TW202327541A - Adaptive system for the treatment of myopia progression - Google Patents

Abstract

Treatment for the progression of refractive error of an eye is adapted based on a subject's response to therapy. The optical property of an eye can be measured before and after treatment, and a subsequent treatment configured based on the subject's response. The optical property of the eye may comprise one or more of refractive data or axial length data. The optical properties before and after treatment can be compared, and the subsequent treatment configured in response to the comparison. A characteristic of the stimulus can be adjusted in response to the comparison, such as a duration of daily treatment or an intensity of the stimulus during treatment. In some embodiments, the comparison corresponds to a transient change in the optical property of the eye, and the treatment adjusted in response to the transient change.

Description

Adaptive system for treating myopia progression

Previous approaches for treating refractive errors such as myopia have been less than ideal in at least some respects. Spectacle lenses, contact lenses and refractive surgery are used to treat refractive errors of the eye. However, lenses must be worn in order to correct the error, and uncorrected refractive error can affect a person's ability to achieve and fully participate in school, sports, and other activities. Although surgery can be performed to reduce refractive errors, in at least some cases, surgery carries risks, such as infection and loss of vision. Also, these approaches do not address the underlying changes in eye length that are positively associated with refractive errors such as myopia.

Work related to the present invention has shown that the retina of many species, including humans, responds to out-of-focus images and is repositioned through sclera remodeling to reduce blur caused by out-of-focus. The mechanism by which the growth signal is generated is still under investigation, but one observable phenomenon is an increase in the thickness of the choroid. An out-of-focus image can cause changes in choroidal thickness, which correlates with the axial length of the eye. Changes in the axial length of the eye can alter the refractive error by changing the position of the retina relative to the cornea. For example, an increase in axial length can increase the myopia of an eye by increasing the distance between the cornea and the retina.

While defocus of the image can contribute to changes in choroidal thickness and axial length of the eye, previous methods are less than ideal for addressing refractive errors of the eye that are related to axial length. Although drug treatments have been proposed to treat myopia associated with axial length growth, such treatments can have suboptimal results and have not been shown to safely treat refractive errors in at least some instances. Although light has been proposed as a stimulus to alter the growth of the eye, at least some previous devices have provided less than ideal results. Also, treatment times can be longer than desired, and at least some previous methods can be more complex than desired.

It would be useful to have an effective amount for determining therapy for treating refractive error progression. Previous methods can be somewhat less predictable than ideal, and improved predictability would be helpful. Also, it would be useful to determine the appropriate amount of therapy in response to treatment, and in at least some instances, the previous methods may be somewhat open-loop. Furthermore, previous methods may not be well suited for adapting therapy in response to the properties of different eyes, which may respond differently to therapy.

Accordingly, there is a need for new approaches to treating refractive errors of the eye that improve at least some of the above limitations of previous approaches.

The systems, methods and devices of the present disclosure relate to improved treatment of refractive error progression that can be tailored based on a subject's response to therapy. The treatment may include an optical stimulus delivered to the eye at a focal point at a distance from the retina to provide a blurred image on the retina, which may reduce myopia progression. Optical properties of an eye can be measured before and after treatment, and a subsequent treatment configured based on the subject's responses. The optical properties of the eye can include one or more of refractive data or axial length data that can be used to assess the subject's response to treatment. The optical properties before and after treatment can be compared, and the subsequent treatment configured in response to the comparison. In some embodiments, a characteristic of the stimulus, such as a duration of a daily treatment or an intensity of the stimulus during treatment, is adjusted in response to the comparison. In some embodiments, the comparison corresponds to a transient change in the optical properties of the eye, and the treatment is adjusted in response to the transient change. In some embodiments, a display is used to generate the stimulus, which allows the stimulus to be easily configured in response to the transient change in the optical properties of the eye.

Related applications

This application claims priority to U.S. Provisional Patent Application No. 63/262,419, filed October 12, 2021, entitled "ADAPTIVE SYSTEM FOR THE TREATMENT OF MYOPIA PROGRESSION," which is incorporated by reference in its entirety In this article.

The subject matter of this application is related to: PCT/US2019/043692, filed on July 26, 2019, entitled "ELECTRONIC CONTACT LENS TO DECREASE MYOPIA PROGRESSION," which was published on February 6, 2020 as WO/ 2020/028177; PCT/US2020/044571, filed 31 July 2021, entitled "DEVICE FOR PROJECTING IMAGES ON THE RETINA," which was published as WO/2021/022193 on 4 February 2021; PCT/US2021/036100 titled "PROJECTION OF DEFOCUSED IMAGES ON THE PERIPHERAL RETINA TO TREAT REFRACTIVE ERROR" filed on June 7, which was published as WO 2021/252319 on December 16, 2021; on June 7, 2021 PCT/US2021/036102 titled "STICK ON DEVICES USING PERIPHERAL DEFOCUS TO TREAT PROGRESSIVE REFRACTIVE ERROR" filed on 16 December 2021 as WO 2021/252320; and filed on 13 May 2021 PCT/US2021/032162, entitled "ELECTRO-SWITCHABLE SPECTACLES FOR MYOPIA TREATMENT," was published as WO 2021/231684 on November 18, 2021, the entire disclosures of which are incorporated herein by reference. incorporated by reference

All patents, applications, and publications mentioned and identified herein are hereby incorporated by reference in their entirety and should be deemed fully incorporated by reference, even if mentioned elsewhere in the application.

The following detailed description provides a better understanding of the features and advantages of the invention described in this disclosure from the embodiments disclosed herein. While the detailed description contains many specific embodiments, these are provided by way of example only and should not be construed as limiting the scope of the inventions disclosed herein.

The methods and devices of the present disclosure can be configured in many ways to provide retinal stimulation, as described herein. The systems, methods and apparatuses of the present disclosure are well suited for use in combination with many prior devices, such as an ophthalmic device, a TV screen, a computer screen, a virtual reality (“VR”) display, an augmented reality (“AR”) ) display, a handheld device, a mobile computing device, a tablet computing device, a smart phone, a wearable device, a spectacle lens frame, a spectacle lens, a near-eye display, a head-mounted display, and goggles , one or more of a contact lens, an implantable device, a corneal onlay, a corneal inlay, a corneal prosthesis, or an intraocular lens. While specific reference is made to eyeglasses and contact lenses, the methods and apparatus of the present disclosure are well suited for use with any of the aforementioned devices, and based on the teachings provided herein, one of ordinary skill will readily appreciate how one or more of the components of the present disclosure may be used. Interchange among devices.

In some embodiments, stimulating the retina using out-of-focus light provides a measurable change in one of axial length and choroidal thickness. Stimuli can be provided in many ways and can include, for example, active stimulation using a light source or passive stimulation, such as using a natural scene. In some embodiments, stimulation is provided using a device that includes a chin rest to allow the subject to rest comfortably. Alternatively or in combination, for example, stimulation may be provided using a wearable device such as a helmet or glasses, wherein the stimulation and projection system may be worn and supported by the subject.

In some embodiments, active stimulation is provided using an optical device comprising a chin rest, wherein the subject positions their cheeks on the chin rest and watches a video or video with a primary gaze at a distance of 20 feet or greater A still scene. In some embodiments, the optical device includes an optical bench. Alternatively or in combination, the device may comprise a wearable device, as described herein. For example, distance may include a real physical distance from an image or a distance from a subject's pupil to a virtual image. In some embodiments, the optical device includes lenses that correct the refractive error of the subject and provide the subject with a corrected visual acuity, such as a best corrected visual acuity of the subject. When positioned as described, the device focuses the image, for example, using a myopic viewing angle to a focused image in front of the retina such that the image reaches the retina with at least some viewing angle and blur. Although the device can be configured in many ways, the device can include light sources, masks, microlenses, and beam splitters to produce an image with one of the quantities in the range from +2.00 D to +8.00 D Myopic out-of-focus images. While defocus can be used to generate images in many ways, in some embodiments the images are transmitted through lenses provided to correct the subject's refractive error and projected through the natural pupils of the subject's eyes at an angle such that the The projected image is incident on the retinal surface at an appropriate eccentricity relative to the fovea and the subject's line of sight without vignetting. The eccentricity angle may be any suitable angle as described herein, such as an angle (half angle, 12 degrees to 45 degrees, full angle) in a range from 6 degrees to 22.5 degrees, and the angle may correspond to those included in ( For example) an angle in a range from 12 degrees to 45 degrees a diameter an annular area a circle.

Work related to the present invention demonstrates that axial length or choroidal thickness can be measured and detected after completion of irritant treatment of one eye of a subject (e.g., within about one hour of completion of an irritant treatment). one or more changes. In some embodiments, the transient changes in axial length and choroidal thickness are measured by measuring the subject's axial length and choroidal thickness immediately after cessation of stimulation. The duration of a stimulus treatment may be any suitable duration, such as, for example, a duration of from 1 to 6 hours and may range from one of 60 to 90 minutes. In some embodiments, therapy is administered and transient changes are measured in the morning local time. In some embodiments, the transient change in axial length comprises the difference between a first axial length measured before initiation of treatment on the day of treatment and a second axial length measured after completion of treatment with the stimulant on the day of treatment. a difference between. In some embodiments, transient changes from one or more treatment sessions are used as input to determine whether a particular device configuration for inhibiting myopia progression is effective. Alternatively or in combination, transient changes may also be used to modify one or more parameters of the device, such as the magnitude of defocus, brightness of projected myopic out-of-focus images, chromaticity of projected images, and other characteristics of stimuli such as described in this article.

The present inventors have performed clinical studies according to the present invention and measured transient changes in axial length. Transient changes in axial length in response to a stimulus according to the present invention have been measured in a clinical study, as described herein.

In some embodiments, a transient change in one or more of axial length, choroidal thickness, or refractive data is used as a proxy for long-term clinical validation of the therapeutic device. Transient changes in response to treatment may be measured over any suitable duration, such as before and after treatment on the same day or for a longer duration, such as before treatment on multiple days and after treatment on multiple days, such as after treatment One month after the treatment of the following week or multiple days. In some embodiments, treatment over a duration of one week or one month includes one treatment on at least half of the days of the duration (eg, on at least 4 days of a week or at least 16 days of a month).

Transient changes in response to treatment may be measured in any suitable manner, such as one or more of refractive data of the eye, axial length of the eye, or choroidal thickness of the eye. Refractive data may include any suitable data related to the refractive properties of the eye, such as spheres, cylinders, axes, aberrations, spherical aberrations, coma trilobes, wavefront data for the illuminated location of the retina , one or more of Zernike coefficients or wavefront maps. Refractive data may be measured using any suitable device, such as a phoropter, trial lens, an autorefractometer, a widefield autorefractometer, a narrowfield autorefractometer, a scanning slit autorefractometer light meter, an aberrometer or a wavefront sensor. In some embodiments, a natural pupil is used to measure the refractive data. Alternatively or in combination, when the eye has been dilated with a mydriatic, refraction data can be measured using a dilated pupil to provide cycloplegic refraction data. Axial length and choroidal thickness can be measured using any suitable instrument that measures the length of the eye from the cornea to the retina, such as an optical coherence tomography (OCT) biometer. Choroidal thickness can be measured using a similar or equivalent instrument to one that measures axial length.

Figure 1A shows a retinal stimulating device for one or more of reducing myopia progression or at least partially reversing myopia progression. The device comprises an optic 10 for supporting one of the plurality of light sources. A plurality of light sources can be coupled to one or more optical components to provide a stimulus to the retina, as described herein. In some embodiments, lens 10 includes a spectacle lens 72 . In some embodiments, the lens 10 is shaped to correct the user's spherical and cylindrical refractive errors to provide corrected visual acuity through the lens. The plurality of light sources may include one or more of the projection unit 12 or a display 74 such as a near-eye display. A plurality of light sources are arranged around the central portion of the lens to provide light stimulation to an outer location of the retina, such as the peripheral retina, as described herein. In some embodiments, the light source is positioned in an approximately annular region to provide stimulation to the peripheral retina. The light sources may be arranged in a generally circular pattern (eg, in quadrants) so as to correspond to quadrants of the peripheral retina outside the macula. Each of the plurality of light sources can be configured to project a pattern in front of the retina using an appropriate pattern of stimuli, as described herein. In some embodiments, light from the light source passes through one of the optical axes of the eye to stimulate the retina at a location on the side of the retina opposite the light source.

In some embodiments, projection unit 12 is configured to emit light rays into the pupil of the eye without substantial aliasing. In some embodiments, the pupil of the eye can be enlarged by an appropriate amount of illumination or application of a mydriatic agent so that a larger area of the retinal surface can be accessed by the stimulus projected by the projection unit 12 .

In some embodiments, the plurality of light sources are configured to remain static while a user observes an object. Alternatively, the light source may be configured to move in response to eye movement, for example using selective activation of pixels, as described herein.

Although reference is made to a plurality of light sources supported on a mirror, the light sources may be supported on any suitable optically transmissive substrate such as a beam splitter or a substantially flat optical component, and the light source may comprise a pixelated display such as an AR or VR display) light source. In some embodiments, display 72 includes pixels 94 that are selectively activated to provide a stimulus to the retina, as described herein. Alternatively or in combination, projection unit 12 may include a shaped structure for delivering stimuli to the retina, as described herein.

In some embodiments, the pixels are configured to emit a plurality of colors such that the projected light can be combined to produce any suitable color or hue, such as, for example, white light.

In some embodiments, the plurality of light sources are supported by a head-mounted support, such as eyeglass frame 76 on eyeglasses 70 .

Figures IB and 1C depict eyeglasses 70 for treating a refractive error of the eye, such as a spherical refractive error, although any suitable vision device as described herein may be suitably modified in accordance with the embodiments disclosed herein. A plurality of light sources can be coupled to one or more optical components to provide a stimulus to the retina, as described herein. Glasses 70 may include one or more components of commercially available augmented reality glasses. Eyewear 70 may include one or more displays 72 for retinal stimulation. Near-eye display 72 may be mounted to lens 74 . Lens 74 may be a spectacle lens supported by spectacle frame 76 . Lens 74 may be a corrective or non-corrective lens. The lens 74 may be a plano lens, a spherical corrective lens, an astigmatic corrective lens, or a spheroidal corrective lens. In some embodiments, the near-eye display is positioned away from an optical zone to provide a clear center perception. An optical axis may extend from an object the subject is looking at through lens 74 along a line of sight to a fovea of the eye. In some embodiments, eyewear 70 includes an eye tracker suitable for incorporation in accordance with the present invention. Near-eye display 72 may be programmed to selectively activate pixels 94 to provide peripheral stimulation to the retina, as described herein. In some embodiments, a layer of a plastic substrate carrying microlenses is attached to a microdisplay to produce a desired level of defocus and stimulation at the retina. Selectively actuatable pixels may include groups of pixels that are selectively actuatable together, for example, a first group of pixels 94a, a second group of pixels 94b, a third group of pixels 94c, and A fourth group of pixels 94d. Groups of pixels can be configured to provide an appropriate eccentricity relative to a line of sight of the subject in order to provide peripheral retinal stimulation, as described herein.

In some embodiments, a near-eye display 72 includes a combination of a microdisplay and a micro-optics. In some embodiments, the micro-optics are configured to collect, substantially collimate, and focus light emitted from the microdisplay. In some embodiments, the micro-optics are configured to form an image in front of or behind the retina, as described herein. In some embodiments, the distance of the near-to-eye display from the entrance pupil of the eye is in a range from about 10 mm to about 30 mm, for example about 15 mm. The microdisplay can be placed on a transparent substrate such as the front or back surface of the lens 74 of the glasses 70 . When the microdisplay is placed on the front surface of the lens 74, then the focus of the microdisplay can be affected by the cylindrical correction on the rear surface of the lens 74.

In some embodiments, the focus of pixels in a microdisplay can be varied based on their position on the lens 74 and the refractive correction provided by the lens in that area. In some embodiments, the focal point of a pixel may be fixed. In some embodiments, the focal point of the pixel can be changed based on the sensed position of the cornea to account for the refraction of the cornea and the lens of the eye. In some embodiments, the pixels are defocused to produce an out-of-focus on the retina with a diameter of about 1 mm.

Light emitted by pixels 94 in a microdisplay of a near-eye display may be substantially one or more of collimated or focused before being directed to the pupil of the eye. In some embodiments, a microlens array is aligned with the pixels of the near-eye display so that light from the near-eye display can enter the pupil and form an image in front or behind the retina. In some embodiments, the width of the near-eye display corresponds to a field of view of a subject. In some embodiments, the extent of the near-eye display may be substantially similar to the extent of the lenses 74 of the glasses 70 .

