned in front of the retina of the eye in pulses of at least one of a femtosecond duration, a nanosecond duration, or a picosecond duration. Some of the exemplary apparatus described herein for improving vision of an eye with central vision impairment by causing ambient light from within the eye's field of view to defocus at the PRL and/or focus at numerous and discrete retinal locations that are not PRL may direct laser light to at least one of the cornea, natural lens, contact lens, intracorneal insert, intraocular lens, intraocular device, or any other structure positioned in front of the retina of the eye in pulses of at least one of femtosecond duration, nanosecond duration, or picosecond duration. In some examples, one or more of the exemplary apparatus described herein may modify any of the volumetric-shaped micro-volumes. For example, the micro-volume may be characterized by a determinable depth no deeper than 200 microns, and the feature may be a surface area having a minimum diameter no less than 0.05mm and a maximum diameter no greater than 5 mm. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any shape. Further, in some examples, one or more of the exemplary apparatus and methods described herein may modify the refractive index or radius of curvature.

Some of the exemplary apparatus described herein may include a laser that produces laser thermal keratoplasty but does not produce corneal photo-vitrification to modify a plurality of discrete volumes of at least an acellular layer, cornea, or any other acellular or collagenous structure positioned in front of the retina of the eye. Some of the exemplary apparatus described herein may include, but are not limited to, lasers, such as holmium and thulium lasers, producing laser thermokeratoplasty but not corneal photo-vitrification, to modify a plurality of discrete volumes of at least non-cellular layers, cornea, or any other non-cellular or collagenous structures positioned in front of the retina of an eye by causing light to be redirected away from the PRL to a plurality of retinal locations other than the PRL and/or by causing ambient light from within the field of view of the eye to defocus to the PRL and/or focus at a plurality of discrete retinal locations other than the PRL to cause a restart of the visual system of the eye. Some of the exemplary apparatus described herein may include a laser that generates laser thermal keratoplasty to modify a plurality of discrete volumes of at least one of the corneal stroma and the corneal epithelium.

Some of the exemplary apparatus described herein may be configured to deliver radio frequency current (350 to 400 kHz) to modify a plurality of discrete volumes of at least the acellular layer of the cornea or any other acellular or collagenous structure positioned in front of the retina of an eye. Moreover, in some examples, one or more of the exemplary apparatus described herein may be configured to deliver radio frequency current (350 to 400 kHz) to modify at least an acellular layer or a plurality of discrete volumes of any other acellular or collagenous structures of the cornea positioned in front of the retina of the eye by redirecting light away from the PRL to a plurality of retinal locations that are not PRL and/or by causing ambient light from within the field of view of the eye to defocus to the PRL and/or focus at a plurality of discrete retinal locations that are not PRL to restart the vision system of the eye. Some of the exemplary apparatus described herein may be configured for conductive keratoplasty and additionally or alternatively configured to deliver radio frequency current (350 to 400 kHz) to modify a plurality of discrete volumes of at least one of the corneal stroma and corneal epithelium or any other non-cellular or collagenous structure positioned in front of the retina of an eye to redirect light away from the PRL to a plurality of retinal locations that are not PRL.

Some of the exemplary devices described herein that improve vision of an eye with central vision impairment may cause ambient light from within the eye's field of view to defocus at the preferred retinal gaze site of the eye by modifying the mechanical properties or behavior of portions of the structure that are located outside the central optical zone in front of the retina. Furthermore, some of the exemplary devices described herein that improve vision of an eye with central vision impairment may cause ambient light from within the eye's field of view to defocus at the PRL of the eye by modifying the mechanical properties or behavior of portions of the cornea outside of the central optical zone. Some of the exemplary devices described herein may also modify mechanical behavior or properties of the cornea in portions outside the central optical zone. Portions of the cornea may, for example, comprise mechanically active portions of the cornea, such as (but not limited to) the anterior acellular layer.

