Novel retinal irradiance distribution modification device and method to improve and restore vision without corneal vitrification

Abstract

Methods and devices are described herein for improving or restoring vision by inducing a reboot of the eye's visual system with a modification of visual search, sampling, and stimulation in a direction away from the eye's eccentric fixation zone to enhance neural integration and perception of visual information from within the visual field. Some embodiments induce a temporary, reversible, or repeatable redirection of ambient light to multiple retinal locations away from the eye's eccentric fixation zone and not in the eccentric fixation zone. Some embodiments reduce the exposure of ambient light in the eccentric fixation zone of the eye at a determinable rate for a determinable interval. Some embodiments induce a defocus of ambient light in the eccentric fixation zone of the eye in an eye with visual impairment or vision loss.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part of U.S. Application No. 17 / 071,106, filed October 15, 2020, which claims the benefit of priority to U.S. Application No. 16 / 593,269, filed October 4, 2019 (now U.S. Patent No. 10,835,417), which claims the benefit of priority to U.S. Application No. 15 / 693,208, filed August 31, 2017. The disclosures of each of these applications are incorporated herein by reference in their entirety.

[0002] The disclosed exemplary embodiments relate to devices and methods for novel retinal irradiance distribution modification (IDM) to improve, stabilize, or restore vision. The disclosed exemplary embodiments also relate to devices and methods for reducing vision loss due to illnesses, injuries, and diseases associated with damaged and / or dysfunctional and / or deprived 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. Therapy 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, pharmacological therapy, retinal laser therapy, gene therapy, and stem cell therapy. [Background technology]

[0003] Conventional devices and methods provide suboptimal solutions to improve and / or restore vision, reducing vision loss due to diseases, injuries, and disorders associated with damaged and / or dysfunctional and / or deprived retinal cells, including, but not limited to, age-related macular degeneration (AMD), Stargardt's disease, Best vitelliform macular dystrophy, light-induced retinal injury, cone dystrophy, inverse retinitis pigmentosa, myopic macular degeneration, macular scars, diabetic retinopathy (DR), macular edema, macular holes, macular detachment, macular pucker, retinal vascular disorders (including, but not limited to, retinal vein occlusion and Coats disease), retinitis pigmentosa, glaucoma or other neuroretinal or ganglion cell disorders, and amblyopia (caused by refractive errors, medial opacities or blockages, ocular motility conditions, or combinations thereof). AMD, DR, and other retinal diseases and disorders are the leading causes of vision impairment, including blindness, worldwide. There is a large unmet need for solutions that provide meaningful vision and vision-related quality of life improvements to patients suffering from vision loss caused by retinal problems. Conventional devices and methods provide suboptimal improvement or compensation for some symptoms of vision loss due to such diseases, injuries, and disorders.

[0004] Conventional devices and methods for improving or compensating for symptoms of vision loss, such as telescopes (handheld, in electronic devices, in glasses, in contact lenses, in intraocular lenses, or in the cornea) or annular multifocal corneal laser treatment, only magnify images in a small area of ​​the visual field. Devices or methods for improving or compensating for symptoms of vision loss using prisms or prism effects (in glasses, in contact lenses, or in intraocular lenses) only shift images from objects in the visual field at an angle onto a small area of ​​the retina. Handheld and electronic telescopes require the patient to remain still, and these telescopes magnify only a small area of ​​the patient's visual field. Telescopes in glasses, contact lenses, and intraocular devices require visual training over weeks to months, cause visual field constriction, and interfere with binocular vision, resulting in reduced movement vision. Telescopes or prisms in intraocular devices involve surgery and are at risk of serious intraoperative and postoperative complications and adverse events. Oculomotor training for eccentric fixation requires training periods ranging from weeks to months, with diminishing effectiveness over time, abnormal head positioning, minimal improvement in reading speed, and minimal or no improvement in vision. Prisms in glasses, contact lenses, or intraocular lenses are less durable and can cause diplopia. All optical devices, glasses or contact lenses, are unable to maintain a constant moment-to-moment vision correction as the eye moves, preventing the full effect of neural adaptation from occurring. Retinal prostheses, such as eyeglass-type cameras that wirelessly transmit to microelectrode arrays implanted intraocularly in or on the patient's retina, cannot provide high-resolution vision and can only provide vague motion detection and shape discrimination. Intraocular implants using telescopes, prisms, or microelectrode arrays involve surgery that carries the risk of serious intraoperative and postoperative complications and adverse events, including death, loss of an eye, and complete blindness.

[0005] Conventional visual aids provide symptomatic improvement or compensation for vision loss, but do not provide the beneficial effects of recovery, including but not limited to repairing damaged retinal cells or improving retinal cell function.

[0006] Conventional drug therapy, including but not limited to anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular AMD, diabetic macular edema, and other neovascular retinal diseases, and prostaglandin analogues for glaucoma, prevents further progression of vision loss, but does not provide significant vision recovery for most patients.Conventional device therapy, including but not limited to retinal laser photocoagulation, photodynamic laser therapy, radiation therapy, photobiomodulation, subthreshold micropulse laser therapy, glaucoma laser therapy, and glaucoma surgery with or without shunt implantation, does not significantly improve vision.For patients suffering from dry AMD, which is characterized by retinal dysfunction with drusen formation and eventual retinal atrophy, there is no effective treatment other than lifestyle modification, use of glasses that block ultraviolet or blue light over the entire visual field, and use of vitamins and other supplements. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Williams DR and Coletta NJ, "Cone spacing and the visual resolution limit", J Am Opt Soc A (1987) Summary of the Invention [Problem to be solved by the invention]

[0008] In some examples, the IDM devices and methods may optically modify the spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information distribution of ambient light from the ocular field with simultaneous light redirection from the retinal fixation region to at least two other spatially separated retinal regions, with the modification permanently, temporarily, or varying over time within at least three retinal regions, including the retinal fixation region (hereinafter referred to as "IDM devices and methods"). The devices and methods described herein generate novel retinal irradiance distribution modifications (IDM) for improving vision. One or more of the exemplary IDM devices and methods described herein also provide beneficial effects of vision improvement, vision stabilization, and / or vision restoration to patients with visual symptoms or suffering from vision loss due to disease, injury, and disorder, including, but not limited to, eyes with damaged and / or dysfunctional and / or deprived 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 improving vision and / or restoring vision to overcome vision loss caused by diseases, injuries, and disorders including, but not limited to, age-related macular degeneration (AMD), Stargardt's disease, Best vitelliform macular dystrophy, light-induced retinal damage, cone dystrophy, inverse retinitis pigmentosa, myopic macular degeneration, macular scars, diabetic retinopathy (DR), macular edema, macular hole, macular detachment, macular pucker, retinal vascular disorders (including, but not limited to, retinal vein occlusion and Coats disease), retinitis pigmentosa, nutritional retinal diseases, glaucoma or other neuroretinal or ganglion cell diseases, and amblyopia (caused by refractive errors, medial opacities or obstructions, ocular motility conditions, or combinations thereof). In contrast to conventional devices and methods, the IDM devices and methods described herein also provide better vision and / or quality of life outcomes, fewer and less serious complications or adverse effects, and greater patient convenience and comfort for patients treated with retinal IDM, without the need for eye movement or sensory training. [Means for solving the problem]

[0009] Exemplary embodiments of retinal IDM devices described herein include, but are not limited to, retinal IDM lasers and other light sources that produce photoablation, photodisruption, photoionization, photochemical and / or photothermal keratoplasty but do not produce corneal vitrification, retinal IDM corneal crosslinking devices, retinal IDM radio frequency transmission devices, retinal IDM contact lenses, retinal IDM spectacles, retinal IDM corneal inlays, and retinal IDM intraocular lenses, all of which are configured to perform retinal IDM for vision improvement with or without the beneficial effect of vision restoration, including, but not limited to, retinal cell repair and / or retinal regeneration.

[0010] 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 cell, genetic, epigenetic and optogenetic therapies.

[0011] Although the description herein shows, describes, and points out novel features as applied to various embodiments, it will be understood that various omissions, substitutions, and changes in the form and details of the illustrated devices or methods may be made without departing from the spirit of the disclosure. As will be seen, some of the exemplary embodiments described herein may be embodied in forms that do not include all of the features and advantages set forth herein, since some features may be used or practiced separately from others. All changes that come within the meaning and range of equivalence of the claims are to be embraced within the scope of the invention. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a cutaway view of an eye showing the main ocular structures. [Diagram 2] 1 is a diagram of the eyeball in the vicinity of the macula showing the structure and dimensions of the retina. [Diagram 3] FIG. 1 is a schematic diagram of retinal microstructure and visual transformation. [Figure 4] FIG. 1 is a schematic diagram of a simplified visual pathway. [Diagram 5] FIG. 1 is a schematic retinal diagram showing the fovea (right circle), optic disc (left circle), and retinal blood vessels (wavy lines extending to the optic disc). [Figure 6] 1 is a graph of visual acuity versus retinal eccentricity using the foveal center as the zero eccentricity reference. [Figure 7] 1 is a schematic diagram of an eye with two light rays entering the paracentral cornea at points 1 and 2. [Figure 8] FIG. 1 is a schematic diagram of a retina showing a fovea A with a central dysfunctional retinal area B. [Figure 9] FIG. 1 is a schematic retinal diagram showing four-quadrant retinal irradiance distribution from the central region to quadrants I to IV. [Figure 10] FIG. 13 is a schematic retinal diagram showing the fovea A with non-centrally dysfunctional retinal regions B, C, and D, and a candidate functional retinal region E where the retinal IDM can increase retinal irradiance by redirecting irradiance away from B, C, and D. [Figure 11A] 1 is a corneal map showing the local radius of curvature after IDM treatment. [Figure 11B] FIG. 11B shows the expanded central region of FIG. 11A. [Figure 12] FIG. 1 is a schematic diagram showing the corneal anterior radius of curvature (ROC) profile for the retina IDM. [Figure 13] FIG. 1 shows a cross section through a schematic retinal irradiance distribution. [Figure 14] FIG. 1 shows a cross-section of the cornea after femtosecond laser treatment resulting in a change in the radius of curvature (ROC) relative to the retinal IDM. [Figure 15] 1 is a drawing of an IDM intraocular lens with a modification in the paracentral region. [Figure 16] 1 is a diagram of an IDM intraocular lens having two prism sectors. [Figure 17] FIG. 1 is a schematic cross-sectional view of an IDM contact lens having a paracentral steepening region. [Figure 18] FIG. 1 is a schematic cross-sectional view of an IDM corneal inlay implanted within the cornea. [Figure 19] 1 is a diagram of an exemplary device for improving or restoring vision, according to some exemplary embodiments. [Figure 20] 1 is a diagram of an exemplary device for improving or restoring vision, according to some exemplary embodiments. [Figure 21] FIG. 1 is a cross-sectional view of a cornea showing the acellular and collagen layers. [Figure 22] An anisotropic map of the cornea, where 0 corresponds to isotropy and values ​​>2 correspond to high anisotropy. [Diagram 23] 1 is a diagram of an exemplary device for improving or restoring vision, according to some exemplary embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Exemplary retinal irradiance distribution modification (IDM) devices and methods described herein include retinal IDM devices and methods that optically modify the spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information distribution of ambient light from the ocular field with simultaneous light redirection from a retinal fixation region to at least two other spatially separated retinal regions, with the modification permanently, temporarily, or varying over time within at least three retinal regions, including the retinal fixation region. The retinal IDM devices and methods have applications for vision improvement or stabilization and / or vision restoration and / or amelioration and / or compensation of visual symptoms due to ocular conditions, diseases, injuries, and disorders, including, but not limited to, eyes with vision loss due to diseases, injuries, and disorders associated with damaged and / or dysfunctional and / or deprived retinal cells. The IDM devices and methods reduce vision loss caused by diseases, injuries, and disorders including, but not limited to, age-related macular degeneration (AMD), Stargardt's disease, Best vitelliform macular dystrophy, light-induced retinal damage, cone dystrophy, inverse retinitis pigmentosa, myopic macular degeneration, macular scars, diabetic retinopathy (DR), macular edema, macular holes, macular detachment, macular pucker, retinal vascular disorders (including, but not limited to, retinal vein occlusion and Coats' disease), retinitis pigmentosa, nutritional retinal diseases, glaucoma or other neuroretinal or ganglion cell diseases, and amblyopia (caused by refractive errors, medial opacities or obstructions, ocular motility conditions, or combinations thereof).

[0014] Visual processing involves interactions between both eyes and the brain through a network of neurons, receptors, and other specialized cells. The first step in this sensory process involves the stimulation of photoreceptors in the retina, the conversion of light stimuli into neural signals, the processing of these neural signals through many types of retinal interneurons, and the transmission of electrical signals containing spatial, temporal, spatiotemporal, and colored visual information from each eye to the brain. Processing by retinal interneurons involves chemical and electrical messages sent between retinal cell types, including feedforward communication pathways from photoreceptors to bipolar cells and ganglion cells, along with interactions between these cell types and horizontal and amacrine cells. This information is further processed in the brain. Functional vision results when the brain integrates retinal information across space, time, and saccades.

[0015] Retinal irradiance is the amount of light power per unit area incident on the retina. Irradiance is expressed in W / m 2The spectral irradiance is measured in units of W, where W is the light power in watts, and m is the length in meters. In eyes with retinal disease, the retinal sensitivity to light irradiance of retinal regions may be reduced to various degrees. The reduced retinal sensitivity may be demonstrated by diagnostic tests, including but not limited to microperimetry. There is inaccurate and / or unbiased visual processing of light rays in the environmental field of retinal regions with reduced retinal sensitivity. After retinal IDM treatment with one or more of the exemplary retinal IDM devices and methods described herein, the distribution of visual information in the environmental field of the eye is corrected by redirecting light rays multiple times, spatially separated, onto multiple retinal regions, including areas with better retinal sensitivity. Thus, retinal IDM is distinct from and may or may not include correction of total radiant irradiance to the entire retina. Retinal spectral irradiance is the amount of light 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, mesopic, and scotopic lighting conditions. The IDM devices and methods are useful in all lighting conditions, including but not limited to daylight and scotopic lighting conditions. Unless otherwise specified in this application, retinal irradiance is always considered for visible light having a spectral distribution, including but not limited to sunlight or light with a color rendering index (CRI) similar to sunlight (i.e., CRI≧80, with a maximum value of 100, which is a perfect match of the spectral distribution to sunlight), and photopic lighting conditions, including but not limited to daylight.

[0016] It is understood that retinal irradiance and retinal irradiance distribution can be measured for both model and in vitro eyes by using photometric instruments known to those skilled in the art, including, but not limited to, photodiode arrays, charge-coupled device (CCD) sensors, and complementary metal-oxide semiconductor (CMOS) sensors. It is also understood by those skilled in the art that retinal irradiance and retinal irradiance distribution can be predicted using ray tracing calculations with model eyes.

[0017] The retinal irradiance distribution may be specified at various spatial and temporal scales, along with its spatiotemporal, chromatic, achromatic, and contrast information. Spatial scales include, but are not limited to, A) the receptive field of a region of retinal cells, including but not limited to spatial scales as small as individual photoreceptors, and including both the center and periphery of each cell's receptive field, B) the entire fovea, C) the entire macula, D) the entire central visual field extending out to approximately 20° eccentricity, E) the entire visual field. The location on the retina with respect to the center of the fovea may 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.

[0018] Time scales include, but are not limited to, A) moment-to-moment time scales that may be as short as 10 milliseconds, during which irradiance and contrast may be modified i) from changes in radiance of objects in visual space, ii) from eye movements, including both fixation movements and saccades that cause light (from different objects in visual space) to illuminate a spatial region of the retina, or iii) from any combination of i and ii above; B) intermediate time scales, ranging in duration from minutes, during which the process of retinal adaptation occurs; C) longer time scales, ranging in duration from days to years, during which the overall irradiance over a spatial region of the retina may affect the health of retinal cells; and D) a second longer time scale, ranging in duration from days to years, during which the process of neuroadaptation occurs.

[0019] Contrast refers to changes in irradiance across the spatial and temporal scales described above. Contrast may also refer to changes in irradiance on time scales that correspond to the dynamics of light responses in retinal cells. Contrast may also refer to changes in irradiance on spatiotemporal scales that correspond to the dynamics of motion-sensitive cells in the retina. Contrast may also refer to changes in spectral irradiance that correspond to the color sensitivity of retinal cells.

[0020] The retina of the eye is illustrated in the cutaway view of the eye shown in FIG. 1. The major ocular structures are the cornea, iris (which defines the pupil opening), lens, and the retina, including the fovea, macula, optic disc, and blood vessels. The region of the retina near the macula is shown in FIG. 2, with the fovea and other retinal regions identified along with their dimensions. A retinal schematic microstructure and visual transformation diagram is shown in FIG. 3, in which light generated by IDM devices and methods is shone on the retina, generating electrical signals from photoreceptor (cone and rod) cells, which are preprocessed by specialized retinal (horizontal, bipolar, amacrine, ganglion) cells, and triggers action potentials (electrical "spikes") that propagate through the axons (nerve fibers) emanating from the retinal ganglion cells and down the optic nerve (and ultimately to the visual cortex). The choroid contains capillaries that provide nutrients to the retinal cells and transport waste products away from the retina.

[0021] FIG. 4 shows a simplified schematic pathway diagram for cortical processing of visual information. Retinal ganglion cell axons connect to the lateral geniculate nucleus (LGN) as well as other subcortical structures, including but not limited to the superior colliculus, not shown. LGN relay cells connect to the primary visual cortex (area VI). The primary visual cortex further connects to multiple cortical visual areas (including but not limited to the ventral and dorsal visual pathways) that process information and provide visual outcomes, including but not limited to spatial vision, motion perception, depth perception, form perception, and color vision. The visual cortex interacts with the thalamus through recurrent loops to produce integrated vision. Visual cortical areas also interact with subcortical structures, including but not limited to the basal ganglia, thalamus, cerebellum, superior colliculus, and brainstem, to control eye movements. Subcortical visual processing includes but is not limited to eye and head movements, pupil size, and circadian rhythms. It is understood that visual improvement, including but not limited to neural adaptation, involves a complex interplay of neural processing throughout all stages of the visual pathway.

[0022] A schematic retinal diagram is shown in Figure 5. The fovea is shown as a circle on the right in Figure 5, with meridians from 0° to 180° (temporal-nasal) and 90° to 270° (superior-inferior) dividing the retinal region into four quadrants, namely 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 relative to the foveal center "X". The fovea is at a radius of approximately 0.75 mm (2.5° eccentricity), which contains the highest density of photoreceptors (cones) for the best spatial resolution of vision. The optic nerve head is shown as a circle on the left in Figure 3, with retinal blood vessels represented by wavy lines.

[0023] FIG. 6 shows the change in visual acuity (both in logMAR and Snellen units) as a function of retinal eccentricity. FIG. 6 is redrawn from FIG. 3 in Williams DR and Coletta NJ, "Cone spacing and the visual resolution limit," J Am Opt Soc A (1987). Measurements are for two subjects (circle and square symbols) and the average value, 0.907 logMAR (20 / 162 Snellen), was also measured at 20° retinal eccentricity. A quadratic fit to the measurements is shown. Conversion from retinal eccentricity: 1° retinal eccentricity = approximately 0.3 mm. The fovea extends to approximately 2.5° retinal eccentricity. Maximum visual acuity is obtained for light focused at the foveal center of a fully functional retina. Both defocus and lack of full retinal functionality can reduce visual acuity. Conventional visual aids, including but not limited to glasses and contact lenses, can improve focus but not retinal functionality. Useful visual acuity may be based on using large areas of the retina outside the fovea (i.e., outside a retinal eccentricity of approximately 2.5°)--see FIG. 6--and these areas outside the fovea may not be fully utilized when higher spatial resolution visual information from the fovea is preferentially weighted in the visual cortex.