In some embodiments, the device provides unimpaired central vision such that the user's quality of life and vision are not adversely affected. In some embodiments, central vision includes a field of view covering +/- 5 degrees or greater, preferably +/- 7.5 degrees or greater, such as +/- 12.5 degrees, of the macula for a fixed central vision. Concave vision has a field of view of +/- 1.0 degrees. In some embodiments, the out-of-focus image is at an outer portion of the retina toward the periphery of the retina (e.g., between 15 degrees (full angle, or +/- 7.5 degrees) and 40 degrees (full angle, or +/- 7.5 degrees) to 40 degrees (full angle, or +/- -20 degrees)) is projected and may be in a range from 20 degrees to 40 degrees, for example in a range from 20 degrees to 30 degrees. In some embodiments, the microdisplay 72 does not obstruct the central vision field of view. In some embodiments, pixels 94 do not obstruct the central vision field of view.

In some embodiments, the microdisplay and optics are configured to project light onto outer regions of the retina that are far enough away from the fovea that the illumination remains substantially fixed even as the eye moves. In some embodiments, the point of gaze is monitored and the desired location of a pixel to be activated on the microdisplay is determined, such as by using a processor to perform an operation such that an image is projected at the desired location on the retina, This allows for continued stimulation at the same retinal location. In some embodiments, the gaze point on the plane of the glasses or the plane of the microdisplay is calculated by monitoring the horizontal, vertical and torsional displacement of the eye relative to the principal position.

Gaze point can be determined in many ways (eg using an eye position sensor such as a magnetic sensor or an optical sensor). In some embodiments, a search coil embedded in the eyeglass frame is used to track eye movement. A coil embedded in the eyeglass frame can be coupled to a magnetic structure placed on the eye, such as a coil on a contact lens, a coil implanted in the eye, a magnetic material on a contact lens, or one implanted in the eye One or more magnetic materials. In some embodiments, the sensor includes an optical sensor such as a position sensitive detector or an array sensor to optically measure a position of the eye. The optical sensor can be configured to measure a position of the eye in many ways, for example configured to measure one or more of corneal reflections from a light source, a pupil, a limbus, or a sclera Location. The eye box may support an additional light source to illuminate the eye, for example to create a corneal reflection. Data from the sensor can provide the position of the coaxial view film light reflection ("CSCLR"), and thus the direction of the visual axis and the position of the fovea. Point of fixation, visual axis, optical axis, knot and CSCLR are described in "Ocular axes and angles: time for better understanding" in J CATARACT REFRACT SURG, Srinivasan, S. - Vol. 42, March 2016. In some embodiments, a processor using an eye position sensor can be configured to adjust optics, such as pixels in a microdisplay, to reduce movement of the stimulated position of the retina in response to eye movement. In some embodiments, the target position of the peripheral image is calculated from the fovea based on information from the eye position sensor and a real-time ray tracing calculation provides the position of the pixel to be activated in the microdisplay. The time for selectively switching to the second plurality of pixels in response to eye movement may be less than 100 milliseconds, such as less than 20 milliseconds.

In some embodiments, the position of a pixel in a microdisplay to be activated to form an external image towards the periphery of the retina is referenced from the optical center of the eyeglass optics because it is the point of fixation during primary gaze. In some embodiments, the position of the gaze point is calculated by taking into account the eye movement relative to the position of the eye at the time of primary gaze and calculating the position of the pixel to be activated with reference to the new gaze point. For example, FIG. 1B shows active pixels 94 when a subject is looking straight ahead horizontally (the so-called primary gaze), while FIG. 1C shows active pixels 94 when a subject is looking up and to the left. In this case, the shape of the pixel array may be the same, but shifted up and to the left, or the shape of the array may change.

In some embodiments, the device is dual purpose and includes a microdisplay and optics for each eye of the user. The microdisplay can be optically coupled with one or more micro-optical components designed to substantially collimate the illumination generated by the pixels of the microdisplay and appearing convergent before entering the pupil.

In some embodiments, a display 72 is mounted on the outside of a spectacle lens and is aligned with the spectacle lens optics so that the near-eye display can provide a field of view of +/- 40 degrees or more so that the microdisplay can continue to be normal A range of eye movements (typically +/-15 degrees laterally and +10 to -20 degrees vertically, including downward gaze when reading or viewing nearby objects) provides peripheral retinal stimulation. In some embodiments, light from the microdisplay is transmitted through eyeglass lens optics and provides refractive correction to the user.

In some embodiments, the optical system is configured to form an image in front of the retina and includes a single microlens (lentlet), a plurality of microlenses (lenslet array), a composite lens such as a Gabor lens , a micro-screen or a micro-mirror) or a combination of one or more of them. In some embodiments, the light baffles and micromirrors are configured to ensure that the amount of light not captured by the micro-optics is substantially reduced (eg, minimized) in order to reduce stray light and light escaping from the front side of the display.

In some embodiments, a pixel fill factor of less than 10% (0.1) is sufficiently sparse to provide a clear view of the fovea and macula images. In some embodiments, the fill factor is in the range of 0.01 to 0.3 and may be in a range from 0.05 to 0.20. For example, an array of pixels with a pixel size of 5 microns and a pixel pitch of 20 microns results in a fill factor of 0.06. A low fill factor also reduces the complexity of the manufacturing process and lowers the cost of these micro-optical displays.

In some embodiments, the micro-optics array is designed to be optically aligned with the display so that light from a single or plurality of pixels 94 can be collected, collimated and focused to be directed to the user's pupil when primarily gazing. The density of these micro-optical elements can control the overall visibility of near-eye displays. In some embodiments, the micro-optics have a low fill factor (preferably equal to or less than 0.1) such that the overall light transmission through the near-eye display will be acceptable to the user and allow the subject to view the object.

In some embodiments, for example, the device includes a liquid crystal or an LC-based material that can be switched by optoelectronic components, for example, that can switch from one index of refraction to another or from one polarization to another. A switchable micro-optic array is switched between a plano (no optical power) state and an activated state. In some embodiments, the micro-optics array does not scatter light or distort images of the real world when not activated.

In some embodiments, the position of a pixel in a microdisplay to be activated to form an external image towards the periphery of the retina is referenced from the optical center of the eyeglass optics because it is the point of fixation during primary gaze. In some embodiments, the position of the gaze point is calculated by taking into account the eye movement relative to the position of the eye at the time of primary gaze and calculating the position of the pixel to be activated with reference to the new gaze point.

In some embodiments, a plurality of pixels are activated to form a light source imaged by micro-optics. The optical design of the micro-optics and its separation from the micro-display can be configured to provide the focal length of the image delivery system, the image magnification of the image projected on the retina, and the blurring caused by diffraction, as measured for the optical delivery system The diameter of the Airy disc.

Work related to the present invention has shown that changes in retinal perception of image blur (in addition to spherical defocus) are caused by higher order aberrations present in out-of-focus images, including longitudinal chromatic aberration (LCA), which is sensitive to out-of-focus signs, Higher order spherical aberration, astigmatism, etc. Based on the teachings provided herein, one of ordinary skill can conduct experiments to determine whether the retina can discern a myopic blur and a hyperopic blur when the depth of focus of the device is greater than or approximately equal to the magnitude of the defocus. For example, a device as described herein may approximately be configured to provide an appropriate amount of defocus at an appropriate location.

The device can be configured to provide an appropriate image magnification that limits the image resolution and depth of focus associated with the magnitude of the applied myopic defocus and the rate of change of image blur that varies depending on the magnitude of the defocus or the gradient of image sharpness , Diffraction.

In some embodiments, the near-eye display is configured to provide a clear, substantially undistorted field of view of the foveal and macular images for comfortable vision. In some embodiments, for example, the field of view of the central image is at least +/- 5 degrees and may be larger (eg, +/- 12 degrees), eg, to account for differences in interpupillary distance (IPD) of different users. The image quality and field of view of realistic images can be provided while making a substantially transparent near-eye display transparent and by reducing the fill factor of light-emitting pixels in the microdisplay. In some embodiments, a fill factor of less than 10% (0.1) is sufficiently sparse to provide a clear view of the fovea and macula images. In some embodiments, the fill factor is in the range of 0.01 to 0.3 and may be in a range from 0.05 to 0.20. For example, an array of pixels with a pixel size of 5 microns and a pixel pitch of 20 microns will result in a fill factor of 0.06. A low fill factor also reduces the complexity of the manufacturing process and lowers the cost of these micro-optical displays.

In some embodiments, the micro-optics array is designed to be optically aligned with the display so that light from a single or multiple pixels can be collected, collimated and focused to be directed to the user's pupil when primarily gazing. The population density of these micro-optical elements can control the overall visibility of near-eye displays. In some embodiments, the micro-optics have a low fill factor (preferably equal to or less than 0.1) so that the overall light transmission through the near-eye display will be acceptable to the user.

In some embodiments, for example, the device includes a liquid crystal or an LC-based material that can be switched by optoelectronic components, for example, that can switch from one index of refraction to another or from one polarization to another. A switchable micro-optic array is switched between a plano (no optical power) state and an activated state. In some embodiments, the micro-optics array does not scatter light or distort images of the real world when not activated.

2A and 2B depict a contact lens 10 comprising light sources configured to project an out-of-focus image on the retina away from the central field containing the macula in order to stimulate a change in choroidal thickness. A plurality of light sources can be coupled to one or more optical components to provide a stimulus to the retina, as described herein. Although reference is made to a contact lens, lens 10 may include a projector, ophthalmic equipment, a TV screen, a computer screen, an augmented reality display, a virtual reality display, a handheld device such as a smartphone ), a wearable device (such as a spectacle lens), a near-eye display, a head-mounted display, a goggle, a contact lens, a corneal onlay, a corneal inlay, a corneal prosthesis, or an intraocular lens One or more lenses.

The contact lens 10 comprises a substrate or carrier contact lens containing embedded electronics and optics. The base soft contact lens 10 is made of a biocompatible material, such as a hydrogel or silicone hydrogel polymer, designed for long-lasting wearing comfort. The contact lens includes a maximum overall distance across, for example a diameter 13 . Biocompatible materials may encapsulate the components of soft contact lens 10 . In some embodiments, contact lens 10 has a central optical zone 14 designed to cover the pupil of a user's eye under many lighting conditions. In some embodiments, the optical zone comprises a circular zone bounded by a radius 15 . In some embodiments, projection units 12 are positioned a distance 17 from the center of one of the optical zones. Each of the plurality of projection units 12 includes a spanning distance 19 . In some embodiments, the distance between the projection units is sized to place the projection units outside the optic zone to stimulate a peripheral area of the retina, although the projection units can also be placed inside the optic zone to stimulate the peripheral retina, as herein describe.

Optical zone 14 can be appropriately sized for the pupil of the eye and the lighting conditions during treatment. In some embodiments, for example, when the contact lens is configured for use during the day, the optic zone includes a diameter of 6 mm. Optical zone 14 may have a diameter in a range of from 6 mm to 9 mm, such as in a range of from 7.0 mm to 8.0 mm. The central optic zone 14 is designed to provide emmetropia or other suitable correction to the user and may have both spherical and astigmatic corrections. The central optical zone 14 is circumscribed by an outer annular zone, such as a peripheral zone 16 having a width in the range of 2.5 mm to 3.0 mm. The peripheral zone 16 (sometimes called the hybrid zone) is primarily designed to provide a good fit (including good centrality and minimal decentering) to the cornea. The outer annular region is surrounded by an outermost edge region 18 having a width in the range from 0.5 mm to 1.0 mm. Optic zone 14 is configured to provide refractive correction and may be spherical, toric, or multifocal in design, eg, having a visual acuity of 20/20 or better. The outer annular zone surrounding the optic zone 14 is configured to match the curvature of the cornea and may include a rotational stabilization zone for translational and rotational stability while allowing the contact lens 10 to move over the eye after blinking. The edge region 18 may comprise a thickness in a range from 0.05 mm to 0.15 mm and may end in a wedge shape. The overall diameter 13 of the soft contact lens 10 may be in a range from 12.5 mm to 15.0 mm, for example in a range from 13.5 mm to 14.8 mm.

The contact lens 10 includes a plurality of embedded projection units 12 . Each of the plurality of projection units 12 includes a light source and one or more optics for focusing the light in front of the retina, as described herein. Each of the optics may include one or more of a mirror, mirrors, a mirror, a plurality of mirrors, a refractive optic, a Fresnel mirror, a light pipe, or a waveguide. The contact lens 10 can include a battery 20 and a sensor 22 . The contact lens 10 may include a flex printed circuit board (PCB) 24 and a processor may be mounted on the flex PCB 24 . A processor may be mounted on PCB 24 and coupled to sensor 22 and light sources 30 . The soft contact lens 10 may also include wireless communication circuitry and one or more antennas 41 for electronic communication and for inductively charging the battery 20 of the contact lens 10 . Although reference is made to a battery 20, the contact lens 10 may comprise any suitable energy storage device.

Projection unit 12 may be configured to provide an out-of-focus image to a peripheral portion of the retina as described herein and may include a light source and projection optics. In some embodiments, one or more projection optics are configured with a light source to project an out-of-focus image from the light source onto the peripheral retina away from the central field of vision including the macula to stimulate a change in choroidal thickness, such as the choroid One of the thickness increases or decreases. One or more projection units 12 may be configured to stimulate the retina without degrading central vision and corresponding images formed on one or more of the fovea or macular area of the retina. In some embodiments, the one or more projection optics do not degrade the image forming characteristics of the vision correction optics prescribed to correct the user's refractive error. This configuration may allow a user to have good visual acuity while receiving therapy from an out-of-focus image, as described herein.

In some embodiments, the light from the light source of projection unit 12 is substantially collimated and focused by one or more projection optics, as described herein. The function of the light source and projection optics is to substantially collimate the light emitted by the light source and direct it at a focal point designed to be in front or behind the retina to provide the proper defocus to stimulate a change in choroidal thickness. For example, for myopic out-of-focus, an in-focus image may appear about 1.5 mm to 2.5 mm in front of the peripheral retina, and for myopia up to about 2.0 D to 5.0 D (eg, 2.0 D to 4.0 D, or preferably 2.5 D to 3.5 D). For example, for hyperopic defocus, the focused image may be presented approximately 1.5 mm to 2.5 mm behind the peripheral retina for hyperopia of approximately -2.0 D to -5.0 D, such as -2.0 D to -4.0 D, or preferably -2.5 D to - 3.5 D.

The plurality of stimuli and clear zones can be configured to allow movement of the eye relative to the projection optics and clear zone, which may be well suited for embodiments where the eye is relative to the projection optics, such as eyeglasses, AR and VR applications. According to some embodiments, the light from the projection unit may be oriented at an oblique angle relative to an optical axis of the eye so as to enter the pupil while maintaining a zone of sharp central vision substantially larger than the pupil in order to provide a large field of view of the zone of sharpness, e.g., A big eye box. The clear zone can be sized in many ways, and can include a circular zone, an oval, a square zone, or a rectangular zone. In some embodiments, the eye box may be 5.0 mm by 4.0 mm. In some embodiments, the clear zone includes an eye box that may be 15 mm by 4.0 mm. A larger area of clear viewing (e.g., a larger eye box) allows a greater level of eye movement and, for example, the edge of the pupil when the eye changes gaze direction and the area of clear viewing defined by the eye box remains stationary. Does not block irritants. In some embodiments, the oblique angle at which the stimulus is projected into the eye depends on the size of the eye box.

According to some embodiments, the lens 10 or other suitable optical support structure includes a projection unit comprising projection optics and a microdisplay as a light source. Microdisplays can include an OLED (Organic Light Emitting Diode) or an array of micro LEDs. The light emitted by such displays can be Lambertian. In some embodiments, the microdisplay is optically coupled to a micro-optics array that substantially collimates and focuses light emitted from the microdisplay. A microdisplay can include one or more miniaturized pixels. In some embodiments, the microdisplay forms an extended pixel array characterized by a pixel size and a pixel pitch, where the pixel size and pixel pitch together correspond to a fill factor of the microdisplay. As described herein, for example, each pixel can have a size ranging from about 2 microns to about 100 microns, and the pixel pitch can range from 10 microns to 1.0 mm. Corresponding fill factors may range from 0.1% to 10% or more. In some embodiments where real world viewing may be desired, a smaller fill factor blocks less light from the real environment and provides a greater level of comfort and vision. Alternatively or in combination, a larger fill factor may enhance the overall brightness of the stimuli and may be well suited for applications that do not rely on real world viewing and omnidirectional vision. In some embodiments, the optical array is optically coupled with a micro-optic array to substantially collimate and focus light from the pixels.