In some examples, one or more of the exemplary apparatus described herein may mechanically enhance portions of the cornea outside the central optical zone. For example, the central optical zone may be characterized by a diameter of at least 2mm. Furthermore, some of the exemplary apparatus described herein may cause a restart of the ocular vision system by mechanical strengthening and/or isotropic modification of at least the acellular layer or collagen layer or any other acellular or collagen structure of the cornea positioned in front of the retina of the eye, and may include at least one component including at least one of a light directing component, an obstructer, a programmable obstruction microarray, a light delivery element, a laser beam shaping element, a laser beam pulsing element, a laser beam aiming element, a chemical reagent container, a chemical reagent release component, or a chemical reagent delivery element. Some of the exemplary methods and apparatus described herein may perform operations that mechanically enhance corneal collagen, including but not limited to increasing incorporation within corneal collagen (e.g., using one or more components of the exemplary apparatus described herein).

Some of the exemplary apparatus described herein may include several components, including, but not limited to, components for containing and/or releasing chemicals and/or gases and/or components for directing light from a light source for photochemical, photodynamic, or photoionization modification of corneal collagen. In some examples, one or more of the exemplary apparatus and methods described herein may mechanically enhance multiple corneal microvolume outside of a central optical zone that is greater than 2mm in diameter. For example, each micro-volume may be any determinable volumetric shape of corneal tissue. Further, the micro-volume may also be characterized by a depth no deeper than any determinable depth of 200 microns, and the feature may be a region having a minimum diameter no less than 0.05mm and a maximum diameter no greater than 5 mm. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

Furthermore, in some examples, one or more of the exemplary methods described herein may utilize an apparatus including an ultraviolet light source, a controller electrically coupled to the ultraviolet light source, and a component or separate apparatus disposed between the ultraviolet light source and the cornea to direct ultraviolet light to or release a chemical agent onto a plurality of discrete portions of at least a pre-acellular layer of the cornea based on determinable diameters of a central Optical Zone (OZ) and determinable locations and volumes of the discrete cornea portions based on isotropic behavior or properties of the portions and other criteria. For example, one or more of the exemplary apparatuses described herein for restarting an ocular vision system may be configured with an occlusion component to transepithelially direct one or more of the following beyond a central OZ to at least a discontinuous corneal portion of determinable depth of an anterior non-cellular layer: (i) Commercial riboflavin formulations having a determinable concentration for a determinable amount of time to photosensitize the portion for mechanical enhancement with minimal penetration into other portions of the cornea; and (ii) ultraviolet-Sup>A (UV-Sup>A) radiation for Sup>A determinable amount of time under determinable irradiance for Sup>A determinable depth of the pre-activation corneSup>A.

In some examples, one or more of the exemplary apparatus described herein may include components that facilitate manual control of one or more of the processes described herein. Moreover, some of the exemplary apparatus described herein may include: a programmable microarray to direct activating light to at least a discontinuous corneal portion of the anterior non-cellular layer and/or to contain and release a photosensitizer (e.g., riboflavin); and a controller programmed to cause controlled trans-epithelial mechanical enhancement of, for example, four circular cornea portions (including at least the anterior non-cellular layer and having a depth of about 30 microns beneath the epithelium) of diameter 1 mm. For example, the four portions may be centered about 6mm OZ centered on the PRL (by looking the patient at the light), and overlie the approximately isotropic corneal portion of the anterior-most cornea at the 12 o 'clock, 3 o' clock, 6 o 'clock, and 9 o' clock positions (as shown in fig. 22).

Examples of embodiments are described in the following numbered clauses:

1. an apparatus for improving or restoring vision, the apparatus comprising:

one or more transparent components positioned in front of the retina of the eye;

one or more deformable components disposed on or within a surface of the one or more transparent components; a kind of electronic device with high-pressure air-conditioning system

A controller coupled to the one or more deformable components via conductive components, the controller configured to generate and route control signals to the one or more deformable components,

wherein upon receipt of the control signal, the one or more deformable components reorganize at least one mode of guidance of ambient light from within a field of view of the eye to the retina at a determinable rate of up to 50 kilohertz, and

wherein the at least one mode causes defocus at a preferred retinal gaze site of the eye, and wherein the at least one mode does not produce an aperture.