[0024] Exemplary retinal irradiance distribution modification (IDM) devices and methods described herein include retinal IDM devices and methods that optically modify spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information distribution of ambient light from the eye's field of view with light redirection from the fovea or another retinal fixation region to at least two other spatially separated retinal regions, with the modification permanently, temporarily, or varying over time within at least three retinal regions, including the fovea or another retinal fixation region. The retinal regions are defined by the extent of polar coordinates, the spatially separated retinal regions are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping regions and partially overlapping regions, and the amount and placement of retinal IDM is for a given spatial distribution with or without a given temporal distribution. The retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information, or any combination thereof.

[0025] The exemplary retinal IDM devices and methods described herein have applications for both vision improvement and vision restoration in diseased eyes as described herein, with A--improvement of vision and quality of life, and B--beneficial effects of vision restoration, including but not limited to retinal cell repair and / or retinal regeneration. It is understood that in some embodiments, vision improvement can be obtained by retinal IDM treatment using the retinal IDM devices and methods described herein without obtaining the beneficial effect of vision restoration, in that some areas of the retina may remain partially or completely dysfunctional after retinal IDM treatment, or may even become less functional over time. It is also understood that in some other embodiments, both vision improvement and beneficial vision restoration effects, including enhanced functionality of some areas of the retina that were partially or completely dysfunctional before retinal IDM treatment, may be obtained due to retinal IDM treatment.

[0026] In some exemplary embodiments described herein for the purpose of improving vision, retinal IDM devices and methods are configured to optically redirect light from one or more partially or completely 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, where the dysfunctional retinal region includes, but is not limited to, at least one of a region of dysfunctional foveal photoreceptors, a plurality of regions of dysfunctional foveal photoreceptors, a dysfunctional eccentric visual field (PRL), a plurality of dysfunctional PRLs, a plurality of spatially separated dysfunctional retinal regions of photoreceptors, or any combination thereof, and the functional retinal region includes, but is not limited to, at least one of a retinal region of functional photoreceptors, a plurality of retinal regions of functional photoreceptors, and a plurality of spatially separated functional retinal regions of photoreceptors, and all functional retinal regions of the photoreceptors have functional signaling to functional ganglion cells.

[0027] In certain exemplary embodiments described herein, functional retinal regions include, but are not limited to, a. at least two spatially separated regions in at least two different quadrants (see FIG. 5), and b. at least one spatially separated region in each of four retinal quadrants (see FIG. 5).

[0028] The retinal regions are defined by ranges of polar coordinates, the spatially separated retinal regions are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping and partially overlapping regions, the amount and location of retinal IDM is for a given spatial distribution with or without a given temporal distribution, and the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information or any combination thereof.

[0029] In some exemplary embodiments described herein, the spatially separated retinal regions include multiple regions within each of the four retinal quadrants to increase the likelihood of redirecting light a. onto one or more functional regions in an eye with many dysfunctional regions, b. onto multiple functional regions to be used for different visual tasks, and c. onto multiple functional regions that can be used if or as retinal disease progresses.

[0030] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM alters the moment-to-moment pattern of light irradiance coming from edges and objects to increase the relative irradiance difference on nearby photoreceptors (i.e., increase contrast).

[0031] In some embodiments of the exemplary retinal IDM devices and methods described herein, the pattern of retinal irradiance distribution modification (IDM) improves neural computations by integrating additional and / or better encoded retinal information from macular and peripheral retinal cells, including but not limited to photoreceptors, bipolar cells, amacrine cells, horizontal cells, Muller glial cells, ganglion cells, or any combination of retinal cells, allowing for more complete processing of stimulus patterns; and / or (ii) improves the function of retinal circuits, including connectivity functions in visual processing involving photoreceptors, ganglion cells, amacrine cells, bipolar cells, horizontal cells, and Muller cells, or any combination thereof; and / or (iii) reroutes visual information encoded by peripheral regions of the retina to neurons at higher levels of the visual cortex whose receptive fields are typically responsible for encoding objects at the center of gaze, including but not limited to: a. and / or b. changing the target of saccadic eye movements (referred to herein as "fixations") to new retinal locations, and / or c. favorably changing the amplitude and / or velocity of eye movements within fixations, and / or d. favorably altering the interaction of saccadic firing circuits with the rest of the visual cortex, and / or e. triggering processes of neuroadaptation including, but not limited to, the use of alternative, occult, and / or new visual pathways in the retina and brain, including, but not limited to, generating more effective spontaneous search to achieve more effective integration of more and more correct visual information by search mechanisms including, but not limited to, generating motor learning in eye movement strategies to use more functional retinal cells for the improved visual information.

[0032] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM reroutes central visual information (typically, but not limited to, gaze-centered information) through alternative retinal pathways, thereby restoring the transmission of high-resolution spatial information from these regions of visual space to the rest of the brain, including, but not limited to, the cerebral cortex, basal ganglia, thalamus, superior colliculus, and other brainstem nuclei, thereby enhancing global visual processing mechanisms, including, but not limited to, a. enhancing global pooling of contour information, and / or b. improving shape discrimination, and / or c. improving motion processing, and / or d. improving color processing, and / or e. improving visually guided behavior, or any combination thereof.

[0033] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM triggers a process of neuroadaptation in central brain circuits (including but not limited to the visual cortex and / or visual thalamus and / or superior colliculus or any combination thereof), including but not limited to structural and synaptic plasticity, including but not limited to: a. restoring vision to areas of visual space corresponding to damaged areas of the retina that had little or no vision before treatment (i.e., were scotomas) by causing neurons in the central brain circuits to generate spatial receptive fields that cover these areas that were previously scotomas, and / or b. reducing and / or eliminating distortions of the visual field in the areas of visual space around the scotomas by incorporating these new spatial receptive fields into local spatial maps and reorganizing them into a continuous, undistorted map of visual space (i.e., correcting inaccurate filling-in).

[0034] In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDM improvement of vision occurs by the formation of new visual pathways from functional areas of the retina that encode high fidelity information about areas of visual space that were within the scotoma before treatment. For example, the distortion of visual field perceived by patients with macular degeneration may result from incorrect remapping of spatial receptive fields of neurons in the central brain. In this remapping, the receptive fields of neurons that cover dysfunctional areas of the retina expand and shift to include areas of visual space that correspond to functional areas of the retina. This causes neurons to remap in the same way farther away, and so on. Taken together, these processes induce global distortions in the receptive field map, resulting in the clinical symptom of wavy linear objects such as letters, telephone poles, and signs, also known as metamorphopsia. After treatment with some embodiments of the exemplary retinal IDM devices and methods described herein, the newly formed receptive fields that cover areas of visual space that were within the scotoma before treatment become integrated into the spatial map in each visual field. This incorporation triggers a process of reorganization that reverses the distortions caused by macular degeneration, thereby restoring a contiguous, undistorted map of visual space within each visual cortex: wavy letters, telephone poles, and signs become straight again.

[0035] In some embodiments of the exemplary retinal IDM device and method described herein, the retinal IDM allows for favorable cortical reorganization, including altered crowding characteristics with smaller critical intervals in the retinal periphery, and the retinal IDM directs attention to the new eccentric viewing zone or other retinal field. The altered crowding characteristics include, but are not limited to, loss of radial tangential anisotropy of the crowding zone. After spontaneous repeated use of the new eccentric viewing zone ("PRL") and / or PRLs and / or retinal field, the retinal IDM allows for a reduction in the size of the crowding zone around the new PRL or PRLs or retinal field through cortical plasticity. This plasticity makes the spatial characteristics of the PRL / PRL / retinal field more similar to the fovea. Both the magnitude and spread of crowding are reduced to the amount normally seen around the fovea. The reduced spread of crowding along the long axis contributes to a less elliptical shape of the crowding zone in the PRL / PRL / retinal visual field, which reduces the deleterious effects of crowding and improves visual acuity and visual function.

[0036] Some embodiments of the exemplary retinal IDM devices and methods described herein, unlike conventional devices and methods, improve vision by awakening remaining functional visual pathways without the need for eye movements or perceptual training, thereby enabling patients to discover and use the resulting vision immediately, or within days, or within weeks, with further improvement over the course of several months.

[0037] In some embodiments of the exemplary retinal IDM devices and methods described herein, vision improvement is greatly enhanced by having a retinal IDM pattern that is stable over time from moment to moment as the eye naturally moves through the field of vision.

[0038] Some exemplary embodiments described herein create a natural recognition in a treatment subject of one or more alternative functional visual pathways without requiring perceptual or oculomotor training and without causing tunnel vision, polyopia or binocular diplopia in the treatment subject, resulting in natural sensorimotor learning.

[0039] Some exemplary embodiments of the retinal IDM devices and methods described herein stabilize vision following vision loss due to disease, injury, or disorder involving retinal cell damage, retinal cell dysfunction, retinal cell sensory deprivation, or any combination thereof, and / or reduce the rate of vision loss and / or improve vision compared to untreated controls. Vision improvements include, but are not limited to, visual acuity (including both uncorrected and best spectacle-corrected visual acuity for distance, intermediate, and near vision), hyperacuity, stereoacuity, vernier acuity, contrast sensitivity, depth of focus, color vision, peripheral vision, night vision, face recognition, light adaptation, dark adaptation, vision-related quality of life, or any combination thereof.

[0040] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM allows for sustained and / or transient attention. While sustained attention enhances sensitivity strictly through contrast gain when spatial potential attention is directed to a target configuration, transient attention involves a mixture of both contrast gain and response gain.

[0041] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM improves visual function, including but not limited to, connectivity function in the visual processing of retinal tertiary meshwork cells, including but not limited to ganglion cells, amacrine cells, bipolar cells, Muller cells, or any combination thereof.

[0042] In some embodiments of the exemplary retinal IDM devices and methods described herein, the retinal IDM improves visual field defects in perimetry and / or microperimetry and / or preferential hyperacuity perimetry, and / or restores electroretinogram (ERG) amplitude and / or visual evoked potentials.

[0043] Some embodiments of the exemplary retinal IDM devices and methods described herein enable repositioning of one or more eccentric viewing zones to one or more more functional configurations, both continuously and for different binocular vision tasks.

[0044] Several embodiments of the exemplary retinal IDM devices and methods described herein, unlike conventional devices and methods, (i) enable unilateral or bilateral treatment of patients with vision loss due to diseases that damage and / or reduce the function of and / or deprive retinal cells of sensation, and / or (ii) provide rapid vision improvement that continues over months and years with additional sensory and / or oculomotor neural adaptations without the need for sensory or oculomotor control training.

[0045] Some embodiments of the exemplary retinal IDM devices and methods described herein provide improved vision following vision loss due to retinal disease, corneal decompensation, corneal epithelial cell loss, infection, or loss of visual function including, but not limited to, best corrected distance visual acuity, best corrected near visual acuity, contrast sensitivity, and stereopsis, without the associated life-threatening or vision-loss complications or adverse events, including, but not limited to, clinically significant changes in intraocular pressure, central corneal thickness, corneal endothelial cell density.

[0046] In some embodiments of the exemplary retinal IDM devices and methods described herein intended for vision restoring effects including, but not limited to, retinal cell repair and / or retinal regeneration, the retinal IDM devices and methods are configured to: a. reduce retinal irradiance from a field of view over spatially separated retinal regions, including partially or completely dysfunctional retinal regions, by at least 0.1%, where the reduction continues over a defined, extended timescale; and a. increase retinal irradiance from a field of view over spatially separated (different than in a.) retinal regions, including more functional retinal regions, by at least 0.1%, where the increase continues over a defined, extended timescale; it is understood that retinal irradiance and retinal irradiance distribution can be measured for both model and ex vivo eyes by using photometric measurement equipment known to those skilled in the art, including, but not limited to, photodiode arrays, charge-coupled device (CCD) sensors, and complementary metal-oxide semiconductor (CMOS) sensors.

[0047] Some embodiments of the exemplary retinal IDM devices and methods described herein improve vision after loss due to diseases that damage and / or reduce the function of retinal cells and / or deprive retinal cells of sensation, with a single, quick treatment that is comfortable, painless, does not require medication after treatment, and does not require retreatment. By comparison, conventional devices and methods have numerous drawbacks and treatment burdens, including, but not limited to, at least one of the following: being inconvenient for the patient, requiring the patient to remain motionless for use, being limited to use on only one eye or one eye at a time, being limited to treatment of only one eye (or only sequential treatments if the method can be performed on both eyes), requiring long and / or painful procedures, requiring postoperative medication, requiring constant uncomfortable or difficult insertion, inducing retinal inflammation, and requiring multiple / repeated procedures.

[0048] Some embodiments of the exemplary retinal IDM devices and methods described herein repair and / or restore retinal cells, and / or enhance retinal cell function, and / or reduce progressive damage to retinal cells, in addition to significant improvements in vision with rapid improvements in neural computation and beneficial neural adaptations continuing over the long term (i.e., over a period ranging from days to years following treatment).

[0049] Some exemplary embodiments of the retinal IDM devices and methods described herein compensate for retinal deterioration caused by damage to photoreceptors or other retinal cells, with or without retinal cell repair, and / or trigger visual repair processes, including, but not limited to, beneficial modulation of nutrients and biological repair processes, including, but not limited to, regeneration of outer photoreceptors in subjects with diseased photoreceptors, retinal pigment epithelial cells, and / or Bruch's membrane, reprogramming of Muller cells, regeneration of retinal cells, and reduction of drusen volume.

[0050] Some embodiments of the exemplary retinal IDM devices and methods described herein repair and / or restore retinal cells and / or enhance retinal cell function with fewer adverse effects and increased patient convenience. One or more of the exemplary retinal IDM devices and methods described herein overcome the shortcomings and deficiencies of the prior art, including conventional devices and methods that repair retinal cells, enhance retinal cell function, or reduce progressive retinal cell damage by targeting different mechanisms with novel retinal IDMs, resulting in more comfortable, more convenient, and better treatment outcomes with fewer adverse systemic and ocular effects. In some exemplary embodiments described herein, the retinal IDM not only improves vision by altering neural computation and neural adaptation, but also improves vision by repairing and / or restoring retinal cells.In some embodiments described herein, the retinal IDM also triggers visual system repair processes, including biological repair processes, including, but not limited to, regeneration of outer photoreceptors, reprogramming of Muller cells, regeneration of retinal cells, and reduction of drusen volume; the retinal IDM reduces retinal irradiance from the visual field of a spatially separated retinal region in at least one of the foveal region, another PRL, a plurality of PRL, a non-PRL retinal region, a plurality of non-PRL retinal regions, or a combination thereof, by at least 0.1%, the reduction continuing over a long time scale as previously defined; the reduced retinal irradiance reduces deleterious processes, including, but not limited to, photooxidative stress, metabolic stress, or a combination thereof, in viable retinal cells, and reduces such deleterious processes. The reduction in processes includes, but is not limited to, sparing photoreceptors, slowing the progression of photoreceptor loss, reducing drusen volume, or combinations thereof; b. increasing retinal irradiance from the visual field over retinal regions (other than in a.), including regions having viable retinal cells, by at least 0.1%, the increase continuing over a long timescale as previously defined, the increased retinal irradiance enhancing activation by at least one of surviving cells of cell repair, cell regeneration, or a combination thereof, in at least one of the retinal regions having damaged or non-functional retinal cells; and c. redirecting spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information contained in the irradiance distribution from one or more dysfunctional regions of the retina to one or more functional regions.

[0051] In some exemplary embodiments described herein, the retinal IDM improves retinal sensitivity, including, but not limited to, improved sensitivity of viable cone photoreceptors, viable rod photoreceptors, viable ganglion cells, amacrine cells, viable bipolar cells, and / or partially or completely regenerated retinal cells. It is understood that retinal sensitivity can be measured by those skilled in the art by using diagnostic equipment, including, but not limited to, microperimetry equipment. In some exemplary embodiments described herein, the retinal IDM generates at least one of the following over a period of months or years in treated eyes with retinal diseases, including, but not limited to, macular degeneration: a. increased retinal sensitivity within the retinal area; b. reduced rate of loss of retinal sensitivity compared to untreated controls; c. reduced rate of photoreceptor loss compared to untreated controls; d. reduced area of ​​photoreceptor loss; e. reduced volume of drusen; f. regeneration of retinal cells; or g. any combination thereof.

[0052] In some exemplary embodiments described herein, the retinal IDM enhances retinal absorption of photons in some retinal regions and improves visual processing for visual acuity and retinal image quality, while reducing cumulative light absorption and photodamage in other retinal regions, including, but not limited to, the foveal region, other fixation regions, other macular regions, peripheral regions, and any combination of retinal regions in which cumulative light absorption and photodamage is to be reduced.

[0053] In some exemplary embodiments described herein, the retinal IDM selectively reduces light irradiance over regions including, but not limited to, the fovea, other fixation regions (eccentric viewing), other macular regions, peripheral retinal regions, and any combination of retinal regions, and selectively reduces oxidative stress and / or phototoxicity and / or reduces cumulative light damage to retinal structures including, but not limited to, photoreceptors, retinal pigment epithelial cells, Bruch's membrane, and choriocapillaris by reducing oxidative stress and / or phototoxicity in regions including, but not limited to, the fovea, other fixation regions (eccentric viewing), other macular regions, peripheral retinal regions, or any combination of retinal regions.

[0054] In some exemplary embodiments described herein, the retinal IDM provides beneficial effects including, but not limited to, selective prevention of photoreceptor loss, selective reduction in the rate of progression of photoreceptor loss, and reduction in photoreceptor loss, including, but not limited to, apoptosis and / or necrosis and / or pyroptosis and / or autophagy.

[0055] In some exemplary embodiments described herein, the retinal IDM selectively reduces light-induced oxidative stress and reactive oxygen species in retinal regions where irradiance is reduced, resulting in beneficial effects including, but not limited to, protecting photoreceptor DNA, promoting DNA repair, reducing pathophysiological innate inflammation, reducing inflammasome activation, reducing deleterious autophagy including, but not limited to, chaperone-mediated autophagy (also known as microautophagy), reducing retinal cell death via apoptosis, reducing activation of pro-inflammatory and pro-angiogenic pathways, and reducing oxidative stress and other deleterious processes associated with the resulting excess of reactive oxygen species.

[0056] In some exemplary embodiments described herein, the retinal IDM selectively reduces the photooxidation of the retinoid A2E in outer photoreceptors. In some exemplary embodiments described herein, the retinal IDM selectively reduces A2E formation in outer photoreceptors and / or promotes A2E reduction without the ocular adverse events related to delayed dark adaptation, such as night blindness, color blindness, blurred vision, and photophobia, of current investigational agents that reduce A2E formation.

[0057] In some exemplary embodiments described herein, the retinal IDM selectively reduces retinal irradiance and / or cumulative retinal irradiance in a retinal region to reduce oxidative phosphorylation in the retinal region and reduce reactive oxygen species, thereby preventing and / or reversing mitochondrial dysfunction. In some exemplary embodiments described herein, the retinal IDM reduces the metabolism 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 membrane in some retinal regions, resulting in beneficial effects including, but not limited to, reduced damage and / or repair and / or regeneration of 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 membrane in some retinal regions.

[0058] In some exemplary embodiments described herein, the retinal IDM selectively reduces retinal irradiance and / or cumulative retinal irradiance in some retinal regions and / or reduces oxidative stress, providing beneficial effects including, but not limited to, utilizing Müller glial cells for photoreceptor cell protection and / or regeneration, and / or increasing Müller glial cell transdifferentiation, and / or reducing Müller glial cell gliosis, and / or preventing deleterious retinal remodeling, and / or maintaining glutamine synthetase expression in Müller cells, and / or enabling the retinal microenvironment around Müller cells to support cone function.

[0059] In some exemplary embodiments described herein, the retinal IDM selectively reduces retinal irradiance and / or cumulative retinal irradiance in some retinal regions, thereby causing a reduction in drusen volume (i.e., the number and / or size of drusen).

