Method for nonpharmacologic temporary constriction of a pupil

A method for temporarily constricting a pupil of an eye by an ophthalmic stimulator comprises generating an irradiation control signal by an irradiation control system, generating an irradiation by an irradiation source, coupled to the irradiation control system, receiving the irradiation and delivering a patterned irradiation to an iris of the eye with an irradiation delivery system, and controlling at least one of the irradiation source and the irradiation delivery system by the irradiation control signal of the irradiation control system so that the patterned irradiation is causing a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

FIELD OF INVENTION

This invention relates to a system for pupil constriction, more precisely, to a system of temporary, non-pharmacological construction of a pupil of an eye.

BACKGROUND

A number of devices that make use of the increased depth of field of a small aperture have been proposed for use in ophthalmology, and developed to improve vision. These devices are particularly promising to improve near vision for those who have presbyopia. Examples of such devices include small aperture corneal inlays, reduced-aperture intraocular lenses, as well as other aperture implants that are meant to impact light propagation along the visual axis. While effective, these surgically implanted permanent inlays carry the risk inherent with any implantable device, such as inflammation, infection, or displacement that may require secondary surgical procedures to remove the implant and may necessitate performing other procedures.

Pharmacological methods have also been proposed using medications such as pilocarpine and other agents to temporarily constrict the pupil. While these drugs can temporarily improve vision, they generally require frequent instillation of drops, and can be associated with undesirable side effects, such as headaches.

An alternative approach has been proposed by Hickenbotham in U.S. patent application 2013/0226161, which utilizes a laser to cauterize certain portions of the iris to cause a permanent constriction of the pupil. While this approach offers some advantages over implants and medications, the permanent constriction of the pupil, achieved by a controlled damaging of the iris dilator muscle, does not allow for a trial of the effect, and once performed, leaves the patient with a permanent deficit in iris function. In addition, the exact shape of the constricted pupil may be difficult to control, and may result in odd, irregular, oval, or other undesired pupil shapes. Therefore, the medical need persists to develop a non-pharmacological, non-permanent vision improvement that does not involve inserting a small-aperture object surgically into the eye.

In some embodiments, an ophthalmic stimulator for temporarily constricting a pupil of an eye comprises an irradiation control system, to generate an irradiation control signal; an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, coupled to the irradiation control system, to receive the irradiation from the irradiation source, and to deliver a patterned irradiation to an iris of the eye; wherein the irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments, a method for temporarily constricting a pupil of an eye by an ophthalmic stimulator comprises generating an irradiation control signal by an irradiation control system; generating an irradiation by an irradiation source, coupled to the irradiation control system; receiving the irradiation and delivering a patterned irradiation to an iris of the eye with an irradiation delivery system; and controlling at least one of the irradiation source and the irradiation delivery system by the irradiation control signal of the irradiation control system so that the patterned irradiation is causing a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for constricting a pupil of an eye comprises an irradiation control system, to generate an irradiation control signal; an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, coupled to the irradiation control system, to receive the irradiation from the irradiation source, and to deliver a patterned irradiation to an iris of the eye; wherein the irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a long-term constriction of the pupil of the eye.

In some embodiments, an ophthalmic stimulator for temporarily constricting a pupil of an eye comprises an irradiation control system, to generate an irradiation control signal; a light source, coupled to the irradiation control system, to generate a light beam; and a beam-shaping optics, coupled to the irradiation control system, to receive the light beam from the light source, and to deliver a light ring to an iris of the eye; wherein the irradiation control system controls at least one of the light source and the beam-shaping optics with the irradiation control signal so that the light ring causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarily constricting a pupil of an eye comprises a digital beam controller, to generate a digital beam-control signal; a light source, coupled to the beam controller, to generate a light beam; and a digitally controlled beam modulator, to receive the digital beam-control signal from the beam controller, to receive the light beam from the light source, and to modulate the received light beam into a patterned light, delivered to an iris of the eye; wherein the beam controller controls at least one of the light source and the digitally controlled beam modulator with the digital beam-control signal so that the patterned light causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarily constricting a pupil of an eye comprises an irradiation control system, having a feedback system, to generate an irradiation control signal using a feedback of the feedback system, an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, having a targeting system and coupled to the irradiation control system, to receive the irradiation from the irradiation source, and to direct a patterned irradiation in a pattern to a treatment region of an iris of the eye using the targeting system; wherein the irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a temporary constriction of the pupil, without causing a permanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarily constricting a pupil of an eye comprises a mobile irradiation control system, to generate an irradiation control signal; an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, coupled to the mobile irradiation control system, to receive the irradiation from the irradiation source, and to deliver a patterned irradiation to an iris of the eye; wherein the mobile irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments, a networked system of ophthalmic stimulators for temporarily constricting eye-pupils comprises a set of ophthalmic stimulators, each ophthalmic stimulator including a mobile irradiation control system, to generate an irradiation control signal; an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, coupled to the mobile irradiation control system, to receive the irradiation from the irradiation source, and to deliver a patterned irradiation to an iris of the eye; wherein the mobile irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil; and a central station, including a central image processor, wherein the mobile irradiation control systems of the of the ophthalmic stimulators and the central station are configured to communicate through a communication network.

DETAILED DESCRIPTION

Embodiments of the invention address the above described needs in the following manner. Some embodiments provide systems and methods for a temporary constriction of the pupil without the need of medication therapy. The duration of the constriction can be controlled by a selection of treatment parameters. In a suitable range of treatment parameters, the procedure can be fully reversible: after a characteristic time, the pupils return to essentially their original diameter without further treatment. The pupils can be re-constricted by applying the treatment repeatedly. Therefore, the here-described methods and devices provide the advantages of a temporary, but long lasting vision improvement, while avoid the hazards associated with (1) aperture implants and inlays, inserted by a surgical procedure, (2) permanent destruction of tissue, and (3) pharmaceutical approaches and their undesirable side-effects.

Some embodiments achieve these advantages by heating the iris by an irradiation to a suitable temperature range, (1) to cause a temporary inactivation of the iris dilator muscle, and, in some cases, (2) to enhance an action of the iris constrictor sphincter muscle. This irradiative heat treatment can be applied for a time sufficiently long to cause a reduction in contractile activity, but short enough to avoid causing permanent tissue damage. While the detailed mode of action is yet to be clarified, this effect may be mediated by inactivation of the actin-myosin complex in the exposed muscle.

FIG. 1shows a cross section of an eye1. The eye1includes the well known constituents: a cornea5, where light enters the eye1and a sclera7, an opaque, fibrous protective outer layer of the eye1that contains collagen and elastic fibers. Distal to the cornea5is an anterior chamber9that contains an aqueous humor. The anterior chamber9is separated from a posterior chamber15by an iris11. An opening at a center of the iris11is a pupil13that allows the light to proceed toward the posterior segment of the eye1. Behind the pupil13, ciliary muscles17hold a lens19in a central position. These ciliary muscles17can also deform the lens19as part of accommodating the vision to the distance of the target the eye is looking at. With advancing age, the ciliary muscles17slowly loose their ability to deform and adapt the lens19to varying vision distances: a condition typically referred to as presbyopia. Behind the lens19is a vitreous21. As the light crosses the vitreous21, it eventually hits the retina23. The electric stimuli, generated by the incoming light in the retina23, are transmitted by the optic nerve25towards the brain.

FIG. 2A-8illustrate that the iris11includes a circular sphincter muscle40around the pupil13, capable of shrinking the perimeter of the pupil13, thus constricting it. At the same time, the iris11also includes radial dilator muscles30that specialize in expanding, or enlarging, the pupil13. The competition of the sphincter muscles40and dilator muscles30determines the eventual radius of the pupil13.FIG. 2Aillustrates in its left panel that in strong light the contracting sphincter muscles40constrict the pupil13,FIG. 2Aillustrates in its middle panel the pupil13in an average light.FIG. 2Aillustrates in its right panel that in low light conditions, the radial dilator muscles30dominate the sphincter muscles40and dilate the pupil to enhance the amount of light directed to the retina23.

FIG. 2Billustrates a cross section of the iris11from the side. It is well visible that the sphincter pupillae40is positioned along the edge of the pupil13, the pupillary ruff while the radial dilator pupillae30are located radially outward, farther from the edge of the pupil13.

The anatomy of the muscles of the iris11is also important. The dilator muscle30fibers are typically located near the distal portion of the iris11, adjacent to the iris pigmented epithelium. In contrast, the constrictor sphincter muscles40are more superficial and central, located towards the pupil's edge or margin. Details of the anatomy of these muscles can be found in much greater detail in Junqueira. L. C., Carneiro 2005. Basic Histology, Eleventh Edition. The McGraw-Hill Companies, Inc. United States of America.

FIGS. 3A-Billustrate a principle of embodiments of the invention.FIG. 3Aillustrates that a patterned irradiation can be applied to the iris11for a limited time period, such as 1-100 seconds, with less time required when higher temperatures are applied. The pattern is typically a ring of light, or light-ring. The irradiation raises the temperature of the iris11in a treatment region. The tissue of the iris11can be heated to temperatures that are not sufficient to cauterize or destroy the tissue, but are capable of reducing an activity, or responsiveness of the targeted tissues.