2. The apparatus of clause 1, wherein the at least one mode of directing ambient light to the retina causes focusing at a plurality of non-consecutive retinal locations that are not the preferred retinal gaze site.

3. The apparatus of clause 1, further comprising at least one lens.

4. The apparatus of clause 1, wherein the one or more deformable components comprise at least one component having at least one of isotropic properties or isotropic behavior.

5. The device of clause 1, wherein the pattern of the directing of ambient light to the retina is reorganized by at least isotropic modification.

6. The apparatus of clause 1, wherein the pattern of the directing of ambient light to the retina is reorganized by at least deformation of one or more optomechanical components.

7. An apparatus, comprising:

at least one or more deformable components positioned in front of the retina of the eye; a kind of electronic device with high-pressure air-conditioning system

wherein upon receipt of the control signal, the device causes a weighting of exposure of ambient light from within a field of view of the eye to reduce exposure of ambient light from within the field of view of the eye to a preferred retinal central site of the eye by at least 10% over a determinable interval, and

wherein the ambient light within the field of view is exposed to the retina at a determinable rate of up to 50 kilohertz.

8. An apparatus for improving or restoring vision, the apparatus comprising

One or more components that direct light from a light source to at least a plurality of non-continuous corneal portions, the light source comprising at least one of a laser or a non-laser light source,

Wherein the discontinuous cornea portion is positioned outside the central optical zone and comprises at least an acellular layer of a cornea of normal age,

wherein the light source does not produce corneal vitrification, and

wherein the device causes at least one modification of corneal isotropy outside the central optical zone.

9. The apparatus of clause 8, wherein the apparatus modifies at least one of mechanical properties and mechanical behavior in at least one direction.

10. The apparatus of clause 8, wherein the apparatus modifies at least one of optical properties and optical behavior in at least one direction.

11. The apparatus of clause 8, wherein the light source emits at least one of ultraviolet radiation and infrared radiation.

12. The apparatus of clause 8, further comprising: one or more components configured to cause at least one of: ambient light from within the field of view of an eye is defocused at a preferred retinal gaze site of the eye and focused at a plurality of non-contiguous retinal locations that are not the preferred retinal gaze site.

13. The apparatus of clause 12, wherein the defocusing of ambient light from within the field of view of an eye at the preferred retinal gaze site of the eye and focusing at the plurality of non-continuous retinal locations that are not the preferred retinal gaze site do not require measurement of optical errors at the non-continuous retinal locations.

14. The apparatus of clause 8, further comprising one or more components configured to cause the corneal surface to be patterned, and wherein the corneal surface patterning is at least one of optically tunable and approximately reversible.

15. The apparatus of clause 8, further comprising one or more components configured to cause mechanical enhancement of the plurality of discontinuous portions to which light from the light source is directed.

16. The apparatus of clause 8, further comprising one or more components configured to release the mechanical enhancer.

17. A method comprising weighting exposure of ambient light from within a field of view of an eye using a device positioned in front of the retina of the eye to reduce exposure to a preferred retinal central site of the eye by at least 10% over a determinable interval, wherein the ambient light from within the field of view is exposed to the retina at a determinable rate of up to 50 kilohertz.

18. A method for improving vision of an eye having central vision impairment, the method comprising causing ambient light within a field of view from the eye to defocus at a preferred retinal gaze site of the eye using a device.

19. The method of clause 18, further comprising causing, using the apparatus, the focusing of ambient light within at least one of a genetically altered portion of the retina, an epigenetic altered portion of the retina, and a neurodegenerative altered portion of the retina.

20. The method of clause 18, further comprising causing, using the apparatus, the focusing of ambient light within portions of the retina that include at least one of a retinal transplant, an implanted retinal cell, an implanted stem cell, or an implanted prosthesis.