According to some embodiments, the lens 10 or other suitable optical support structure includes a projection unit comprising projection optics and a microdisplay as a light source. Microdisplays can include an OLED (Organic Light Emitting Diode) or an array of micro LEDs. The light emitted by such displays may be Lambertian. In some embodiments, the microdisplay is optically coupled to a micro-optics array that substantially collimates and focuses light emitted from the microdisplay. A microdisplay can include one or more miniaturized pixels. In some embodiments, the microdisplay forms an extended pixel array characterized by a pixel size and a pixel pitch, where the pixel size and pixel pitch together correspond to a fill factor of the microdisplay. As described herein, for example, each pixel can have a size ranging from about 2 microns to about 100 microns, and the pixel pitch can range from 10 microns to 1.0 mm. The corresponding fill factor may range from 0.1% to 10%. In some embodiments, the optical array is optically coupled with a micro-optic array to substantially collimate and focus light from the pixels.

Images produced by these displays are out of focus and can be placed symmetrically in the four quadrants of the eye's field of view (eg, infranasal, supranasal, infratemporal, and supratemporal). The microdisplay can be positioned away from the optical center of the lens by a distance in the range from 1.5 mm to 4.0 mm, preferably 2.5 mm to 3.5 mm. The central optic of the contact lens can be selected to bring the user to emmetropia and can have a diameter in the range of 3.0 to 5.0 mm. In some embodiments, each microdisplay can be circular, rectangular, or arcuate in shape and have a shape in the range from 0.01 mm ² to 8.0 mm ² (eg, in the range from 1 mm ² to 8 mm ^{2 )} . within, or preferably within a range from 1.0 mm ² to 4.0 mm ² ).

The microdisplay can be coupled to the body of a corrective optic such as a contact lens or a spectacle lens, an augmented reality ("AR") headset, or a virtual reality ("VR") headset and use the body of the corrective optic support. In some embodiments, the microdisplay is coupled to and supported using one or more of an intraocular lens, a corneal prosthesis, a corneal onlay, or a corneal inlay. For example, optical configurations described herein with reference to a contact lens may similarly be used with one or more of an intraocular lens, a corneal prosthesis, a corneal onlay, or a corneal inlay.

In some embodiments, the microdisplay and microoptic array are mounted in close proximity to each other on the same corrective optic, separated by a fixed distance in order to direct a beam of light in such a way that it forms an out-of-focus image at a desired location on the retina. Projection to the pupil of the eye, as described herein. In some embodiments, one or more projection optics are mounted on or in one or more corrective optics such that light from the projection optics is refracted through the corrective optics. The corrective optics refract light from the projection optics to converge or diverge to aid in clear vision so that the micro-optics array can provide a desired amount of extra diopters, positive or negative depending on the magnitude and sign of the desired defocus. For example, microdisplays can be monochrome or multicolor.

In some embodiments, the projected out-of-focus image may be provided by one or more of a screen including an LCD screen, one or more screens driven by OLEDS (Organic Light Emitting Diodes), TOLEDS, AMOLEDS, PMOLEDS or QLEDS Microdisplay provided.

FIG. 3 shows a system diagram of the function of components of a retinal stimulation device, such as lens 10 in FIGS. 1A-2B . Such components may be supported using PCB 24 . For example, a power source such as a battery 20 may be mounted on the PCB 24 and coupled to other components to provide a power function 21 . The sensor 22 can be configured to provide an activation function 23 . The sensor 22 can be coupled to a processor mounted on the PCB 24 to provide a control function 25 of the lens 10 . Control functions 25 may include a light intensity setting 27 and a light switch 29 . The processor may be configured to detect a signal from the sensor 22 corresponding to an increase in intensity, a decrease in intensity, or a signal from the sensor 22, for example, using an encoded sequence of signals from the sensor 22. One of the on/off signals. The processor is coupled to a light projection unit 18 which may include a light source 30 and optics 32 to provide a projection function 31 . For example, a processor may be coupled to a plurality of light sources 30 (eg, projection unit 12 or one or more displays 72 ) to control each light source 30 in response to user input to sensor 22 .

The retinal stimulation device may include global positioning system (GPS) circuitry for determining the user's location and an accelerometer for measuring body movement, such as head movement. The retinal stimulation device may include a processor coupled to one or more of the GPS or accelerometer to receive and store the measured data. In some embodiments, a processor uses GPS in conjunction with a local clock (the one keeping local time) to calculate the occurrence of diurnal variations in the axial length of the wearer's eyes. In some embodiments, application of stimuli can be aligned with the occurrence of maximum axial length under diurnal variation. The retinal stimulation device may include communication circuitry (such as wireless communication circuitry (eg, Bluetooth or WIFI) or wired communication circuitry (eg, a USB)) to transmit data from the device to a remote server (such as a cloud-based data storage system). This transfer of data to a remote server may allow for therapy and compliance of the user to be monitored remotely. In some embodiments, the processor includes a graphics processing unit (GPU). GPUs can be used to efficiently and quickly process content from web pages for utilization in forming stimuli, as described herein.

Methods and apparatus for retinal stimulation as described herein can be configured in many ways and can include one or more attributes for encouraging a user to receive therapy. For example, retinal stimulation as described herein can be combined with a display for a game to encourage a user to wear the therapy device. In some embodiments, retinal stimulation may be combined with another stimulus, such as an emoji, to encourage a user to wear the device for therapy. Components of the system may communicate with or receive information from a game or other stimulus to facilitate retinal stimulation using the game or other stimulus.

Additional examples of suitable optical configurations and components for projecting stimuli (such as light pipes, reflectors, and mirrors) suitable for incorporation in accordance with the present invention are described in: 26 July 2019 application titled "ELECTRONIC CONTACT LENS TO DECREASE MYOPIA PROGRESSION", PCT/US2019/043692, published as WO2020028177A1 on February 6, 2020; and PCT/US2020, filed on July 31, 2021, entitled "DEVICE FOR PROJECTING IMAGES ON THE RETINA" /044571, which was published as WO/2021/022193 on February 4, 2021, the entire disclosure of which was previously incorporated herein by reference.

Figure 4 shows a lens, such as a contact lens or eyeglasses, including an inner zone for providing clear vision and an outer zone for providing out-of-focus to treat refractive errors. Lens 400 includes a clear inner zone 410 (eg, a clear central zone) configured to provide clear vision to the wearer's eye and an outer zone 420 configured to focus the image in front of the retina. In some embodiments, interior region 410 includes a center 412 of lens 400 . For example, inner zone 410 may include one or more of a hyperopia correction, a near vision correction, an intermediate correction, or a progressive addition correction. Outer zone 420 may include any suitable optical structure for focusing the image in front of the retina and may include an annular zone extending around clear zone 410 . Lens 400 may comprise any suitable lens material such as, for example, glass, plastic, or polycarbonate. In some embodiments, the inner region 410 includes an optical power for correcting a refractive error of the eye, wherein the optical power is determined by the curvature of the lens 400, a diffractive structure (such as an echelle grating), or a refractive structure (such as a Fresnel lens) One or more are provided. In some embodiments, the outer zone 420 includes a greater optical power than the clear zone 410 to focus the image in front of the retina to treat a deepening of the refractive error of the eye.

In some embodiments, the outer region 420 includes an image for focusing an image of a stimulus to a location in front of or behind the retina at a location away from the retina to provide the stimulus at a location at the retina away from the fovea. One blurs the image. One or more optical structures include a lens, a disc, a wedge, an optical glass plate, a diffractive optical device, a Fresnel lens, a plurality of echelle gratings, an aspheric profile, a liquid crystal, a plurality of small One or more of a lens, regions of positive optical power, annular regions of increased optical power, or gaps extending between regions of increased optical power.

In some embodiments, the one or more optical structures include a first optical structure for providing a first stimulus and a second optical structure for providing a second stimulus, the second optical structure being responsive to A comparison of the optical properties of the eye before and after the treatment described in . In some embodiments, the second optical structure is configured responsive to the comparison to have a focal length, a tilt angle, a diffraction pattern, an echelle pattern, an aspheric profile, a liquid crystal refractive index change, positive optical power One or more of the position or gap of the area. Examples of suitable liquid crystal materials and optical properties are described in the following patent applications: PCT/US2021/036102, filed June 7, 2021, entitled "STICK ON DEVICES USING PERIPHERAL DEFOCUS TO TREAT PROGRESSIVE REFRACTIVE ERROR"; and May 2021 PCT/US2021/032162, filed on March 13, entitled "ELECTRO-SWITCHABLE SPECTACLES FOR MYOPIA TREATMENT," the full disclosure of which was previously incorporated herein by reference.

Clear zone 410 may be sized in any suitable manner to treat the deepening of the refractive error of the eye and provide clear viewing. In some embodiments, for example, the zone of clarity includes a radius corresponding to 10 to 15 degrees at the distance of the zone of clarity from the pupil and may include a dimension on an eyeglass ranging from about 7 mm to about 12 mm.

Outer region 420 may include optical structures for providing increased optical power that may be configured in any suitable manner to provide increased optical power, and may include curvature, an aspheric profile, diffractive structures such as echelle gratings, or refractive One or more structures such as Fresnel lenses. In some embodiments, the outer region 420 includes an adhesive layer to provide additional optical power. In some embodiments, the clear inner region 410 is bounded by an aperture formed in an adhesive layer in the outer region 420 . For example, the outer layer may comprise a layer of lens material configured to provide additional optical power, such as Fresnel "press-in" lenses commercially available from 3M Health Care. The amount of additional diopters in zone 420 may include any suitable amount of diopters, such as one spherical optical diopter in a range from about +2D to about +6D.

Although reference is made to the outer region 420 including an adhesive layer, any suitable structure to provide near focus may be used, such as those used in commercially available lenses.

FIG. 5 shows a lens 400 in which the outer region 420 includes a plurality of lenslets 430 . Lenslets 430 may comprise any suitable optical power for focusing the image in front of the retina. For example, the lenslet may include an optical power in a range from about +2D to about +6D. In some embodiments, one or more gaps 432 extend between the lenslets having the optical power of the lens in which the gap extends. The size and spacing of the gaps can be configured such that the lenslets include a portion of the outer zone 420 and an appropriate percentage of the zone 420 in order to provide an appropriate ratio of myopia correction to stimuli for the outer zone.

Figure 6 shows a lens 400 in which the outer zone 420 includes a plurality of separate positive zones 440 to focus light from the outer zone 420 in front of the retina. Plurality of positive zones 440 may comprise any suitable optical power for focusing the image in front of the retina. For example, positive zone 440 may include one optical power in a range from about +2D to about +6D. In some embodiments, one or more gaps 442 extend between the positive regions. The optical power of the lens in which the gap extends is similar to that of zone 410 . The size and spacing of the gaps can be configured such that positive zone 440 includes a portion of outer zone 420 and an appropriate percentage of zone 420 to provide an appropriate ratio of myopia correction to stimuli for the outer zone.

The optical power of zone 420 may be adjusted in response to treatment as described herein. Alternatively or in combination, a percentage area of coverage of positive optical structures (eg, lenslets 430 ) of region 420 may be adjusted in response to treatment as described herein. For example, the size of the central zone of sharpness may also be adjusted in response to treatment. In some embodiments, for example, the optical power of the optical structure of region 420 may be reversed in response to treatment to project an image behind the retina.

Lens 400 can be configured in many ways to provide therapy as described herein. In some embodiments, the lens 400 provides viewing of a natural scene, such as when the lens is worn during normal everyday use. Alternatively or in combination, lens 400 may be used with an artificial light source, such as a display, to provide stimuli to the retina, as described herein. Also, while reference is made to lens 400, lens 400 may not include an effective optical power, eg, have similarly curved front and back surfaces.

Although reference is made to one of the lenses in FIGS. 4-6 , optical structures such as clear zone 410 and outer zone 420 may be combined with any suitable optical structure such as, for example, having an optically transmissive AR and VR device as described herein. Substrate, an optical glass plate, a wedge, a rim, a mirror or a beam splitter) combination. In some embodiments, therapy is provided when a user views a display having a clear zone 410 and an outer zone 420 . Also, while reference is made to focusing the plurality of stimuli in front of the retina, in some embodiments, the optics of zone 420 are configured to focus the plurality of stimuli behind the retina while central zone 410, for example, in a similar amount. Out of focus focuses the image on the retina.

FIG. 7 shows stimuli 702 and an image 704 on a display 706 as seen by a user. The stimulus 702 is positioned around a display 706, where the display corresponds to an area of clear central vision and the stimulus corresponds to the user's peripheral vision, eg, vision outside the macula. Multiple stimuli can be imaged in front of the retina with a myopic defocus to provide a stimulus to increase choroidal thickness and reduce growth in the axial length of the eye.

Stimuli can be configured in a number of ways as described herein. In some embodiments, the stimulus includes a light pattern 708 on a dark background 710, such as a black and white pattern. In some embodiments, the stimulus comprises a multicolored pattern on a darker background, such as a white or near-white stimulus on a gray or substantially black background. In some embodiments, each stimulus includes a dark inner area and one or more light outer areas on a dark background, eg, a dark cross passing through a white circular area on a dark background. Stimuli may be selected based on their iso-global contrast factors, their isopolarity (eg, white on black background or multicolor versus white or black on multicolor background). Stimuli can be configured in many ways and can include a plurality of repeated graphics shown on a display. The stimuli may be arranged in repeating one of the circular or circular patterns shown. The stimuli may comprise any suitable global contrast factor, such as, for example, a global contrast factor of at least 0.5, at least 0.7 or at least 0.8.

Figure 8A shows the stimuli 702 on one of the screens 800 used to provide the myopic out-of-focus stimuli to the retina, and Figure 8B shows the corresponding sizes of the myopic out-of-focus stimuli on the retina in degrees. The size of the stimuli on the display is related to the distance between the user and the display, and can vary in size according to the viewing distance to provide an appropriate angular distance to the retina. One of ordinary skill can readily perform calculations to determine the size of the stimulus on the display to provide the appropriate angular sizing of the out-of-focus projected image.

As shown in Figures 8A and 8B, each stimulus included a spanning distance 802 (eg, 18 mm) corresponding to an angular illumination 812 (eg, 3.3 degrees) on the retina. The stimuli are arranged on the display to provide a clear central field of view 804 with a spanning distance 806 (eg, 70 mm across) to provide an uninterrupted central field of view 804 with a spanning distance 814 of 15 degrees. The plurality of stimuli includes a maximum spanning distance 615 corresponding to an angular span 616 of 35 degrees, eg, 178 mm. The stimuli may be configured in any suitable object size to provide an appropriate image size on the retina. Although reference is made to specific dimensions, any suitable size may be used, for example by varying the distance from the eye and the corresponding angular cross-distance. In some embodiments, the stimuli can be configured to provide a clear central field of view (eg, 15 mm across) in order to provide an uninterrupted central field of view of 15 degrees. In some embodiments, the plurality of stimuli includes a maximum spanning distance corresponding to an angular spanning distance of 35 degrees, eg, 70 mm.

FIG. 9 shows a stimulus 702 depicting a natural scene 900, such as a ring flower pattern. Although a flower pattern is shown, any image may be used. For example, stimuli may be provided on a display instead of or in combination with stimuli 702 shown in FIGS. 8A and 8B. The size and angle of the stimuli shown in Figure 9 can be sized similarly to the stimuli shown in Figures 8A and 8B. The central field of view 814, shown as a dark circle, can include, for example, a spanning distance corresponding to about 15 degrees, and, for example, the maximum distance across the annular region 806 can be about 35 degrees. Work related to the present invention has shown that a multicolor natural scene, such as a flower pattern, can be more pleasing to the user. Work related to the present invention also showed that, in some embodiments, although other stimuli could be used, more Sex scenes are even less effective as a stimulus.

Figure 10 shows image contrast and histograms with red (R), blue (B) and green (G) values for the stimuli shown in Figures 8A-9. The histogram shows a pixel count of approximately 3.5 x ¹⁰⁵ stimulus pixels at an intensity value of approximately 255 for the circular pattern as shown in Figures 9A and 9B. Black pixels have been excluded in the histogram to increase the clarity of the graphical representation (intensity=0). For the flower pattern shown in Figure 9, the blue intensity profile exhibited an intensity peak at about 50, a red peak at about 110, and a green peak at about 120, with counts below 0.5 x ¹⁰⁵ .

In some embodiments, contrast is defined as the distance between the lowest and highest intensity of an image. The Global Contrast Factor (GCF) can also be used to define the contrast of stimulus images. GCF measures the richness of detail as perceived by a human observer. In some embodiments, the GCF of a stimulus is determined as described in: Global contrast factor-a new approach to image contrast , Matkovic, Kresimir et al., 2005; Computational Aesthetics in Graphics, Visualization and Imaging (2005 ); L. Neumann, M. Sbert, B. Gooch, W. Purgathofer (Editors).