FIG. 3Billustrates the outcome of the irradiation. The heat treatment reduces the activity of the iris dilator muscle and this allows the pupillary constrictor, or sphincter, muscle to reduce the pupil's diameter. Reducing the pupil's diameter reduces the aberrations of the imaging of the eye, sometimes referred to as the pinhole effect in optics. Reducing the aberrations extends the depth of focus, and thereby compensates the emergence of presbyopia in an aging eye. Since this method utilizes the natural constrictor muscle to effect the pupil size change, the risk of pupil de-centration is less than in the case of surgical implants, discussed previously.

FIGS. 4A-Billustrate that heat treatments have been already studied and demonstrated to reduce muscle activity in human tissues, such as in the lung and the prostate, which have smooth muscle tissues similar to that of the iris. The heat treatment can reduce, or inhibit, muscle activity in these tissues. The duration of inactivity can last for hours to days in these systems (see Am. J. Respir. Cell Mol. Biol. Vol 44, pp 213-221, 2011).FIG. 4Aillustrates the effect of heat treatments on lung smooth muscle. The muscle tissue was heated for a treatment time between 5 s and 60 s. After the heat treatment, a test stimulus was administered to the heat-treated and the untreated muscles. The graph reports the ratio of responses to this test as a function of the treatment temperature of the tissue. Visibly, as the treatment temperature exceeded 50 Celsius, or Centigrade, the response of the treated muscle to the test stimulus gradually decreased. For heat treatments above 55-60 Celsius, the response became negligible: the muscle was deactivated by the treatment.

FIG. 4Billustrates the same ratio of responses of treated muscles to non-treated muscles, with the difference that it indicates how long the effect lasted. As the curves show, the de-activation of the smooth muscle with heat treatments raising the muscle temperature above 50-55 Celsius lasted at least for 28 hours, and possibly longer. This remarkably long-lasting deactivation of smooth muscle in response to such a mild and short temperature increase is utilized by embodiments described in this document.

FIG. 5Aillustrates, an ophthalmic stimulator100for temporarily constricting a pupil13of an eye1, building on the just-described observations, comprising an irradiation control system110, to generate an irradiation control signal; art irradiation source120, coupled to the irradiation control system110, to generate an irradiation200; and an irradiation delivery system130, coupled to the irradiation control system110, to receive the irradiation200from the irradiation source120, and to deliver a patterned irradiation200pto an iris11of the eye1in a pattern210. In embodiments, the irradiation control system110controls at least one of the irradiation source120and the irradiation delivery system130with the irradiation control signal so that the patterned irradiation200pcauses a temporary constriction of the pupil13of the eye1, without causing a permanent constriction of the pupil13.

The irradiation control system110can include a memory, to store executable programs and applications; a processor, to execute at least one of a stored program and an installed application; and a user interface, to receive input from a user in relation to an operation of the memory and the processor.

In some embodiments of the ophthalmic stimulator100, the irradiation source120can include an incoherent light source, such as a light source, a LED, a lamp, an infrared source, a broad-band source, a narrow-hand source, a radio-frequency source, an electromagnetic radiation source, or a sound source, to generate a light beam, an electromagnetic irradiation, an infrared beam, a LED light, or a sound. A separate class of irradiation sources can include a coherent light source, such as a laser, a pulsed laser, or a continuous wave (CW) laser.

The just discussed classes of incoherent and coherent irradiation sources have different advantages and drawbacks. Lasers offer good control and unparalleled precision. At the same time, laser beams have a very small diameter, often less than 100 microns. Therefore, to affect larger treatment regions, they require a complex and expensive, digitally controlled optical system, such as a scanning system. These laser-plus-scanning systems offer great control and precision. At the same time, they can be expensive, and can introduce multiple sources of unreliability and performance degradation, a potential problem in medical applications, where high reliability is essential. Using lasers and scanners may therefore necessitate regular maintenance. Also, laser beams can be very intense, thus if a laser gets pointed to an unintended part of an ophthalmic tissue, it can cause substantial damage. Therefore, much stronger safety systems and precautions are needed in laser systems.

In contrast, non-coherent light sources, such as LEDs, infrared sources, lamps, infrared sources, and others may offer less precision and control. However, this control may be sufficient for the purposes of the here-described treatment. Also, incoherent light sources can make the ophthalmic stimulator100much simpler, lighter, and smaller at the same time. Since they typically do not require a digitally controlled scanning system, these incoherent light sources can also be cheaper to maintain and can be more robust and reliable. Finally, since these light sources are less intense, systems with incoherent light sources may require less stringent safety systems and measures. All in all, a comparative analysis of the competing advantages and disadvantages is performed when a system designer decides whether to use a coherent, or an incoherent light source as the irradiation source120of the ophthalmic stimulator100.

Embodiments of the ophthalmic stimulator100can be characterized by numerous treatment parameters. These treatment parameters can include the followings. A power density of the patterned irradiation200pof the irradiation delivery system130can be in the range of 0.1-1000 mW/cm2, in some designs in the range of 1-100 mW/cm2. A total power delivered by the patterned irradiation200pto the iris can be in the range of: 0.1-1.000 mW, in some designs in the range of 1-100 mW. A total energy, deposited by the patterned irradiation200pduring the treatment can be in the range of 10 microJ-10 J, in some designs in the range of 100 microJ-100 mJ.

A wavelength of the irradiation source120can be in the range of 400-4,000 nm, in some designs, in the range of 600-1,500 nm. The wavelength of some stimulators100can be selected by noting inFIG. 2B, that the muscle fibers of the radial dilators30are located in the proximity of the pigmented epithelium of the iris11. This fact can be used to selectively target and heat the dilator muscles30indirectly. The pigmented epithelium layers may not have essential functions that would be negatively affected by heating, such as undergoing an irrecoverable reactivity change. To build on this, irradiation sources120can emit the irradiation200with a wavelength close to the wavelength where the absorption of the pigmented epithelium shows a maximum, or is at least greatly enhanced. Such irradiation sources120can heat the pigments particularly efficiently, possibly to temperatures 55 C, 60 C. possibly even to 60-65 Celsius. The heated pigmented epithelia can then provide a secondary, or indirect heating to the dilator muscles30, located in their immediate proximity, to the medically preferred 50-55 Celsius temperatures.

FIG. 2Balso illustrates that the dilator muscles30are in the distal region of the iris11. Therefore, irradiation with wavelengths that penetrate the iris tissue more efficiently and to greater depths can be favored to make sure that the dilator muscles30are well heated. In several ophthalmologic studies, irradiation with longer wavelengths showed greater penetration into ophthalmic tissues. Therefore, some irradiation sources120may emit irradiation200with longer wavelengths to penetrate more deeply into the iris, with eventual absorption by the pigmented epithelium, to achieve secondary heating of the dilator muscle fibers30. Accordingly, a depth of a treated tissue within the iris can be in some designs in the range of 10 microns-3,000 microns, in some designs, in the range of 500-2,000 microns.

Some irradiation sources may emit a continuous, or continuous wave (CW) irradiation200. Others, such as lasers, or LEDs, may emit pulsed irradiation. A frequency of the pulsed irradiation200can be in a range of 1 Hz to 1 MHz, in some designs, in the range of 100 Hz to 100 kHz. The length of the emitted pulses can vary from 10 femtoseconds to 1 second, in some designs from 1 microsecond to 1 millisecond. The total treatment time can be in the range of 1 sec to 300 sec, in some embodiments in the range of 10 sec to 100 sec 4. A beam profile of the patterned irradiation200pcan be a rectangular, a flat top, a smoothed, a Gaussian, or a Lorentzian profile.

An inner radius Rp (inner) of the pattern210can be in the range of 2-10 mm, in some designs in the range of 3-6 mm. An outer radius Rp (outer) of the pattern210can be in the range of 3-15 mm, in some designs, in the range of 5-10 mm. The pattern210can be such that a treated fraction of the iris has an area that is 10-80% of the total area of the iris11, in some design, this fraction can in the range of 20-50%.

In some embodiments, the irradiation delivery system130can include a pattern generator, an optical beam shaper, a patterning optics, a beam profiler, or a digitally controlled irradiation optics. Some of these elements can be built mostly from passive optical elements, such as lenses and mirrors, with some system characteristics controlled electronically, such as a telescopic distance between two lenses. In other embodiments, the irradiation delivery system130can include optical elements that are actively operated and controlled by electronic or digital circuitry, as described below.

Some embodiments of the ophthalmic stimulator100can be configured to increase a temperature of a treatment region of the iris to a range of 45-60 degrees Celsius. Other embodiments can increase the temperature of the treatment region of the iris to a range of 50-55 degrees Celsius. As discussed in relation toFIGS. 4A-B, treatments with temperatures in these ranges have been demonstrated to impact the responsiveness of smooth muscle tissue temporarily, in a reversible and repeatable manner.

The actual effect of the heat treatment depends on several factors, since different temperatures and treatment durations can have a multitude of effects on smooth muscle cells and function. On the cellular level, first, a beat treatment can induce biochemical changes and secretions that can affect the functioning of the treated tissue, such as heat shock proteins. Second, it can cause loss of cells through various mechanisms, such as apoptosis, or programmed cell death. Finally, on a much shorter time scale, heat treatment can lead to specific loss of contractility due to denaturation of myosin molecules or inhibition of ion channels.

On a higher, physiological level, the effect of the heat treatment on the pupil may depend on factors such as dilator muscle fiber orientation, and on opposing, constrictor, muscle action. Finally, the heat treatment can change the physical properties of the muscles in different aspects as well, including shrinking or expanding the length of the muscle strands, making the strands more or less aligned, and changing of the elastic moduli of the muscles, among others.