[0060] In some exemplary embodiments described herein, the retinal IDM selectively reduces retinal irradiance and / or cumulative retinal irradiance in several retinal regions, resulting in beneficial effects including, but not limited to, beneficial modulation of nutrients, and regeneration and / or salvage of retinal cells (including, but not limited to, photoreceptors, retinal pigment epithelial cells, Muller glial cells, and ganglion cells) and retinal structures including Bruch's membrane and the outer limiting membrane.

[0061] 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 corneal photodisruption, intralenticular photodisruption, corneal photoionization, corneal photodissection, corneal photoablation, thermal keratoplasty, photowelding), corneal crosslinking systems, corneal radiofrequency generators, eyeglasses, contact lenses, corneal inlays, intraocular lenses for insertion into a phakic, aphakic or pseudophakic eye, and combinations thereof, that utilize designs, materials, and optics for retinal IDM to generate retinal illuminance distribution patterns in many regions of or throughout the retina and are configured to stabilize vision, improve vision, restore vision, or reduce the rate of vision loss compared to untreated controls following vision loss due to diseases involving damaged and / or dysfunctional and / or sensory-deprived retinal cells; and retinal IDM devices and a method configured to optically modify spatial, temporal, spatiotemporal, chromatic, achromatic, and contrast information distribution of environmental light from an ocular field of view with simultaneous light redirection from the fovea or another retinal fixation region to at least two other spatially separated retinal regions, with the modification permanently, temporarily, or varying over time within at least three retinal regions, including the fovea or another retinal fixation region, wherein the retinal regions are defined by ranges of polar coordinates, the spatially separated retinal regions are non-overlapping regions, partially overlapping regions, or any combination of non-overlapping regions and partially overlapping regions, the amount and placement of retinal IDM is for a predetermined spatial distribution with or without a predetermined temporal distribution, and the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, chromatic, 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 that simultaneously optically redirects light from a partially or completely dysfunctional retinal region and redirects the light, in whole or in part, onto one or more functional retinal regions, and the retinal irradiance distribution modification includes information including, but not limited to, spatial, temporal, spatiotemporal, chromatic, 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 retinal IDMs, the amount and arrangement 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 arrangement of such retinal IDMs are for a predetermined spatial distribution with or without a predetermined temporal distribution, the amount and arrangement of retinal IDMs have a pattern and symmetry that is different from that caused by self-generated image modifications including, but not limited to, i) eye movements that cause a single translational movement of the entire field on the retina, ii) lens accommodation that causes a change in focus of the entire field on the retina, iii) pupil dilation / constriction that causes rapid lightening / darkening of the entire field on the retina, which prevents the central brain from being able to compensate and thus partially counteract the effect of the retinal IDM, and the retinal IDM inhibits at least one visual pathway used for fixation without the need for eye movements and / or perceptual training, and provides at least one alternative functional visual pathway for fixation within the eye. The retinal IDM excites a visual pathway that is functional in the visual sense, and the retinal IDM produces in the treated subject the perception of at least one or more alternative functional visual pathways without the need for eye movement and / or sensory training, and the retinal IDM may also produce beneficial effects including, but not limited to, reduction in damage and / or repair and / or regeneration of damaged retinal structures, including, but not limited to, retinal cells (including, but not limited to, photoreceptors, retinal pigment cells, Muller glial cells, ganglion cells) and Bruch's membrane in several retinal regions, and the retinal IDM may reduce retinal cell damage, Improve vision following vision loss due to one or more of a disease, injury, or disorder, including one or more of retinal cell dysfunction, retinal cell sensory deprivation, or any combination thereof, where the vision improvement is configured to result in improved vision-related outcomes including, but not limited to, visual acuity (including both uncorrected and best spectacle-corrected visual acuity for distance, intermediate, and near vision), hyperacuity, depth of focus, color vision, peripheral vision, contrast sensitivity, stereoacuity, vernier acuity, light adaptation, dark adaptation, vision-related quality of life, or any combination thereof.

[0062] Some of the exemplary retinal IDM devices and methods described herein modify the cornea of ​​the eye. In some corneal embodiments, a laser retinal IDM device is used to modify the radius of curvature (ROC) of the cornea as shown diagrammatically in FIG. 7. In an unmodified cornea, light rays incident at points 1 and 2 are focused on the fovea, as shown by the solid lines in FIG. 7. Reducing the ROC at points 1 and 2 (not shown in FIG. 7) redirects the light rays to illuminate locations L1 and L2 outside the fovea. In FIG. 7, the modified ROC at point 2 is more greatly reduced compared to the modified ROC at point 1, both of which are reduced with respect to the unmodified radius of curvature, where the greater the reduction in the radius of curvature at point 2, the greater the redirection of the light rays illuminating location L2, which is a greater distance away from the fovea compared to the light rays illuminating location L1. The relocation of light rays at any point on the cornea can be caused by corneal modifications, including but not limited to, modifications of the corneal radius of curvature, corneal refractive index, corneal diffraction, corneal scattering, and any combination of these corneal modifications. It is understood that the sample rays shown in FIG. 7 are only representative of the entire set of light rays that are mapped from object space to image space on the retina. In some exemplary embodiments described herein, the retinal IDM includes light ray relocation caused by corneal modifications in two or more corneal regions, including but not limited to, from the central sector to the paracentral sector, extending to an optical zone of 7 mm or more with sectors that alternate between steep and flat within a full 360° angular range on the cornea.

[0063] 8 is a retinal schematic diagram showing a fovea A with a central dysfunctional region B. In this case, a retinal IDM device, including but not limited to a corneal modifying device, should be designed to redirect light rays having spatiotemporal, contrast, chromatic, and achromatic information away from the central dysfunctional region B to a functional retinal region, including but not limited to a functional region of the fovea outside region B. FIG 9 is a retinal schematic diagram illustrating a four-quadrant retinal IDM that can be generated by using a retinal IDM device to retinal IDM from a central dysfunctional retinal region to four functional retinal regions.

[0064] Figure 10 shows dysfunctional and functional retinal regions having various shapes and arrangements on the retina. It will be understood by those skilled in the art that any retinal IDM device should be configured to generate retinal IDMs on functional retinal regions in a direction away from dysfunctional retinal regions (B, C, and D in the example of Figure 10), where functional retinal region E is a candidate region where retinal IDMs may be used for vision and visual function improvement.

[0065] Some embodiments of retinal IDM devices and methods generate a treatment pattern of corneal radius of curvature (ROC) shown in FIG. 11A, and an expanded portion of FIG. 11A shown in FIG. 11B. FIG. 11B shows boundaries of 0.1 mm increments in radius of curvature, but the actual ROC varies continuously from one incremental boundary to another. FIG. 12 shows a continuous ROC profile that approximates the ROC profile along the 30°-210° meridian of the treatment pattern shown in FIG. 11A. The ROC can be symmetric as shown in FIG. 12, or asymmetric with variable shape. The placement of the minimum ROC may be centered or off-center with respect to the pupil centroid (or another central reference). As an example, if an untreated cornea has an ROC of about 7.6 mm in the central optical zone (within a 3 mm diameter), the treated cornea may have an ROC within the range of 7.2-7.8 mm in the same zone. Some embodiments of IDM treatment also induce significant ROC changes throughout the cornea, extending into the peripheral cornea at the 7 mm optical zone. The resulting IDM treatment changes can be approximately described as four sets of alternating steep / flat sectors in the central (3 mm diameter) optical zone surrounded by four sets of flat regions in the paracentral cornea between approximately the 5 and 7 mm optical zone, as shown in FIG. 11A. The ROC changes induce redirection of light rays from four aspheric elongated "lenslets" that redirect retinal irradiance onto functional retinal regions similar to those illustrated in FIG. 9, as well as from other regions of the cornea. The ROC patterns shown in FIGS. 11A and 11B are generated by a retinal IDM device inducing IDM treatment of four small volumes of corneal stromal tissue located beneath the superficial treatment region, shown as small white circles on FIG. 11A. Due to the biomechanical properties of the cornea, the highly localized treatment within four small volumes of corneal stromal tissue produces a non-localized effect that extends from each treatment volume toward the center of the cornea, with a peak effect approximately halfway between the treated volume and the center of the cornea.Some embodiments of IDM treatments produce non-localized ROC changes across the entire cornea extending from the center of the cornea to at least 7 mm of the optical zone.

[0066] In some exemplary embodiments described herein, the device for retinal IDM uses various patterns, including but not limited to, four circular non-central volume treatments, to produce corneal modifications throughout the cornea, including but not limited to, modifications of corneal radius of curvature, corneal refractive index, corneal diffraction, corneal scattering, and any combination of these corneal modifications. In corneal radius of curvature modifications, the IDM treatment induces various non-central locations and magnitudes of major depressions and / or elevations in the anterior corneal surface, resulting in an increase and / or decrease in the anterior corneal radius of curvature throughout the cornea.

[0067] 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, the retinal IDM produces a decrease or increase in irradiance and / or contrast in retinal regions and / or microregions, and the changed ratio of light and dark edges of objects in the field of view changes the irradiance contrast. In some embodiments, the exemplary pattern for the retinal IDM is centered on the pupil centroid (PC) or the corneal apex (CV) or the coaxial viewing corneal light reflex (CSCLR). In some embodiments, the pattern for the retinal IDM is off-centered with respect to the PC, CV, or CSCLR.

[0068] In some exemplary embodiments described herein, retinal IDM does not cause adverse 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 light or light-emitting diode (LED) light to irradiate the retina, and some IDM embodiments use only natural ambient light to irradiate the retina, thus eliminating the adverse retinal effects associated with exposing the retina to laser light and other non-natural non-ambient light. In some embodiments of IDM treatment, only "eye-safe" light is used to irradiate the cornea, and "eye-safe" light is completely absorbed by the cornea and other preretinal eye structures, thereby preventing direct irradiation of the retina.

[0069] In some exemplary embodiments described herein, the retinal IDM continues to compensate for ongoing damage or loss of function of retinal cells from the underlying disease process for months to years after treatment. In some embodiments, the ongoing neural compensation for ongoing damage or loss of function of retinal cells from the underlying disease process is facilitated by ongoing changes in the retinal IDM produced by one or more of the exemplary methods described herein, for example, allowing for changes in the depression and / or elevation of the anterior corneal surface over days, weeks, months, or years. A portion of the anterior corneal curvature gradually changes over days, weeks, months, or years to continue to compensate for ongoing damage or loss of function of retinal cells throughout the cornea.

[0070] In some exemplary embodiments described herein, the amplitude of the corneal ROC change due to IDM treatment decreases over time. In some exemplary embodiments described herein, IDM treatment can be modified by changing the treatment pattern and / or treatment energy density delivered to the cornea to make the IDM change in the corneal ROC temporary for various periods of time. The temporary IDM-induced ROC change is particularly useful for treating amblyopia in children, adolescents, and young adults. IDM treatment of both eyes of an amblyopic subject can prevent the vision impairment caused by conventional amblyopia treatment with monocular deprivation. IDM treatment of both eyes of an amblyopic subject can improve binocular vision in normal daily functioning, in contrast to conventional monocular methods. Binocular vision is inhibited by monocular deprivation treatment for amblyopia and is not usually improved in daily functioning when conventional binocular vision training is performed with or without video games. IDM treatment of both eyes of a subject does not prevent the use of peripheral vision of both eyes. The peripheral vision of amblyopic subjects is usually normal and may be impaired by occlusion therapy, which may contribute to the improvement of central vision in the amblyopic eye after IDM treatment.

[0071] In application of some embodiments of the retinal IDM device, IDM treatment of eyes with age-related macular degeneration (AMD) using a treatment pattern similar to FIG. 11A results in significant retinal IDM vision improvements in mean best spectacle-corrected distance and near visual acuity (CDVA and CNVA), contrast sensitivity and other visual functions, and vision-related quality of life. Distance and near versions of the ETDRS eye chart are available to measure distance and near visual acuity, respectively. ETDRS measurements are reported in several ways in terms of Snellen values, logMAR values, decimal values, and / or number of letters read correctly (starting with 0 letters for a Snellen value of 20 / 1000). Vision improvement is often reported in terms of number of letters gained and / or number of lines gained on the ETDRS eye chart, which has 5 letters per line.

[0072] It can be understood by those skilled in the art that individualized customized retinal IDM treatments can be performed by one or more of the exemplary retinal IDM devices and methods described herein. These individualized customized retinal IDM treatments can be performed based on diagnostic information, including, but not limited to, individualized optical coherence tomography, microperimetry, high definition perimetry, and fundus autofluorescence examination.

[0073] In some embodiments described herein, retinal IDM treatment patterns can be configured based on the degree of macular damage and visual field defects to improve the visual acuity of glaucoma patients. Glaucomatous damage to the macula occurs early in the disease process and is more prevalent in the upper visual field, where focal and deep arcuate defects may appear near fixation. Early glaucomatous damage causes a significant decrease in binocular contrast sensitivity scores and depth perception, which can be improved by bilateral retinal IDM.

[0074] FIG. 13 shows uncorrected and corrected retinal irradiance distributions that illustrate the effect of the central dysfunctional retinal region (shaded gray). In the uncorrected retinal irradiance distribution (top graph), only a small portion of light (4.3%) illuminates the functional retinal region outside the dysfunctional retinal region. Conventional correction by 2× magnification as caused by IMT implantation (bottom left graph) increases the useful retinal irradiance to 30%, which is outside the dysfunctional retinal region and inside the functional retinal region. The optimized correction described herein (bottom right graph) produces a retinal IDM similar to that shown in FIG. 7, increasing the useful retinal irradiance to 83%, which is outside the dysfunctional retinal region and therefore inside the functional retinal region. Conventional correction by magnification, which is the basis of IMT and similar intraocular telescope devices, has always been of limited effectiveness in improving the vision of eyes with central vision loss. In addition, IMT devices cause "tunnel vision" due to the limited field of view of the telescope optics. Corneal treatment according to some of the exemplary embodiments described herein is highly effective in improving vision in eyes with central vision loss, and also improves peripheral vision rather than causing "tunnel vision."

[0075] Some exemplary embodiments described herein involve IDM devices and methods configured to generate corneal modifications, including but not limited to, corneal radius of curvature modification, corneal refractive index modification, corneal diffraction, corneal scattering, and any combination of these corneal modifications, for redirecting light from the fovea or another retinal fixation area to at least two other retinal areas for retinal IDM. These embodiments include corneal devices and methods for, but not limited to, corneal photodisruption, corneal photoionization, corneal dissection, corneal photoablation, photothermal keratoplasty (LTK), corneal photowelding, corneal crosslinking (CXL), conductive keratoplasty (CK), and corneal inlays, all configured for retinal IDM. For optimal retinal IDM, the change in radius of curvature and / or refractive index should create as much retinal IDM as possible outside the dysfunctional retinal area and inside the functional retinal area. IDM treatment devices and methods may be configured to produce corneal radius of curvature (ROC) changes, including but not limited to those shown in Figures 11 and 12 for anterior corneal ROC changes to the retinal IDM. IDM treatments and devices may be configured to produce natural crystalline lens radius of curvature or refractive index modifications to the retinal IDM using devices, including but not limited to femtosecond lasers for photodisruption. It is understood that corneal modifications may occur initially (first modifications) and at later times (subsequent modifications).

[0076] In some exemplary embodiments described herein, femtosecond (FS) or nanosecond lasers may be used to produce intrastromal photodisruption or photoionization or photodissociation or any combination thereof for retinal IDM with corneal modification. FIG. 14 illustrates a schematic cross-sectional view through a cornea that has undergone a femtosecond (FS) laser treatment (Tx) pattern configured to generate a retinal IDM. In the illustrated example, the intrastromal FS laser irradiation is configured to remove an intrastromal corneal volume that results in a depression (depth is exaggerated in FIG. 14), and thus the radius of curvature (ROC) changes at the anterior corneal surface; alternatively, the FS laser irradiation may be configured to generate other corneal modifications, including but not limited to, intrastromal refractive index modifications, intrastromal diffraction modifications, intrastromal scattering modifications for retinal IDM. Any combination of corneal modification changes may be used for retinal IDM. The FS laser pattern for corneal tissue removal or refractive index change may be spherical as shown in FIG. 14, or may have any volumetric shape. The FS treatment volume may be placed at any depth within the corneal stroma. Two or more FS treatment volumes may be generated centrally (within the 3mm optical zone), paracentrally (within the 3 to 6mm optical zone), or peripherally (>6mm optical zone), with the treatment pattern being centered or off-centered with respect to the pupil centroid or another central reference. The treatment volumes may be equal or unequal in shape and / or depth to produce a custom effect. Unlike FS annular intrastromal treatments previously used for other applications such as presbyopia correction, FS laser correction is not a 360 degree annular volume and therefore does not induce corneal expansion.

[0077] In some exemplary embodiments described herein, laser tissue removal procedures, including but not limited to laser photodisruption, photoionization or photodissociation, and / or laser photoablation devices and methods, including but not limited to small incision lenticule extraction (SMILE), laser in situ keratotomy (LASIK) and laser photorefractive keratectomy (PRK) devices and methods, may be used to generate corneal modifications useful for retinal IDM. Figure 12 shows a cross-section of a cornea with an anterior ROC profile configured to be useful for retinal IDM. Laser tissue removal procedures, including but not limited to femtosecond laser treatment to form a corneal lenticule for SMILE treatment, and laser photoablation of the stromal bed for LASIK and PRK treatment, should be configured to cause sufficient corneal modifications to provide retinal IDM.

[0078] In some exemplary embodiments described herein, for corneal crosslinking (CXL) procedures, corneal crosslinking devices, including but not limited to ultraviolet A (UVA) light emitting devices, LTK devices, and other devices that may be combined with photosensitizers, including but not limited to riboflavin, or other photoactivation systems with photoactivators, including but not limited to glyceraldehyde, glutaraldehyde, genipin, nitroalcohol, or formaldehyde-releasing agents, are configured to generate focal regions of crosslinking (FCXL). In some embodiments of FCXL IDM procedures, non-treated corneal regions are masked from UVA light or other light or photoactivators within two or more spatially separated treatment regions of the cornea to administer retinal IDM. FCXL may be performed with or without the removal of all or part of the corneal epithelium to enhance penetration of the photosensitizer into the corneal stroma, including but not limited to administration of a photosensitizer (including but not limited to riboflavin) to the cornea followed by UVA or other light exposure. FXCL may also be performed using high irradiance (10 W / cm2) lasers, including but not limited to GaN diode lasers and diode-pumped solid-state (DPSS) lasers operating in the 360 ​​to 460 nm wavelength region.2 FXCL IDM devices and methods can also be created by combining laser thermokeratoplasty+CXL using a photosensitizer, including but not limited to riboflavin, activated by a visible or UVA light source of irradiance of 100 nm or more. The FXCL IDM devices and methods are configured to generate corneal modifications, including but not limited to corneal radius of curvature modifications, shown in Figures 11 and 12, using various treatment patterns, including but not limited to two or more non-central treatments inducing various configurations and amplitudes of corneal modifications to redirect light away from the fovea to two other retinal regions. Within each treatment pattern, the FCXL is configured to generate a treatment volume that is at least 0.1 mm in diameter and located paracentrally (within the 3 to 6 mm optical zone) or peripherally (>6 mm optical zone), with the treatment pattern being centered or off-centered with respect to the pupil centroid or another central reference.

[0079] In some exemplary embodiments described herein, conventional corneal reshaping procedures and devices, including but not limited to conductive keratoplasty (CK), and devices, including but not limited to radio frequency emitting devices, are configured to generate corneal modifications in two or more spatially separated treatment regions of the cornea relative to the retinal IDM. The CK-generated corneal modifications include, but are not limited to, corneal radius of curvature modifications as illustrated in Figures 11 and 12 using various treatment patterns, including but not limited to, two or more non-central treatments inducing various placements and amplitudes of ROC modifications. Within each treatment pattern, the CK is configured to generate a treatment volume that is at least 0.1 mm in diameter and located paracentrally (within the 3 to 6 mm optical zone) or peripherally (>6 mm optical zone), with the treatment pattern being centered or off-centered with respect to the pupil centroid or another central reference.