The obtained GCF values are as follows:

Flower: 6.46

Circular pattern (b/w): 9.94

Work related to the present invention showed that white circles on a black background may be better compared to a field of flowers due to higher GCF.

Figure 11 shows an image 1100 suitable for modification and incorporation as a stimulus as described herein. Image 1100 may include a processed image to provide a suitable spatial frequency distribution, as described herein. The image can include a natural image or a computer generated image. Images can be labeled to define a circular stimulus similar to, for example, FIG. 9 . FIG. 12 shows an image 1200 similar to that of FIG. 11 that has been processed to provide a modified stimulus. This processed image can be digitally labeled to form a circular stimulus as shown in FIG. 9 at the appropriate spatial frequency and contrast.

While images can be processed in many ways, in some embodiments an image is processed using a digital spatial frequency filter and contrast adjusted to provide an image with an appropriate spatial frequency distribution to produce an improved response of the eye. At one step in the process, the image is processed using a moving average filter with a length (eg, a filter with a length of 400 pixels). In another step, the RGB image is converted into a grayscale image. At another step, the RGB image is adjusted according to the moving average image. At yet another step, the moving average filter is reapplied to the new image. In some embodiments, the moving average of brightness is smoothed. For example, the original image may have a 100% difference in brightness and the adjusted image may have a 25% difference in brightness.

FIG. 13 shows one image 1300 of the spatial frequency distribution of the image of FIG. 11 .

FIG. 14 shows an image 1400 of the spatial frequency distribution of the image of FIG. 12 (which can be used as a stimulus in FIG. 9).

Figure 15 shows a graph of the image spatial frequency in cycles/degree and the logarithm of the energy at each frequency for the stimulus images shown in Figures 8B and 9. In the graph shown in FIG. 15, the average radial profile of the spatial frequency spectrum is shown, where the logarithm of the amplitude (in arbitrary units, "au") is related to the number density of the signature at a particular spatial frequency. This graph shows the 1/f, 1/f ² and 1/f ^0.5 lines for reference. The processed image comprising the flower pattern with a circle shown in FIG. 9 has a frequency dependence similar to the white circle pattern with black crosses shown in FIGS. 7-8B . These curves show that both the flower pattern and the circle pattern exhibit a slope dependence of about 1/f at intermediate (eg, mid-range) frequencies from about 2 to 10 cycles/degree. In some embodiments, the stimulus comprises a change in intensity (energy, au) with a frequency dependence from 1/f to 1/ ^f2 of frequency in a range from about 2 to 10 cycles/degree. Frequency dependence within a range.

Stimuli can be configured in many ways to have an appropriate spatial frequency distribution, for example, to have one of the profiles of the spatial frequency distribution. In some embodiments, each of the plurality of stimuli includes a length, edge, and an intensity profile distribution to produce a range of 1×10 ⁻¹ to 2.5× ¹⁰ cycles/degree as imaged into the eye in front of or behind the retina Medium and optionally within a range of spatial frequencies from 1X10 ⁻¹ to 1X10 ¹ cycles/degree. In some embodiments, the plurality of stimuli as imaged in the eye comprises an increase in spatial frequency providing a decrease in spatial frequency amplitude in a spatial frequency range from about 1×10 ⁻¹ to about 5×10 ⁰ cycles/degree A spatial frequency distribution. In some embodiments, the reduction in spatial frequency intensity is in a range from 1/(spatial frequency) to 1/(spatial frequency) ² for an arbitrary unit of spatial frequency amplitude. In some embodiments, the spatial frequency ranges from about 3×10 ⁻¹ to about 1.0×10 ¹ cycles/degree and optionally within a range from about 3×10 ⁻¹ to about 2.0×10 ⁰ and further optionally from about 3×10 ^-1 to about ^1.0X100 in the range of one.

Instead or in combination with spatial frequency properties, stimuli may be configured to have an appropriate ratio of stimulus intensity to background intensity. In some embodiments, the brightness of the plurality of out-of-focus stimulus images is at least 3 times the brightness of the ambient lighting, optionally at least 5 times the brightness of the background lighting, and optionally at least 5 times the brightness of the background lighting. In the range of from 3 to 20 times and further depending on the situation a factor in the range of from 5 to 15 times the brightness of the background lighting.

In some embodiments, stimuli including spatial frequency and intensity properties are presented at an appropriate ratio to one or more of background lighting or ambient lighting. In some embodiments, each of the plurality of stimuli as imaged in the eye is superimposed onto a substantially uniform gray background. In some embodiments, each of the plurality of stimuli includes a multi-color icon (e.g., a white icon) on a darker background to provide contrast, such that the icon has a characteristic generated primarily from 1×10 ⁻¹ cycles/ Degrees to 2.5×10 ¹ cycles/degree, and optionally a spatial frequency in the range from 1×10 ⁻¹ cycles/degree to 1×10 ¹ cycles/degree characterizes an edge profile or a total length of the edge.

Additional examples of stimuli and associated properties suitable for incorporation in accordance with the present invention are described in PCT/US2021/036100, filed June 7, 2021, entitled "PROJECTION OF DEFOCUSED IMAGES ON THE PERIPHERAL RETINA TO TREAT REFRACTIVE ERROR" , the full disclosure of which was previously incorporated by reference.

Figure 16 shows a system 1600 for treating refractive errors of the eye. System 1600 includes a treatment device 1602, such as a user device operably coupled to a server 1604 using a secure two-way communication protocol. The server 1604 is configured to communicate with a therapy professional device 1608 using a secure two-way communication protocol 1606 . In some embodiments, the server 1604 is coupled to a caregiver device 1610 using a secure two-way communication protocol 1606 . In some embodiments, system 1600 includes a treatment database 1612 that stores treatment parameters and results from a plurality of treatments. The therapy database 1612 can be configured to communicate with the server 1604 using a secure two-way communication protocol 1606 . In some embodiments, system 1600 includes one or more clinical measurement devices 1614 configured to communicate with a server using a secure two-way communication protocol 1606 . Each device may be operatively coupled to another device using a secure two-way communication protocol 1606 . Secure communication may include any suitable secure communication protocol in which encrypted data is transmitted and the data may be stored in any suitable encrypted format. For example, the device shown in FIG. 16 can be configured to comply with HIPAA and GDPR, as will be appreciated by those of ordinary skill. Server 1604 may include any suitable server, such as a cloud-based server that includes a plurality of servers that may be located at different geographic locations. Therapy database 1612 may include one component of the server, although shown separately.

Therapeutic device 1602 can be configured in many ways as described herein, which can include a user device including an ophthalmic device, a TV screen, a computer screen, a virtual reality ("VR") display , an Augmented Reality (“AR”) display, a handheld device, a mobile computing device, a tablet computing device, a smart phone, a wearable device, a spectacle lens frame, a spectacle lens, a near-eye display , one or more of a head-mounted display, a goggle, a contact lens, an implantable device, a corneal onlay, a corneal inlay, a corneal prosthesis, or an intraocular lens. For example, treatment device 1602 may include an optical system with a beam splitter, as described herein. In some embodiments, therapeutic device 1602 includes a user device such as, for example, a smartphone or tablet computer. The display 1620 of the user device can be configured to provide the plurality of stimuli 702, as described herein. In some embodiments, user device 1602 includes a lenslet array 1622 positioned over plurality of stimuli 702 to provide an image of stimuli 702 in front of or behind the retina, as described herein. In some embodiments, each lenslet of the lenslet array is aligned with one of a plurality of stimuli. A user device may be configured to have a clear viewing area 804 as described herein, for example, without extending the lenslet array into the clear viewing area. Clear viewing area 804 can be configured for the user to view images (such as video) and to allow the user to use the device in a substantially normal manner (for example) to use a web browser, play video games, send and receive text and email mail etc. Lenslet array 1622 may be positioned at a distance from the pixels in order to provide an appropriate amount of defocus, as described herein. In some embodiments, therapy system 1600 includes one or more clinical measurement devices 1614 .

Therapy professional device 1608 may be configured for the therapy professional to receive data from the user device 1602, such as therapy data. Therapy data may include any suitable therapy data, such as duration of therapy per day, daily usage, screen time, screen time for activating stimuli. Therapy professional device 1608 may also be configured to send and receive data from ophthalmic instruments, such as refraction data as described herein, in order to assess treatment effectiveness. Therapy professional device 1608 may be configured to transmit therapy instructions to user device 1602 . For example, a therapy instruction may include any suitable parameters as described herein and may include a duration and a time of therapy. Work related to the present invention has shown that circadian rhythms can play a role in the therapeutic effect, and that treatment instructions can include having the user set a time of day or range of times (e.g., in the morning, e.g., in which the subject is located at local time) at one of the times within the range of about 6 am to about 9 am) to execute the order for treatment.

Clinical measurement device 1614 may include any suitable clinical measurement device, such as, for example, one or more of an automated refractometer or an OCT system. Alternatively or in combination, subject records (such as manifest refraction) may be stored at the clinical website and transmitted to a server.

Caregiver device 1610 may include any suitable device with a display, such as a smartphone or tablet computer. The caregiver device 1610 may be configured to transmit and receive data related to the user's treatment. The caregiver device 1610 can be configured for a caregiver, such as a parent, to monitor therapy and facilitate compliance with a therapy protocol. For example, server 1604 may be configured to transmit notifications to caregiver device 1610 , such as a notification that a user is scheduled for therapy and a caregiver may interact with the user to encourage the user to receive therapy.

Treatment database 1612 may be configured to store treatment-related data. For example, data related to treatment may include treatment data and effect data. The effect data may include one or more of refractive data and axial length data. The refractive data may include refractive data, eg, longitudinal data, of the user's eye (eg, sphere, cylinder, and axis) at a point in time. Axial length data may include data such as OCT data collected at time points. Therapy data 1612 may include data related to stimulus parameters as described herein, and may include, for example, treatment duration per day, intensity of stimulus, type of stimulus, and defocus data.

In some embodiments, algorithms such as artificial intelligence, machine learning, neural networks, or convolutional neural networks are used to process the data to determine improved treatment parameters, such as treatment duration, time of day, defocus, stimulation The shape and intensity of the object, the amount of defocus, the spatial frequency of the stimulus, the ratio of the stimulus to ambient light, the background of the stimulus, or any other parameter relevant to the treatment. These parameters can be adjusted to provide improved therapy and can be suggested to the treating professional on the treating professional device for the treating professional to push instructions to the user device.

Although therapeutic device 1602 (such as a user device) can be configured in many ways, in some embodiments device 1602 includes a sensor 1624 for detecting one or more of luminance or spectral data, such as an illuminance sensor or a spectrophotometer. Sensor 1624 may be configured to measure and detect ambient light exposure of a subject, such as a wearer or user, and ambient light may include ambient light measured using sensor 1624 . In some embodiments, sensors are supported (eg, mounted) on a therapeutic device as described herein, such as eyeglasses, a wearable device, or a user device.

For example, the system of Figure 16 is well suited for use with clinical trials to conduct clinical trials and generate efficacy data.

experiment

FIG. 17 depicts an optical system 1700 for projecting stimuli 702 onto the retina 33 . In the studies performed, system 1700 included a desktop system. Although reference is made to optical system 1700 in the context of an experimental system, system 1700 can be readily configured to perform treatments in accordance with the present invention, such as treatment of both eyes. The system was configured to admit one left eye and one right eye of the subject for testing purposes. The test eye 1702 is placed in front of a first beam splitter 1706 and the control eye 1704 is placed in front of a second beam splitter 1708 . The test eye 1702 and control eye 1704 are allowed to similarly view a central display 1710 in front of a passive background 1712 . Display 1710 may include a clear central vision area and display suitable content and include a computer screen. In some embodiments, the central vision zone includes an entertainment area as seen by the subject through the clear central vision zone with the entertainment displayed on the display. The active stimulation system includes a tabletop device with a head and chin rest. The system was configured to provide a background image for optical infinity of both eyes and a video for central (foveal) vision. A stimulus 502 is displayed on a display 1720 placed in front of a lens 1722 (eg, an achromatic lens) to provide the test eye with an overlay stimulus image with a myopic defocus. Myopic stimuli are projected in front of the retina of the eye. The distance of the stimulus from the lens 1722 was shown and the optical power of the lens 1722 was configured to provide an appropriate amount of defocus. The stimulus 502 overlays the center display 1710 and the passive background 1712 overlays the first beam splitter 1706 . The second beam splitter 1708 is similar to the first beam splitter and the ambient light is blocked by a shield 1724 . The beam splitter included a 50/50 ratio of reflectance and transmittance for each eye to transmit 50% of the light and couple 50% to the stimulus. The stimulus is provided on a screen, such as display 1720, at an appropriate distance from the achromat.

Parameters including magnitude of defocus, coverage of stimuli on the retina (e.g., retinal image envelope), dominance of background images (e.g., contrast and brightness), and chromaticity (e.g., wavelength) were adjusted as described herein. distributed).

Background patterns were also considered in these experiments. The background pattern can include a uniform pattern 1730a or a patterned background 1730b (eg, a grid pattern). The background pattern is projected onto the peripheral retina with hyperopic defocus 1730 . In some embodiments, this hyperopic defocus is provided so as to push the focus of distant objects toward optical infinity rather than hyperfocus. Work related to the present invention shows that, according to some embodiments, a patterned background can compete with myopic out-of-focus stimuli and that a uniform background pattern can be preferred. While the background can be presented in many ways, the background is presented as a poster with an appropriate test pattern.

A camera 1726 may be used to observe one or more eyes. In the experiments performed, the right eye was the test eye 1702 and the control eye 1704 was the left eye. While Figure 8 shows the left eye as the test eye and the right eye as the control eye, this can easily be changed by coupling an achromat and a display to the right eye and providing a shutter to the left eye. For example, the position of a display with a pattern of stimuli and an achromatic lens can be placed on the right, and the shutter moved to the left.

A clinical study was successfully conducted in which transient changes were measured in subjects. These subjects were myopic and diagnosed with progressive myopia. They can then be provided with similar active stimuli on a daily basis for a similar period of approximately daily (4-6 days per week) to measure transients in axial length and refraction over a period of four months Change. Axial length and refraction were measured once a month for all subjects. Measurements were monocular, using the contralateral eye as a control. It was found that the subjects experienced a long-term (4 months) change in refraction of the test eye relative to the control eye, and a long-term change in the axial length of the test eye relative to the control eye. This correlation was established between transient and long-term (4 months) data on the refractive state of the test eye after defining the applied long-term stimulus.

The optical test equipment includes a non-wearable augmented reality ("ANWAR") device, as described herein, for example, with reference to FIGS. 7-8B and FIG. 17 . The equipment includes 2 partial reflective mirrors for both eyes, an achromatic lens (aberration minimizing lens), a viewing aperture, a chin rest and a head rest for the purpose of delivering precise optical convergence. The chin rest and head rest are designed to be comfortable for subjects using alternative latex-free dressings. The stimulus for peripheral myopic defocus is provided by a monitor that projects an image onto an aberration-minimizing achromat (which refracts the stimulus image) and is then reflected by the mirror into the peripheral retina. Starting at a retinal eccentricity of 7.5°, the stimuli moved outward to partially defocus the peripheral field of the right eye, as described herein, for example, with reference to Figure 8B. The left eye served as one of the controls for all conditions and received no exposure to the projected light stimulus. The clear viewing image of the central 15° diameter comes from a television screen which is used as a central target and adjusted for brightness. The two partial reflectors similarly reflect light from the TV screen in both eyes. There is one uniformly illuminated gray poster without any pattern around a 15° central target area (TV monitor). The poster was used as an additional background stimulus over 15° diameter in the field of view of both control and test eyes.

The stimuli were configured substantially as described with reference to Figures 7-8b and projected peripherally using the binocular device. A black and white stimulus was used to generate high contrast images. In addition, the system allows to control the brightness and illuminance of 1) projected myopic out-of-focus LED lights, 2) TV monitor and 3) gray poster background. The test illuminance conditions for projected out-of-focus stimuli were approximately 20 times greater than the illuminance of the gray poster background.

Refraction was measured using a commercially available WAM binocular open-field automatic refractometer and a commercially available Nidek automatic refractometer. Axial length and choroidal thickness were measured using a Haag-Streit Lenstar APS optical coherence tomography measurement system.

Description of controlled conditions during out-of-focus operations phase

Because the choroid is an extremely vascularized layer of the retina that responds to small movements, subject's head and body movements were restricted during the out-of-focus session and during data collection.