For all these reasons, the iris of the individual patients can be analyzed by the ophthalmologist before the treatment with the ophthalmic stimulator100. Based on the analysis, the desired medical outcomes can be cross-referenced with the patient data of the individual patients. Subsequently, the treatment region, treatment parameters and specifically the treatment temperatures can be set. As discussed further below, for some medical outcomes heating the radial dilator muscles30can be preferable, for others, heating the circular sphincter muscles40can be preferable. The treatment regions can be set according to these medical considerations.

FIGS. 6A-Dillustrate that in some embodiments of the ophthalmic stimulator100, the irradiation control system110can include an irradiation controller112, an imaging system114and a user interface118. The imaging system114can be electronically coupled to the irradiation controller112, to relay images, image-related data, and control information. The imaging system114can include an image processor114ip, whose functions will be described later.

FIGS. 6A-Billustrate two implementations of the imaging system114. InFIG. 6A, an imaging light220is reflected out from the optical pathway of the patterned irradiation200pby a beam splitter131towards the imaging system114that is positioned outside the irradiation optical pathway. InFIG. 6B, a small imaging system, such as a small CCD camera114can be placed on the distal end of the irradiation delivery system130, directly receiving the imaging light220. The imaging light220can be a reflection of an imaging light, projected on the iris11by an imaging light source. In other designs, the imaging light220can be simply the ambient light reflected from the iris11.

The imaging system114can be any one of the well known ophthalmic imaging systems, including a CCD camera, feeding into a video monitor, any other electronic or digital imaging system, a video mircroscope, or a surgical microscope.

The irradiation control system110can generate the irradiation control signal by generating an image of the iris11of the eye with the imaging system114for a user, followed by receiving an image-based input from the user through the user interface118, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pin accordance with the received image-based input.

In a typical example, the patterned irradiation200pcan impact the iris11in a ring pattern210with an inner radius Rp(inner) and an outer radius Rp(outer). In this embodiment, the user of the system, such as ophthalmologist, or an ophthalmic surgeon, can be prompted via the user interface118to enter the image-based input, which in this case can be a selection of the inner radius Rp(inner) and the outer radius Rp(outer) of the ring pattern210, based on the surgeon analyzing the image, relayed by the imaging system114.

FIGS. 12D-Eillustrate that setting these radii Rp(inner) and Rp(outer) determines whether the ring pattern210, and thus the treatment region, is the region of the radial dilator muscles30, or the circular sphincter muscles40. Denoting the outer radius of the sphincter muscles with R(sphincter), if the surgeon selects the inner radius Rp(inner) of the ring pattern210to be greater than R(sphincter):Rp(inner)>R(sphincter), then the ring pattern210will fall on the radial dilator muscles30, and those muscles will receive the heat treatment. Whereas, if the surgeon selects the outer radius Rp(outer) of the ring pattern210to be smaller than R(sphincter):Rp(outer)<R(sphincter), then the ring pattern210will all on the circular sphincter muscles40, and the circular sphincter muscles40will be treated by the patterned irradiation200p. As discussed, an ophthalmologist can select either treatment region based on a prior analysis of the patient's specific data, and the desired medical outcomes.

In some embodiments, the irradiation control system110can include an image processor114ipin the imaging system114. The image processor114ipcan be integrated with the imaging system114, can be partially integrated, or can be a separate electronic or computational system. In these embodiments, the irradiation control system110can generate the irradiation control signal by generating an image of the iris11with the imaging system114for the image processor114ip, receiving an image-based input from the image processor114ip, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pin accordance with the received image-based input.

In a representative embodiment, the patterned irradiation200pcan impact the iris11in a ring pattern210with inner and outer radii Rp(inner) and Rp(outer). The imaging system114can image the iris11, and relay this image to the image processor114ip, in response, the image processor114ipcan run an image recognition program, possibly including an edge-recognition software, and identify the inner and outer radii of the iris11, and the radius R(sphincter) that demarcates the radial dilator muscles30from the circular sphincter muscles40. Then, the image processor114ipcan generate the image-based input that sets, or suggests to set, the Rp(inner) and Rp(outer) radii of the ring pattern210. The effect of these choices on the treatment region and the corresponding medical effects have been explained earlier.

FIG. 12A-Cillustrate that in some embodiments of the ophthalmic stimulator100, the irradiation control system110can include an alignment system135.

FIG. 12Aillustrates that in some embodiments the ophthalmic stimulator100can include an objective133, the last optical element that guides the patterned irradiation200ptoward the eye1. In these embodiments, the alignment system135can include a frame, or chin-rest136, on which the patient can rest her/his chin to minimize the motion of the eye1relative to the stimulator100. The alignment system135can also include a patient interface137that contacts the eye1of the patient. Many types of patient interfaces137are known in the art and can be used here.FIG. 12Aillustrates a patient interface137, whose proximal end is attached to the objective133of the ophthalmic stimulator100, and whose distal end the patient presses her eyes against. The patient interface137can ensure a firm coupling, or docking, to the eye by involving a vacuum suction system, or a forceps. The patient interface137can be a one-piece or a two-piece patient interface. The distal end of the patient interface137can include a contact lens, to ensure a smoother, softer connection to the eye. Such a contact lens also minimizes the optical distortions of the patterned irradiation200pas it exits the patient interface137and enters the cornea5of the eye1.

FIG. 12Billustrates another embodiment of the alignment system135, where the patient interface137is coupled to the frame136instead of the stimulator100. Since the frame136is rigidly coupled to the ophthalmic stimulator100, the optical pathway of the patterned light200pis similarly secure from the objective to the eye1in this embodiment as well. One of the differences is that there is a distance between the stimulator100and the patient interface,137, so the patient does not have to lean forward to receive the treatment, and the doctor sees where the patterned light200phits the patient interface137. As before, this patient interface137can also be a one-piece and a two-piece patient interface137.

The patient interfaces137of eitherFIG. 12A or 12Bis preferably aligned and centered with the eye1before coupling, or docking them to the eye1.FIG. 12Cillustrates a corresponding aligning, or centering, pattern138of the alignment system135. This centering pattern, or aligning pattern, can include an aligning ring138a, or an aligning cross-hair138b, or both. This aligning pattern138can be formed in, projected into, or digitally overlaid, the image formed by the imaging system114, in a position that is concentric with the optical axis of the objective133. The ophthalmic surgeon, or any other user or operator, can dock the patient interface137of the stimulator100to the eye with increased precision, with aligning, or centering, the aligning element138with the pupil1during the docking procedure.

In a video-monitor-based embodiment, the surgeon can make the centering of the aligning ring138aon the video image with the edge of the pupil13part of the docking. During the docking, the surgeon can instruct the patient to move her/his head and eye around, until the circular edge of the pupil13is concentric with the aligning ring138a. Then the surgeon can complete the docking of the patient interface137to the eye1. Further embodiments of the alignment system135will be described later.

In some designs, the stimulator100can include a fixation light202, and the surgeon can instruct the patient to stare at the fixation light202during docking. The patient staring, or fixating at the fixation light202can further help centering the patient interface137with the pupil13during the docking.

In these embodiments, the irradiation control system110can generate the irradiation control signal by processing alignment data with the alignment system135, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pto the iris in a pattern210aligned with the pupil13of the eye.

In some embodiments of the ophthalmic stimulator100, the processing alignment data can include generating an image of the iris11with the imaging system114, and overlaying an alignment pattern138on the generated image. The generating the irradiation control signal can include generating a misalignment-warning signal, or generating an alignment-guidance signal, if a misalignment is detected during the processing of the alignment data that is part of the docking. The misalignment-warning signal can alert the operating surgeon to instruct the patient to move his/her head, eye, or both to improve the alignment to help making the docking precise. Also, for stimulator designs where the stimulator100or the patient interface137itself can be moved or adjusted, the misalignment-warning signal can alert the surgeon for the need to adjust the stimulator100or the patient interface137.

An example for an adjustable patient interface137is a two-piece patient interface137, where one piece of the patient interface137can be attached to the stimulator100at its objective133, the other piece of the patient interface137can be coupled to the eye with vacuum-suction, or pressing, and the docking includes the surgeon maneuvering the two pieces of the patient interface137to dock to each other.

FIGS. 6C-Dalso show a feedback system116. This system will be described in detail below.

FIG. 10illustrates that the irradiation controller112can include a number of blocks. These blocks can be implemented as a dedicated processor or circuitry, or can be implemented as a software, code, program, or application, implemented on a computer of the irradiation controller112, or a combination of hardware and software blocks. In various embodiments, the irradiation controller112can include:a feedback block112a, to receive feedback data and to send a feedback signal to a processor113;an imaging block112b, to receive imaging data and to send an imaging signal to the processor.113;an alignment block112c, to receive alignment data and to send an alignment signal to the processor113;a memory block112d, to receive patterns for storage and patient data, to store algorithms and codes, and to send stored, patterns, patient data, or executable algorithms to the processor113;a pattern generator block112e, to receive pattern parameters and to send generated patterns to the processor113;a user interface block112f, to receive a user input, for example through a user interface118, that can be patterns, commands, and irradiation parameters, and to send the received patterns, commands and irradiation data as a user input signal to the processor113.