[0080] In some exemplary embodiments described herein, the retinal IDM is generated by the insertion of an intraocular lens (IOL) and / or an intraocular lens accessory device (IOLAD) configured to modify the retinal IDM. The IOLAD includes, but is not limited to, a light steering structure, including, but is not limited to, a refractive structure, a diffractive structure, or any combination thereof that operates in combination with the IOL to modify the retinal IDM. IOLs and IOLADs for phakic, aphakic, or pseudophakic eyes include, but are not limited to, IOLs and IOLADs positioned in the sulcus or lens, anterior chamber IOLs and IOLADs, iris-fixed IOLs and IOLADs, and transscleral sutured IOLs and IOLADs. FIG. 15 illustrates IOL modifications suitable for the retinal IDM, including four paracentral regions with IOL modifications including, but are not limited to, IOL radius of curvature, IOL refractive index, IOL diffraction, IOL scattering modifications, and any combination of those IOL modifications, compared to other regions of the IOL. In the case of IOL diffractive corrections, the exemplary corrections described herein are distinct from the annular (ring-like pattern centered on the IOL lens center) corrections used in diffractive multifocal IOLs; FIG. 15 illustrates four separate paracentral regions, one or more of which incorporate IOL diffractive corrections. Additional IOL modifications include, but are not limited to, the inclusion of a light steering structure (including, but not limited to, one or more reflectors, one or more optical fibers, one or more prisms, or any combination of light steering structures) in at least one paracentral region of the IOL. It is understood that two, three, or more spatially separated central, paracentral, or peripheral regions may be used to generate an IOL correction in any or all of the regions for redirecting light to two or more retinal regions in a direction away from the fovea or another retinal fixation region, with or without overlap of the regions.It is also understood that IOL and IOLAD modifications can be configured within the IOL and IOLAD before and / or after IOL and IOLAD insertion, after which a FS laser, another light source, and / or electronic means may be used to generate IOL and IOLAD modifications in situ, thereby generating adjustments to IOL and IOLAD radii of curvature, IOL and IOLAD refractive index, IOL and IOLAD light steering structures, IOL and IOLAD diffraction, IOL and IOLAD scattering, and any combination of these adjustments.

[0081] FIG. 16 illustrates an IOL modification suitable for retinal IDM that includes two or more prisms that direct irradiance onto a functional region 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 overlapping regions to modify the radius of curvature and / or refractive index in any or all of the regions, and two or more prisms may be used for retinal IDM. For optimal retinal IDM in an eye with a dysfunctional retinal region, the change in radius of curvature, the change in refractive index, the prism effect, or any combination thereof should create as much retinal IDM as possible outside the dysfunctional retinal region and inside the functional retinal region.

[0082] Some exemplary embodiments described herein involve a retinal IDM generated by spectacles, contact lenses, or any combination thereof, with modifications including, but not limited to, radius of curvature, refractive index, diffraction, scattering modifications, and any combination of modifications, for redirecting light away from the fovea or another retinal fixation region to at least two other retinal regions configured to generate a retinal IDM. FIG. 17 shows a cross-sectional view of a modified contact lens (CL, dimensions: diameter 8 mm, thickness 0.2 mm, anterior and posterior radius of curvature 7.8 mm) including a paracentral steepening region designed to redirect retinal irradiance from dysfunctional retinal regions to functional retinal regions. The CL dimensions may differ from those shown to include smaller or larger diameters, thicknesses, and radii of curvature. Spectacle lenses may also be designed for retinal IDM. The spectacle lens (SL) and CL may be fabricated from a single material or multiple materials. The CL may be corneal, scleral, 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, placing light steering structures, including but not limited to at least one reflector and at least one optical fiber array, in one or both eyeglass lenses. There may be one, two, or more modified regions located centrally, paracentrally, or peripherally within the CL diameter and / or SL shape. SLs and CLs may be used in one eye, both eyes, or in any combination of SL and CL. All SL and CL properties, dimensions, and modifications are designed to direct light rays to an optimal retinal irradiance distribution for the patient retinal IDM requirements. The SL and CL can be statically or actively configured, with static configuration being completed prior to incorporation into the visual system, and active configuration being achieved one or more times after incorporation into the visual system using adjustments including, but not limited to, electronic and / or photonic adjustments to corneal radius of curvature changes, refractive index changes, diffraction changes, scattering changes, and any combination of these changes.

[0083] Some further exemplary embodiments described herein involve using a "trial" spectacle lens (SL), a "trial" contact lens (CL), or any combination thereof, for screening and / or customization purposes. In screening applications, the "trial" lens may help determine whether the patient's eye can achieve vision and visual function improvement with retinal IDM devices and methods. In customization applications, the "trial" lens may have characteristics altered to determine the optimal retinal IDM configuration. In both screening and customization applications, it may be desirable for the patient to use the "trial" lens for an extended period of days or weeks to obtain the beneficial effects of neuroadaptation.

[0084] Some exemplary embodiments described herein involve a retinal IDM created by a corneal inlay (CI). FIG. 18 shows a corneal inlay (CI) implanted in the cornea, the corneal segment shown is about 1.8 mm long with a central thickness of 0.55 mm, although the corneal segment can have a length extending to about 11 mm. Two lenses are shown on the inlay, which can have the same or different modifications, including but not limited to radius of curvature, refractive index, diffraction, scattering modifications, and any combination of these modifications. The CI shape can be circular or non-circular. The dimensions of the CI include but are not limited to length 1 to 8 mm, width 1 to 8 mm, diameter 3 to 8 mm, and uniform or variable thickness within the range of 0.01 to 0.5 mm. There can be one, two, or more inlays, each with zero, one, two, or more lenses. The inlay can be centrally located as shown in FIG. 18, or can be off-centered. The inlays may be implanted at depths including, but not limited to, 0.05 to 0.5 mm from the anterior corneal surface. The lens on each corneal inlay may be placed at any location on each inlay. The CIs are composed of materials including hydrogels, biocompatible materials, and other materials known to those skilled in the art. The corneal inlays may be statically or actively configured, with static configuration being completed prior to implantation within the cornea, and active configuration being achieved one or more times after implantation within the cornea using tuning including, but not limited to, electronic and / or photonic tuning of corneal radius of curvature changes, refractive index changes, diffraction changes, scattering changes, and any combination of these changes.

[0085] In some exemplary embodiments described herein, the retinal IDM devices and methods combine retinal IDM teachings with prior art retinal treatments, including pharmacological and / or retinal laser and / or radiation and / or stem cell transplantation and / or epigenetic and / or genetic and / or nutritional and / or age-related retinal diseases (hereinafter "retinal diseases"). The exemplary retinal IDM devices and methods described herein overcome the shortcomings and deficiencies of the prior art by introducing different mechanisms of 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 deficiencies of the prior art by synergistically combining them with retinal IDM along with other therapies to improve visual and / or anatomical outcomes and also improve patient compliance with the prior art therapies. The combination therapy may be administered during the same patient visit or sequentially at different times. In some embodiments of the combination therapy, the retinal IDM therapy is administered once, either before the non-retinal IDM therapy or at a time after the initiation of the non-retinal IDM therapy. In some embodiments of the combination therapy, the retinal IDM therapy is administered separately, either before the other therapy or at variable times after the initiation of the non-retinal IDM therapy.

[0086] In some exemplary embodiments described herein, retinal IDM treatments are combined with other therapies for retinal diseases, including but not limited to retinal laser therapy, including but not limited to photobiomodulation, 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, microtrabeculectomy, internal or external tube shunt implantation, suprachoroidal shunt implantation), stem cell transplantation, and radiation therapy (including but not limited to focal intraocular strontium 90 beta radiation).

[0087] In some embodiments of the exemplary retinal IDM devices and methods described herein, retinal IDM treatments are combined with other treatments for retinal diseases, including, but not limited to, genetic, epigenetic, and photogenetic therapies.

[0088] In some exemplary embodiments described herein, retinal IDM therapy is combined with pharmacological treatment of retinal diseases, including pharmacological agents, including nutritional agents, given orally, topically to the cornea, via subconjunctival injection, via intravitreal injection, intraretinal, via an implant, and via iontophoresis.

[0089] In some exemplary embodiments described herein, retinal IDM treatment is combined with anti-angiogenic drug therapy.

[0090] In some exemplary embodiments described herein, the retinal IDM provides a method for improving or treating ocular diseases, including but not limited to macular degeneration, choroidal neovascularization, or diabetic retinopathy in a subject, including treatment with the retinal IDM, in combination with administering a therapeutically effective amount of any vascular endothelial growth factor (VEGF) antagonist, including but not limited to ranibizumab, bevacizumab, brolucizumab, and aflibercept, in combination with administering a therapeutically effective amount of any PDGF antagonist, including but not limited to volociximab and P200, or in combination with any combination of the above drugs. As used herein, the term "improve" or "treat" or "compensate" means that the clinical signs and / or symptoms associated with an ocular disease (e.g., macular degeneration) are alleviated as a result of the action taken. The signs or symptoms to be monitored are characteristic of ocular diseases and are familiar to a physician skilled in the art, as are the methods for monitoring the signs, symptoms, and conditions.

[0091] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administration of a therapeutically effective amount of betalanib or pazopanib or any other tyrosine kinase inhibitor or any other inhibitor of phosphorylation of VEGF and PDGF receptors to improve or treat ocular diseases including macular degeneration, choroidal neovascularization, or diabetic retinopathy in a subject comprising treatment with a retinal IDM.

[0092] In some exemplary embodiments described herein, a retinal IDM provides a method of treating an ocular disease in a subject comprising treatment with a retinal IDM in combination with administration of a therapeutically effective amount of an inhibitor of VEGF activity.

[0093] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administering a therapeutically effective amount of an inhibitor of α5β integrin activity to treat or ameliorate an ocular disease in a subject, comprising treatment with a retinal IDM.

[0094] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administering a therapeutically effective amount of an inhibitor of PDGF activity to treat or ameliorate ocular diseases, including but not limited to, neovascular ocular diseases and / or wet macular degeneration, and / or diabetic retinopathy, in a subject comprising treatment with a retinal IDM.

[0095] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administering a therapeutically effective amount of an inhibitor of tyrosine kinase activity to treat or ameliorate ocular diseases, including, but not limited to, neovascular ocular diseases and / or wet macular degeneration, and / or diabetic retinopathy, in a subject comprising treatment with a retinal IDM.

[0096] In some exemplary embodiments described herein, the retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, neovascular ocular diseases and / or wet macular degeneration, and / or diabetic retinopathy, in a subject comprising treatment with the retinal IDM in combination with administering a therapeutically effective amount of an mTOR inhibitor (sirolimus).

[0097] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administering a therapeutically effective amount of fluocinolone acetonide or any other anti-inflammatory agent to treat or ameliorate ocular diseases, including but not limited to, neovascular ocular diseases and / or wet macular degeneration, and / or diabetic retinopathy, in a subject, comprising treatment with a retinal IDM, wherein the anti-inflammatory agent is delivered by intravitreal injection or by an intraocular implant.

[0098] In some exemplary embodiments described herein, retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM in combination with administering a therapeutically effective amount of an active inhibitor of complement, including but not limited to, complement 3 or 5.

[0099] In some exemplary embodiments described herein, retinal IDM is provided in combination with administering a therapeutically effective amount of avacincaptado pegol, LEG316, POT￢4, eculizumab, JPE-1375, ARC1905, or any other complement inhibitor to treat or ameliorate ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM.

[0100] In some exemplary embodiments described herein, the retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with the retinal IDM in combination with administering a therapeutically effective amount of doxycycline.

[0101] In some exemplary embodiments described herein, retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM in combination with administering a therapeutically effective amount of glatiramer acetate or other T helper 2 inducer or immunomodulatory agent.

[0102] In some exemplary embodiments described herein, retinal IDM is provided in combination with administering a therapeutically effective amount of OT551, or other down-regulators of overexpression of the protein complex nuclear factor (NF)￢B or other antioxidants, or combinations of antioxidants, including, but not limited to, combinations of vitamin C, vitamin E, beta-carotene or lutein and zeaxanthin, and omega-3 fatty acids, such as, for example, those in the Age-Related Eye Disease Study (AREDS) and AREDS 2 studies, to treat or ameliorate ocular diseases, including, but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM.

[0103] In some exemplary embodiments described herein, retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM in combination with administering a therapeutically effective amount of nicotinamide adenine dinucleotide (NAD) or any precursor of NAD, including but not limited to, nicotinamide riboside or nicotinamide mononucleotide.

[0104] In some exemplary embodiments described herein, the retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with the retinal IDM in combination with administering therapeutically effective amounts of nutrients, including but not limited to, pigment epithelium-derived factor (PEDF), fibroblast growth factor (FGF), and lens epithelium-derived growth factor (LEDGF).

[0105] In some exemplary embodiments described herein, retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM in combination with administering a therapeutically effective amount of ciliary neurotrophic factor (CNTF) or any other neurotrophic factor or any other inhibitor of photoreceptor apoptosis.

[0106] In some exemplary embodiments described herein, a retinal IDM is provided for the treatment or amelioration of an ocular disease, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with a retinal IDM in combination with administering a therapeutically effective amount of a neuroprotective agent, including but not limited to, brimodinin.

[0107] In some exemplary embodiments described herein, retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration, in a subject comprising treatment with retinal IDM in combination with administering a therapeutically effective amount of a Fas inhibitor or other agent designed to protect retinal cells from cell death.

[0108] In some exemplary embodiments described herein, the retinal IDM provides methods of treating or ameliorating ocular diseases, including but not limited to, geographic atrophy and / or dry macular degeneration and / or neovascular macular degeneration and / or glaucoma, in a subject comprising treatment with the retinal IDM in combination with administering a therapeutically effective amount of a statin, including but not limited to, atorvastatin, lovastatin, rosuvastatin, fluvastatin, or simvastatin.

[0109] In some exemplary embodiments described herein, the retinal IDM provides methods of treating or ameliorating an ocular disease, including but not limited to glaucoma or ocular hypertension, in a subject comprising treatment with the retinal IDM in combination with administering a therapeutically effective amount of an intraocular pressure (IOP)-reducing 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.

[0110] In some exemplary embodiments described herein, a retinal IDM is provided in combination with administration of a therapeutically effective amount of a pharmacological agent to treat or ameliorate ocular diseases, including but not limited to glaucoma, in a subject comprising treatment with a retinal IDM, to reduce retinal ganglion cell dysfunction and / or pathology associated with ischemia or excitotoxicity.

[0111] In some exemplary embodiments described herein, the retinal IDM provides methods for treating or ameliorating ocular diseases, including but not limited to, glaucoma, in a subject comprising treatment with the retinal IDM in combination with administering a therapeutically effective amount of a pharmacological agent that reduces excess excitatory amino acid (EAA) stimulation (EAA allow bipolar and amacrine cells to communicate with ganglion cells), including but not limited to, glutamate antagonists and / or any combination of a glutamate antagonist and at least one IOL lowering agent.

[0112] In some exemplary embodiments described herein, a retinal IDM is provided that treats or ameliorates an ocular disease, including but not limited to, glaucoma, in a subject comprising treatment with a retinal IDM in combination with administering a therapeutically effective amount of a pharmacological agent that provides neuroprotection and / or neuroregeneration of retinal ganglion cells, including but not limited to, a Rho-kinase (ROCK) inhibitor or an adenosine receptor agonist.

[0113] The retinal location used by the eye to attempt fixation on a visual target is known as the eccentric field of fixation (e.g., "PRL"). The PRL of an eye may be determined by visual fixation, e.g., the eye fixating on a light. The PRL may also be determined by perimetry or microperimetry. For example, the PRL may correspond to the common center of gravity of a group of fixation points in microperimetry. In some cases, the retinal location of the PRL may be described with respect to the center of the fovea of ​​the eye, or with respect to an estimated center of the fovea, and may be specified in terms of polar coordinates r,θ or r',θ, where r is a distance in mm, or r' is a distance in degrees for retinal eccentricity, and θ is an angular coordinate.

[0114] The PRL in normal-sighted eyes is located within the fovea, but not necessarily at the foveal center. Furthermore, in normal-sighted eyes, the PRL is usually located within the foveal region. The fovea covers only about 1° of visual angle, which corresponds to less than 0.1% of the visual field. In some cases, the PRL may be displaced from the location of the highest foveal cone by an average of about 10 minutes of angle in normal-sighted eyes. Furthermore, in some cases, there may be no correlation between the magnitude of the offset from the PRL and the corresponding foveal specialization measurements, including but not limited to pit volume, FAZ area, and peak cone density.

[0115] The PRL is located within the fovea or eccentrically relative to the fovea in eyes with central retinal damage or defects. The visual system includes the ocular and brain elements that capture and process visual information, as illustrated in Figures 3 and 4. The spatial and temporal characteristics of neural processing within the visual system are factors that influence the placement of the eccentric field of fixation. Furthermore, minimal fixation eye movements are known to have an amplitude between about 0.01° and about 0.1°.

[0116] In some examples described herein, the method and device can cause the redirection of ambient light away from the PRL of the eye to a plurality of retinal locations that are not PRL. One or more of these exemplary methods and devices can cause the safe and effective redirection of ambient light from within the visual field of the eye to a plurality of retinal locations that are not PRL away from the PRL of the eye. In some cases, one or more of these exemplary methods and devices can cause the redirection to shift the common center of gravity of the group of fixation points of the eye by at least 0.01°, for example, as measured by microperimetry. In some cases, one or more of these exemplary methods and devices can cause the redirection to shift the common center of gravity of the group of fixation points of the eye by at least 0.1°, for example, as measured by microperimetry.

[0117] Further, in some cases, one or more of the exemplary methods and devices described herein may cause the redirection of light away from the PRL of the eye to multiple non-PRL retinal locations to enhance neural integration and perception of visual information within the visual field and promote ongoing neural adaptation, e.g., modify visual search, retinal sampling, and stimulation of retinal and brain cells to "reboot" the visual system, including the eye and brain.

[0118] One or more of the exemplary methods and devices described herein may reboot the visual system to safely and effectively improve and / or restore vision. Vision may include, but is not limited to, discrimination of spatial detail, visual acuity (including uncorrected and / or best spectacle-corrected visual acuity for distance, intermediate and / or near vision), hyperacuity, stereoacuity, vernier acuity, contrast sensitivity, depth of focus, color vision, peripheral vision, night vision, facial recognition, light adaptation, dark adaptation, visual field and / or vision-related quality of life, or any combination thereof.

[0119] Additionally, one or more of the exemplary methods and devices may reboot the visual system, which may include, but is not limited to, (i) integrating additional and / or better encoded retinal information from macular and peripheral retinal cells, including but not limited to, photoreceptors, bipolar cells, amacrine cells, horizontal cells, Muller glial cells, ganglion cells, or any combination of retinal cells, to improve neural computations and allow for more complete processing of stimulus patterns, (ii) improving the function of retinal circuits, including connectivity functions in visual processing involving photoreceptors, ganglion cells, amacrine cells, bipolar cells, horizontal cells, and Muller cells, or any combination thereof, and / or (iii) triggering a process of neural adaptation, including but not limited to, the use of alternative, potential, and / or new visual pathways in the retina and brain, to integrate visual information encoded by peripheral regions of the retina, The present invention may include any or any combination of triggering, including rerouting to neurons at higher levels of the visual cortex that have receptive fields that are normally responsible for encoding objects at the center of gaze, allowing beneficial changes in crowding characteristics with narrow critical intervals in their surrounding areas, changing the target of fixation eye movements, advantageously changing the amplitude and / or velocity of eye movements, advantageously changing the interaction of saccadic firing circuits with the rest of the visual cortex, and / or triggering more effective and spontaneous search to achieve more effective integration of more and more correct visual information by a search mechanism, including, but not limited to, spontaneously generating motor learning in eye movement strategies to gather information from a wider area of ​​the visual field and at the same time use more retinal cells for visual perception of the visual field. In addition, one or more of the exemplary methods and devices described herein that cause the redirection of light away from the PRL of the eye to multiple non-PRL retinal locations enhance beneficial homeostatic plasticity maintenance mechanisms that promote cell signaling and visual function.