To minimize and capture the natural, diurnal, and inherent variability of the choroid over time, both eyes were fully distance corrected. Only projected peripheral defocus was applied to the right eye and the left eye was used as a control. During the test period, the ambient light level was maintained at a medium photopic (natural) level. Subject is seated comfortably and instructed to watch television on a color monitor approximately 4 meters away. During the out-of-focus task session, subjects kept their body movement to a minimum.

statistical methods

The mean of replicate measurements of spherical equivalent refractive error and axial length obtained from each eye at each visit was used to determine the primary outcome measure (summarized in the next section). Generalized linear modeling was used to assess the relationship between cumulative differences and study return. Models were constructed to assume a linear relationship with a y-pitch at zero (eg, no treatment difference at baseline visit). This method allows controlling for inherent correlations between measurements obtained from the same research subject. The initial model investigates the linear relationship within each individual subject and a final model to determine composite effects using all subjects in one model.

result

Table 1: Demographic characteristics and post-treatment cycloplegic refractive endpoints of enrolled subjects after the out-of-focus working session with ANWAR optics (n=7). subject # 4 62 63 66 67 69 70 age twenty four twenty one 29 32 twenty four 28 twenty two gender f m f f f f m deepen yes no yes yes yes yes yes out of focus phase 56 77 79 79 80 77 76 Total hours out of focus 84 115.5 118.5 118.5 120 115.5 114 Sphere (OD) -1.25 -2 -1.25 -1.5 -5.25 -10.25 -5 Cylinder (OD) -0.25 0 -0.75 0 -0.5 0 -1.25 Spherical Equivalent (OD) -1.375 -2 -1.625 -1.5 -5.5 -10.25 -5.625 Sphere (OS) -1.25 -1.75 -1.5 -1.5 -3.75 -7.5 -4.75 Cylinder (OS) 0 0 -1 0 -0.5 0 -0.5 Spherical Equivalent (OS) -1.25 -1.75 -2 -1.5 -4 -7.5 -5

To understand the statistical method, one can review the calculation of the adjusted treatment effect and the cumulative adjusted treatment effect. If one assumes that the treatment (light exposure) is given to the right eye only, then any changes seen in the control eye would be due to natural fluctuations in that eye or possible progression of myopia. Any intereye differences at baseline visits are a result of anisometropia and must be considered when examining treatment effects. Thus, the treatment effect at visit i (i = 2, 3, or 4 months) is the magnitude of the observed inter-eye difference at that visit minus the anisometropia at the baseline visit. As an example, the table below contains the mean spherical equivalent refractive error for ID 66 at each study visit. At baseline, the test eyes were slightly more nearsighted, with an inter-eye difference of -0.096 D. This was reversed at the 1 month follow-up where the test eye was now 0.428 D less myopic. Therefore, the adjusted difference is 0.428 D - (-0.096 D) = 0.524 D. These calculations continued at each study visit. The cumulative variance for month 2 is defined as the cumulative variance for month 1 plus the adjusted variance for month 2. Research return visit SPHEQ (OD ; test eye ) SPHEQ (OS ; control eyes ) difference between eyes adjusted variance Cumulative Adjusted Difference baseline -0.9185 -0.8230 -0.096 0 0 first month -0.85 -1.278 0.428 0.524 0.524 February -0.8855 -0.9455 0.060 0.156 0.6795 March -1.0965 -1.1935 0.097 0.193 0.872 April -0.80 -0.6595 -0.141 -0.045 0.827

Table 2: The spherical equivalent refractive error, adjusted treatment effect and cumulative adjusted treatment effect of ID 66 at each study visit.

This method takes into account small changes seen between visits and is not biased in any direction (eg, positive or negative changes). Given the relatively unknown nature of the demonstrated yoke effect of stimuli, a trend analysis rather than an individual data point provides a better guide as to whether a treatment is effective. Cumulative effects were chosen as opposed to percent changes because percent changes can lead to very misleading findings. Additionally, cumulative changes are often used to express treatment effects.

Analysis 1 : Spherical Equivalent Refractive Error from WAM in Direct Gaze ID slope P valuea ^_ 04 -0.015 .049 62 0.055 .013 63 0.216 .004 66 0.195 <.001 67 -0.117 .004 69 -0.027 .079 70 0.043 .007 ^a P-value from a regression model testing hypothesis with a slope greater than zero

Table 3: Slope estimates (by ID) associated with cumulative adjusted SPHEQ and study month.

As shown in Table 3, 4 of 7 study subjects had a positive and statistically significant slope associated with the cumulative effect and study month. This would suggest that continued treatment resulted in a reduction in the level of myopia in the test eyes of these subjects. Using all subjects in a linear model, the estimated treatment effect was 0.068 D of treatment improvement per month (95% CI: 0.011 to 0.125; p = .011). That is, with each month of treatment, the test eye became 0.068 D less myopic than the control eye. Given the high variability associated with biological data, model R ² was acceptable at 14.9%. Using the estimated slope, the predicted treatment effect after 12 months would be 0.816 D with 95% confidence that the true effect falls within the interval of 0.132 D to 1.5 D. These calculations assume the same improvement pattern from months 5 to 12 as observed in months 1 to 4.

analyze 2 : in direct gaze Nidek acquired spherical equivalent refractive error ID slope P value ^a 04 -0.223 <.001 62 0.078 .004 63 -0.170 <.001 66 0.046 .029 67 0.142 <.001 69 0.748 <.001 70 0.205 0.001

^a P-value from a regression model testing hypothesis with a slope greater than zero

Table 4: Slope Estimates (by ID) Associated with Cumulative Adjusted Spherical Equivalent ("SPHEQ") and Study Month.

As shown in Table 4, 5 of 7 study subjects had a positive and statistically significant slope associated with the cumulative effect and study month. This would suggest that continued treatment resulted in a reduction in the level of myopia in the test eyes of these subjects. Using all subjects in a linear model, the estimated treatment effect was 0.118 D of treatment improvement per month (95% CI: 0.014 to 0.223; p = .014). That is, with each month of treatment, the test eye became 0.118 D less myopic than the control eye. Given the high variability associated with biological data, model R ² was acceptable at 13.7%. Using the estimated slope, the predicted treatment effect after 12 months would be 1.42 D with 95% confidence that the true effect falls within the interval of 0.166 D to 2.67 D. These calculations assume the same improvement pattern from months 5 to 12 as observed in months 1 to 4.

There was a difference in the estimated slope values from the WAM and Nidek measurements of spherical equivalent refractive error. For ID 63, the WAM measure showed a 0.216 D improvement per month (the test eye was less myopic), while the Nidek measure showed a 0.170 decrease per month (the test eye was more myopic). In both cases, the slope estimates differ significantly from zero. While ID 69 showed a large improvement using the measure from Nidek (slope=+0.748 D), the WAM measure for this same participant showed a non-significant negative treatment effect (slope=-0.027). The composite slope estimate from the repeated measures analysis when using the Nidek data value (0.118) was nearly twice that observed in the WAM data (0.068). This difference is most likely related to the observed change in ID 69.

Results indicated similar cumulative treatment effects when using WAM or Nidek to measure refractive error. Work related to the present invention showed that Nidek autorefractometer instruments consistently produced more negative measurements than open field autorefractometers like WAM. This is confirmed in our data files because most of the inter-instrument variance is biased towards one of the more negative measurements from Nidek. Also, for the measurements obtained from the test eyes, there is greater inter-instrument variability (Nidek is more nearsighted). This factor may explain why the endpoints seen with Nidek are relatively larger compared to WAM. However, we observed that the same polarity in the trends showed some effect on the refractive endpoints using treatment with two different instruments, which is a significant finding.

analyze 3 : Axial length in direct gaze ID slope P value ^a 04 12.733 .005 62 -8.337 <.001 63 -8.257 .008 66 -1.703 .015 67 4.413 .004 69 16.373 .003 70 27.130 <.001

^a P-value from a regression model testing hypothesis with a slope greater than zero

Table 5: Slope estimates (by ID) associated with cumulative adjusted axial length (microns) and study months.

As in spherical equivalent refractive error, most individual slope estimates were statistically significant and positive (4 of 7 subjects, Table 5). Using all subjects in a linear model, the estimated treatment effect was 6.051 microns of treatment improvement per month (95% CI: 1.500 to 10.604 microns; p = .006). That is, with each month of treatment, the test eye became 6.051 microns shorter compared to the control eye. Given the high variability associated with biological data, model R ² was acceptable at 17.9%. Using the estimated slope, the predicted treatment effect after 12 months would be 72.606 microns with 95% confidence that the true effect falls within the interval of 18.0 to 127.25 microns. These calculations assume the same improvement pattern from months 5 to 12 as observed in months 1 to 4.

The pattern of change in axial length observed for each participant would appear to correlate with data obtained from Nidek, with the exception of ID 4. Although this participant demonstrated a significant shortening of his eyes during the 4-month treatment cycle, data from Nidek indicated a negative treatment effect.

Experimental calculation

Based on WAM open-field autorefractometer results, the estimated treatment effect was 0.068 D of treatment improvement per month (95% CI: 0.011 to 0.125; p = .011).

Based on NIDEK autorefractor results, the estimated treatment effect was 0.118 D of treatment improvement per month (95% CI: 0.014 to 0.223; p = .014).

For axial length as measured by Lenstar APS, the estimated treatment effect was a treatment improvement of 6.051 microns per month (95% CI: 1.500 to 10.604 microns; p = .006).

The estimated annual effect of treatment on change in refractive error exceeded expected myopia progression, as reported by Zhou et al. In this study, the annual deepening rate of refraction was 0.43 D. See Zhou WJ, Zhang YY, Li H, Wu YF, Xu J, Lv S, Li G, Liu SC, Song SF Five-year progression of reactive errors and incidence of myopia in school-aged children in western China, J Epidemiol , 2016 Jul 5;26(7):386-95, Epub 2016 Feb 13.

The purpose of this experimental study was to determine whether transient changes to axial length and refraction using a device as described herein would result in long-term and possibly permanent changes. The study demonstrated that the treatment effect persisted for at least 4 months and was also statistically significant in at least some instances. Given the relatively small number of subjects (n=7), this is an important expected. Using within-subject estimates of effects mitigates the effect of large between-subject variability relative to between-subject comparisons. A statistical analysis method using the "cumulative adjusted difference" provides an indication of the treatment effect.

Those of ordinary skill will recognize that additional studies can be performed in accordance with the present invention and that treatment parameters can be adjusted as described herein to provide improved treatment outcomes. For example, studies may be conducted to measure a transient change in one or more of axial length or refraction data over any suitable duration of stimulus and measurement time frame, such as before and after treatment on the same day as treatment Measure the eyes. Also, the number of subjects can be increased compared to the clinical tests described herein.

Figure 18 shows a method 1800 of reducing the deepening of the refractive error of an eye.

At step 1805, the eye is diagnosed as having a deepening refractive error. In some embodiments, the eye is diagnosed as having a progression of a refractive error such as myopia in a range from 0.25 D to 1.5 D per year and wherein the progression of myopia decreases by at least 0.25 D. In some embodiments, the progression of the refractive error, such as myopia, is greater than 0.6 D per year, and wherein the progression of myopia decreases by an amount in the range from 0.6 D to 0.9 D per year.

At step 1810, an optical property of the eye is measured at a first time.

At step 1820, a first light therapy is provided to the eye.

At step 1830, optical properties of the eye are measured at a second time.

Optical properties may include any suitable optical properties as described herein. In some embodiments, the optical properties include one or more of refractive data, axial length data, or choroidal thickness data. In some embodiments, optical properties include an axial length, a binocular measured axial length, a refraction, a dominant refraction, a cycloplegic refraction, an automatic refraction, a binocular automatic Refraction, an open-field automatic refraction, a binocular open-field automatic refraction, a scanning slit automatic refraction, a wavefront map, a wavefront coefficient, a sphere coefficient, a cylinder coefficient, and a coma image one or more of aberration, a spherical aberration, or a trilobe. In some embodiments, the optical property includes refractive data and wherein a change in refractive data between the first time and the second time corresponds to a change in axial length of the eye. In some embodiments, a change in axial length is determined in response to a change in refractive data.

Optical properties can be measured using a fixed stimulus presented to the eye to measure refractive data. In some embodiments, the eye is exposed to a binocular stimulus to measure an optical property at a first time and a second time.

At step 1840, a comparison of the optical properties of the eye from the first time to the second time is generated. In some embodiments, the comparison includes a difference between the measured property at the second time and the first time.

In some embodiments, the comparison includes a difference between the second optical property and the first optical property, and the second treatment is adjusted in response to the difference.

Differences can be determined in a number of ways. In some embodiments, the difference includes a transient change in an optical property of the eye between the first time and the second time. In some embodiments, the first time occurs on a first day, the first light treatment occurs on a plurality of days within the plurality of weeks after the first day, and the second time occurs on a plurality of weeks later and the second light treatment occurs on After the second time. The first time occurs on a first day, the first light treatment occurs on the plurality of days after the first day, the second time occurs on the last day of the plurality of days after the first light treatment, and the second light treatment occurs on the plurality of days One day after the last day. In some embodiments, the first time occurs on a first day, the second time occurs on the first day, the first light treatment occurs on the first day and the second light treatment occurs on a second day after the first day .

At step 1850, a second light treatment is configured in response to the comparison.

The first and second light treatments can be configured in a number of ways as described herein. In some embodiments, the first light therapy projects a first image to a focus in front (or behind) the retina and the second light therapy projects a second image to a focus in front (or behind) the retina. In some embodiments, the first image is focused at a first distance in front of (or behind) the retina and the second image is focused at a second distance in front of (or behind) the retina, the first distance being different from the first distance Two distances.

The first and second images can be focused using any suitable optical structure as described herein. In some embodiments, the first lens is projected using a first lens comprising a first clear central region for focusing the first image on the retina and a first outer region for focusing the first image in front of the retina. The image is projected using a second lens including a second clear zone for focusing the second image on the retina and a second outer zone for focusing the second image in front of the retina.

The first and second images may include any suitable images as described herein. In some embodiments, the first image and the second image each include an image of an object viewed through the lens.

In some embodiments, the first outer zone and the second outer zone include one or more of an aspheric profile, a plurality of lenslets, or alternating annular zones of increased and decreased optical power.

In some embodiments, the first lens and the second lens differ by one or more of: a difference between a first optical power of the first outer zone and a second optical power of the second optical zone ; a difference between a diameter of a first clear zone and a diameter of a second clear zone; a difference between an area of a first outer zone and a second outer zone; a first area of a first clear zone versus a first outer A difference between a first ratio of a first area of a first area and a second ratio of a second area of a second clear area to a second area of a second outer area; the ratio of the lenslets of the first outer area A difference between a first number and a second number of lenslets of the second outer zone; a first optical power of the first plurality of lenslets of the first outer zone and a second complex number of the second outer zone A difference between a second optical power of a lenslet; a first percentage of a first area of a first outer zone for providing a first image to the focal point in front of the retina and a first percentage for providing a second The image provides a difference between a second percentage of a second area of a second outer region of focus to the front of the retina.

In some embodiments, the first image is focused at a first angle relative to an optical axis of the eye and the second image is focused away from the fovea at a second angle relative to the optical axis of the eye. Each of the first and second angles may be within a range of from 5 degrees to 35 degrees, and optionally within a range of from about 15 degrees to 35 degrees. In some embodiments, the second angle is adjusted to an angle different from the first angle in response to the comparison.

The amount of out-of-focus of the stimulus can include any suitable amount of focus as described herein and can be focused in front of or behind the retina. In some embodiments, the first image is focused in front of the retina by a first amount in a range from 3D to 10D and the second image is focused in front of the retina by a range from 3D to 10D A second amount in the range and optionally in the range from 4.5 D to 8 D. In some embodiments, the second amount is adjusted to an amount different from the first amount in response to the comparison.

Stimuli may be configured in any suitable manner as described herein. In some embodiments, the first light treatment includes a first light stimulus and the second light treatment includes a second light stimulus, and the second light stimulus is configured in response to the comparison. The second light stimulus can be configured in many ways and can be different from the first stimulus in response to the comparison. In some embodiments, the first optical stimulus includes one or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on a display. The second optical stimulus includes a position, a size, a spatial frequency distribution, an intensity, or a second one or more of an intensity relative to a background on a display, and the second optical stimulus is characterized by position, size A difference in one or more of , spatial frequency distribution, intensity, or intensity relative to a background on the display differs from the first optical stimulus.

In some embodiments, the first image includes a first stimulus on a first background and the second image includes a second stimulus and a second background. In some embodiments, a first ratio of a first intensity of the first stimulus to a first intensity of the first background of the first stimulus is in a range from 10 to 50, and the second stimulus is to A second ratio of a second intensity of a second background is in a range from 10 to 50 and optionally in a range from 10 to 30. In some embodiments, the second ratio is adjusted to a value different from the first ratio in response to the comparison. In some embodiments, a display is used to project the first and second stimuli onto the retina.