Each of these blocks can receive, their input from corresponding hardware blocks, such as sensors, controllers, hardware blocks and user interfaces. For example, the feedback block112acan be a dedicated circuitry that receives the feedback data from the feedback system116, as described below. The imaging block112bcan be a software algorithm, implemented on a processor that receives the imaging data from the imaging system114that can include a CCD camera, a video monitor, or a surgical microscope.

In response to signals, received from any of the blocks112a-f, the processor113can send an irradiation control signal to the irradiation source120, or to the irradiation delivery system130, or to both.

In some detail, in embodiments of the ophthalmic stimulator100the irradiation control system110can include the memory112d, and the generating the irradiation control signal can include recalling stored data from the memory112d, representing at least one of an irradiation pattern and patient data, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pto the iris11in accordance with the recalled stored data.

In embodiments, the irradiation control system110can include a pattern generator; and the generating the irradiation control signal can include venerating an electronic representation of the irradiation pattern210; and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pwith the generated irradiation pattern210.

Returning to the medial effects and treatments, embodiments of the ophthalmic stimulator100can cause a temporary constriction of the pupil13of the eye that includes an at least 5% reduction of a radius of the pupil13that lasts less than one hour. In some cases, the reduction of the radius of the pupil can last for a time interval more than one hour and less than one day. In other embodiments, the temporary constriction of the pupil of the eye includes an at least 5% reduction of the radius of the pupil that lasts for a time interval between one day and one week; or between one week and one month; or between one month and three months; or between three months and one year.

Each of these time intervals has their own medical and patient advantages. The longer the pupil constriction lasts, the less often the treatment may need to be applied, which can be preferred by patients. Also, the overall paradigm of use of the ophthalmic stimulator100depends on the duration of the constriction. Stimulators that constrict a pupil for a month or longer can be deployed in the offices of ophthalmologists, and patients can schedule regular visits for re-constriction treatments on a monthly basis. Stimulators that constrict the pupil for a day or longer could be tabletop systems that the individual patients buy, or lease, and they self-administer the treatment, for example, as part of a daily routine. Finally, stimulators that constrict the pupil for an hour, or for a few hours, can be mobile systems which the patient can carry with themselves and apply the treatment on demand. Obviously, stimulators operated by untrained patients have to have much more robust safety, monitoring and control systems to prevent undesirable medical outcomes. In sum, embodiments that constrict the pupil for different time intervals can offer very different medical outcomes, may be operated by very different personnel, and may need very different safety, monitoring and control systems.

FIG. 11Aillustrates embodiments of a method300, related for the preceding description, for temporarily constricting a pupil13of an eye by an ophthalmic stimulator100. The method300includes the following steps:generating310an irradiation control signal by an irradiation control system110;generating320an irradiation200by an irradiation source120, coupled to the irradiation control system110;receiving330the irradiation200, and delivering332a patterned irradiation200pto an iris11of the eye with an irradiation delivery system130; andcontrolling340at least one of the irradiation source120and the irradiation delivery system130by the irradiation control signal of the irradiation control system110so that the patterned irradiation is causing a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In embodiments, the generating320the irradiation200can include generating a flat beam, an electromagnetic irradiation, a LED light, a narrow-band light, a broad-band light, an infrared beam, an incoherent light, a radio-frequency beam, or a sound by the irradiation source120. Another class of irradiation sources120can include a coherent light source, a laser beam, a continuous wave laser beam, or a pulsed laser beam. Marked differences between the preceding incoherent irradiation sources and the just-listed coherent and laser sources will be discussed below.

The delivering332of the patterned irradiation200pcan include patterning the irradiation200by at least one of a pattern generator112e, an optical beam shaper132, a patterning optics, a beam profiler, a beam scanner134, and a digitally controlled irradiation optics.

In embodiments, the causing the temporary constriction of the pupil can include increasing a temperature of a treatment region of the iris to a range of 45-60 degrees Celsius. In some embodiments, the temperature of the treatment region of the iris can be raised into a range of 50-55 degrees Celsius.

FIG. 10illustrates, that in some embodiments of the method300, the irradiation control system110can include an imaging system114, in some cases with a corresponding imaging block112bin the irradiation controller112, and a user interface118, in some cases with a corresponding user interface block112fin the irradiation controller112. In these embodiments, the generating310of the irradiation control signal can include generating an image of the iris11of the eye with the imaging system114for a user, receiving an image-based input from the user through the user interface118, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pin accordance with the received input. In embodiments, the patterned irradiation200pcan impact the iris in a ring pattern210; and the image-based input can be an inner radius Rp (inner) and an outer radius Rp (outer) of the ring pattern210, selected by the user.

In some embodiments of the method300, the irradiation control system110can include an imaging system114, and an image processor114ip, in some cases implemented in the imaging block112bof the irradiation controller112. The generating310of the irradiation control signal can include generating an image of the iris of the eye with the imaging system114for the image processor114ip; processing the image of the iris and generating an image-based input by the image processor114ip; receiving the image-based input from the image processor114ip; and generating310the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pin accordance with the received image-based input. In some designs, the patterned irradiation200pcan impact the iris11in a ring pattern210; and the image-based input can be an inner radius Rp (inner) and an outer radius Rp (outer) of the ring pattern.

In some embodiments of the method300, the irradiation control system110can include an alignment system135, in some cases with its alignment block112cin the irradiation controller112; and the generating310of the irradiation control signal can include processing alignment data with the alignment system135, and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pto the iris in a pattern210aligned with the pupil13of the iris11.

In some embodiments of the method300, the processing alignment data can include generating an image of the iris with an imaging system114, and overlaying an alignment pattern138on the image, in some cases with the alignment block112c, or with the image processor114ip; and the generating310the irradiation control signal can include generating a misalignment warning signal, or generating an alignment-guidance signal.

In some embodiments, the irradiation control system110can include a memory block112d; and the generating the irradiation control signal310can include recalling stored data from the memory block112d, representing at least one of an irradiation pattern210and patient data; and generating310the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pto the iris11in accordance with the recalled stored data. In some designs, the irradiation control system can include the pattern generator112e; and the generating310of the irradiation control signal can include generating the irradiation pattern210; and generating the irradiation control signal to control the irradiation delivery system130to deliver the patterned irradiation200pwith the generated irradiation pattern210.

Some embodiments of the method300can include acquiring and analyzing patient data; selecting a treatment region based on the analyzing of the patient data; and delivering the patterned irradiation200pto the selected treatment region. A notable embodiment of this step is the ophthalmologist analyzing patient data and deciding whether the treatment radiation shall be applied to the radial dilator muscles30, or to the circular sphincter muscles40. This analysis and decision can involve selecting the appropriate treatment parameters among the large number of treatment parameters described previously.

In some cases, the selecting the treatment region can include selecting a ring pattern210rwith an inner radius Rp(inner) larger than R(sphincter), a radius of a region of the circular sphincter muscles40.

In some cases, the selecting the treatment region can include selecting a ring pattern210rwith an outer radius Rp(outer) smaller than R(sphincter), the radius of a region of the circular sphincter muscles40.

Some embodiments of the method300can include controlling the irradiation source120, or the irradiation delivery system130, or both, so that the patterned irradiation200pis causing a temporary constriction of the pupil of the eye that includes an at least 5% reduction of a radius of the pupil that lasts less than one hour.

In some cases, the temporary constriction of the pupil can last between one hour and one day. In some cases, the temporary constriction of the pupil can last between one day and one week; in some cases between one week and one month; in some cases between one month and three months; and in some cases between three months and one year. The medical, patient, implementation, and safety differences between embodiments involving temporary constrictions of different duration have been discussed earlier.

The ophthalmic stimulators100described up to now shared a common trait: they caused a temporary constriction of the pupil.

FIG. 5Billustrates a distinct class of permanent ophthalmic stimulators100′ that can cause a long-term, or even a permanent constriction of the pupil. These ophthalmic stimulators100′ share some of the major engineering elements with the temporary constriction stimulators100, but have different medical modes of action, different irradiation sources, and stronger safety systems, among others.

In some embodiments, an ophthalmic stimulator100′ for constricting a pupil of an eye can include an irradiation control system110′, to generate an irradiation control signal; an irradiation source120′, coupled to the irradiation control system110′, to generate an irradiation200′; and an irradiation delivery system130′, coupled to the irradiation control system110′, to receive the irradiation200′ from the irradiation source120′, and to deliver a patterned irradiation200p′ to the iris11of the eye1; wherein the irradiation control system110′ controls the irradiation source120′, or the irradiation delivery system130′, or both, with the irradiation control signal so that the patterned irradiation200p′ causes a long-term constriction of the pupil of the eye.

In a class of the ophthalmic stimulator100′, the irradiation source120′ can include an incoherent light source, such as a lamp, a LED, an infrared light source, a radiofrequency source, an electromagnetic source and a sound source. In another class, the irradiation source120′ can include a coherent light source, such as laser, a pulsed laser and a continuous wave laser. There are substantial differences between irradiation sources that employ incoherent light sources and those that employ coherent light sources, as discussed above.

In some embodiments, the irradiation delivery system130′ can include an optical beam shaper and a patterning optics.

In some embodiments, the ophthalmic stimulator100′ can be configured to increase a temperature of a treatment region of the iris to a range of 50-80 degrees Celsius. In some embodiments, the ophthalmic stimulator100′ can be configured to increase a temperature of the treatment region of the iris to a range of 55-70 degrees Celsius.