[0120] In some cases, one or more of the exemplary methods and devices described herein can cause the rebooting of the visual system of eye by reducing the exposure of ambient light from within the visual field of eye to the PRL.One or more of the exemplary methods and devices described herein can cause the rebooting of the visual system of eye by reducing the exposure of ambient light from within the visual field of eye to the PRL by at least 10%, i.e., by any amount or cumulative amount of 10% or more.The exposure of ambient light can be reduced at the PRL to force the visual system, including the eye and the brain, to find and use alternative, potential, and / or new visual pathways that originate from retinal locations other than the PRL.

[0121] One or more of the exemplary methods and devices described herein may cause the rebooting of the visual system of the eye by weighting the exposure of the environmental light from within the field of view of the eye to reduce the exposure of the eye to PRL by at least 10% for a determinable interval. The interval may be defined in milliseconds, seconds, minutes, hours, days, weeks, months, and / or years, and may be determined at any time before or after initial application. The determinable interval may be determined by 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 visual data, and / or post-treatment visual data. One or more of the exemplary methods and devices described herein may cause the weighting of the exposure of the environmental light from within the field of view of the eye to reduce the exposure of the eye to PRL by at least 10% for a determinable interval. In some cases, the environmental light within the field of view is exposed to the retina at a determinable rate of up to 50 kilohertz, which may cause the rebooting of the processing of the environmental light from within the field of view of the eye.

[0122] In some cases, the determinable rate may be any rate below 50 kilohertz, and may be determined by 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 visual data, and / or post-treatment visual data. Some of the exemplary methods and devices described herein may allow exposure rates of any rate up to 50 kilohertz, allowing modulation of light capture by retinal photoreceptors from within the entire visual field, and causing altered temporal neural integration in the eye and brain before perception. One or more of the exemplary methods and devices described herein may cause altered temporal neural integration in the eye and brain, allowing stable and seamless perception after neural processing while reducing the exposure of ambient light from within the visual field to the PRL of the eye by at least 10% for a determinable interval. Additionally, some of the exemplary methods and devices described herein may cause a weighting of the exposure of the ambient light from within the field of view of the eye, reducing the exposure of the eye to PRL by at least 10%, at least 25%, at least 50%, at least 75%, at least 90%, or any amount for a determinable interval, and rebooting the processing of the ambient light from within the field of view of the eye. Some exemplary embodiments cause a weighting of the exposure of the ambient light from within the field of view of the eye, reducing the exposure of the eye to PRL by at least 10% for a determinable interval, and causing an improvement in vision or restoration of vision.

[0123] Some of the exemplary methods and devices described herein may be configured to cause weighting of the exposure of ambient light from within the field of view of the eye, increasing the exposure to a number of retinal locations that are not the central eccentric visual field of the eye by at least 10% for a determinable interval, and cause improvement of vision or restoration of vision. One or more of the exemplary methods and devices described herein may also cause weighting of the exposure of ambient light from within the field of view of the eye, increasing the exposure to a number of retinal locations that are not the PRL by at least 10% for a determinable interval, and cause improvement of vision or restoration of vision. Some of the exemplary methods and devices described herein may allow exposure rates of any rate up to 50 kilohertz, allow modulation of light capture by retinal photoreceptors from within the entire field of view, and allow stable and seamless perception after neural processing while increasing the exposure of ambient light from within the field of view to the PRL of the eye by at least 10% for a number of retinal locations that are not the PRL for a determinable interval compared to the PRL.

[0124] Furthermore, one or more of the exemplary methods and devices described herein may cause rebooting of the visual system of the eye by causing defocusing of the ambient light from within the field of view of the eye at the PRL of the eye. The ambient light from within the field of view of the eye may be defocused at the PRL to force the visual system, including the eye and the brain, to find and use alternative, potential, and / or new visual pathways that originate from retinal locations other than the PRL. Some of the exemplary methods and devices described herein may cause rebooting of the visual system, including the eye and the brain, by causing focusing at multiple, non-contiguous retinal locations that are not the PRL of the eye. Furthermore, one or more of the exemplary methods and devices described herein may also cause rebooting of the visual system of the eye by causing defocusing of the ambient light from within the field of view of the eye at the PRL of the eye and / or causing focusing at multiple non-contiguous retinal locations that are not the PRL of the eye, causing improvement of vision and / or restoration of vision of an eye with impaired and / or lost central and / or peripheral vision.

[0125] Some of the exemplary methods and devices described herein may improve the vision of an eye with impaired or lost central vision by defocusing the ambient light from within the field of view of the eye at the PRL to a determinable distance. Some of the exemplary methods and devices described herein may defocus the image of an object located within the field of view of the eye at a fixed or varying distance from the eye at the PRL. Furthermore, one or more of the exemplary methods and devices described herein may cause defocusing of the ambient light from within the field of view of the eye at the PRL without requiring the determination of optical error or image quality at the PRL. Some of the exemplary methods and devices described herein may focus the image of an object located within the field of view of the eye at a fixed or varying distance from the eye at multiple non-PRL retinal locations. Some of the exemplary methods and devices described herein may cause the rebooting of the visual system of the eye by causing focusing at multiple non-PRL retinal locations of the eye without requiring the determination of optical error or image quality at the non-PRL retinal locations.

[0126] Some of the exemplary methods and devices described herein may also cause rebooting of the visual system of the eye by causing focusing on multiple, non-contiguous retinal locations that are not the PRL of the eye. For example, these exemplary methods and devices may achieve random or non-random focusing on multiple, non-contiguous retinal locations by modifying a range of optical and / or mechanical parameters.

[0127] Some of the exemplary methods and devices described herein may cause light redirection away from the PRL of the eye to multiple non-PRL retinal locations, and reboot the visual system immediately after light redirection.In contrast to such immediate rebooting, some of the exemplary methods and devices described herein may cause light to be redirected temporarily and / or the number of redirections and / or the magnitude of redirection to be reduced over time to enhance efficacy and safety.Some of the exemplary methods and devices described herein may include deformable components and / or cause deformable changes in the eye or a structure inserted in the eye to enhance safety and effectiveness of redirecting light away from the PRL of the eye to multiple non-PRL retinal locations. Some of the exemplary methods and devices described herein may cause the number of redirections and / or the magnitude of redirections and / or changes in the redirected retinal portion of the ambient light to improve the continuous, intermittent, or repeated rebooting of the visual system after the redirection of light for any determinable time interval for the first use and / or repeated use. Some of the exemplary methods and devices described herein may cause the redirection of light to multiple, non-contiguous retinal locations away from the PRL of the eye and not the PRL, instantly and / or continuously and / or intermittently and / or repeatedly reboot the visual system after the redirection of light for any determinable interval for the first use and / or repeated use. The determinable interval for the first use and / or repeated use may be determined by 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, thereby improving safety and / or efficacy and / or allowing for alternative redirection at determinable intervals and / or facilitating other therapies.Some of the example methods and devices described herein may cause reversible redirection of light and / or reversible modification to ocular tissue and / or reversible modification of at least one component of the device.

[0128] Some of the exemplary methods and devices described herein may cause the redirection of light away from the PRL of the eye to multiple retinal configurations disposed within a portion of the retina that includes at least one of a normal portion of the retina, a damaged portion of the retina, a diseased portion of the retina, a genetically modified portion of the retina, an epigenetically modified portion of the retina, a neuroregeneratively modified portion of the retina, or a retinal transplant, transplanted retinal cells (including, but not limited to, retinal epithelial cells, photoreceptors, ganglion cells, retinal progenitor cells), transplanted stem cells, or an implanted prosthesis.

[0129] Some of the exemplary methods and devices described herein may cause the exposure of the ambient light from within the field of view of the eye to be weighted to reduce the exposure of the eye to PRL by at least 10% for a determinable interval.In some cases, 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 modified portion of the retina, an epigenetic modified portion of the retina, a neuroregeneratively modified portion of the retina, or a retinal transplant, a transplanted retinal cell, a transplanted stem cell, or an implanted prosthesis.

[0130] Some of the exemplary methods and devices described herein can improve the vision of an eye with impaired central vision, and can cause the defocusing of ambient light from within the visual field of the eye at the PRL of the eye and the focusing of ambient light in at least one of the genetically modified portion of the retina, the epigenetic modified portion of the retina, or the neural regenerative modified portion of the retina.Some of the exemplary methods and devices described herein can cause the defocusing of ambient light from within the visual field of the eye at the PRL of the eye, and the focusing of ambient light in multiple portions of the retina, including at least one of a retinal transplant, a transplanted retinal cell, a transplanted stem cell, or an implanted prosthesis.

[0131] Some of the exemplary devices described herein may include deformable components or may be configured to cause deformable modification of ocular structures or structures placed within the eye to cause temporary or reversible or repeatable redirection of ambient light away from the PRL to multiple non-PRL retinal locations in an eye with progressive retinal disease or degeneration. Some of the exemplary devices described herein may also include deformable components or may be configured to cause deformable modification of ocular structures or structures placed within the eye to cause weighting of ambient light exposure from within the visual field of the eye to reduce the eye's exposure to PRL by at least 10% for a determinable interval in an eye with progressive retinal disease or degeneration. Some of the exemplary devices described herein may also include deformable components or may be configured to cause deformable modification of ocular structures or structures placed within the eye to cause defocusing of ambient light from within the field of view of the eye at the PRL of the eye and / or focusing at multiple non-contiguous retinal locations that are not the PRL of an eye with progressive retinal disease or degeneration. Some of these exemplary devices and methods may enable repeated rebooting of the visual system after progressive damage to photoreceptors, ganglion cells, or other retinal tissues. Some of these exemplary devices and methods may enable safe and effective rebooting of the visual system to improve vision and / or enhance retinal repair and / or myelination.

[0132] Some of the exemplary methods and devices described herein may facilitate a safe and effective increase in activity in a plurality of retinal cells and / or stimulate metabolic processes and / or repair mechanisms in living retinal cells. Additionally, some of the exemplary methods and devices described herein may facilitate a safe and effective reduction in cumulative focal light exposure or cumulative oxidative stress in individual retinal cells within some portions of the retina and / or slow the progression of macular and / or peripheral retinal degeneration in inherited and acquired diseases and disorders. Unlike currently proposed and researched, but not yet approved, therapies for slowing the progression of macular degeneration, such as selective thermolysis, photobiomodulation, or intravitreal photovoltaic stimulation, which may damage and / or overstimulate retinal cells and / or cause harmful amounts of complement activation and / or cause early retinal atrophy, some of the exemplary methods and devices described herein slow macular and / or peripheral degeneration without overstimulation and / or damage to retinal tissue.

[0133] Some of the exemplary devices described herein may include deformable components or may be configured to cause deformable modification of ocular structures or structures placed in the eye to cause temporary or reversible redirection of ambient light to multiple retinal locations that are not PRL in the genetic or epigenetic modification portion.Some of the exemplary devices described herein may cause weighting of exposure of ambient light from within the visual field of the eye in the genetic modification portion of the retina or the epigenetic modification portion of the retina.One or more of the exemplary devices and methods described herein may enable repeated rebooting of the visual system of the eye by redirecting ambient light to multiple other retinal locations in the genetic modification portion in a direction away from PRL, or by weighting of exposure of ambient light, or by focusing on the genetic modification portion while reducing the focus on the PRL to achieve proper tissue conversion and transgene expression, and increase the number of retinal locations that can contribute to neural integration and perception.

[0134] Some of the exemplary devices described herein may include deformable components or may be configured to cause deformable modification of ocular structures or structures placed in the eye to cause temporary or reversible or repeatable redirection of ambient light to multiple retinal locations away from the PRL in the retina including retinal implants, transplanted retinal cells, transplanted stem cells, or implanted prostheses. Some of the exemplary devices described herein may cause weighting of exposure of ambient light from within the field of view of the eye to a portion of the retina including retinal implants, transplanted retinal cells, transplanted stem cells, or implanted prostheses. Current diagnostic techniques often fail to provide reliable assessment of the visual function of individual retinal cells or regions and / or prostheses. Some of the exemplary devices and methods described herein may safely and effectively enable repeatable rebooting of the visual system in the retina including retinal implants, transplanted retinal cells, transplanted stem cells, or implanted prostheses, allowing more retinal regions to contribute to neural integration and perception, where ambient light is focused or light is redirected or exposed with weighting.

[0135] Some of the exemplary methods and devices described herein may safely and effectively reboot the visual system in conjunction with natural visual processing. Some of the exemplary methods and devices described herein may reboot the visual system without requiring sensory or oculomotor training. Some of the exemplary methods and devices described herein may also reboot the visual apparatus without damaging the retinal architecture or natural visual processing mechanisms. As an example of these advantages, and unlike some currently investigated (but not yet approved) strategies for vision loss, such as retinal prosthetic implants, which irreversibly destroy retinal architecture and natural visual processing, some of the exemplary methods and devices described herein do not damage or replace any ocular tissues and do not destroy natural visual processing. As another example of some advantages, and unlike some currently investigated (but not yet approved) strategies for central vision loss, such as electronic retinal remapping, which replaces real visual information from the visual field with simulated and distorted information in the paracentral region of the visual field and does not transmit all images within the visual field, some of the exemplary methods and devices described herein may transmit the actual full visual field and do not distort the visual information within the visual field.

[0136] Some of the exemplary methods and devices described herein may facilitate the redirection of ambient light to multiple non-PRL retinal locations in a direction away from the PRL of the eye, either optically, mechanically, or both optically and mechanically. Some of the exemplary methods and devices described herein may facilitate easy, safe, effective, efficient, and / or timely optical, mechanical, or opto-mechanical weighting of ambient light exposure from within the field of view of the eye to reduce the exposure of the eye to the PRL by at least 10% for a determinable interval. In some cases, ambient light within the field of view may be exposed to the retina at a determinable rate of up to 50 kilohertz, and the determinable interval may include milliseconds, seconds, minutes, hours, days, weeks, or years, and the exemplary methods and devices described herein may determine the determinable interval based on the user's visual response, device configuration, eye disease / disease, and / or progression of visual impairment, vision loss, and / or eye disease / disease. Some of the example devices described herein may include optical and / or mechanical components.

[0137] Some of the exemplary methods described herein may be implemented by or utilize a device, and may cause defocusing of ambient light from within the field of view of the eye at the PRL, and may change the optical properties or behavior of a number of portions outside the optical zone of a structure positioned in front of the retina. Some of the exemplary methods described herein may be implemented by or utilize a device, and may cause defocusing of ambient light from within the field of view of the eye at the PRL of the eye, and may change the mechanical properties or behavior of a number of portions outside the optical zone of a structure positioned in front of the retina. Some of these exemplary methods may improve and / or restore vision in an eye with impaired and / or lost central and / or peripheral vision.

[0138] Some of the exemplary methods described herein may be implemented by or utilize a device positioned in front of the retina of the eye. In some cases, positioning a device "in front of the retina" may include positioning a device outside the eye, positioning a device on the surface of the eye, positioning a device within the cornea, and / or positioning a device within the eye. Some of the exemplary devices described herein may include glasses and other eye-wearable devices, contact lenses, corneal inlays, intraocular lenses (IOLs), and other intraocular devices.

[0139] Some of the exemplary devices described herein may be configured to cause a programmable, temporary, reversible, and / or repeatable redirection of ambient light to multiple non-PRL retinal locations in a direction away from the PRL of the eye. In some cases, the exemplary devices 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 device in a tangible non-transitory memory or included in a received signal), cause the exemplary devices to cause a programmable, temporary, reversible, and / or repeatable redirection of ambient light.

[0140] Furthermore, some of the exemplary methods or devices described herein may cause temporary, reversible, and / or repeatable redirection of ambient light to multiple non-PRL retinal locations in a direction away from the PRL of the eye by mechanically, electromechanically, optically, or opto-mechanically directing light to multiple retinal locations in a direction away from the PRL of the eye. In addition, one or more of the exemplary devices described herein may be configured to redirect ambient light to multiple non-PRL retinal regions in a direction away from the PRL of the eye, and may include one or more transparent components disposed in front of the retina of the eye and coupled to a 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 components (e.g., based on software instructions executed by one or more processors, etc.), which may cause the transparent components to redirect ambient light to multiple non-PRL retinal locations in a direction away from the PRL of the eye.

[0141] In some examples, one or more of these exemplary devices may include one or more transparent components, one or more opto-mechanical components disposed on or within the one or more transparent components, and a controller electrically coupled to the one or more opto-mechanical 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 one or more processors or the like) to the one or more opto-mechanical components, and upon receiving the control signals, the one or more opto-mechanical components may cause a redirection of ambient light away from the PRL of the eye and to a number of non-PRL retinal locations.

[0142] Some of the exemplary devices described herein that may be configured to redirect ambient light to a plurality of non-PRL retinal locations in a direction away from the PRL of the eye 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 a conductive component. The controller may perform any of the exemplary operations described herein to generate and route a control signal to the transparent components via the conductive component. For example, the exemplary device may include one or more components disposed on or within a surface of the one or more transparent components, and after receiving a control signal, the one or more components cause redirection of ambient light to a plurality of non-PRL retinal locations in a direction away from the PRL. The one or more components may include, in some examples, a refractive component, a diffractive component, or a combination of a diffractive component and a refractive component, and the control signal may cause modification of the refractive component, the diffractive component, or a combination of a diffractive component and a refractive component to redirect ambient light to a plurality of non-PRL retinal locations in a direction away from the PRL of the eye. Additionally, one or more of the example devices described herein may also include at least one lens for correcting refractive errors of the eye.

[0143] Some of the exemplary devices described herein include at least one control unit (e.g., a controller) and may be configured (e.g., based on a control signal generated by the controller) to generate a programmable weighting of the exposure of the ambient light from within the field of view of the eye to reduce the exposure of the eye to the PRL by at least 10% for a determinable interval. Some of the exemplary devices described herein include at least one control unit (e.g., a controller) and may be configured (e.g., based on a control signal generated by the controller) to generate a programmable weighting of the exposure of the ambient light from within the field of view of the eye to reduce the exposure to the PRL by at least 10% for a determinable interval at a determinable rate of 0 to 50 kilohertz, or to increase the exposure to retinal locations that are not PRL by more than 10% compared to the PRL. Some of the exemplary methods and devices described herein may cause a temporary, reversible, and / or repeatable redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not PRL by mechanically, electromechanically, optically, and / or opto-mechanically directing the light to multiple retinal locations in a direction away from the PRL. Additionally, some of the exemplary methods and devices may include or perform mechanical, electromechanical, optical, and / or opto-mechanical operations that generate a weighting of the exposure of ambient light from within the field of view of the eye, thereby reducing the exposure to the PRL by at least 10% or increasing the exposure to multiple retinal locations that are not PRL by more than 10% compared to the PRL for a determinable interval at a determinable rate of 0 to 50 kilohertz.

[0144] 19 illustrates an exemplary device 1900 for improving or restoring vision. In some examples, the device 1900 may include one or more transparent components 1902 positioned in front of the retina 1901A of the eye 1901 (including the fovea 1901B and the optic nerve 1901C), one or more deformable components 1904 disposed on or within one or more of the transparent components 1902, and a controller 1906 coupled to the deformable components 1904 via a conductive component 1908. Additionally, the controller 1906 may be coupled to a source of electrical energy, such as a power source 1910, and may be configured to generate and route a control signal 1912 to the deformable components 1904 (e.g., based on electrical energy received from the power source 1910).

[0145] 19, the controller 1906 may be configured to receive one or more elements of input data 1905, process the received elements of 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, a positioning of the PRL 1918 of the eye 1901, information characterizing a pattern of component deformation that directs the ambient light to cause defocus for a determinable distance of the ambient light at the PRL 1918, and a determinable rate (e.g., in the range of 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 in a tangible non-transitory memory or included in a received signal), cause the controller to generate and transmit the control signals 1912 to the deformable component 1904.