21. The method of clause 18, further comprising modifying at least a plurality of corneal portions of the cornea outside of the central optical zone using the apparatus, wherein the plurality of corneal portions of the cornea comprises a mechanically active portion of the cornea.

22. The method of clause 18, further comprising modifying, using the apparatus, optical properties or behavior of portions of the structure positioned in front of the retina other than the central optical zone.

23. The method of clause 18, further comprising modifying, using the apparatus, mechanical properties or behavior of portions of the structure positioned in front of the retina other than the central optical zone.

Claims

1. An apparatus for improving or restoring vision, the apparatus comprising:

wherein upon receipt of the control signal, the one or more deformable components reorganize at least one mode of guidance of ambient light from within a field of view of the eye to the retina at a determinable rate of up to 50 kilohertz, and wherein the at least one mode causes defocus at a preferred retinal gaze site of the eye, and wherein the at least one mode does not produce an aperture.

2. The apparatus of claim 1, wherein the at least one mode of guidance of ambient light to the retina causes focusing at a plurality of non-consecutive retinal locations that are not the preferred retinal gaze site.

3. The apparatus of claim 1, further comprising at least one lens.

4. The apparatus of claim 1, wherein the one or more deformable components comprise at least one component having at least one of isotropic properties or isotropic behavior.

5. The device of claim 1, wherein the pattern of the directing of ambient light to the retina is reorganized by at least isotropic modification.

6. The apparatus of claim 1, wherein the pattern of the directing of ambient light to the retina is reorganized at least by deformation of one or more optomechanical components.

7. An apparatus, comprising:

8. An apparatus for improving or restoring vision, the apparatus comprising

wherein the light source does not produce corneal vitrification, and

9. The apparatus of claim 8, wherein the apparatus modifies at least one of mechanical properties and mechanical behavior in at least one direction.

10. The apparatus of claim 8, wherein the apparatus modifies at least one of optical properties and optical behavior in at least one direction.

11. The apparatus of claim 8, wherein the light source emits at least one of ultraviolet radiation and infrared radiation.

12. The apparatus of claim 8, further comprising: one or more components configured to cause at least one of: ambient light from within the field of view of an eye is defocused at a preferred retinal gaze site of the eye and focused at a plurality of non-contiguous retinal locations that are not the preferred retinal gaze site.

13. The apparatus of claim 12, wherein the defocusing of ambient light from within the field of view of an eye at the preferred retinal gaze site of the eye and focusing at the plurality of non-continuous retinal locations that are not the preferred retinal gaze site do not require measurement of optical errors at the non-continuous retinal locations.

14. The apparatus of claim 8, further comprising one or more components configured to cause corneal surface patterning, and wherein the corneal surface patterning is at least one of optically tunable and approximately reversible.

15. The apparatus of claim 8, further comprising one or more components configured to cause mechanical enhancement of the plurality of discontinuous portions to which light from the light source is directed.

16. The apparatus of claim 8, further comprising one or more components configured to release a mechanical enhancer.

19. The method of claim 18, further comprising causing, using the apparatus, ambient light to be focused within at least one of a genetically altered portion of the retina, an epigenetic altered portion of the retina, and a neurodegenerative altered portion of the retina.

20. The method of claim 18, further comprising causing, using the apparatus, ambient light to focus within portions of the retina that include at least one of a retinal transplant, an implanted retinal cell, an implanted stem cell, or an implanted prosthesis.

21. The method of claim 18, further comprising modifying at least a plurality of corneal portions of a cornea outside a central optical zone using the apparatus, wherein the plurality of corneal portions of the cornea comprises a mechanically active portion of the cornea.

22. The method of claim 18, further comprising modifying optical properties or behaviors of portions of a structure positioned in front of the retina other than the central optical zone using the apparatus.

23. The method of claim 18, further comprising modifying mechanical properties or behavior of portions of a structure positioned in front of the retina other than the central optical zone using the apparatus.