Some embodiments of the ophthalmic stimulator100′ can cause a long-term constriction of the pupil that lasts longer than a year. In some cases, the ophthalmic stimulator100′ can be designed to cause an irreversible change in the iris of the eye. This long-term, or permanent, change can be a change of the length, or spatial extent, of the treated muscle tissue. In other cases, it can be a reduced, or enhanced, elasticity, or flexibility. In some cases, it can be an altered stiffness. In some cases, it can be an altered reactivity to stimuli.

The ophthalmic stimulator100′ achieves the long-term reduction of constriction of the pupil by applying the irradiation200′ with treatment parameters critically different from the ones used by the temporary stimulator100. The critical difference can be one of many factors that cause permanent, or long-term constriction of the pupil, including the followings. Beams with wavelength short enough to cause permanent change. Beams with intensity per area high enough to cause long-term change. Beams with total deposited energy high enough to cause permanent change. Beams with treatment times long enough to cause permanent change. Beams with beam pulses long enough, and frequencies high enough to cause permanent change. Which specific parameters are sufficient to make the change permanent is patient specific and is selected by the surgeon.

In some embodiments, the irradiation control system110′ can include an imaging system114′ and a user interface118′. In these embodiments, the irradiation control system110′ can, generate the irradiation control signal by generating an image of the iris of the eye with the imaging system114′ for a user, receiving an image-based input from the user through the user interface118′, and generating the irradiation control signal to control the irradiation delivery system130′ to deliver the patterned irradiation200p′ in accordance with the received input.

Some of the engineering details of the permanent ophthalmic stimulator100′ are analogous to that of the temporary ophthalmic stimulator100′. To contain the length of this document, some of these details of the stimulator100′ will not be provided with their own figures, but the corresponding figures in the description of the stimulator100will be referenced, with the understanding that those need to be modified to cause a long term, not temporary constriction of the pupil.

In some embodiments of the ophthalmic stimulator100′, the irradiation control system110′ can include an alignment system135′; and the irradiation control system110′ can generate the irradiation control signal by processing alignment data with the alignment system135′, and generating the irradiation control signal to control the irradiation delivery system130′ to deliver the patterned irradiation200p′ to the iris in a pattern210, aligned with a pupil13of the iris11.

FIG. 11Billustrates a related method300′ for causing a long-term constriction of a pupil of an eye by the ophthalmic stimulator100′. The method300′ can include the following steps:generating310′ an irradiation control signal by an irradiation control system110′;generating320′ an irradiation by an irradiation source120′, coupled to the irradiation control system110′;receiving330′ the irradiation and delivering332′ a patterned irradiation to an iris of the eye with an irradiation delivery system130′; andcontrolling340′ at least one of the irradiation source120′ and the irradiation delivery system130′ by the irradiation control signal of the irradiation control system110′ so that the patterned irradiation causes a long-term constriction of the pupil of the eye.

In the method300′, the causing the long-term constriction of the pupil can include increasing a temperature of a treatment region of the his to a range of 50-80 degrees Celsius. In some cases, the method300′ can include increasing a temperature of the treatment region of the iris to a range of 55-70 degrees Celsius. While these ranges have some overlap with temperature ranges described in relation to the temporary stimulator100, for a particular patient the temperature range where the constriction is temporary can be quite well separated from the temperature range, where the constriction is permanent. For example, for a particular patient, temperatures in the range of 50-55 C may constrict the pupil for a day or less; temperatures in the 55-60 C range may cause the pupil to constrict for a time between a week and a month, temperatures in the 60-65 C range can cause the pupil to constrict for a time between a month and a year, and temperatures in the 65-70 C range may cause the pupil to constrict for a time longer than a year. These long-term changes can very well be associated with an irreversible change in the iris of the eye.

As before, in some embodiments of the method300′ the irradiation control system110′ can include an imaging system114and a user interlace118; and the generating the irradiation control signal can include generating an image of the iris of the eye with the imaging system114for a user, receiving an image-based input from the user through the user interface118, and generating the irradiation control signal to control the irradiation delivery system130′ to deliver the patterned irradiation200p′ in accordance with the received input.

In some embodiments of the method300′, the irradiation control system110′ can include an alignment system135; and the generating the irradiation control signal can include processing alignment data with the alignment system135, and generating the irradiation control signal to control the irradiation delivery system130′ to deliver the patterned irradiation200p′ to the iris in a pattern210aligned with a pupil of the iris.

As discussed, the ophthalmologist operating the stimulator100′ can analyze several factors when practicing the method300′. The analysis can include the determination what treatment parameters to use to achieve a long-term or permanent constriction change, to go beyond the previously described temporal changes. The analysis can also be focused at which treatment regions to irradiate. As discussed before, some vision-improvement goals can be better achieved by heat-treating the radial dilator muscles30, others by heat-treating the circular sphincter muscles40.

Both of these analyses can involve acquiring and analyzing patient data. In a typical example, a patient may have used the temporary ophthalmic stimulator100by practicing the method300repeatedly and for an extended period, and may have grown comfortable with its effect to the degree that she/he decided to make the constriction of the pupil permanent. During these preceding temporary treatments, the irradiation controller110of the stimulator100, or its operator may have acquired and collected a substantial amount of data about the particular patient. An ophthalmologist, who is planning administering a higher energy irradiation by practicing the method300′ with a permanent ophthalmic stimulator100′ to permanently change the constriction of the pupil, may evaluate and analyze the data that was collected during the previous, repeated temporary constrictions of the pupil of this particular patient. This analysis can be followed by selecting a treatment region based on the analyzing of the patient data; and delivering the patterned irradiation200p′ to the selected treatment region to cause the long-term constriction of the pupil.

FIG. 7Aillustrates that some embodiments of the ophthalmic stimulator100may include an irradiation control system110, to generate an irradiation control signal; a light source120, coupled to the irradiation control system110, to generate a light beam200; and a beam-shaping optics132, coupled to the irradiation control system110, to receive the light beam200from the light source120, and to deliver a light ring200rto an iris11of the eye in a ring pattern210r. In embodiments, the irradiation control system110can control the light source120, or the beam-shaping optics132, or both, with the irradiation control signal so that the light ring200rcauses a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil. The beam-shaping optics can also include an objective133, to direct the light ring200ptowards the iris of the eye, to provide additional control.

Embodiments of the here-described ophthalmic stimulator100can be analogous, or equivalent to the embodiments described in relation to the stimulator100in relation toFIGS. 5A-Band6A-D. In particular, the embodiments of the irradiation source120can also serve as the light source120here. For example, the light source can be an infrared light, source. Also, the beam-shaping optics132can be an embodiment of the irradiation delivery system130.

FIG. 7Billustrates that the beam-shaping optics132can include a proximal axicon lens140, positioned with its base-plane oriented toward the light source120, to transform the received light beam200into the light ring200r.

Here it is recalled that an axicon lens is a glass cone with a circle as its base. An axicon lens can be also visualized as an isosceles triangle, rotated around its axis of symmetry. Direct ray tracing establishes that axicon lenses transform a regular, full light beam into a light ring200r. Generating the light ring200r“passively”, without any scanners, or other digitally controlled active optics with moving parts, makes an axicon lens a very useful, simple, and reliable implementation of the beam-shaping optics132for the purposes of the stimulator100.

However, it is also noted that the radius r(ring) of the light ring200rincreases with the distance d(target) from the axicon lens140. Therefore, if the patient moves her/his head along the optical axis, doing so changes the radius r(ring) of the light ring200rand can have undesirable medical effect.

FIG. 7Cillustrates an embodiment of the beam-shaping optics132that resolves this problem. This embodiment includes the proximal axiom lens140-1, with its base-plane oriented towards the light source120. It further includes a second, distal, “complementary” collimating axicon lens140-2, that is co-axial with the proximal axicon lens140-1, positioned with its cone-tip oriented toward a cone-tip of the proximal axiom lens140-1, to collimate the light ring with the increasing radius into a light ring with a constant radius, independent of the distance d (target).

Embodiments with such a complementary axicon lens pair140-1and140-2can further include a lens position actuator141, to adjust an axicon distance d(axicon) between the proximal axicon lens140-1and the distal axicon lens140-2. Changing the axicon distance d(axicon) can be used to adjust the radius r(ring) of the light ring210as part of the setting of the overall ring pattern210by the ophthalmic surgeon inFIGS. 12D-E.

Additional optical solutions may be needed to tune Rp(inner) independently from Rp(outer), to tune the radius of the ring independently from its width. Examples of such solutions include (a) a beam blocker to block out part of the light ring; (b) a deformable axicon lens140, capable of changing the angle of the cone of the axicon lens; and (c) a deformable mirror, in some cases a deformable conical mirror.

An important aspect of ophthalmic irradiation systems is to ensure that the patient's eye is aligned with the optical axis of the irradiation system. Previously, various alignment systems135have been already described. A particularly useful element of such alignment systems135can be a fixation light202, as mentioned. The surgeon may instruct the patient to stare, or fixate, on a centrally positioned fixation light. Such fixation lights202can be provided by a small bright LED, positioned centrally, projected into, or superimposed into the optical pathway.

FIG. 7Dshows that the beam-shaping optics132that uses an axicon lens140offers a particularly simple implementation of the fixation light202. In some embodiments, the tip of the cone of the axicon lens140may be flattened. Such flattened tip axiom lenses140do not redirect or refract the small central portion of the incoming light200, so that they propagate centrally and thus can act as the fixation light202. Such embodiments are attractive because the fixation light202is naturally centered with the beam-shaping optics132, without the need to introduce any additional structures to hold the fixation light in place that can at the same time block part of the light200, and without the need of centering the fixation light202by a finely adjustable system.