[0146] In some examples, upon receiving the control signal 1912, one or more of the deformable components 1904 may rearrange at least one pattern directing the ambient light 1914 to the retina 1901A at a determinable rate of up to 50 kilohertz. The at least one pattern directing the ambient light may cause a reboot of the processing of the ambient light 1914 by the visual system of the eye 1901. The at least one pattern may cause, for example, defocusing at the PRL of the eye 1901 (e.g., PRL 1918 of FIG. 19 ) and / or focusing at multiple non-contiguous retinal locations that are not the PRL, such as location 1920. Additionally, in some examples, the at least one pattern does not generate an aperture.

[0147] In some examples, the signal to generate the pattern causing the focusing or defocusing of the ambient light may continue (e.g., by the controller 1906 using any of the exemplary processes described herein) for milliseconds, seconds, minutes, hours, days, months, or years to cause and / or maintain and / or repeat a reboot of the processing of the ambient light 1914 by the visual system. Additionally, although not illustrated in FIG. 19, some of the exemplary devices described herein, such as device 1900, may include at least one lens, such as, but not limited to, at least one lens for correction of at least one refractive error.

[0148] In some cases, the deformable component 1904 may include at least one of an optically active component, an optical mechanical component, an electromechanical component, or a projection component. Additionally, some of the example devices 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 cases, in response to the control signal 1912, the deformable component 1904 may rearrange at least one pattern of directing the ambient light 1914 to the retina 1901A at a determinable rate of up to 50 kilohertz. For example, the deformable component 1904 may rearrange at least one pattern of directing the ambient light 1914 to the retina 1901A with at least an isotropic modification.

[0149] Further, for example, the deformable components 1904 may include one or more deformable components having isotropic properties or behavior, such as optically isotropic liquid crystals. In some cases, optically isotropic liquid crystals may provide faster switching times and wider viewing angles than anisotropic liquid crystals in response to control signals 1912. For example, an in-plane switching electrode generating a horizontal electric field may cause the liquid crystal to appear optically isotropic with voltage off, resulting in a dark state, and anisotropic refractive index profile with voltage on, resulting in transmission.

[0150] In some examples, not illustrated in FIG. 19, the deformable component 1904 may be combined with a fixed focus monofocal lens. For example, the deformable component 1904 may be combined with a lens of glass or plastic or any determinable material with a curved surface. Furthermore, the deformable component 1904 may be arranged in a pattern that produces approximately isotropic behavior. For example, the deformable component 1904 may include an optically isotropic polymer layer having an inverse lens shape on a first surface and a lens portion in which the surface of the optically isotropic polymer layer is filled with a liquid crystal polymer in some embodiments. The deformable component 1904 may also include an electro-optical component, including, but not limited to, liquid crystal and polymer gel.

[0151] Additionally, although not illustrated in FIG. 19, the device 1900 may comprise ultra-thin planar lenses, such as, but not limited to, lenses comprised of periodic sub-wavelength dielectric or metallic structures and liquid crystal lenses. In some cases, the device 1900 may also include Pancharatnam-Berry phase lenses with spatially separated foci that shift outside the PRL axis. Furthermore, in some cases, the deformable components 1904 of the device 1900 may include electrically tunable liquid crystal lenses, such as, but not limited to, diffractive index lenses, refractive index lenses, and gradient index lenses. For example, the device 1900 may deform the pixel configuration and / or the refractive index and / or the optical axis orientation. Furthermore, in response to the control signal 1912, one or more of the deformable components 1904 may control the length of the generated focused optical path at a spatial point that is comprised of multiple non-contiguous retinal configurations that are not the PRL 1918. Furthermore, the exemplary device 1900 may also include optical orientation components and / or optical patterning components.

[0152] In some cases, based on the control signals 1912 generated by the controller 1906 and provided to the deformable components 1904, the device 1900 may perform exemplary processes including, but not limited to, optical polarization rotation, voltage-controllable diffraction, or fast switching of the LC refractive index. Additionally, in some cases, the device 1900 may incorporate or utilize electro-optical techniques, for example, as the local refractive index at any given location within the active area of ​​the electro-optical component is determined by a voltage waveform applied on the electro-optical component at that location and controlled to a reorganization pattern by circuitry coupled to the electrodes. Design features related to the refractive index, voltage, and electro-active material of the deformable components can be determined based on the device location, the manufacturer's needs, and the user's needs.

[0153] In some examples, although not illustrated in FIG. 19 , the device 1900 may include actuation components configured to independently control the positions of corresponding ones of the opto-mechanically deformable components 1904, such as micromirrors (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 in the PRL 1918 and focusing in multiple non-PRL, non-contiguous retinal configurations, such as configuration 1920. In some instances, one or more modifications of the focal length may be controlled by translation and / or rotation of corresponding ones of the micromirrors. Furthermore, the focal length may be modified by the device 1900 without requiring a determination of optical error or image quality in the PRL 1918 and / or in non-PRL, non-contiguous retinal configurations, such as configuration 1920.

[0154] Some of the exemplary methods described herein may temporarily, reversibly, or repeatedly deform the refractive index, radius of curvature, and / or diffraction of one or more refractive or diffractive components in at least one of the device or eye to cause a safe and effective redirection of ambient light to multiple non-PRL retinal locations in a direction away from the PRL of the eye. In some cases, some of the exemplary devices described herein may include one or more deformable components configured (e.g., via control signals generated by a corresponding controller) to cause temporary, reversible, and / or repeatable changes in the refractive index and / or radius of curvature and / or diffraction in the device or eye. Additionally, some of the exemplary devices described herein may include one or more lenses and / or adjustable lenses.

[0155] Some of the exemplary devices 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 cases, the controller may be configured to generate and route a control signal (e.g., based on executed software instructions, etc.) to the one or more deformable components. Based on receiving the control signal by the one or more deformable components, the device may be configured to cause a weighting of the exposure of ambient light from within the field of view of the eye, which may reduce the exposure of ambient light from within the field of view of the eye to the PRL of the eye by at least 10% for 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.

[0156] Additionally, some of the exemplary methods and apparatus described herein may temporarily, reversibly, repeatedly, or continuously deform the refractive index, radius of curvature, and / or diffraction of one or more refractive or diffractive components in at least one of the ophthalmic device and the eye to cause a weighting of the exposure of ambient light from within the field of view of the eye to reduce the exposure to PRL by at least 10% for a determinable interval at a determinable rate of 0 to 50 kilohertz. Some of the exemplary apparatus described herein may include one or more deformable components that may cause a temporary, reversible, and / or repeatable change in the refractive index, radius of curvature, and / or diffraction within the device or eye to cause a weighting of the exposure of ambient light from within the field of view of the eye to reduce the exposure to PRL by at least 10% for a determinable interval of time at a determinable rate of 0 to 50 kilohertz in response to receiving a control signal generated by a corresponding controller. In some cases, 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-optical components, such as liquid crystals and polymer gels, and / or opto-mechanical components. In additional or alternative examples, the deformable components may include, but are not limited to, photo-directing and / or photo-patterning components. Some of the exemplary methods described herein that utilize deformable components may include, but are not limited to, optical polarization rotation processes, voltage-controllable diffraction processes, and / or processes for fast switching of LC refractive index.

[0157] In some cases, a controller coupled to the power source and the circuitry may be configured to control the voltage applied to the excitation electrodes to shift the optical axis of the lens (e.g., based on the 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, the PRL placement and / or axis of the eye. The controller may process the input data and, based on the processed input data, generate and apply a control voltage to the excitation electrodes to perform any of the exemplary processes described herein to control the size and / or placement of the initial shift of the optical axis. By controlling the size and / or placement of the initial shift of the optical axis, some of the exemplary methods described herein may cause a reboot of the visual system by defocusing at the PRL, focusing at a non-PRL non-contiguous placement, and / or weighting the exposure of ambient light from within the field of view of the eye to reduce the exposure to the PRL by at least 10% for a determinable time interval at a determinable rate of 0 to 50 kilohertz. Although diagnostic methods such as microperimetry can determine the location of the PRL, clinically available microperimetry tests cannot yet accurately detect all areas of reduced or increased retinal sensitivity in diseased or damaged retinas. Furthermore, clinically available diagnostic tests cannot yet accurately predict which retinal location has the best-functioning photoreceptors connected to the best-functioning ganglion cells, nor do they measure the integration and summation potential of multiple areas of functioning retinal cells. If the amount of vision improvement after the initial reboot is not satisfactory, some of the exemplary devices described herein may modify the initial light defocusing at the PRL, the initial light focusing at non-PRL locations, and / or the initial weighting of exposure reduction at the PRL to repeat the reboot using any of the exemplary operations described herein.

[0158] Some of the exemplary methods and devices described herein may temporarily, reversibly, or repeatedly modify the refractive index, radius of curvature, and / or diffraction of one or more refractive or diffractive components in at least one of the device and the eye to cause a safe and effective redirection of ambient light. In some cases, one or more of the exemplary methods or devices described herein may cause a modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements in the device or eye. Some of the exemplary methods or devices described herein may cause a modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements in the device or eye, which modification may vary over time. Some of the exemplary methods or devices described herein may cause a modification of the refractive index, radius of curvature, or diffraction of one or more refractive or diffractive elements in the device or eye, which may be controlled by the device, a health care provider, or a user of the device at any time before, during, or after rebooting.

[0159] In some cases, one or more of the exemplary devices described herein may determine PRL placement and / or axis prior to use or insertion of the device. In other cases, one or more of the exemplary devices described herein may determine PRL placement and / or axis may be determined during use or after insertion of the device. Additionally, in some cases, PRL placement and / or axis may be determined by a healthcare provider or user using existing clinical techniques, including, but not limited to, visual fixation or microperimetry.

[0160] As described herein, some of the exemplary devices described herein may include one or more deformable components coupled to a controller via corresponding conductive components. The one or more deformable components may include, for example, liquid crystal (LC), supertwisted liquid crystal, ferroelectric liquid crystal, surface stabilized ferroelectric liquid crystal (SSFLF), bistable liquid crystal, polymer light emitting diode (PLED), bistable liquid crystal, transparent color tunable organic light emitting diode (OLED), or any other suitable material. The one or more deformable components may be disposed on or within a surface of one or more transparent components, flat or curved, composed of glass, plastic, polymer, or any other suitable material, such as, but not limited to, polysulfone, polyetherimide, and / or other thermoplastic materials.

[0161] As described herein, one or more of the exemplary methods may incorporate diffraction and may utilize an apparatus having components including, but not limited to, at least one of a lens, a diffraction grating, an electroactive material, a deformable material, a deformable polymer, an actuator, and any determinable diffractive component. Additionally, one or more of the exemplary apparatuses described herein may also include opto-mechanical components, such as, but not limited to, a polarizer, a digital micromirror device, a micromirror array, a deformable mirror, and / or a lens.

[0162] Some of the exemplary devices described herein include at least one control unit (e.g., a controller) and may be configured (e.g., based on a control signal generated by the controller) to generate a programmable weighting of the exposure of the ambient light from within the field of view of the eye to reduce the exposure to the PRL by at least 10% or increase the exposure to the non-PRL retinal location by more than 10% compared to the PRL for a determinable interval at a determinable rate of 0 to 50 kilohertz. In some examples, one or more of these exemplary devices may include one or more transparent components, one or more deformable components disposed on or within the 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 control signals (e.g., based on software instructions executed by one or more processors, etc.) to the one or more deformable components, and after receiving the control signals, the one or more deformable components may cause the weighting of the exposure of the ambient light from within the field of view of the eye. In some cases, an exemplary device for improving and / or restoring vision, such as device 2000 of FIG. 20, may include one or more transparent components 2002 positioned in front of the retina 2001A of the eye 2001 (including the fovea 2001B and optic nerve 2001C), one or more deformable components 2004 disposed on or within a surface of the transparent component 2002, and a controller 2006 coupled to the one or more deformable components 2004 via a conductive component 2008. Additionally, the controller 2006 may be coupled to a source of electrical energy, such as a power source 2010, and may be configured to generate and route control signals 2012 to the deformable components 2004 (e.g., based on electrical energy received from the power source 2010).

[0163] The controller 2006 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 2012 to the deformable component 2004. As illustrated in FIG. 20, the controller 2006 may be configured to receive one or more elements of input data 2005, process the received elements of input data 2005, and generate and route control signals 2012 to the deformable component 2004. In some examples, the elements of the input data 2005 may include, but are not limited to, placement of the PRL 2018 on the eye 2001, information characterizing a pattern of component deformation that reduces ambient light exposure at the PRL 2018, a weighting interval, and a determinable rate (e.g., in the range of 0 to 50 kHz).

[0164] In some examples, upon receiving the control signal 2012, the one or more transformable components 2004 may rearrange at least one pattern of exposure of ambient light in the non-PRL arrangement 2020 from within the field of view of the eye 2001 to the retina 2001A at a determinable rate of up to 50 kilohertz for a determinable interval. Further, in some examples, the at least one pattern does not include an aperture. Further, in some examples, the determinable interval in units of milliseconds, seconds, minutes, hours, days, weeks, months, and / or years may be continuous or intermittent.

[0165] Further, for example, the pattern reorganization may cause a weighting of the ambient light exposure to reduce the exposure to PRL 2018 by at least 10% for a determinable interval at a determinable rate within a range of 0 to 50 kilohertz. The weighting of the ambient light exposure to reduce the exposure to PRL 2018 may cause a reboot of the processing of the ambient light 2014 by the visual system of the eye 2001. Although not illustrated in FIG. 20, the device 2002 may also comprise at least one lens. Furthermore, in some examples, the exemplary device 2000 may perform any of the operations described herein to reorganize at least one pattern of exposure of the ambient light 2014 to the retina 2001A based on a deformation of at least one of the opto-mechanical components of the device 2000. The opto-mechanical components may include, but are not limited to, a polarizer, a digital micromirror device, a micromirror array, a deformable mirror, and / or a lens.

[0166] In some cases, the deformable component 2004 may include one or more micromirrors or lenses. For example, one or more micromirrors in the deformable component 2004 may be arranged in a determinable array of determinable shapes, and one or more lenses in the deformable component 2004 may be of determinable shapes, sizes, and positions. Additionally, although not illustrated in FIG. 20, the device 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 device 2000 may include actuation components configured to independently control the positions of corresponding ones of the micromirrors (e.g., based on control signals generated by the controller 2006).

[0167] Some of the exemplary methods and devices described herein may cause a reboot of the visual system of an eye (e.g., eye 1901 of FIG. 19 or eye 2001 of FIG. 20) and may cause focusing at multiple, non-contiguous retinal locations that are not the PRL (e.g., PRL 1918 of FIG. 19 or PRL 2018 of FIG. 20). In some cases, focusing may be achieved randomly or non-randomly by modifying the focal length and / or optical axis range at the different retinal locations. In additional cases, some of the exemplary methods and devices described herein may cause defocusing at the PRL of the eye (e.g., PRL 1918 of eye 1901 of FIG. 19, PRL 2018 of eye 2001 of FIG. 20, etc.) by determining the optical axis of the PRL and modifying the optical axis of the lens.

[0168] Some of the exemplary methods and devices described herein may cause a reboot of the visual system to improve or restore vision in the eye through the execution of one or more projection methods. For example, one or more of the exemplary devices described herein may include one or more projection components, such as a projector, that are functionally coupled to a controller. The controller may include one or more processors that, after 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 signal, the projector may selectively redirect ambient light to a plurality of retinal locations that are not the PRL in a direction away from the PRL of the eye. Based on the received control signal, the projector may weight the ambient light exposure to reduce the exposure at the PRL by at least 10%. In some cases, the exemplary device may include a projection component and a waveguide, and the exemplary device may be configured to utilize the projection component and the waveguide to redirect ambient light away from the PRL of the eye to multiple retinal locations that are not the PRL, or to weight the ambient light exposure to reduce exposure at the PRL by at least 10%.

[0169] Some of the exemplary methods and devices described herein can improve visual acuity by causing the redirection of ambient light to a suitable number of non-PRL retinal locations in a suitable number of retinal quadrants away from the PRL of the eye. Some of the exemplary methods and devices described herein that cause the redirection of ambient light to multiple non-PRL retinal locations in a suitable number of retinal quadrants away from the PRL of the eye may require the determination of the location and / or axis of the PRL before using or inserting it into the eye. The PRL location and / or axis may be determined by methods including, but not limited to, fixation or microperimetry. In eyes with low visual acuity, some of the exemplary processes described herein that redirect ambient light to multiple locations away from the PRL may reboot the visual system and allow visual attention by other non-PRL retinal locations.

[0170] Although diagnostic methods such as microperimetry can determine the location of the PRL, clinically available tests, including microperimetry, cannot accurately detect all areas of reduced or increased retinal sensitivity in diseased or damaged retinas. Furthermore, clinically available diagnostic tests cannot yet predict which retinal location contains the photoreceptors and ganglion cells that can most effectively process visual information for integration, summation, and perception. Thus, current clinical procedures cannot accurately target specific retinal locations to improve vision. Some of the exemplary methods and devices described herein that cause redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not PRL, and are reversible and / or safely repeatable to allow multiple redirections to improve vision, can be implemented in addition to or as a replacement for current clinical procedures that lack reversibility and / or repeatability.

[0171] In some cases, one or more of the exemplary devices described herein may include one or more light-guiding components positioned in front of the retina of the eye. Furthermore, in addition to the light-guiding components, 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 devices described herein may include one or more components that guide light from a light source (e.g., at least one of a laser light source and a non-laser light source) to multiple non-contiguous parts of at least one structure in front of the retina, redirecting ambient light away from the PRL to multiple retinal locations that are not PRL, or reducing the exposure of ambient light at the PRL for a specified interval, or defocusing ambient light at the PRL and focusing light at multiple non-contiguous non-PRL retinal locations, or any combination thereof, thereby rebooting the processing of ambient light by the visual system.

[0172] Structures to which light from a laser or non-laser light source may be directed include, but are not limited to, acellular and / or collagenous structures with or without cells in the eye in front of the retina. The phrase "intraocular (or in the eye)" as defined herein may include, but is not limited to, the cornea of ​​the eye (e.g., as illustrated in FIG. 21), the anterior chamber of the eye, the lens of the eye, and the posterior chamber of the eye. Additionally, intraocular acellular structures as defined herein may include native structures of the eye and non-native structures placed in or on the eye. Examples of acellular structures that are not native to the eye but are found in the eye include, but are not limited to, intraocular lenses, donor acellular corneal lenticular lenses, and biosynthetic collagen inlays. Additionally, examples of native acellular structures of the eye include, but are not limited to, the cell-free corneal layer, the acellular portion of the lens.

[0173] In some cases, one or more of the exemplary methods and devices described herein that direct light from a light source to acellular or mostly acellular structures rather than cellular structures within the eye may improve safety and efficacy by reducing potential wound healing effects, potential adverse effects, or potential poor efficacy caused by targeting cellular structures. Collagen structures are structures that contain collagen, including native structures of the eye and structures inserted in or on the eye, such as, but not limited to, cell-bearing structures, including, but not limited to, biosynthetic collagen, corneal stroma, portions of the sclera, and portions of the lens.

[0174] Some of the exemplary methods and devices described herein target structures for laser and non-laser light therapy based on collagen fibril entanglement and collagen fibril dispersion, which can change the biomechanical and optical behavior of the structure. In some cases, targeting structures or portions of structures with increased collagen fibril entanglement and collagen fibril dispersion can increase the effectiveness and efficiency of procedures that cause redirection of ambient light away from the PRL of the eye and into multiple non-PRL configurations. For example, in the cornea, individual collagen fibrils are most densely entangled in the anterior acellular layer between the epithelium and the stroma. The high density of interconnections makes the corneal portion stiffer and more mechanically active. Atomic force microscopy has demonstrated that the anterior acellular layer has the greatest elastic modulus in the cornea, which is, for example, about three times greater than the elastic modulus of the anterior stroma (20 μm deep or less). In addition, as can be demonstrated using second harmonic imaging confocal microscopy, many of the anterior stromal fibrils are inserted into the anterior acellular layer. Beneath the anterior acellular layer, fibrils in the anterior stroma are also intertwined, but less densely than in the anterior acellular layer. From the anterior to the posterior cornea, the density of fibril branching and the inclination of the fibrils decrease exponentially with depth, with the average collagen inclination being parallel to the tissue surface at almost all depths. However, in the central cornea, the spread in inclination angle is greatest in the anterior-most stroma (reflecting the increased intertwining of lamellar tissue in this region) and decreases with tissue depth. The anterior-most portion of the stroma (<20 μm from the anterior acellular layer) may be characterized by the highest elastic modulus within the stroma. For example, stiffness is three times greater in the anterior third of the stroma than in the posterior third of the stroma.