In some embodiments, an intensity of one of the stimuli correlates to an amount of ambient lighting. In some embodiments, the eye is exposed to a first ambient illumination when focusing on the first image and a second ambient illumination while focusing on the second image. In some embodiments, a first ratio of a first intensity of the first stimulus to the first ambient lighting is in a range from 1.5 to 10 and wherein a second intensity of the second stimulus is to the second ambient lighting A second ratio is in a range from 1.5 to 10 and optionally in a range from 2.5 to 5. In some embodiments, the second ratio is adjusted to a value different from the first ratio in response to the comparison.

A stimulus may include a plurality of stimuli that may be configured in any manner as described herein. In some embodiments, the first and second treatments each comprise a plurality of stimuli distributed over regions of the retina located away from a fovea of the eye, each of the plurality of stimuli imaged in front of the retina and in Blurring on the retina where the stimuli are configured to define a treatment area on the retina. In some embodiments, the first treatment includes a first treatment area within a first percentage of the retina and the second treatment includes a second treatment area within a second percentage of the retina and wherein the response In comparison, the second treatment area is adjusted to an amount different from the first treatment area. In some embodiments, the first treatment area comprises a first percentage of the total area of the retina and the second treatment area comprises a second percentage of the total area of the retina and wherein the second hundred The fraction is adjusted to an amount different from the first percentage and optionally wherein the first percentage and the second percentage range from about 15% to about 65% of the total area of the retina. In some embodiments, the first treatment area and the second treatment area comprise annular areas having a fovea positioned outside the annular areas.

The first and second stimuli can comprise any suitable wavelength and the wavelength can be tuned as described herein. In some embodiments, the first treatment comprises a first wavelength of light corresponding to a first peak sensitivity of the cone of the eye and the second treatment comprises one of light corresponding to a second peak sensitivity of the cone of the eye The second wavelength and optionally wherein the peak sensitivity of the cone corresponds to light at a wavelength within a range of from about 420 nm to about 440 nm, from about 534 nm to about 545 nm, or 564 to about 580 nm. In some embodiments, the first peak corresponds to a first range and the second peak corresponds to a second range that differs from the first range in response to the comparison. In some embodiments, the first light treatment includes a first distribution of wavelengths and the second light treatment includes a second distribution of wavelengths, wherein the second distribution is different from the first distribution responsive to the comparison.

In some embodiments, the first distribution of wavelengths corresponds to a first temperature and the second distribution corresponds to a second temperature, and optionally wherein the first temperature and the second temperature are between about 5000 Kelvin and about Within one range of 11,000 degrees.

In some embodiments, one or more of the first image or the second image is projected into the eye and the amount of astigmatism is provided by an optical structure, as described herein. In some embodiments, the first treatment projects a first image of a stimulus with a first amount of astigmatism in front of the retina and the second treatment projects a second image with a second amount of astigmatism onto the retina ahead. In some embodiments, the first amount of astigmatism is different from the second amount of astigmatism responsive to the comparison. In some embodiments, the first amount of astigmatism is in a first range from 0.5D to 4D and the second amount of astigmatism is in a second range from 0.5D to 4D.

The intensity of the stimulus may include any suitable intensity as described herein. In some embodiments, the first treatment includes projecting a first stimulus at a first intensity in front of the retina and the second treatment includes projecting a second stimulus at a second intensity in front of the retina. In some embodiments, responsive to the comparison, the second intensity is different from the first intensity. In some embodiments, the first intensity and the second intensity each comprise a brightness in a range of 1 to 1000 Troland. In some embodiments, the first intensity and the second intensity each comprise an illuminance in a range of from 100 to 50,000 nits or in a range of from 1 to 10,000 nits.

Stimuli may include any suitable spatial frequency properties as described herein. In some embodiments, the first treatment comprises a first plurality of stimuli projected in front of the retina with a first spatial frequency distribution and wherein the second treatment comprises a second plurality of stimuli projected in front of the retina with a second spatial frequency distribution. irritant. In some embodiments, responsive to the comparison, the second spatial frequency distribution is different from the first spatial frequency distribution. In some embodiments, each of the first and second plurality of stimuli includes a length, edge, and an intensity profile to produce a cycle between 1×10 ⁻¹ and 2.5×10 ¹ as imaged into the eye in front of or behind the retina Spatial frequency in a range of /degree and optionally in a range from 1×10 ⁻¹ to 1×10 ¹ cycles/degree. In some embodiments, each of the first and second plurality of stimuli as imaged in the eye comprises from about 1×10 ⁻¹ to about 2.5×10 ¹ cycles/degree, and optionally from 1×10 ⁻¹ to about 5×10 ⁰ An increase in spatial frequency of a spatial frequency range of cycles/degree provides a spatial frequency distribution of a decrease in spatial frequency amplitude. In some embodiments, the reduction in spatial frequency intensity is in a range from 1/(spatial frequency) ^0.5 to 1/(spatial frequency) ² for arbitrary units of spatial frequency amplitude and optionally for arbitrary units of spatial frequency amplitude From 1/(spatial frequency) to 1/(spatial frequency) ² . In some embodiments, the spatial frequency ranges from about 3×10 ⁻¹ to about 1.0×10 ¹ cycles/degree and optionally within a range from about 3×10 ⁻¹ to about 2.0×10 ⁰ and further optionally from about 3×10 ^{−1 1} to about 1.0X10 ⁰ .

The light stimulus can include any suitable stimulus as described herein and can include a pulsed stimulus or a continuous stimulus. In some embodiments, the first light therapy projects a first image of a first pulsed stimulus and wherein the second light therapy projects a second image of a second pulsed stimulus. In some embodiments, the first pulse stimulus includes a first duty cycle and the second pulse stimulus includes a second duty cycle, the second duty cycle being different than the first duty cycle in response to the comparison. In some embodiments, the first pulsatile stimulus includes a first frequency and the second pulsatile stimulus includes a second frequency that is different from the first frequency in response to the comparison.

The image of the projected stimulus can be projected either in front or behind the retina, and can change position from anterior to posterior or vice versa in response to the comparison. In some embodiments, the first phototherapy projects a first image of a first stimulus to a first location in front of or behind the retina, and the second phototherapy projects a second stimulus in front of or behind the retina One of the second positions. In some embodiments, responsive to the comparison, the second location is different than the first location. In some embodiments, the first location is on a first side of the retina and responsive to the comparison, the second location is on a second side of the retina opposite the first side.

At step 1860, a second light therapy is provided to the eye in response to the comparison.

In some embodiments, the first light therapy includes a first light stimulus and the second light therapy includes a second light stimulus.

The first and second light treatments may be provided to the eye in any suitable manner as described herein. In some embodiments, the first treatment includes a first day for a first duration and the second treatment includes a second day for a second duration, the second duration being different from the first duration in response to the comparison . In some embodiments, the first duration is in the range of one from 1 hour to 8 hours and the second duration is in the range of one from 1 hour to 8 hours and optionally in the range of from 1.5 to 3 hours.

In some embodiments, the first treatment occurs at a first local time of day and the second light treatment occurs at a second time of day that differs from the first time of day in response to the comparison. A first treatment may occur at a first local time for a first duration and a second treatment may occur at a second local time for a second duration, responsive to comparing the first duration of the first day's first local time The time does not overlap with the second duration of the second local time of the next day. In some embodiments, the time of day is within a range of one of from 7 am to noon local time or within a range of one of from 5 pm to midnight local time. In some embodiments, responsive to the comparison, the second local time of day is different from the first local time of day.

Although reference is made to the treatment and measurement of one eye, the contralateral eye can also be treated and measured. In some embodiments, the eye is treated using a pair of eyes for the first treatment and the second treatment.

In some embodiments, the refractive error of the eye is corrected using appropriate lenses during treatment, as described herein. In some embodiments, a first refractive correction is used during the first treatment to correct a first refractive error of the eye to provide a view on a first clear center zone and for a second treatment on a second clear center A second refractive error of the eye is corrected regionally using a second refractive correction. In some embodiments, the first refractive correction is different from the second refractive correction responsive to the comparison.

While reference is made to a method 1800 of reducing the deepening of the refractive error of an eye, many adaptations and variations will be recognized by those of ordinary skill. For example, steps may be performed in any suitable order, and some steps may be removed and some steps repeated. Also, a processor as described herein may be configured with instructions to perform any one or more steps of method 1800 . Alternatively or in combination, any of optical components, optical structures, displays, treatment devices and systems may be configured according to method 1800, such as system 1600, treatment device 1602 or system 1700 and such components may be readily interchanged according to the present invention, It will be understood as normal technology.

As described herein, computing devices and systems described and/or illustrated herein broadly represent any type or form of computing capable of executing computer-readable instructions, such as those contained within the modules described herein. device or system. In their most basic configurations, the computing device(s) may each include at least one memory device and at least one physical processor.

The term "memory" or "memory device" as used herein generally refers to any type or form of volatile or non-volatile storage device or media capable of storing data and/or computer readable instructions. In one example, a memory device can store, load and/or maintain one or more modules described herein. Examples of memory devices include, but are not limited to, random access memory (RAM), read only memory (ROM), flash memory, hard disk drives (HDD), solid state drives (SSD), optical drives, Cache, variation or combination of one or more of them or any other suitable storage memory.

Additionally, as used herein, the terms "processor" or "physical processor" generally refer to any type or form of hardware-implemented processing unit capable of interpreting and/or executing computer-readable instructions. In one example, a physical processor can access and/or modify one or more modules stored in the aforementioned memory device. Examples of physical processors include, but are not limited to, microprocessors, microcontrollers, central processing units (CPUs), field programmable gate arrays (FPGAs) implementing software processors, application specific integrated circuits (ASICs), A portion of one or more of them, a variation or combination of one or more of them, or any other suitable physical processor. The processor may include a distributed processor system (eg, running parallel processors) or a remote processor (such as a server) and combinations thereof.

Although shown as separate elements, method steps described and/or disclosed herein may represent part of a single application. Additionally, in some embodiments, one or more of these steps may represent or correspond to one or more software programs that, when executed by a computing device, cause the computing device to perform one or more tasks, such as method steps. application or program.

Additionally, one or more of the devices described herein can transform data, a physical device, and/or a representation of a physical device from one form to another. Additionally or alternatively, one or more of the modules described herein can connect a processor, volatile memory, memory, non-volatile memory, and/or any other portion of a physical computing device from one form of computing device to another form of computing device.

As used herein, the term "computer-readable medium" generally refers to any form of device, carrier, or medium that is capable of storing or executing computer-readable instructions. Examples of computer-readable media include, but are not limited to: transmission-type media, such as carrier waves; and non-transitory-type media, such as magnetic storage media (e.g., hard disk drives, tape drives, and floppy disks), optical , compact discs (CDs), digital video discs (DVDs) and Blu-ray discs), electronic storage media (eg, solid state drives and flash media) and other distribution systems.

Those of ordinary skill will recognize that any procedure or method disclosed herein may be modified in numerous ways. Program parameters and sequences described and/or disclosed herein are given by way of example only and may be varied as desired. For example, although steps shown and/or described herein may be shown or discussed in a particular order, the steps do not necessarily need to be performed in the order shown or discussed.

Various exemplary methods described and/or disclosed herein may also omit one or more steps described or discussed herein or may also include additional steps in addition to the disclosed steps. Furthermore, one step of any method as disclosed herein may be combined with any one or more steps of any other method, as disclosed herein.

A processor as described herein may be configured to perform one or more steps of any method disclosed herein. Alternatively or in combination, the processor may be configured to combine one or more steps of one or more methods as disclosed herein.

Unless otherwise stated, the terms "connected to" and "coupled to" as used in this specification and claims should be interpreted to allow both direct and indirect (eg, via other elements or components) connection. In addition, the term "a" or "an" as used in this specification and the scope of claims of invention should be interpreted as meaning "at least one of...". Finally, for ease of use, the terms "comprising" and "having" (and their derivatives) as used in this specification and claims of invention may be used interchangeably with the word "comprising" and shall have the same meaning as the word "comprising" "Same meaning.

A processor as disclosed herein may be configured with instructions to perform any one or more steps of any method as disclosed herein.

It should be understood that although the terms "first", "second", "third", etc. may be used herein to describe various layers, elements, components, regions or sections without implying any particular order or sequence of events. These terms are only used to distinguish one layer, element, component, region or section from another layer, element, component, region or section. A first layer, element, component, region or section as described herein could be termed a second layer, element, component, region or section without departing from the teachings of the present invention.

As used herein, the term "or" is used inclusively to refer to items both alternatively and in combination.

As used herein, characters such as numbers refer to the same element.

The invention consists of the following numbered clauses.

Clause 1. A method of treating an eye to reduce the progression of myopia, the method comprising: measuring an optical property of the eye at a first time; providing a first light therapy to the eye to reduce the progression of myopia ; measuring the optical property of the eye at a second time after the first light treatment; comparing the optical property of the eye at the second time with one of the optical properties of the eye at the first time; and providing a second light therapy to the eye in response to the comparison.

Clause 2. The method of Clause 1, wherein the first light treatment comprises a first light stimulus and the second light treatment comprises a second stimulus, and wherein the second light stimulus is responsive to the comparison And configured.

Clause 3. The method of Clause 2, wherein the first optical stimulus comprises one or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on a display, and the first photostimulant is based on the position between the first photostimulus and the second photostimulus, the size, the spatial frequency distribution, the intensity, or the intensity relative to the background on the display The one or more differ from the second photostimulant.

Clause 4. The method of Clause 1, wherein the comparison includes a difference between the measured optical property at the second time and the first time and wherein the second treatment is adjusted in response to the difference.

Clause 5. The method of Clause 4, wherein the difference comprises a transient change in the optical property of the eye between the first time and the second time and optionally wherein the transient change comprises a A change in choroidal thickness.

Clause 6. The method of clause 5, wherein the first time occurs on a first day, the first phototherapy occurs on days within a plurality of weeks on or after the first day, and the second time occurs on The plurality of weeks is later and the second light treatment occurs at or after the second time.

Clause 7. The method of clause 5, wherein the first time occurs on a first day, the first phototherapy occurs on or after the first day, and the second time occurs on the first day The last day of the plurality of days of treatment, and the second light treatment occurs on a second day after the last day of the plurality of days.

Clause 8. The method of clause 5, wherein the first time occurs on a first day, the second time occurs on the first day, the first phototherapy occurs on the first day and the second phototherapy occurs on the first day Treatment occurs on one of the second days following the first day.

Clause 9. The method of Clause 1, wherein the optical property comprises one or more of refractive data, axial length data, or choroidal thickness data.

Clause 10. The method of Clause 1, wherein the first light therapy projects a first image at a focal point in front of the retina, and the second light therapy projects a second image at a focal point in front of the retina .

Clause 11. The method of Clause 10, wherein the first image is focused at a first distance in front of the retina, and the second image is focused at a second distance in front of the retina, the first The distance is different from the second distance.

Clause 12. The method of Clause 10, wherein using a first central region of focus for focusing the first image on the retina and a first region for focusing the first image in front of the retina is used. A first lens in the outer zone projects the first image and uses a second clear zone for focusing the second image on the retina and a first lens for focusing the second image in front of the retina. The second lens, one of the two outer regions, projects the second image.

Clause 13. The method of Clause 12, wherein the first image and the second image comprise images of an object viewed through the lens.

Clause 14. The method of Clause 12, wherein the first outer zone and the second outer zone comprise an aspheric profile, a plurality of lenslets, or alternating annular zones of increased optical power and decreased optical power one or more.

Clause 15. The method of clause 12, wherein the first lens and the second lens differ by one or more of: a first optical power of the first outer zone and a first optical power of the second optical zone a difference between the second optical powers; a difference between a diameter of the first clear zone and the second clear zone; a difference between an area of the first outer zone and the second outer zone; A first ratio of a first area of the first clear zone to a first area of the first outer zone and a second area of the second clear zone to a second area of the second outer zone A difference between the second ratio; a difference between a first number of lenslets of the first outer zone and a second number of lenslets of the second outer zone; a first ratio of the first outer zone a difference between a first optical power of a plurality of lenslets and a second optical power of a second plurality of lenslets of a second outer zone; for providing the first image to the focal point in front of the retina A first percentage of a first area of the first outer zone and a second hundred of a second area of the second outer zone for providing the second image to the focal point in front of the retina A difference between the scores.

Clause 16. The method of Clause 10, wherein the first image is focused at a first angle relative to an optical axis of the eye and the second image is focused at a second angle relative to the optical axis of the eye Angles away from the fovea are focused.

Clause 17. The method of Clause 16, wherein each of the first angle and the second angle is in a range from 5 degrees to 35 degrees and optionally in a range from about 15 degrees to 35 degrees .