In the case when the treatment light200is an infrared light, the flattened tip can be covered by a luminescent material, a phosphor, an upconverting material, a higher harmonic generating material, a multi-photon induced fluorescence material, or any optical material or structure that converts the infrared light200into a visible light, needed as a fixation light202.

FIG. 7Eillustrates an embodiment of the beam-shaping optics132. The incoming light200can be guided through a pair of beam-expanding lenses: a diverging, lens142, followed by a collimating lens143. This142-143lens combination can expand the radius of the incoming beam200to the Rp(outer) outer radius, set or desired by the ophthalmic surgeon. The beam radius can be adjusted by adjusting the distance of the diverging lens142from the collimating lens143by an actuator. Next, the expanded beam can be directed at an adjustable beam stop144that can block out a central portion of the expanded beam so that the transmitted beam has an inner radius equaling Rp(inner) as set by the surgeon. The radius of the adjustable beam stop144can be adjusted by a number of known mechanical designs. Further, since the stopped beam carries an energy with it that can undesirably heat the beam-shaping optics132, a heat sink145can be employed, configured to absorb, or guide away the energy of the stopped beam. Many heat sinks are known, such as metallic ribs, and air-cooled systems. It is also possible to reflect the stopped beam out of the beam-shaping optics132and absorb it or release it peripherally. These solutions reduce the need for heat management greatly.

FIG. 7Fillustrates another embodiment of the beam-shaping optic132. This embodiment132can be configured to generate a light beam directly with a ring shape, without the need of an optics that would transform the generated light. In a typical embodiment, the light source200can include a ring of LEDs146-1,146-2, . . .146-N, collectively referenced as146-i, to generate light beamlets; and a ring-shaped diffuser147, to transform the light beamlets into a light beam with a well-distributed intensity profile to form the light ring200r. In some embodiments, there can be more than one ring of LEDs146-i. Activating a different number of LED rings can be one way to adjust the radius of the light ring200r. (Throughout this document, elements “x-1, x-2, . . . , x-N” will be sometimes collectively referenced as “x-i”, for brevity.)

Finally, the embodiments ofFIGS. 7B-Fcan be combined. One such combination was already mentioned. The embodiment based on the axicon-lens140, or140-1/140-2, may need additional optical elements to adjust the inner and outer radii Rp(inner) and Rp(outer) independently. In some cases, the beam stop144can be used to adjust the inner radius Rp(inner) of the light ring200rthat was generated by the axicon lens140.

FIG. 11Cillustrates a method302for temporarily constricting a pupil of an eye by an ophthalmic stimulator100. The method302can include the following steps:generating302aan irradiation control signal by an irradiation control system110;generating302ba light beam200by a light source120, coupled to the irradiation control system110;receiving302cthe light beam200, and delivering302da light ring200rto an iris of the eye with a beam-Shaping optics132; andcontrolling302eat least one of the light source120and the beam-shaping optics132by the irradiation control signal of the irradiation control system110so that the light ring200ris causing a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In some embodiments of the method302, the delivering302dthe light ring200rcan include transforming the received light beam200into the light ring200rby a proximal axicon lens140, positioned with its base-plane oriented toward the light source120, wherein the light ring200rhas an increasing radius r(ring) with increasing distance d(target) from the axicon lens140.

In some cases, the delivering302dthe light ring200rcan include collimating the light ring with the increasing radius into a light ring200rwith a constant radius by a distal collimating axicon lens140-2, co-axial with the proximal axicon lens140-1, positioned with its cone-tip oriented toward a cone-tip of the proximal axicon lens140-1. In these embodiments, the delivering the light ring can include adjusting an axicon distance d(axicon) between the proximal axicon lens140-1and the distal axicon lens140-2by a lens position actuator141, thereby adjusting the radius of the light ring, r(ring).

The method302can also include generating a fixation light202by selectively transmitting a small fraction of the received light beam200by a flattened cone-tip of the proximal axicon lens140-1. In embodiments where the light is an infrared light, the small, flattened tip of the axicon lens140-1can be covered by an optical material that can transform the infrared light into a visible light.

In some embodiments of the method302, the delivering302dthe light ring can include utilizing a beam stop144to generate the light ring200rby blocking a central portion of the received light beam200.

Finally, in some embodiments of the method302, the generating302ba light beam can include generating the light beam with a ring shape by the light source including a ring of LEDs146-i.

FIG. 8Aillustrates that embodiments of the ophthalmic stimulator100for temporarily constricting a pupil of an eye can include a digital beam controller110, to generate a digital beam-control signal; a light source120, coupled to the digital beam controller110, to generate a light beam200; and a digitally controlled beam modulator134, for example a beam scanner134, to receive the digital beam-control signal from the digital beam controller110, to receive the light beam from the light source120, and to modulate the received light beam into a modulated light, or modulated light200m, delivered to an iris of the eye. In embodiments, the digital beam controller110can control the light source120, the digitally controlled beam modulator134, or both, with the digital beam-control signal so that the modulated light200mcauses a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

As before, embodiments of the here-described ophthalmic stimulator100can be analogous, or equivalent to the embodiments described in relation to the ophthalmic stimulator100in relation toFIGS. 5A-B,6A-D, and7A-F. In particular, the embodiments of the irradiation control system110can be analogous, or equivalent, to the embodiments of the digital beam controller110, the irradiation source120can also serve as the light source120here, and the digitally controlled beam controller134can be an embodiment of the irradiation delivery system130.

In what follows, numerous examples of the digitally controlled beam modulator134will be described. To emphasize that all these are embodiments of the same block, they axe all labeled with134or as a variant of label134.

For example,FIG. 8Aillustrates a beam scanner134as an embodiment of the digitally controlled beam modulator134, to scan the received light beam200according to a pattern210on the iris. Embodiments described in relation toFIGS. 8A-B, andFIGS. 9A-Ecan be different from the embodiments described in relation toFIGS. 7A-Fin that the latter embodiments utilize dominantly “passive” optical elements, such as lenses and mirrors, and do not need elaborate digital control signals and moving parts, with the possible exception of the lens position actuator141. Also, the systems ofFIGS. 7A-Ftypically irradiate the pattern210simultaneously.

In contrast, the digitally controlled embodiments ofFIGS. 8A-B, andFIGS. 9A-Ecan involve active elements, where extensive digital control signals move or adjust a number of active optical elements. These embodiments typically irradiate the iris on a point-by-point basis, with the help of various types of scanners and optical arrays. As such, these digitally controlled embodiments can offer higher precision and control, at the same time, they can be more complex, raising issues of reliability, maintenance and costs, and the irradiation treatment can take longer. Also, the points of the pattern210are often irradiated sequentially, instead of simultaneously.

FIG. 8Billustrates one embodiment of the digitally controlled beam modulator134in a laser-based ophthalmic stimulator100. The light source120can be a laser source120L, emitting a laser beam200L. The digitally controlled beam modulator134can be an X-Y scanner134L, to scan the received laser beam200L as a scanned laser beam200sL according to a pattern on the iris. A large number of laser scanners are known that can scan the scanned laser beam200sL with a wide variety of complex patterns210.

FIG. 9Aillustrates the first of a set of reflection mode beam modulators134r. While the scanner embodiments inFIGS. 8A-Birradiate the iris in a pattern210sequentially, the embodiments ofFIGS. 9A-Ecan irradiate the pattern210either sequentially, or simultaneously. The embodiment ofFIG. 9Aincludes a reflective LCD array150with an addressable array of LCD pixels152. Switching the LCD pixels152on-off can control how much of an incoming light the LCD array reflects from through the LCD pixels.

FIG. 9Billustrates another embodiment of the reflection-mode beam modulator134rthat includes a deformable reflector160, with a substrate162; a mechanical actuator array164, positioned on the substrate162; and a deformable mirror166, positioned to be deformable by the mechanical actuator array164according to the digital beam-control signal.

FIG. 9Cillustrates yet another embodiment of a reflection-mode beam modulator134r. This is an acousto-optical modulator170that includes a set of acoustic piezo transducers172, to deform a deformable reflector174, according to the beam-control signal. This embodiment has similarities to the previous one inFIG. 9B. One of the differences is that the deformation is performed not by an array that can be controlled point-by-point, but in a global manner, where the transducers are operated to form patterns across the entire deformable reflector174simultaneously.

FIG. 9Dillustrates yet another embodiment of a reflection-mode beam modulator134r. This is a digital mirror device180that includes a substrate182; an array of mechanical actuators184-i, positioned on the substrate182; and an array of rotatable mirrors186-i, where the rotatable mirrors186-iare rotatable individually by the actuators184-iaccording to the beam-control signal. Such digital mirror arrays are well known in digital projectors, for example.

FIG. 9Eillustrates a different, transmission-mode beam modulator134t. This embodiment can include an addressable pixel array190of variable transparency pixels192-i. This embodiment190has design aspects analogous to the embodiment150inFIG. 9A, as it also builds on the principle of individual pixels changing their optical (reflective or transmissive) properties under electric, control, thereby modulating the beam on a pixel-by-pixel basis. As indicated earlier, the irradiation can be either sequential or in parallel, the latter type embodiments requiring much less moving parts and allowing shorter irradiation times.