[0175] In addition to second harmonic generation imaging, fibril dispersion can be measured by X-ray diffraction and scattering studies. Fibrils are more dispersed in the anterior acellular layer than in the underlying stroma. Collagen fibrils are proportionally less dispersed and more aligned in the posterior two-thirds of the cornea, whereas in the anterior third of the central and paracentral cornea (and especially the anterior sixth with the greatest dispersion closest to the anterior acellular layer), collagen fibrils are arranged in a multi-directional manner. In addition, fibril dispersion shows spatial variation on the corneal surface, with fibrils strongly aligned along the nasal-temporal and superior-inferior meridians, and more dispersed within the transition zones within the four quadrant regions of the corneal surface, with fibril dispersion greatest in the central sections within each quadrant. The amount of collagen fiber dispersion within the transition zones may vary between individual corneas. Furthermore, X-ray diffraction has also shown variability in the percentage of fibrils oriented within the 45° sectors of the nasal-temporal and superior-inferior meridians among different healthy human corneas.

[0176] The spatial distribution of fibril dispersion may also differ between healthy and diseased corneas. Areas where fibrils are most completely dispersed are roughly isotropic (i.e., arranged in all directions), and roughly isotropic parts where fibrils are almost completely dispersed exhibit roughly isotropic biomechanical and / or optical properties or behavior (i.e., roughly equivalent isotropic biomechanical and / or optical properties or behavior in all directions). A corneal property, such as elastic modulus or other property, is anisotropic when, after examination along one radial meridian of the cornea, the value differs from the value obtained along a different meridian. For example, Brillouin microscopy measures corneal anisotropy both in vivo and in vitro, and clinical measurements by en-face Brillouin corneal mapping may be used to determine areas of maximal isotropy.

[0177] In some cases, a greater amount of surface deformation, corneal mechanical behavior may occur in the central section in each quadrant of the cornea compared to the nasal-temporal and superior-inferior sections due to the greater degree of fibril dispersion. Some of the exemplary methods and devices described herein modify corneal portions with fibril dispersion and / or modify fibril dispersion within the corneal portion. For example, the more flexible the portion of the cornea is, the easier it is to deform. Modifying a portion of the area of ​​entangled collagen fibers may also change the stiffness of the anterior stroma, change the corneal curvature, change the light refraction, change the visual acuity of the eye, or any combination thereof. Some of the exemplary methods and devices described herein modify corneal portions with entangled fibrils / fibers and / or modify the entanglement of fibrils / fibers within the corneal portion. Measurement of the flexibility of a corneal layer or portion can be performed, for example, by corneal indentation, estimation of Young's modulus based on a fluid-filled spherical shell model by Scheimpflug imaging, and ultrasonic surface wave elastography.

[0178] Although clinical techniques for measuring corneal biomechanical response have been available for about 15 years, these clinical techniques were not able to measure local biochemical behavior until recently. Although in vitro analysis of the corneal surface has existed for several decades, methods to study corneal biomechanics in vivo have only recently been developed. Furthermore, although clinical measurements of corneal biomechanical response have been used to diagnose glaucoma, keratoconus, and other corneal ectatic diseases, local biomechanical criteria have not been used to date in planning ophthalmic procedures unrelated to abnormal corneas with ectasia. Some of the exemplary methods and devices described herein may receive, process, and utilize input from corneal flexibility, and / or from local corneal flexibility mapping, and / or from corneal anisotropy / isotropy mapping, as illustrated in the corneal anisotropy map of FIG. 22. For example, in FIG. 22, 0 corresponds to an isotropic corneal portion, and values ​​>2 correspond to a highly anisotropic corneal portion.

[0179] In some cases, some of the exemplary methods and devices described herein may safely and effectively reboot the visual system of the eye by transforming the properties or behavior of structures positioned on or within the eye, either native or non-native to the eye, through transformation of an approximately isotropic portion of a structure within the eye, through transformation of at least one portion of a structure on or within the eye into an approximately isotropic structure and / or a structure exhibiting at least one property and / or behavior in all directions, through isotropic transformation of at least one portion of a structure on or within the eye, or through transformation of at least one portion of a structure on or within the eye based on the isotropy or anisotropy of the at least one portion.

[0180] Furthermore, some of the exemplary methods and devices described herein may safely and effectively reboot the visual system of the eye through the modification of mechanical properties of structures within the eye. For example, the mechanical properties may be efficiently and safely modified by removing and / or mechanically reinforcing a small, determinable amount of mechanically active structures or portions of structures at a determinable location on or within the eye. In addition, in some cases, the mechanical properties may be efficiently and safely modified by removing and / or mechanically reinforcing a small, determinable amount of approximately mechanically isotropic structures or portions of structures at a determinable location on or within the eye.

[0181] Some of the exemplary methods and devices described herein can safely and effectively reboot the visual system of the eye through the modification of the optical properties of structures on or within the eye. In some cases, the refractive properties can be efficiently and safely altered by modifying a small, determinable amount of anisotropic and / or approximately isotropic structures or portions of structures. For example, the parameter κ(ρ,θ) represents the continuous distribution of collagen fibrils across the cornea of ​​the eye, exhibiting a minimum value of zero where the fibrils are perfectly aligned along the preferred orientation and a maximum value of 1 / 3 where the fibrils are completely dispersed and the cornea behaves approximately isotropically. Because (i) corneal fibrils are not isotropically oriented everywhere; in precise configurations, (ii) about 60% of the fibrils are uniformly distributed and therefore exhibit isotropic behavior, and (iii) about 40% of the fibrils are oriented with different amounts of anisotropy (as illustrated in FIG. 22 ), some of the exemplary methods and devices described herein may effectively, efficiently, and safely reboot the visual system by applying laser or non-laser light to portions of the cornea based on the isotropic or anisotropic behavior or properties of those portions and / or by modifying the isotropy of portions of the cornea.

[0182] Some of the exemplary methods and devices described herein for rebooting the visual 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 non-contiguous portions of the cornea of ​​the eye. In additional or alternative cases, some of the exemplary methods and devices described herein for rebooting the visual system and / or improving or restoring vision may also include one or more components that direct light from the light source to at least a plurality of non-contiguous portions of at least one anterior acellular layer above the anterior corneal portion, which may be selected based on the degree of isotropy or anisotropy of the corneal portion below the anterior acellular layer. For example, the light from the light source may be directed to an approximately isotropic portion of the cornea. The light source may include at least one of a laser or a non-laser light source.

[0183] For example, as illustrated in FIG. 23, an exemplary device 2300 for improving or restoring vision includes at least one of a light source 2302 and a light directing component 2304 that directs light 2306 from the light source 2302 to at least a plurality of non-contiguous portions of a cornea 2308A of an eye 2308, generally illustrated as non-contiguous portions 2310A and 2310B. In some cases, the cornea may be an age-appropriate normal 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 cause corneal vitrification. Furthermore, the non-contiguous portions, including the non-contiguous portions 2310A and 2310B, may be located outside the central optical zone and may include at least an acellular layer of the cornea, such as the cornea 2308A. In some cases, and through redirecting light 2306 from light source 2302 to at least multiple non-contiguous portions of cornea 2308A, device 2300 may modify corneal isotropy outside of the central optical zone.

[0184] 23, the device 2300 may also include a controller 2312 electrically coupled to a source of electrical energy, such as a power source 2314, the light source 2302, and one or more components, such as a light guide component 2304 disposed between the light source 2302 and the cornea 2308B. Based on the electrical energy received from the power source 2314, the controller 2312 may be configured to generate and route a light source control signal 2316 to the light source 2302 and generate and route a component control signal 2318 to the light guide component 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 included in a received signal), cause the controller 2312 to generate and transmit the light source control signal 2316 to the light source 2302 and generate and route the component control signal 2318 to the light guide component 2304. In some cases, after receiving a light source control signal 2316, the light source 2302 is configured to generate light 2306, which may be illuminated and incident on the light-guiding component 2304. Further, in response to a component control signal 2318, the light-guiding component 2304 may perform any of the example processes described herein to direct the light 2306 to at least a plurality of non-contiguous portions of the cornea 2308A.

[0185] In some examples, the light source 2302 of the device 2300 includes a laser light source, such as an ArF excimer laser emitting 193 nm ultraviolet light (e.g., laser light), and the controller 2312 may be configured to direct the laser light to a plurality of non-contiguous portions of at least an anterior acellular layer of the cornea based on input data 2320, including, among other things, the location of the PRL of the eye 2308, a determinable diameter of the central optical zone (OZ) of the cornea 2308A, and a determinable location, depth, and surface area of ​​the non-contiguous corneal portions, which may be based on the isotropic behavior or properties of those portions. For example, the controller 2312 may be configured (e.g., by executed software instructions) to control the ablation of four circular corneal portions having a diameter of 1 mm, including at least an anterior acellular layer overlying the corneal stroma, to a depth of 20 microns (if the epithelium is manually removed over the portions) or 80 microns (if transepithelial ablation). In some cases, each of the four circular corneal portions may be centered on a 6 mm OZ centered on the PRL (by the patient fixating on the light) and resting on the most isotropic corneal portions at the 1:30, 4:30, 7:30 and 10:30 positions (as illustrated in FIG. 22 and described herein).

[0186] In some examples, one or more of the exemplary processes described herein may utilize a first device comprising 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 device disposed between the laser light source and the cornea, to direct the laser light delivered by the first device to a plurality of non-contiguous portions of at least the anterior acellular layer of the cornea. The central optical zone may, for example, comprise a circular region of the cornea having a diameter of at least 2 mm. In some cases, the central optical zone is at least 3 mm in diameter, and in other cases, the central optical zone is at least 4 mm in diameter. Some of the exemplary methods and devices described herein may include at least one of a light source and a component that directs light from the light source, and may perform any of the operations described herein to cause improvement or restoration of vision. Some of the exemplary methods and devices described herein may include at least one of a light source and a component that directs light from the light source, and may perform any of the operations described herein to modify corneal isotropy. In some cases, the modification to the corneal isotropy outside the corneal optical zone may include a modification in at least one direction of at least one of the mechanical properties or mechanical behavior of the cornea or a portion of the cornea. In additional or alternative cases, the modification to the corneal isotropy outside the corneal optical zone may include a modification in at least one direction of at least one of the optical properties or optical behavior of the cornea or a portion of the cornea.

[0187] In some examples, one or more of the exemplary devices described herein include a light source (e.g., light source 2302 of device 2300 of FIG. 23), which may include at least one of a laser light source and a non-laser light source. The light source may emit, for example, ultraviolet or infrared light. Furthermore, some of the exemplary methods described herein and the exemplary devices described herein may include at least one of a light source and a component that directs light from the light source, which may cause corneal surface patterning. The patterning of the corneal surface may be, for example, phototunable and / or approximately reversible. In addition, in some examples, one or more of the exemplary methods described herein and the exemplary devices described herein may include at least one of a light source and a component that directs light from the light source, which may also cause mechanical reinforcement of multiple non-contiguous corneal portions to which light from the light source is directed. Additionally, some of the exemplary methods described herein and exemplary devices described herein may include at least one of a light source and a component that directs light from the light source and may cause mechanical reinforcement of the portions based on an isotropic / anisotropic basis. In a further example, one or more of the exemplary methods described herein and exemplary devices described herein may include at least one of a light source and a component that directs light from the light source and may also release a mechanical reinforcement agent.

[0188] Some of the exemplary methods and devices described herein include at least one of a light source and a component that directs light from the light source, and may cause defocusing of ambient light from within the field of view of the eye at the PRL and / or focusing at multiple non-contiguous retinal locations that are not the PRL. Some of the exemplary methods and devices described herein may cause defocusing of ambient light from within the field of view of the eye at the PRL of the eye and focusing at multiple non-contiguous retinal locations that are not the PRL, without requiring the optical errors at the non-contiguous retinal locations or PRL to be measured by or input into the device.

[0189] Some of the exemplary methods and devices described herein may include at least one of a light source and a component directing light from the light source, and may cause defocusing of ambient light from within the visual field at the PRL to improve and / or restore vision in an eye with impaired and / or lost central and / or peripheral vision. Some of the exemplary methods and devices described herein may cause defocusing of ambient light from within the visual field at the PRL by modifying at least a plurality of portions of the cornea outside the central optical zone. For example, the plurality of portions of the cornea may include a portion of the cornea having mechanical activity. Some of the exemplary methods and devices described herein may include at least one of a light source and a component directing light from the light source, and may cause defocusing of ambient light from within the visual field at the PRL to modify the optical properties or behavior and / or mechanical properties or behavior of a structure positioned in front of the retina at a plurality of portions outside the central optical zone. The portion of the cornea having mechanical activity may be selected based on the amount of mechanical activity compared to other corneal portions.

[0190] Some of the exemplary methods and exemplary devices described herein may include at least one of a light source and a component that guides light from the light source to cause rebooting of the visual system of the eye and may cause surface patterning of any structure positioned on or within the eye. In some cases, the patterning of the corneal surface may be at least one of phototunable and approximately reversible. Some of the exemplary methods and exemplary devices described herein may include at least one of a light source and a component that guides light from the light source to cause mechanical reinforcement of multiple non-contiguous portions of any structure positioned on or within the eye to which light from the light source is guided. Furthermore, some of the exemplary methods and exemplary devices described herein may include at least one of a light source and a component that guides light from the light source to cause mechanical reinforcement of multiple portions of any structure positioned on or within the eye to which light from the light source is guided, and the reinforcement may be based on an isotropic or anisotropic criterion. Some of the exemplary methods and exemplary devices described herein include at least one of a light source and a component that directs light from the light source and may release a mechanical reinforcing agent to reinforce any structure positioned on or within the eye.

[0191] Some of the exemplary devices described herein, or exemplary components within these devices, may direct light from a light source and may be configured to be positioned intraocularly, intracorneally, or extraocularly in front of the retina of the eye and to enable transmission of the light source, including at least one of a laser light source and a non-laser light source, to multiple non-contiguous portions of at least one structure in front of the retina. The at least one structure in front of the retina may be located intraocularly, intracorneally, or extraocularly and may include, but is not limited to, a native non-cellular structure, such as a structure within the cornea or lens of the eye, or a non-native acellular structure, such as a contact lens, an intracorneal inlay, an intraocular lens, or a donor corneal acellular structure, or another intraocular, intracorneal, or extraocular structure, such as a native or non-native collagen structure, such as corneal stroma, donor corneal stroma, or biosynthetic collagen.

[0192] Some of the exemplary devices described herein that improve vision in an eye with impaired central vision can cause defocusing of ambient light from within the field of view of the eye at the PRL and / or focusing at multiple non-contiguous retinal locations that are not the PRL, and can direct light from a light source to multiple non-contiguous portions of at least one structure in front of the retina. The at least one structure in front of the retina can be placed intraocularly, intracorneally, or extraocularly, and can include, but is not limited to, acellular structures such as contact lenses, intracorneal inlays, intraocular lenses, or other intraocular, intracorneal, or extraocular acellular or collagen structures. Some exemplary devices include a component that directs light from a light source, which can be placed in front of the retina of the eye. In some cases, one or more of these exemplary devices may prevent light from a light source from passing through at least one portion of at least one structure in front of the retina, where the light source includes at least one of a laser light source and a non-laser light source, and where the at least one structure is positioned in front of the retina intraocularly, intracorneally, or extraocularly.

[0193] Some of the exemplary devices described herein improve the vision of an eye with impaired central vision by causing defocusing of ambient light from within the field of view of the eye at the PRL and / or focusing at multiple non-contiguous retinal locations that are not the PRL, and may direct light from a light source, which may be positioned in front of the retina of the eye and configured to allow transmission from the light source (including at least one of a laser light source and a non-laser light source) to multiple non-contiguous portions of at least the acellular and / or collagen structure in front of the retina. In some cases, the at least one acellular and / or collagen structure in front of the retina may be disposed within the cornea or 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 the eye and prevent transmission from the light source to a portion or portions of the at least one acellular or collagen structure in front of the retina. The light source may include, for example, at least one of a laser light source and a non-laser light source, and the at least one acellular and / or collagen structure in front of the retina may be disposed within the cornea or lens of the eye.

[0194] In some cases, one or more of the exemplary methods described herein may include utilizing a laser device, or a device associated with a laser, to direct light from a light source and limit the laser treatment to a plurality of non-contiguous volumes of at least one acellular structure (e.g., layer) of the cornea. Furthermore, some of the exemplary devices described herein may include a laser device, or a device associated with a laser, configured to direct light from a light source and limit the laser treatment to a plurality of non-contiguous volumes of at least one structure (e.g., layer or portion) of the cornea. In addition, some of the exemplary devices described herein, or one or more components of these exemplary devices, may direct laser light from a laser light source and be used for transepithelial laser treatment of the cornea. Some of the exemplary devices described herein, or one or more components of these exemplary devices, may be used after non-laser removal of the corneal epithelium, which may be performed manually with a spatula, diamond burr, or any other instrument, and by any determinable method for corneal epithelial removal.

[0195] Furthermore, in some cases, one or more of the exemplary devices described herein, or one or more components of these exemplary devices, may include one or more additional components that guide light from a light source and have a laser light transmissible opening for laser treatment of at least the acellular layer of the cornea and / or the collagen layer of the cornea, including but not limited to laser light absorbing material surrounding the non-material regions disposed in the non-continuous regions of the one or more components. The additional component or components may, for example, limit laser treatment to at least the acellular layer of the cornea or the non-continuous volumes of the collagen layer of the cornea. The laser light absorbing material may, for example, include polymethylmethacrylate for 193 nm laser light. In some examples, portions of one or more additional components having a laser light absorbing material may surround areas corresponding to the non-contiguous volumes to be removed and may be attached to underlying portions of one or more additional components having a laser light transparent material, such as quartz.

[0196] Some of the exemplary methods and devices described herein may cause a temporary and / or safe repeatable redirection of ambient light away from the PRL of the eye to a plurality of non-PRL retinal locations by directing light from a light source to a plurality of non-contiguous portions of at least one of an acellular structure and a 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 devices described herein may include a light source and a component configured to treat a plurality of non-contiguous portions of a volume within or on the eye that includes at least one of an acellular structure and a collagen structure, and redirect light from the light source away from the PRL to a plurality of non-PRL retinal locations. Additionally, in some cases, one or more of the exemplary methods described herein may utilize an apparatus including a light source and components to treat multiple non-contiguous intraocular volumes that include at least one of acellular ocular structures and collagen ocular structures, and redirect light from the light source away from the PRL to multiple non-PRL retinal locations. The light source may include at least one of a non-laser light source or a laser light source.

[0197] Some of the exemplary devices described herein may include a corneal ablation laser and components configured to ablate at least the acellular layer of the cornea. Furthermore, one or more of the exemplary devices described herein may include a corneal ablation laser and components configured to ablate the corneal epithelium and / or corneal stroma. Examples of ablation lasers include, but are not limited to, argon fluoride excimer lasers that emit far-ultraviolet light with wavelengths including 193 nanometers, and solid-state lasers. One or more of the exemplary devices described herein may direct light from a laser source, including, but not limited to, a laser source that emits infrared or ultraviolet light to produce photoablation.