Clause 18. The method of Clause 16, wherein the second angle is adjusted to an angle different from the first angle in response to the comparison.

Clause 19. The method of Clause 10, wherein the first image is focused in front of the retina by a first amount in a range from 3D to 10D and the second image is focused in front of the retina Up to a second amount in the range of from 3 D to 10 D, and optionally in the range of from 4.5 D to 8 D.

Clause 20. The method of Clause 19, wherein the second amount is adjusted to an amount different from the first amount in response to the comparison.

Clause 21. The method of Clause 10, wherein the first image includes a first stimulus on a first background and the second image includes a second stimulus and a second background.

Clause 22. The method of Clause 21, wherein a first ratio of a first intensity of the first stimulus to a first intensity of the first background of the first stimulus is in the range of from 10 to 50 range and wherein a second ratio of the second stimulus to a second intensity of a second background is in a range from 10 to 50 and optionally in a range from 10 to 30.

Clause 23. The method of Clause 22, wherein the second ratio is adjusted to a value different from the first ratio in response to the comparison.

Clause 24. The method of Clause 21, wherein a display is used to project the first stimulus and the second stimulus onto the retina.

Clause 25. The method of Clause 10, wherein the eye is exposed to a first ambient lighting while focusing on the first image and a second ambient lighting while focusing on the second image.

Clause 26. The method of Clause 25 and wherein the first ratio of the first intensity of the first stimulus to the first ambient lighting is in a range from 1.5 to 10 and wherein the ratio of the second stimulus to A second ratio of a second intensity to the second ambient lighting is in a range from 1.5 to 10 and optionally in a range from 2.5 to 5.

Clause 27. The method of Clause 26, wherein the second ratio is adjusted to a value different from the first ratio in response to the comparison.

Clause 28. The method of Clause 1, wherein the first treatment and the second treatment each comprise a plurality of stimuli distributed over regions of the retina located away from a fovea of the eye, the plurality of Each of the stimuli is imaged in front of and blurred on the retina, wherein the plurality of stimuli are configured to define a treatment area on the retina.

Clause 29. The method of clause 28, wherein the first treatment includes a first treatment area within a first percentage of the retina, and the second treatment includes a second percent of the retina within a second treatment area and wherein the second treatment area is adjusted by an amount different from the first treatment area in response to the comparison.

Clause 30. The method of Clause 29, wherein the first treatment area comprises a first percentage of a total area of the retina and the second treatment area comprises a second percent of the total area of the retina ratio and wherein the second percentage is adjusted to an amount different from the first percentage in response to the comparison and optionally wherein the first percentage and the second percentage are at the retinal The total area ranges from about 15% to about 65%.

Clause 31. The method of Clause 29, wherein the first treatment region and the second treatment region comprise annular regions having the fovea positioned outside the annular regions.

Clause 32. The method of Clause 1, wherein the first treatment comprises a first wavelength of light corresponding to a first peak sensitivity of a cone of the eye and the second treatment comprises a first wavelength corresponding to the A second wavelength of light of a second peak sensitivity of the cones and optionally wherein the peak sensitivity of the cones corresponds to a wavelength from about 420 nm to about 440 nm, from about 534 nm to about 545 nm, or from 564 nm to Light at a wavelength in the range of about 580 nm.

Clause 33. The method of Clause 32, wherein the first peak value corresponds to a first range and the second peak value corresponds to a second range that differs from the first range in response to the comparison.

Clause 34. The method of Clause 1, wherein the first phototherapy comprises a first distribution of wavelengths and the second phototherapy comprises a second distribution of wavelengths, wherein responsive to the comparison, the second distribution is different from the first distribution.

Clause 35. The method of Clause 34, wherein the first distribution of wavelengths corresponds to a first temperature and the second distribution corresponds to a second temperature, and optionally wherein the first temperature and the second temperature are between From about 5000 degrees Kelvin to about 11,000 degrees Kelvin.

Clause 36. The method of Clause 1, wherein the first treatment includes a first day for a first duration and the second treatment includes a second day for a second duration, responsive to the comparison, the The second duration is different than the first duration.

Clause 37. The method of Clause 36, wherein the first duration is in a range from 1 hour to 8 hours and the second duration is in a range from 1 hour to 8 hours and optionally in a range from In the range of 1.5 to 3 hours.

Clause 38. The method of Clause 1, wherein the first treatment occurs at a first local time of day and the second light treatment occurs at one of the days that differs from the first time of day in response to the comparison Second time.

Clause 39. The method of clause 38, wherein the first treatment occurs at the first local time for a first duration and the second treatment occurs at the second local time for a second duration, in response to The comparison, the first duration of the first local time of the first day does not overlap with the second duration of the second local time of the second day.

Clause 40. The method of Clause 38, wherein the time of day is within a range from 7 am to noon local time or within a range from 5 pm to midnight local time.

Clause 41. The method of Clause 38, wherein the second local time of day is different from the first local time of day in response to the comparison.

Clause 42. The method of Clause 1, wherein the first treatment projects a first image of a stimulus in front of the retina with a first amount of astigmatism, and the second treatment projects a first image of a stimulus with a second amount of astigmatism. Astigmatism projects a second image in front of the retina.

Clause 43. The method of Clause 42, wherein responsive to the comparison, the first amount of astigmatism is different than the second amount of astigmatism.

Clause 44. The method of Clause 42, wherein the first amount of astigmatism is in a first range from 0.5 D to 4 D, and the second amount of astigmatism is in a range from 0.5 D to 4 D within the second range.

Clause 45. The method of Clause 1, wherein the eye has been diagnosed with a progression of myopia in a range from 0.25 D to 1.5 D per year, and wherein the progression of myopia is reduced by at least 0.25 D.

Clause 46. The method of Clause 45, wherein the progression of myopia is greater than 0.6 D per year, and wherein the progression of myopia decreases by an amount in the range from 0.6 D to 0.9 D per year.

Clause 47. The method of Clause 1, wherein the first treatment comprises projecting a first stimulus in front of the retina at a first intensity, and the second treatment comprises projecting in front of the retina at a second intensity One of the secondary stimuli.

Clause 48. The method of Clause 47, wherein responsive to the comparison, the second intensity is different from the first intensity.

Clause 49. The method of Clause 47, the first intensity and the second intensity each comprising a brightness in the range of 1 to 1000 torrents.

Clause 50. The method of Clause 47, wherein the first intensity and the second intensity each comprise an illuminance in a range from 100 to 50,000 nits or in a range from 1 to 10,000 nits.

Clause 51. The method of Clause 1, wherein the first treatment comprises projecting a first plurality of stimuli in front of the retina at a first spatial frequency distribution, and wherein the second treatment comprises projecting at a second spatial frequency Distributing the second plurality of stimuli projected in front of the retina.

Clause 52. The method of Clause 51, wherein responsive to the comparison, the second spatial frequency distribution is different from the first spatial frequency distribution.

Clause 53. The method of Clause 52, wherein each of the first and second plurality of stimuli comprises a length, an edge, and an intensity profile to produce an image into the eye such as in front of or behind the retina Its spatial frequency is in the range of 1X10 ⁻¹ to 2.5X10 ¹ cycles/degree and optionally in the range of from 1×10 ⁻¹ to 1×10 ¹ cycles/degree.

Clause 54. The method of Clause 51, wherein each of the first and second plurality of stimuli as imaged in the eye comprises cycling/degree from about 1×10 ⁻¹ to about 2.5×10 ¹ and depending on An increase in spatial frequency for a spatial frequency range from 1×10 ⁻¹ to about 5×10 ⁰ cycles/degree provides a spatial frequency distribution with a decrease in spatial frequency amplitude.

Clause 55. The method of Clause 54, wherein the reduction in spatial frequency intensity is in a range from 1/(spatial frequency) ^0.5 to 1/(spatial frequency) ² for arbitrary units of the spatial frequency amplitude and optionally The spatial frequency amplitude for arbitrary units is from 1/(spatial frequency) to 1/(spatial frequency) ² .

Clause 56. The method of Clause 54, wherein the range of spatial frequencies is from about 3×10 ⁻¹ to about 1.0×10 ¹ cycles/degree and optionally in a range from about 3×10 ⁻¹ to about 2.0×10 ⁰ and Further optionally from about 3X10 ^-1 to about 1.0X10 ⁰ .

Clause 57. The method of Clause 1, wherein the first phototherapy projects a first image of a first pulsatile stimulus and wherein the second phototherapy projects a second image of a second pulsatile stimulus.

Clause 58. The method of Clause 57, wherein the first pulsatile stimulus comprises a first duty cycle and the second pulsatile stimulus comprises a second duty cycle, the second duty cycle being different from the first duty cycle.

Clause 59. The method of Clause 57, wherein the first pulsatile stimulus comprises a first frequency and the second pulsatile stimulus comprises a second frequency different from the first frequency in response to the comparison.

Clause 60. The method of Clause 1, wherein the first light therapy projects a first image of a first stimulus to a first location in front of or behind the retina, and wherein the second light therapy projects a first image of a first stimulus A second stimulus is projected at a second location in front or behind the retina.

Clause 61. The method of Clause 60, wherein responsive to the comparison, the second location is different from the first location.

Clause 62. The method of Clause 61, wherein the first location is on a first side of the retina and responsive to the comparison, the second location is on a second side of the retina opposite the first side superior.

Clause 63. The method of Clause 1, wherein the optical property comprises an axial length, a binocular axial length, a refraction, a manifest refraction, a cycloplegic refraction, an automatic Refraction, one binocular automatic refraction, one open field automatic refraction, one binocular open field automatic refraction, one scanning slit automatic refraction, one wavefront map, one wavefront coefficient, one sphere coefficient, one cylinder One or more of system coefficient, a coma aberration, a spherical aberration or a trefoil.

Clause 64. The method of Clause 63, wherein the optical property comprises refractive data, and wherein a change in the refractive data between the first time and the second time corresponds to a change in axial length of the eye one change.

Clause 65. The method of Clause 64, wherein the change in axial length is determined in response to the change in the refractive data.

Clause 66. The method of Clause 1, wherein a binocular fixed stimulus is provided to the eye to measure the optical property at the first time and the second time.

Clause 67. The method of Clause 1, wherein the eye is treated using a pair of eyes for the first treatment and the second treatment.

Clause 68. The method of Clause 1, wherein during the first treatment a first refractive correction is used to correct a first refractive error of the eye to provide a vision on a first clear central zone and for the The second treatment corrects a second refractive error of the eye using a second refractive correction on a second clear central zone.

Clause 69. The method of Clause 68, wherein responsive to the comparison, the first refractive correction is different than the second refractive correction.

Clause 70. An apparatus for reducing the progression of myopia in an eye, the apparatus comprising: a light source for providing an image of a first stimulus in front of a retina of the eye away from the retina a location; and a processor operatively coupled to the light source to adjust the stimulus to a second stimulus in response to a change in an optical property of the eye from the first stimulus.

Clause 71. The apparatus of Clause 70, wherein the processor is configured to generate the optical property of the eye at a first time prior to a first light treatment with the first stimulus and at the first A comparison of the optical properties of the eye at a second time after light treatment and the second stimulus is configured in response to the comparison.

Clause 72. The apparatus of clause 71, wherein the light source comprises a display and the first stimulus and the second stimulus are each presented on the display and wherein responsive to the comparison, the second stimulus presented on the display Two stimuli are configured to have one or more of a location, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on the display.

Clause 73. The device of Clause 72, wherein the one or more of the location, the size, the spatial frequency distribution, the intensity, or the intensity of the second stimulus relative to a background on the display is different One or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on the display on the first stimulus.

Clause 74. The apparatus of Clause 72, wherein the first stimulus comprises a plurality of first stimuli, and the second stimulus comprises a plurality of second stimuli, and wherein each of the second plurality of stimuli is configured in response to the comparison.

Clause 75. The apparatus of Clause 70, further comprising a device for projecting the image of the first stimulus and the second stimulus in front of the retina and away from the fovea to provide the first stimulus on the retina One or more optical structures blurring images of the stimulus and the second stimulus.

Clause 76. The apparatus of Clause 75, wherein the one or more optical structures comprise a lens, a disc, a wedge, an optical glass plate, a diffractive optic, a Fresnel lens, a plurality of steps of gratings, an aspheric profile, a liquid crystal, lenslets, areas of positive optical power, annular areas of increased optical power, or gaps extending between areas of increased optical power one or more.

Clause 77. The apparatus of Clause 75, wherein the one or more optical structures comprise a first optical structure for providing the first stimulus and a second optical structure for providing the second stimulus, The second optical structure is configured in response to the comparison.

Clause 78. The apparatus of Clause 77, wherein the second optical structure is configured responsive to the comparison to have a focal length, a tilt angle, a diffraction pattern, an echelle pattern, an aspheric profile, an One or more of liquid crystal refractive index change, position of region of positive optical diopter, or gap.

Clause 79. The apparatus of Clause 70, wherein the processor is configured with instructions for performing the method of any one of the preceding method clauses.

Embodiments of the invention have been shown and described as set forth herein and are provided by way of example only. Those of ordinary skill will recognize many adaptations, changes, changes and substitutions without departing from the scope of the present invention. Several alternatives and combinations of the embodiments disclosed herein may be utilized without departing from the scope of the invention and the inventions disclosed herein. Accordingly, the scope of the disclosed invention should be defined only by the scope of the appended patent claims and their equivalents.

10: Lens 12: Projection unit 13: Diameter 14: Central optical zone 15: Radius 16: Surrounding area 17: Distance 18: Outermost peripheral area/light projection unit 19: Distance across 20: battery 21: Power Function 22: Sensor 23: Start function 24: Flex Printed Circuit Board (PCB) 25: Control functions 27: Light intensity setting 29: Optical switch 30: light source 31: Projection function 32: Optics 33: retina 41: Antenna 70: Glasses 72: Display/Near Eye Display 74: Spectacle lenses 76: Spectacle frame 94: active pixel 94a: Pixels 94b: pixels 94c: Pixels 400: lens 410: Clear Internal Area 412: center 420: Outer area 430: small lens 432: Clearance 440: positive area 442: Clearance 502: Irritant 702: Irritant 704: Image 706: Display 708: Bright pattern 710: dark background 800: screen 802: Distance across 804: Clear Central Field/Uninterrupted Central Field 806: Distance across 812: Angle Lighting 814: Spanning Distance/Central Field of View 900: Natural scenes 1100: Image 1200: video 1600: System 1602: Therapeutic Devices 1604: Server 1606: Secure Two-Way Communication Protocol 1608: Therapy Professional Devices 1610: Caregiver Devices 1612: Healing Database 1614: Clinical measuring devices 1620: display 1622: Lenslet Array 1700: Optical system 1702: Test the eyes 1704: Control eyes 1706: First beam splitter 1708: Second beam splitter 1710: Center Display 1712: Passive background 1720: Monitor 1724: Occlusion 1726: camera 1730a: uniform pattern 1800: method 1805: Steps 1810: steps 1820: steps 1830: steps 1840: steps 1850: steps 1860: steps

One of the better understandings of the features, advantages and principles of the invention will be obtained by reference to the following detailed description which sets forth illustrative embodiments and the accompanying drawings, in which:

Figure 1A shows a retinal stimulation device suitable for incorporation according to some embodiments of the present invention;

Figure IB shows a spectacle lens-based retinal stimulation device suitable for use in incorporating a display and a housing for housing electronics for operating the near-eye display, according to some embodiments of the present invention;

Figure 1C shows a spectacle lens based retinal stimulation device as in Figure 1B suitable for incorporation according to some embodiments of the present invention, where the eye has moved and the different display elements have been activated in response to the eye movement;

Figure 2A shows a soft contact lens suitable for incorporation according to some embodiments of the present invention;

Figure 2B shows soft contact lenses with embedded light sources, optics, and electronics for projecting images out of focus onto the periphery of a user's retina suitable for use in incorporating according to some embodiments of the present invention;

Figure 3 shows a system diagram of the functionality of components suitable for glasses and contact lenses as in Figures 1A-2 incorporated according to some embodiments of the present invention;

Figure 4 shows a lens, such as a contact lens or eyeglasses, suitable for incorporation according to some embodiments of the present invention, including an inner zone for providing clear vision and an outer zone for providing defocus to treat refractive errors ;

Figure 5 shows a lens in which the outer region includes a plurality of lenslets, according to some embodiments;

Figure 6 shows a lens in which the outer zone includes a plurality of separate positive zones to focus light from the outer zone in front of the retina.