FIGS. 17A-Dillustrate various patterns210the digitally controlled ophthalmic stimulators100can irradiate on the iris with the modulated beam200m. In embodiments, illustrated inFIG. 17A, the digitally controlled beam modulator134can be controlled by the beam controller110to modulate the received light beam200into a modulated light200m, so that it irradiates a pattern210that is a ring, or multiple rings.FIG. 17Billustrates a pattern210that is a segmented ring.FIG. 17Cillustrates a pattern210that includes radial spokes. Finally,FIG. 17Dillustrates a pattern that is a combination of ring segments and spokes.

FIG. 11Dillustrates a method304that is related to operating the digitally controlled ophthalmic stimulators100. The method304can include the following steps:generating304aa digital beam-control signal by a digital beam controller110;generating304ba light beam200by a light source120, coupled to the digital beam controller110;receiving304cthe light beam200, modulating304dthe light beam200into a modulated light200m, and delivering304ethe modulated light200mto an iris of the eye, with a digitally controlled beam modulator134; andcontrolling304fthe light source110, the digitally controlled beam modulator134, or both, by the digital beam-control signal of the digital beam controller110so that the modulated light200mis causing a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In embodiments, the modulating304dcan include scanning the received light beam on the iris according to a pattern by a beam scanner1341in other embodiments, the modulating304dcan include modulating the light by a reflection-mode beam modulator134r. The reflection-mode beam modulator134rcan be a reflective LCD array150, with an addressable array of LCD pixels, a deformable reflector160, an acousto-optical modulator170, and a digital mirror device180. In some embodiments of the method, the modulating304dcan include modulating the light by a transmission-mode beam modulator134t.

Finally, the modulating304dcan include modulating the received light beam into the modulated light200mwith the pattern being one of a ring, multiple rings, a segmented ring, a pattern of radial spokes, and a combination of ring segments and spokes.

FIG. 15illustrates other embodiments of an ophthalmic stimulator100for temporarily constricting a pupil of an eye that includes an irradiation control system110, having a feedback system, to generate an irradiation control signal using a feedback of the feedback system; an irradiation source120, coupled to the irradiation control system110, to generate an irradiation; and an irradiation delivery system130, coupled to the irradiation control system110, to receive the irradiation200from the irradiation source120, and to direct a patterned irradiation200pin a pattern to a treatment region of an iris of the eye, guided by the feedback-based irradiation control signal; wherein the irradiation control system110controls at least one of the irradiation source120and the irradiation delivery system130with the feedback-based irradiation control signal so that the patterned irradiation200pcauses a temporary constriction of the pupil, without causing a permanent constriction of the pupil. As before, the here-described embodiments can be analogous to the ones described in relation toFIGS. 5A-B,FIGS. 6A-DFIGS. 7A-F, andFIGS. 8A-B, and analogously labeled elements can serve analogous functions.

In what follows, various embodiments and blocks of the feedback system116will be described. These embodiments and blocks typically include a hardware block, such as an imaging system, or a temperature sensor. They are coupled to the irradiation controller112, which processes their feedback and generates irradiation control signals, to be transmitted to the irradiation source120and to the irradiation delivery system130. As discussed in relation toFIG. 10, the irradiation controller112can include corresponding, blocks that are dedicated to receive the feedback. For example, the irradiation controller112can include the dedicated feedback block112ato receive the feedback from an embodiment of the feedback system116. These receiving blocks can be implemented in hardware, such as an application specific integrated circuit ASIC; or they can be implemented in a software form, such as a piece of code or application, implemented in the processor113of the irradiation controller112; or in a shared processor, or input/output controller. In yet other embodiments, the feedback can be coupled straight into the central processor113, whose code can process the feedback directly. A particularly simple implementation can be a simple “stop” feedback signal, triggered by a security concern, which can be directly executed by the processor by shutting down the irradiation source120with a control signal, without the need of any intermediate processing.

In some embodiments, the feedback system116can include at least one of a pupillometer116aand an imaging system114, to sense a diameter of the pupil, and to generate a feedback according to the sensed pupil diameter. As discussed just now, this feedback can be received and processed either by a dedicated feedback block112athat is implemented inside the irradiation controller112, or can be received by the processor113of the irradiation controller112itself. In some embodiments, the pupillometer116acan be coupled to the irradiation controller112directly, in others, through a user interface118-1a. Similarly, the imaging system114can be coupled to the irradiation controller112directly, or through a user interface118-2.

FIGS. 16A-Eillustrate methods, or processes,510-550that operate in relation to the embodiments116a-fof the feedback system116. In general, the methods, or processes,510-550can include the following steps:generating a feedback-based irradiation control signal by an irradiation control system110, using a feedback of a feedback system of the irradiation control system;generating an irradiation200by an irradiation source120, coupled to the irradiation control system;receiving the irradiation200and directing a patterned irradiation200pto a treatment region of an iris of the eye with an irradiation delivery system130, guided by the feedback-based irradiation-control signal; andcontrolling at least one of the irradiation source120and the irradiation delivery system130with the feedback-based irradiation control signal of the irradiation control system110so that the patterned irradiation200pcauses a temporary constriction of the pupil, without causing a permanent constriction of the pupil.

The description continues with details of the processes, or methods,510-550.FIG. 16Aillustrates that in a representative case, the feedback can be generated through the following sequence, method, or process510. A short time after starting to apply the patterned irradiation200pto the iris11according to the pattern210, in step511, the pupillometer116a, or the imaging system114, can sense that “Pupil radius is large relative to a reference or target”, or “Target radius not reached”. This can be followed by a step512, generating the feedback, or feedback signal: “Carry on irradiation”, as indicated by the eye and steps on the left side ofFIG. 16A. Here and in what follows, each “step x of generating feedback signal” may also be referred to with the shorter form of “feedback signal x”, for brevity. Also, the feedback signal can include not only the command to continue or to stop the irradiation, but it can also include the sensed information as well, in the present example, the step512of generating a feedback signal can include sending the feedback signal “Target radius not reached. Carry on.”

With the passing of time, the irradiation increases the temperature of a portion of the iris11, as indicated by the denser dot-filling of the pattern210on the right. The increased temperature induces the constriction of the pupil13, as indicated by the eye1having a smaller pupil13on the right ofFIG. 16A. In step513, the pupillometer116a, or the imaging system114, can sense that “Pupil radius is sufficiently close to the reference”, or “Target pupil radius sensed”, This can be followed by the generation of the feedback in step514: “Power down irradiation”, or “Target radius reached. Power down”, This feedback, or feedback signal514can be transmitted by the feedback system116to the irradiation controller112. In response, the irradiation control system110can send a corresponding feedback-based irradiation control signal to the irradiation source120to power down. The top graph ofFIG. 16Aillustrates that the feedback-induced irradiation control signal514causes the powering down of the irradiation after the receiving of the feedback signal514.

It is mentioned here that pupillometers reached a high level of sophistication and can provide a variety of useful, actionable information. For a review of the field, see Olson D, Stutzman S, Saju C, Wilson M, Zhao, W. Aiyagari V. Interrater of Pupillary Assessments. Neuroctit Care, Published online: 17 Sep. 2015. These pupillometers can assess pupil size, and shape with very high accuracy and reproducibility. In addition, such devices can measure parameters such as onset and peak constriction, constriction and dilation velocity, and latency using various light stimuli, both before and after treatment to assess effects that may not be apparent simply based on pupil diameter.

FIG. 15illustrates that in some embodiments, the feedback system116can include a pupillometer116a, and at least one of an infrared sensor or camera116bto sense a temperature of the treatment region, and to generate a feedback according to the sensed temperature. As before, the infrared camera116bcan be coupled to the irradiation controller112directly, or via a user interface118-1b.

FIG. 16Billustrates the corresponding process520, or method520, or sequence of operation of this infrared sensor/camera116b. At an early time during the irradiation, in a step521, the infrared sensor/camera116bcan sense “Temperature low relative to a reference”, or simply “Low temperature”. In a typical case, a temperature T sensed to be less than 45 C can be classified as “low temperature”. This can prompt generating the feedback in step522: “Carry on irradiation”. Visibly this feedback leads to the maintaining the power of the irradiation, as indicated by the graph on top ofFIG. 16B.

With the progression of the irradiation time, the target region, irradiated according to the pattern210, starts warming up. This is indicated by the dotting of the pattern210getting denser. After some time, in step523, the infrared (thermal) sensor/camera116bcan sense “a medium temperature relative to the reference”, or simply “medium temperature”. In a typical example, this can be a temperature in the 45 C-55 C range. In response, a feedback signal can be generated in step524, sent from the feedback system116to the irradiation controller112: “Start power down the irradiation”, or “Medium temperature. Power down”. As indicated, the irradiation control system110can generate a feedback-based irradiation control signal to the irradiation source120, which is response can start powering down the power of the irradiation gradually, as indicated by the dashed line in the top graph.

In some embodiments, the settings and thresholds can be chosen differently. In such cases, the IR camera116bcan wait until it senses a “high temperature relative to the reference” in step525, such as the IR sensor/camera116bsenses the temperature T that exceeds 55 C. Such a sensing by the IR sensor/camera116bcan prompt the generation of the feedback “Stop the irradiation” in step526, to be sent to the irradiation controller112. Analogously to earlier steps of the process, the irradiation control system110can generate a feedback-based irradiation control signal for the irradiation source120to discontinue the irradiation with a hard stop, as indicated by the solid line in the top graph ofFIG. 16B.