[0198] Some of the exemplary devices 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. The at least one component may be disposed, for example, between the laser light source and the surface of the non-contiguous portions to be ablated, and the at least one component may include a laser light guide component, a laser light guide control, a laser light occluder, a programmable occlusion microarray, and / or a laser light occlusion control. Some of the exemplary devices described herein include a laser light source and a component for corneal ablation, examples of which include, but are not limited to, a sensor, a processor, a controller, a video camera, an eye tracker, a display, a lens, a laser beam shaping component, a laser beam aiming component, a laser scanning component, and / or a delivery optics.

[0199] In some cases, one or more of the exemplary devices and methods described herein may result in the ablation of a microvolume of any desired volumetric shape of corneal tissue, including at least a portion of the acellular layer and / or collagen layer. The microvolume may include, for example, corneal epithelium and / or corneal stromal tissue, while in other cases, the microvolume may include only corneal stromal tissue. Furthermore, in some cases, one or more of the exemplary devices and methods described herein may result in the ablation of a microvolume of any determinable volumetric shape of corneal tissue, including at least a portion of the rigid anterior layer and / or anterior acellular layer. For example, the ablated microvolume may be characterized by a depth of any determinable depth not deeper than 200 microns with or without an anterior surface transition zone, and by a surface area having a minimum diameter of 0.05 mm or more and a maximum diameter of 5 mm or less. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

[0200] In addition, in some cases, one or more of the exemplary devices and methods described herein may cause ablation of a microvolume of any determinable volume shape of a contact lens comprising an ablative material, an intraocular lens comprising an ablative material, or an intraocular lens device comprising an ablative material. The ablated microvolume may be characterized, for example, by a depth of any depth not deeper than 200 microns, with or without a front surface transition zone, and by a surface area having a minimum diameter of 0.05 mm or more and a maximum diameter of 5 mm or less. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

[0201] Some of the exemplary devices described herein may include a corneal ablation laser source and components configured to ablate multiple non-contiguous micro-volumes in areas of the cornea outside the central optical zone having a diameter greater than 2 mm. Examples of ablation centering methods include, but are not limited to, concentric viewing corneal light reflex, concentric viewing, corneal light reflex, and entrance pupil center.

[0202] Some of the exemplary devices described herein include a laser configured to ablate a portion of the cornea, which can be performed while the subject fixates a light target, thereby determining the PRL axis.

[0203] Some of the exemplary devices described herein that are configured to ablate a portion of the cornea do not require determination of the placement or axis of the PRL prior to or during ablation, such as during ablation of multiple non-contiguous portions outside the central optical zone of 4 mm or more.

[0204] Some of the exemplary devices described herein include at least one or more components configured to direct laser light to multiple non-contiguous portions of the cornea or crystalline lens with at least one pulse of femtosecond, nanosecond, or picosecond duration, and may cause rebooting of the visual system of the eye by redirecting light away from the PRL to multiple retinal locations that are not the PRL, and / or by defocusing ambient light from within the field of view of the eye to the PRL and / or focusing to multiple non-contiguous retinal locations that are not the PRL. Furthermore, in some cases, one or more of the exemplary devices 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 with at least one pulse of femtosecond, nanosecond, or picosecond duration. In addition, some of the exemplary devices described herein may include a laser system that produces, but is not limited to, photoablation, photodisruption, photoionization, photodissociation, photochemical effects, or any combination thereof. One or more of the exemplary devices described herein include one or more laser light sources, examples of which include, but are not limited to, laser light sources that emit infrared, visible, or ultraviolet light. One or more of the exemplary devices described herein may direct light from a laser light source, including, but not limited to, laser light sources that emit infrared, visible, or ultraviolet light.

[0205] Some of the exemplary devices described herein may include one or more components configured to direct laser light to at least one of the acellular layer of the cornea, the corneal epithelium, or the corneal stroma with at least one pulse of femtosecond duration, nanosecond duration, or 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 applanation occluder, a contact liquid occluder, an oil immersion lens, a programmable occlusion microarray, a laser light occlusion control, a lens, a laser beam shaping element, or a laser beam aiming element. Furthermore, one or more of the exemplary devices described herein may produce any determinable spot size. In some cases, one or more of the exemplary devices described herein may include components that produce any determinable pulse energy, pulse frequency, and / or laser pattern (e.g., spiral or raster, etc.) and may utilize any determinable contact interface (e.g., curved or flat, etc.) or centering technique (mechanical or computational). For example, any determinable average power up to about 100 W, peak power up to terawatt levels, repetition rates up to 100 megahertz, pulse durations, polarizations, and / or wavelengths from extreme ultraviolet to mid-infrared may be used for laser-matter interactions, including ultrafast laser-matter interactions. In addition, some of the exemplary devices described herein may produce any ultrafast laser-matter interaction, including any pulse duration from femtoseconds to attoseconds.

[0206] Some of the example devices described herein may include at least one component configured to cause temporary, repeatable redirection of ambient light away from the PRL of the eye to multiple retinal locations that are not the PRL, and configured to direct laser light to at least one of the acellular layer of the cornea, the corneal epithelium, or the corneal stroma with at least one pulse of femtosecond duration, nanosecond duration, or picosecond duration to modify and / or remove multiple non-contiguous micro-volumes.

[0207] In some cases, one or more of the exemplary devices and methods described herein may modify and / or remove a microvolume of any determinable volumetric shape of corneal tissue. Some of the exemplary devices and methods described herein may also modify and / or remove a microvolume of any determinable volumetric shape of corneal tissue. Furthermore, some of the exemplary devices and methods described herein may modify and / or remove a microvolume of any determinable volumetric shape within the mechanically active portion of the cornea. In some cases, one or more of the exemplary devices described herein may direct light to a microvolume having any depth not deeper than 200 microns and having a surface area with a minimum diameter of 0.05 mm or more and a maximum diameter of 5 mm or less. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, any determinable shape.

[0208] Some of the exemplary devices described herein may include at least one component configured to direct laser light with at least one pulse of femtosecond, nanosecond, or picosecond duration to at least one of the cornea, natural lens, contact lens, intracorneal inlay, intraocular lens, intraocular device, or any other structure positioned in front of the retina of the eye. Some of the exemplary devices described herein that improve vision in an eye with central vision impairment by causing defocusing of ambient light from within the field of view of the eye at the PRL and / or focusing at multiple non-contiguous retinal locations that are not the PRL may direct laser light with at least one pulse of femtosecond, nanosecond, or picosecond duration to at least one of the cornea, natural lens, contact lens, intracorneal inlay, intraocular lens, intraocular device, or any other structure positioned in front of the retina of the eye. In some cases, one or more of the exemplary devices described herein may modify a microvolume of any determinable volumetric shape. The microvolume may be characterized, for example, by a determinable depth not deeper than 200 microns and by a surface region having a minimum diameter of 0.05 mm or more and a maximum diameter of 5 mm or less. The surface region may be circular, hexagonal, elliptical, oval, square, rectangular, or any shape. Additionally, in some cases, one or more of the exemplary devices and methods described herein may modify the refractive index or radius of curvature.

[0209] Some of the exemplary devices described herein may include lasers that produce laser thermokeratoplasty but do not produce corneal photovitrification to modify at least the acellular layer of the cornea or any other acellular or collagenous structure positioned in front of the retina of the eye, causing a reboot of the visual system of the eye by causing light redirection away from the PRL to multiple retinal locations that are not the PRL, and / or by causing defocusing of ambient light from within the field of view of the eye to the PRL and / or focusing to multiple non-PRL retinal locations that are not the PRL. Some of the exemplary devices described herein may include a laser that produces laser thermal keratoplasty to modify multiple non-contiguous volumes of at least one of the corneal stroma and corneal epithelium.

[0210] Some of the exemplary devices described herein may be configured to deliver high frequency current (350-400 kHz) to modify at least a non-contiguous volume of the acellular layer of the cornea or any other acellular or collagen structure positioned in front of the retina of the eye. Additionally, in some cases, one or more of the exemplary devices described herein may deliver high frequency current (350-400 kHz) to modify at least a non-contiguous volume of the acellular layer of the cornea or any other acellular or collagen structure positioned in front of the retina of the eye to reboot the visual system of the eye by redirecting light away from the PRL to non-PRL retinal locations and / or by causing defocusing of ambient light from within the field of view of the eye to the PRL and / or focusing to non-PRL non-PRL retinal locations. Some of the exemplary devices described herein are configured to perform conductive keratoplasty and, in addition, may be configured to deliver high frequency electrical current (350-400 kHz) to modify non-contiguous volumes of the corneal stroma and corneal epithelium or any other acellular or collagenous structure positioned in front of the retina of the eye to redirect light away from the PRL to non-PRL retinal locations.

[0211] Some of the exemplary devices described herein that improve the vision of an eye with impaired central vision may cause defocusing of ambient light from within the field of view of the eye in the eccentric viewing zone of fixation of the eye by modifying the mechanical properties or behavior of portions of the structure positioned in front of the retina outside the central optical zone. Furthermore, some of the exemplary devices described herein that improve the vision of an eye with impaired central vision may cause defocusing of ambient light from within the field of view of the eye in the PRL of the eye by modifying the mechanical properties or behavior of portions of the retina outside the central optical zone. Some of the exemplary devices described herein may also modify the mechanical behavior or properties of portions of the cornea outside the central optical zone. The portions of the cornea may include, for example, but not limited to, mechanically active portions of the cornea, such as the anterior acellular layer.

[0212] In some cases, one or more of the exemplary devices described herein may mechanically reinforce portions of the cornea outside the central optical zone. For example, the central optical zone may be characterized by a diameter of at least 2 mm. Furthermore, some of the exemplary devices described herein may cause rebooting of the visual system of the eye by mechanical reinforcement and / or isotropic modification of at least an acellular or collagenous layer of the cornea or any other acellular or collagenous structure positioned in front of the retina of the eye, and may include at least one component including at least one of a light-guiding component, an occluder, a programmable occlusion microarray, a light delivery element, a laser beam shaping element, a laser beam pulsation element, a laser beam aiming element, a chemical agent container, a chemical agent release component, or a chemical agent delivery element. Some of the exemplary methods and devices described herein may perform operations to mechanically reinforce corneal collagen, including, but not limited to, increasing bonds in corneal collagen (e.g., using one or more components of the exemplary devices described herein).

[0213] Some of the exemplary devices described herein may include components including, but not limited to, components for containing and / or releasing chemicals and / or gases for photochemical, photodynamic, or photoionization modification of corneal collagen and / or components for directing light from a light source. In some cases, one or more of the exemplary devices and methods described herein may mechanically reinforce multiple corneal microvolumes outside the central optical zone that are greater than 2 mm in diameter. Each microvolume may be, for example, of any determinable volumetric shape of corneal tissue. Furthermore, the microvolumes may also be characterized by a depth of any determinable depth not deeper than 200 microns, and by an area having a minimum diameter of 0.05 mm or more and a maximum diameter of 5 mm or less. The surface area may be circular, hexagonal, elliptical, oval, square, rectangular, or any determinable shape.

[0214] Further, in some cases, 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 device disposed between the ultraviolet light source and the cornea that directs ultraviolet light to or releases a chemical agent at multiple non-contiguous portions of at least the pre-acellular layer of the cornea based on a determinable diameter of the central optical zone (OZ) and a determinable arrangement and volume of corneal portions of the non-contiguous portions based on, among other criteria, criteria of isotropic behavior or properties of these portions. For example, one or more of the exemplary devices described herein for rebooting the eye's visual system may be configured to direct, using an occlusive component, transepithelially outside the central OZ, to non-continuous corneal portions of at least a determinable depth of the anterior acellular layer, one or more of: (i) a commercially available riboflavin preparation of a determinable concentration for a determinable time to sensitize these portions to mechanically reinforce them with minimal penetration into other portions of the cornea, and (ii) ultraviolet A (UV-A) radiation of a determinable irradiance for a determinable time for activation of a determinable depth of the anterior cornea.

[0215] In some cases, one or more of the exemplary devices described herein may include components that facilitate manual control of one or more of the processes described herein. Additionally, some of the exemplary devices described herein may include a programmable microarray for directing activation light to at least the non-continuous corneal portion of the pre-acellular layer and / or for containing and releasing a photosensitizer such as riboflavin, and a controller programmed to cause controlled transepithelial mechanical reinforcement of, for example, four 1 mm diameter circular corneal portions that include at least one pre-acellular layer and have a depth of about 30 microns below the epithelium. For example, the four portions may be centered on a 6 mm OZ centered on the PRL (by the patient's fixation on the light) and rest on the approximately isotropic corneal portions of the most anterior cornea at the 12 o'clock, 3 o'clock, 6 o'clock, and 9 o'clock positions (as shown in FIG. 22).

[0216] Implementation examples are described in the following numbered clauses. 1. A device for improving or restoring vision, 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 controller coupled to the one or more deformable components via the conductive component, the controller configured to generate and route control signals to the one or more deformable components; After receiving the control signal, the one or more deformable components rearrange at least one pattern to direct ambient light from within the field of view of the eye to the retina at a determinable rate of up to 50 kilohertz; The apparatus, wherein at least one pattern induces defocus in an eccentric zone of fixation of the eye, and at least one pattern produces no aperture. 2. The device described in clause 1, wherein at least one pattern for directing ambient light to the retina induces focusing at multiple non-contiguous retinal locations that are not in the eccentric visual field of fixation. 3. The device described in clause 1, further comprising at least one lens. 4. The apparatus described in clause 1, wherein the one or more deformable components include at least one component having at least one of isotropic properties or isotropic behavior. 5. The device described in clause 1, wherein the pattern of directing ambient light to the retina is reorganized by at least an isotropic modification. 6. The device described in clause 1, wherein the pattern of directing ambient light to the retina is reorganized by at least deformation of one or more opto-mechanical components. 7. An apparatus comprising: at least one or more deformable components positioned in front of the retina of the eye; a controller coupled to the one or more deformable components via the conductive component, the controller configured to generate and route control signals to the one or more deformable components; After receiving the control signal, the device causes a weighting of the exposure of the ambient light from within the field of view of the eye to reduce the exposure of the ambient light from within the field of view of the eye to the central eccentric viewing zone of the eye by at least 10% for a determinable interval; An apparatus in which ambient light within the field of view is exposed to the retina at a determinable rate up to 50 kilohertz. 8. A device for improving or restoring vision, comprising: one or more components for directing light from a light source to at least a plurality of non-contiguous corneal portions, the light source comprising at least one of a laser or a non-laser light source; the non-contiguous corneal portion is disposed outside the central optical zone and includes at least an acellular layer of an age-appropriate normal cornea; The light source does not cause corneal vitrification, The device induces at least one modification of corneal isotropy outside of the central optical zone. 9. The device of clause 8, wherein the device modifies at least one of the mechanical properties and the mechanical behavior in at least one direction. 10. The device according to clause 8, wherein the device modifies at least one of the optical properties and the optical behavior in at least one direction. 11. The apparatus of claim 8, wherein the light source emits at least one of ultraviolet and infrared radiation. 12. The device of clause 8, further comprising one or more components configured to cause at least one of defocusing of ambient light from within the field of view of the eye in the eccentric field of fixation of the eye and focusing at a plurality of non-contiguous retinal locations that are not the eccentric field of fixation. 13. The device of clause 12, wherein defocusing of ambient light from within the eye's field of view in the eye's eccentric fixation zone and focusing at multiple non-contiguous retinal locations that are not the eccentric fixation zone do not require measurement of optical error at the non-contiguous retinal locations. 14. The apparatus of clause 8, further comprising one or more components configured to cause corneal surface patterning, the corneal surface patterning being at least one of phototunable and approximately reversible. 15. The apparatus of claim 8, further comprising one or more components configured to cause mechanical reinforcement of a plurality of non-contiguous portions into which light from the light source is guided. 16. The device according to clause 8, further comprising one or more components configured to release a mechanical reinforcement agent. 17. A method, comprising weighting exposure to ambient light from within the field of view of the eye to reduce exposure to a central eccentric viewing area of ​​the eye by at least 10% for a determinable interval, using a device positioned in front of the retina of the eye, 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 in an eye having impaired central vision, the method comprising using a device to cause defocusing of ambient light from within the eye's visual field in the eccentric visual zone of fixation of the eye. 19. The method of claim 18, further comprising using the device to cause focusing of ambient light in at least one of the genetically modified portion of the retina, the epigenetically modified portion of the retina, and the neuroregeneratively modified portion of the retina. 20. The method of clause 18, further comprising using the device to cause focusing of ambient light within a plurality of portions of the retina including at least one of a retinal transplant, transplanted retinal cells, transplanted stem cells, or an implanted prosthesis. 21. The method of claim 18, further comprising using the device to modify at least a plurality of corneal portions of the cornea outside the central optical zone, the plurality of corneal portions of the cornea including a portion of the cornea having mechanical activity. 22. The method of claim 18, further comprising using the device to modify optical properties or behavior in a plurality of portions outside the central optical zone of a structure positioned in front of the retina. 23. The method of claim 18, further comprising using the device to modify mechanical properties or behavior in a plurality of portions outside the central optical zone of the structure positioned in front of the retina. [Explanation of symbols]

[0217] A fovea B Central dysfunctional retinal area 1900 equipment 1901 Eye 1901A Retina 1901B Fovea 1901C Optic nerve 1902 Transparent Components 1904 Deformable Components 1905 Input Data 1906 Controller 1908 Conductive Components 1910 power supply 1912 Control Signal 1914 Ambient light 1918 PRL 1920 arrangement 2000 equipment 2001 Eye 2001A Retina 2001B fovea 2001C Optic nerve 2002 Transparent Components 2004 Deformable Components 2005 Input Data 2006 Controller 2008 Conductive Components 2010 power supply 2012 Control Signal 2014 ambient light 2018 PRL 2020 Non-PRL placement 2300 equipment 2302 Light source 2304 Light-guiding components 2306 light 2308 Eye 2308A Cornea 2308B Cornea 2310A and 2310B Non-continuous parts 2312 Controller 2314 Power supply 2316 Light source control signal 2318 Component Control Signal

Claims

1. 1. A device for improving or restoring vision, 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 controller coupled to the one or more deformable components via a conductive component, the controller configured to generate and route control signals to the one or more deformable components; Equipped with After receiving the control signal, the one or more deformable components rearrange at least one pattern that directs ambient light to the retina for a time interval or for a time interval at a rate up to 50 kilohertz; The at least one pattern induces defocus in an eccentric zone of fixation of the eye.

2. The device of claim 1 , wherein the at least one pattern for directing ambient light to the retina induces focusing at a plurality of non-contiguous retinal locations that are not in the eccentric zone of fixation.

3. The device described in claim 1, wherein the one or more deformable components further comprise at least one lens.

4. The device of claim 1 , wherein the one or more deformable components comprise an isotropic liquid crystal or an optically isotropic polymer layer.

5. The apparatus of claim 1 , wherein the pattern of directing ambient light to the retina is reorganized by modifying at least an isotropic property of the ambient light.

6. The device described in claim 1, wherein the one or more deformable components comprise one or more optical-mechanical components.

7. An apparatus comprising: at least one or more deformable components positioned in front of the retina of the eye; a controller coupled to the one or more deformable components via a conductive component, the controller configured to generate and route control signals to the one or more deformable components; Equipped with After receiving the control signal, the device causes a weighting of ambient light exposure to reduce ambient light exposure to a central eccentric viewing zone of the eye by at least 10% for a time interval, or for a time interval at a rate up to 50 kilohertz.

8. An apparatus comprising: at least one or more deformable components positioned in front of the retina of the eye; a controller electrically coupled to the one or more transformable components, the controller configured to generate and route control signals to the one or more transformable components; Equipped with Upon receiving the control signal, the one or more deformable components rearrange at least one pattern to direct light from a light source to a structure in front of a retina of the eye; The at least one pattern causes defocusing of ambient light in an eccentric viewing zone of fixation of the eye.

9. The device described in claim 8, configured to cause focusing of the ambient light at multiple non-contiguous retinal locations that are not an eccentric region of eye fixation.

Images