Figure 7 shows stimuli as seen by a user and an image on a display, according to some embodiments;

Figure 8A shows an on-screen stimulus for providing a myopic out-of-focus stimulus to the retina, according to some embodiments;

Figure 8B shows the corresponding size in degrees of a myopic out-of-focus stimulus on the retina, according to some embodiments;

Figure 9 shows a stimulus depicting a natural scene, such as a flower ring pattern, according to some embodiments;

Figure 10 shows image contrast and histograms with red (R), blue (B) and green (G) values for the stimuli shown in Figures 8A-9, according to some embodiments;

Figure 11 shows an image suitable for modification and incorporation as a stimulus as described herein, according to some embodiments;

Figure 12 shows an image similar to Figure 11 that has been processed to provide an image of a modified stimulus, according to some embodiments;

Figure 13 shows an image of the spatial frequency distribution of the image of Figure 11 according to some embodiments;

Figure 14 shows an image of the spatial frequency distribution of the image of Figure 13 used as a stimulus, according to some embodiments;

Figure 15 shows a graph of the image spatial frequency in cycles/degree and the logarithm of the energy at each frequency for the stimulus images shown in Figure 8B and Figure 9, according to some embodiments;

Figure 16 shows a system for treating refractive errors of the eye, according to some embodiments;

Figure 17 shows an optical system for projecting stimuli onto the retina, according to some embodiments; and

Figure 18 shows a method of reducing the deepening of the refractive error of an eye, according to some embodiments.

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Claims (79)

A method of treating an eye to reduce the progression of myopia, the method comprising: measuring an optical property of the eye at a first time; providing a first phototherapy to the eye to reduce the progression of myopia; measuring the optical property of the eye at a second time after the first light treatment; a comparison of the optical property of the eye at which the second time occurred with one of the optical properties of the eye at the first time; and A second light therapy is provided to the eye in response to the comparison. The method of claim 1, wherein the first light treatment comprises a first light stimulus and the second light treatment comprises a second light stimulus, and wherein the second light stimulus is configured in response to the comparison . The method of claim 2, wherein the first optical stimulus includes one or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on a display, and the first The photostimulant is one or more of the position between the first photostimulus and the second photostimulus, the size, the spatial frequency distribution, the intensity, or the intensity relative to the background on the display. One of the differences is different from the second photostimulant. The method of claim 1, wherein the comparison includes a difference between the measured optical property at the second time and the first time and wherein the second treatment is adjusted in response to the difference. The method of claim 4, wherein the difference comprises a transient change in the optical property of the eye between the first time and the second time and optionally wherein the transient change comprises a choroidal thickness of the eye Change. The method of claim 5, wherein the first time occurs on a first day, the first phototherapy occurs on a plurality of days within a plurality of weeks on or after the first day, and the second time occurs after the plurality of weeks And the second phototherapy occurs at or after the second time. The method of claim 5, wherein the first time occurs on a first day, the first phototherapy occurs on or after the first day, and the second time occurs on the plurality of days of the first phototherapy on the last day of the plurality of days, and the second light treatment occurs on a second day after the last day of the plurality of days. The method of claim 5, wherein the first time occurs on a first day, the second time occurs on the first day, the first light therapy occurs on the first day and the second light therapy occurs on the One day after the first day. The method according to claim 1, wherein the optical properties include one or more of refractive data, axial length data, or choroidal thickness data. The method of claim 1, wherein the first phototherapy projects a first image at a focal point in front of the retina, and the second phototherapy projects a second image at a focal point in front of the retina. The method of claim 10, wherein the first image is focused at a first distance in front of the retina, and the second image is focused at a second distance in front of the retina, the first distance being different from the second distance. The method of claim 10, wherein using one of a first clear central region for focusing the first image on the retina and a first outer region for focusing the first image in front of the retina The first lens projects the first image and uses a second clear zone for focusing the second image on the retina and a second outer zone for focusing the second image in front of the retina. A second lens projects the second image. The method of claim 12, wherein the first image and the second image include an image of an object observed through the lens. The method of claim 12, wherein the first outer region and the second outer region comprise one or more of an aspheric profile, a plurality of lenslets, or alternating annular regions of increased optical power and decreased optical power . The method of claim 12, wherein the first lens and the second lens differ by one or more of: a first optical power of the first outer zone and a second optical power of the second optical zone a difference between diopters; a difference between a diameter of the first clear zone and a diameter of the second clear zone; a difference between an area of the first outer zone and the second outer zone; the first a first ratio of a first area of the clear zone to a first area of the first outer zone and a second ratio of a second area of the second clear zone to a second area of the second outer zone a difference between a first number of lenslets of the first outer zone and a second number of lenslets of the second outer zone; a first plurality of lenslets of the first outer zone a difference between a first optical power of a lens and a second optical power of a second plurality of lenslets of a second outer zone; the first optical power for providing the first image to the focal point in front of the retina Difference between a first percentage of a first area of an outer zone and a second percentage of a second area of the second outer zone for providing the second image to the focal point in front of the retina a difference between. The method of claim 10, wherein the first image is focused at a first angle relative to an optical axis of the eye and the second image is away from the fovea at a second angle relative to the optical axis of the eye is in focus. The method of claim 16, wherein each of the first angle and the second angle is in a range from 5 degrees to 35 degrees and optionally in a range from about 15 degrees to 35 degrees. The method of claim 16, wherein the second angle is adjusted to an angle different from the first angle in response to the comparison. The method of claim 10, wherein the first image is focused in front of the retina for a first amount in a range from 3D to 10D and the second image is focused in front of the retina for at least 3D A second amount in the range of D to 10 D and optionally in the range of from 4.5 D to 8 D. The method of claim 19, wherein the second amount is adjusted to an amount different from the first amount in response to the comparison. The method of claim 10, wherein the first image includes a first stimulus on a first background and the second image includes a second stimulus and a second background. The method of claim 21, wherein a first ratio of a first intensity of the first stimulus to a first intensity of the first background of the first stimulus is in a range from 10 to 50 and wherein A second ratio of the second stimulus to a second intensity of a second background is in a range from 10 to 50 and optionally in a range from 10 to 30. The method of claim 22, wherein the second ratio is adjusted to a value different from the first ratio in response to the comparison. The method of claim 21, wherein a display is used to project the first stimulus and the second stimulus onto the retina. The method of claim 10, wherein the eye is exposed to a first ambient lighting when focusing on the first image and a second ambient lighting when focusing on the second image. The method of claim 25, and wherein a first ratio of a first intensity of the first stimulus to first ambient lighting is in a range from 1.5 to 10 and wherein a second intensity of the second stimulus is The second ratio of intensity to the second ambient lighting is in a range from 1.5 to 10 and optionally in a range from 2.5 to 5. The method of claim 26, wherein the second ratio is adjusted to a value different from the first ratio in response to the comparison. The method of claim 1, wherein each of the first treatment and the second treatment comprises a plurality of stimuli distributed over a plurality of areas of the retina positioned away from a fovea of the eye, each of the plurality of stimuli are imaged in front of and blurred on the retina, wherein the plurality of stimuli are configured to define a treatment area on the retina. The method of claim 28, wherein the first treatment includes a first treatment area within a first percentage of the retina, and the second treatment includes a first treatment area within a second percentage of the retina A second treatment area and wherein the second treatment area is adjusted by an amount different from the first treatment area in response to the comparison. The method of claim 29, wherein the first treatment area includes a first percentage of a total area of the retina and the second treatment area includes a second percentage of the total area of the retina and wherein the response Adjusting the second percentage to an amount different from the first percentage in the comparison and optionally wherein the first percentage and the second percentage are free from the total area of the retina in the range of about 15% to about 65%. The method of claim 29, wherein the first treatment area and the second treatment area comprise annular areas having the fovea positioned outside the annular areas. The method of claim 1, wherein the first treatment comprises a first wavelength of light corresponding to a first peak sensitivity of a cone of the eye and the second treatment comprises a first wavelength of light corresponding to one of the cones of the eye A second wavelength of light of the second peak sensitivity and optionally wherein the peak sensitivity of the cones corresponds to a wavelength from about 420 nm to about 440 nm, from about 534 nm to about 545 nm, or from 564 to about 580 nm Light at one wavelength within a range. The method of claim 32, wherein the first peak value corresponds to a first range and the second peak value corresponds to a second range different from the first range in response to the comparison. The method of claim 1, wherein the first phototherapy includes a first distribution of wavelengths and the second phototherapy includes a second distribution of wavelengths, wherein the second distribution is different from the first distribution in response to the comparison . The method of claim 34, wherein the first distribution of wavelengths corresponds to a first temperature and the second distribution corresponds to a second temperature, and optionally wherein the first temperature and the second temperature are within about Kelvin In the range of 5000 degrees to about 11,000 degrees Kelvin. The method of claim 1, wherein the first treatment comprises a first duration of a first day and the second treatment comprises a second duration of a second day, in response to the comparison, the second duration different from the first duration. The method of claim 36, wherein the first duration is in a range from 1 hour to 8 hours and the second duration is in a range from 1 hour to 8 hours and optionally from 1.5 to 3 hours within the range. The method of claim 1, wherein the first treatment occurs at a first local time of day and the second light treatment occurs at a second time of day that is different from the first time of day in response to the comparison. The method of claim 38, wherein the first treatment occurs at the first local time for a first duration and the second treatment occurs at the second local time for a second duration, responsive to the comparison, the The first duration of the first local time of the first day does not overlap with the second duration of the second local time of the second day. The method of claim 38, wherein the time of day is within a range from 7 am to noon local time or within a range from 5 pm to midnight local time. The method of claim 38, wherein responsive to the comparison, the second local time of day is different from the first local time of day. The method of claim 1, wherein the first treatment projects a first image of a stimulus in front of the retina with a first amount of astigmatism, and the second treatment projects a first image of a stimulus with a second amount of astigmatism. The second image is projected in front of the retina. The method of claim 42, wherein responsive to the comparing, the first amount of astigmatism is different from the second amount of astigmatism. The method of claim 42, wherein the first amount of astigmatism is in a first range from 0.5D to 4D, and the second amount of astigmatism is in a second range from 0.5D to 4D . The method of claim 1, wherein the eye has been diagnosed as having a progression of myopia in a range from 0.25 D to 1.5 D per year, and wherein the progression of myopia is reduced by at least 0.25 D. The method of claim 45, wherein the progression of myopia is greater than 0.6 D per year, and wherein the progression of myopia decreases by an amount within a range from 0.6 D to 0.9 D per year. The method of claim 1, wherein the first treatment includes projecting a first stimulus in front of the retina with a first intensity, and the second treatment includes projecting a second stimulus in front of the retina at a second intensity. irritant. The method of claim 47, wherein in response to the comparison, the second intensity is different from the first intensity. According to the method of claim 47, each of the first intensity and the second intensity includes a brightness in a range of 1 to 1000 Torrands. The method of claim 47, wherein each of the first intensity and the second intensity comprises an illuminance in a range from 100 to 50,000 nits or in a range from 1 to 10,000 nits. The method of claim 1, wherein the first treatment comprises projecting a first plurality of stimuli in front of the retina with a first spatial frequency distribution, and wherein the second treatment comprises projecting a second spatial frequency distribution at the The second plurality of stimuli in front of the retina. The method of claim 51, wherein responsive to the comparison, the second spatial frequency distribution is different from the first spatial frequency distribution. The method of claim 52, wherein each of the first and second plurality of stimuli includes a length, an edge, and an intensity profile to produce a 1×10 ⁻ Spatial frequencies in the range from ¹ to 2.5×10 ¹ cycles/degree and optionally in the range from 1×10 ⁻¹ to 1×10 ¹ cycles/degree. The method of claim 51, wherein each of the first and second plurality of stimuli as imaged in the eye comprises cycling/degree from about 1×10 ⁻¹ to about 2.5×10 ¹ and optionally from 1×10 ⁻ An increase in spatial frequency for a spatial frequency range of ¹ to about 5×10 ⁰ cycles/degree provides a spatial frequency distribution with a decrease in spatial frequency amplitude. The method of claim 54, wherein the reduction in spatial frequency intensity is in the range from 1/(spatial frequency) ^0.5 to 1/(spatial frequency) ² for arbitrary units of the spatial frequency amplitude and optionally for arbitrary units The spatial frequency amplitude is from 1/(spatial frequency) to 1/(spatial frequency) ² . The method of claim 54, wherein the range of spatial frequencies is from about 3×10 ⁻¹ to about 1.0×10 ¹ cycles/degree and optionally in a range from about 3×10 ⁻¹ to about 2.0×10 ⁰ and further optionally from About 3X10 ^-1 to about 1.0X10 ⁰ . The method of claim 1, wherein the first phototherapy projects a first image of a first pulsed stimulus and wherein the second phototherapy projects a second image of a second pulsed stimulus. The method of claim 57, wherein the first pulse stimulus comprises a first duty cycle and the second pulse stimulus comprises a second duty cycle, the second duty cycle being different from the first duty cycle in response to the comparison . The method of claim 57, wherein the first pulsatile stimulus includes a first frequency and the second pulsatile stimulus includes a second frequency that is different from the first frequency in response to the comparison. The method of claim 1, wherein the first phototherapy projects a first image of a first stimulus to a first location in front or behind the retina, and wherein the second phototherapy projects a second stimulus projected at a second location in front or behind the retina. The method of claim 60, wherein responsive to the comparison, the second location is different from the first location. The method of claim 61, wherein the first location is on a first side of the retina and responsive to the comparison, the second location is on a second side of the retina opposite the first side. The method of claim 1, wherein the optical properties include an axial length, a binocular measured axial length, a refraction, a dominant refraction, a cycloplegic refraction, an automatic refraction, a Binocular automatic refraction, one open field automatic refraction, one binocular open field automatic refraction, one scanning slit automatic refraction, one wavefront map, one wavefront coefficient, one sphere coefficient, one cylinder coefficient, one One or more of coma, a spherical aberration or a trefoil. The method of claim 63, wherein the optical property comprises refractive data, and wherein a change in the refractive data between the first time and the second time corresponds to a change in axial length of the eye. The method of claim 64, wherein the change in axial length is determined in response to the change in the refractive data. The method of claim 1, wherein a binocular fixed stimulus is provided to the eye to measure the optical property at the first time and the second time. The method of claim 1, wherein the eye is treated with a pair of lateral eyes for the first treatment and the second treatment. The method of claim 1, wherein during the first treatment a first refractive correction is used to correct a first refractive error of the eye to provide a view on a first clear central zone and for the second treatment during the A second refractive error of the eye is corrected using a second refractive correction on a second clear central zone. The method of claim 68, wherein responsive to the comparison, the first refractive correction is different from the second refractive correction. An apparatus for reducing the progression of myopia in an eye, the apparatus comprising: a light source for providing an image of a first stimulus in front of a retina of the eye at a location remote from the retina; and A processor operatively coupled to the light source to adjust the stimulus to a second stimulus in response to a change in an optical property of the eye from the first stimulus. The apparatus of claim 70, wherein the processor is configured to generate the optical property of the eye at a first time before a first light treatment with the first stimulus and after the first light treatment A comparison of the optical properties of the eye at a second time and configuring the second stimulus in response to the comparison. The apparatus of claim 71, wherein the light source includes a display and the first stimulus and the second stimulus are each presented on the display and wherein in response to the comparison, the second stimulus presented on the display is Configured to have one or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity relative to a background on the display. The device of claim 72, wherein one or more of the location, the size, the spatial frequency distribution, the intensity, or the intensity relative to a background on the display of the second stimulus is different from the first One or more of a position, a size, a spatial frequency distribution, an intensity, or an intensity of the stimulus relative to a background on the display. The device of claim 72, wherein the first stimulus comprises a plurality of first stimuli, and the second stimulus comprises a plurality of second stimuli, and wherein each of the second plurality of stimuli is responsive to The comparison is configured. The device according to claim 70, further comprising projecting the image of the first stimulus and the second stimulus in front of the retina and away from the fovea to provide the first stimulus and the image on the retina. One of the second stimuli blurs the image of one or more optical structures. The device of claim 75, wherein the one or more optical structures include a lens, a rim, a wedge, an optical glass plate, a diffractive optical device, a Fresnel lens, a plurality of echelle gratings, a non- One or more of a spherical profile, a liquid crystal, lenslets, areas of positive optical power, annular areas of increased optical power, or gaps extending between areas of increased optical power . The device of claim 75, wherein the one or more optical structures include a first optical structure for providing the first stimulus and a second optical structure for providing the second stimulus, the second optical The structure is configured in response to the comparison. The apparatus of claim 77, wherein the second optical structure is configured in response to the comparison to have a focal length, a tilt angle, a diffraction pattern, an echelle pattern, an aspheric profile, a liquid crystal refractive index change 1. One or more of the position or gap of the area of positive optical diopter. The apparatus of claim 70, wherein the processor is configured with instructions for performing the method of any one of the preceding method claims.