One such scenario can be associated with an irregular, or unexpected progress of the irradiation, when, for whatever reason, the iris heats faster than expected. This can be a consequence of an unexpected patient response, or an incorrect calibration of the irradiation's treatment parameters. Once the IR camera116bsenses that the temperature rose to a value high relative to a reference, such as to above 55 C, for safety reasons the feedback-based irradiation control signal can bring the irradiation power to zero via a hard stop.

FIG. 15illustrates that the feedback system116can further include at least one of an alignment system116c, an eye tracker116d, a wavefront sensor116e, an iris scanner116f, and an imaging system114. The alignment system116ccan be related to, combined with, or analogous to any embodiment of the alignment system135, described earlier, for example in relation toFIGS. 12A-C. Any of these feedback implementations can sense an alignment of one of the iris and the pupil relative to the irradiation delivery system130, as discussed earlier.

FIG. 16Cillustrates a mode of operation, or method530for such alignment-related feedback implementations. WhileFIG. 16Cspecifically refers to the eye tracker feedback116d, an analogous process can be practiced with the analogous feedback alignment system1160, iris scanner116f, or imaging system114. In a step531, the eye tracker116dcan “sense alignment” between the iris11, the pupil13and the irradiation delivery system130. Sensing alignment in step531can lead to generating, in step532, the feedback “Eye aligned. Carry on irradiation”, which results in the irradiation source120maintaining the power of the irradiation, as shown by the top graph ofFIG. 16C.

A central concern for the efficacy and safety of the irradiation treatment is that the eye1, iris11, and pupil13remain aligned with the irradiation delivery system throughout the irradiation. However, there is a possibility that the eye, iris, and pupil become misaligned. This can be caused by an involuntary eye movement by the patient, a reaction to a sensation of discomfort or pain by the patient, or a problem developing with the patient interface137, such as the breaking of a vacuum suction, among others. Also, misalignment can be the natural consequence of the ophthalmologist not using a firm eye-fixation method, such as physically restraining the eyeball only by hand, or by pressure with a forceps. In these cases, the gaze of the eye can naturally drift away to a degree that it becomes misaligned with the pattern210and the irradiation delivery system130.

FIG. 16Cillustrates that the eye can get misaligned to a degree that the patterned irradiation200pmay reach the edge of the pupil13. In such cases, the irradiation may start hitting the retina, a much more light-sensitive tissue. This raises a higher level of safety concerns. Embodiments of the feedback system116can handle such developments by the eye tracker116d“sensing a misalignment”, or “misalignment sensed” in step533. This can lead to a generation of a feedback signal “Eye misaligned! Safety Stop!” in step534. The irradiation control system110can generate a corresponding feedback-based irradiation control signal for the irradiation source120, which in response can execute a hard stop of the irradiation, as shown by the tap graph. The step534can be accompanied with a signal to an operator, or user: “Realign at least one of the irradiation delivery system, the iris, and the pupil.”

FIG. 16Dillustrates a process, or method540that flexibly manages naturally occurring misalignments. Steps541-544are analogous to steps531-534, in relation to the eye losing alignment with the irradiation delivery system120. However, the process540can dynamically manage if the misalignment developed not as a safety-threatening problem that required an irreversible hard stop, but as a consequence of a naturally shifting eye, which can be followed by the eye realigning with the irradiation delivery system130. A typical situation can be when the eye is not docked to the ophthalmic stimulator100in a fixed manner with a patient interface137but is left free. In such embodiments, the patient may be fixating on a fixation light, but her gaze can be distracted for a short period by natural processes such as a mild discomfort or blinking, after which the patient re-fixates on the fixation light, thus realigning the eye with the irradiation delivery system130. Such scenarios can be managed by the process540via step545, where the eye tracker116dcan “sense a realignment”, followed by step546, where a feedback signal is generated confirming “Eye realigned. Resume irradiation”. The irradiation control system110can then generate a feedback-based irradiation control signal that makes the irradiation source120to resume the irradiation.

In some cases, the “stop irradiation544—resume irradiation546” sequence can be repeated several times. A notable embodiment can be a hand-held, mobile ophthalmic stimulator100m, described below in relation toFIGS. 13A-C, where the eye can fall out from alignment relative to the irradiation delivery system130mrepeatedly, followed by the eye getting realigned with the irradiation delivery system130mof the mobile ophthalmic stimulator100mrepeatedly, since the eyes of the patient are not held firmly in place by an immobilizing system.

Finally,FIG. 16Eillustrates yet another feedback method or process550. In this method, or process,550, the feedback system116can include at least one of the pupillometer116aand the imaging system114, to sense at least one of a pupil characteristic or an iris characteristic, and to generate a feedback according to the sensed characteristic.

In step551, the imaging system114may sense that the pupil13has a regular shape. In response, it may generate the feedback signal: “Progress regular. Carry on,” in step552. However, in some cases, in step553the imaging system114may sense, or image, that an “irregular pupil shape” is emerging as a consequence of the irradiation. In other embodiments, the imaging system114may sense, or image, that at least one of a pupil characteristic and an iris characteristic is becoming unacceptable relative to a reference as a consequence of the irradiation. These situations can arise, when the pupil does not react according to medical expectations to the irradiation. A simple example can be that the pupil starts to lose its circular shape, and evolve toward an elongated, or irregular shape. A non-circular pupil can be perceived as an undesirable treatment outcome and therefore necessitates safety protocols within the feedback system116to manage or to counter-act it.

A corresponding step554can include the generation of a “modify irradiation pattern” feedback signal, possibly preceded by a “safety stop” feedback signal554. The process550can be continued by the pattern generator112eactually modifying the irradiation pattern210in step555, followed by generating a “Pattern modified. Resume irradiation,” feedback556.

FIG. 16Eillustrates a characteristic example, where the pupil13starts to evolve from circular towards an elongated oval shape because of the irradiation. This undesirable process can be detected by the imaging system114in step553. In response to the corresponding, feedback-based irradiation control signal, the irradiation delivery system130may change the irradiation pattern210from a circle into an oval that is oriented 90 degree opposite to the pupil's oval. Such a modified irradiation pattern210pmay be successful to counter-act the development of the undesirable oval pupil.

Irradiation delivery systems130and134that are digitally controlled and active systems, like the beam modulators and beam scanners134ofFIGS. 8A-B, and the digitally controlled beam modulators134ofFIGS. 9A-E, can modify the irradiation patterns210relatively easily. The beam-shaping optics132of the optical systems inFIGS. 7A-Fwith little or no digital, point-by-point control can also have some such functionalities. A simple embodiment can be the beam-shaping optics132including deformable mirrors. Actuators along the periphery, or along the perimeter of such deformable mirrors can elongate a circular pattern210into an oval pattern210by a simple cylindrical deformation of the mirror. Other low order wavefront deformations can be also introduced by deforming such a deformable mirror. Such deformable mirrors were also described earlier as systems that can enable the independent tuning of the Rp(inner) and the Rp(outer) radii of the pattern210, and also in relation toFIGS. 9B-C.

Further embodiments can include further methods or processes, where the feedback system116includes the wavefront sensor116e, or the iris scanner116f, and the method includes generating a feedback based on a condition of at least one of the iris and the pupil, sensed by the wavefront sensor116e, or the iris scanner116f.

In yet other embodiments, the feedback system116can be configured to carry out a test and then generate a feedback signal based on the test. In a simple embodiment, during the treatment, a short light pulse can be sent to the eye, and the reaction time, or the reaction radius-change of the pupil can be measured and assessed by the feedback system116. A feedback-based irradiation control signal can then be generated based on this assessment.

In some cases, the feedback by the feedback system116can serve only a diagnostic purpose, not necessarily leading to the generation of a feedback signal to impact the irradiation. This feedback can be a visual feedback for the operator, or user of the ophthalmic stimulator100via a user interface118-1ato118-1for118-2. The user may, in response to this visual feedback, then modify the treatment. The feedback can be a wide variety of information, from pupil size to sensed temperature, to a pupil shape or alignment.

FIGS. 13A-Cillustrate a class of mobile implementations of the ophthalmic stimulator100m, indicated by the label “m”. Some of these embodiments will be referred to as a mobile ophthalmic stimulator100m.FIG. 13Aillustrates that this class of embodiments can include a mobile irradiation control system110m, to generate an irradiation control signal; an irradiation source120m, coupled to the mobile irradiation control system110m, to generate an irradiation200; and an irradiation delivery system130m, coupled to the mobile irradiation control system110m, to receive the irradiation from the mobile irradiation source120m, and to deliver a patterned irradiation200pto an iris of the eye. In embodiments, the mobile irradiation control system110mcan control at least one of the irradiation source120mand the irradiation delivery system130mwith the irradiation control signal so that the patterned irradiation200pcauses a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

In embodiments, the mobile irradiation control system110mcan include a mobile communication platform111m, or simply mobile platform111mthat can be a mobile telephone111m, a mobile communication device, and a mobile tablet; and a mobile irradiation controller110cm, installed on the mobile communication platform111m, to generate the irradiation control signal. In a characteristic embodiment, the mobile irradiation controller110cmcan be a software application, downloaded from a provider over the internet and installed or implemented on a mobile phone111m. In other embodiments, the mobile irradiation controller110cmcan be a dedicated processor, for example, in, a separate box that can be installed on the mobile communication platform111mby plugging it into the mobile communication platform111mthrough a USB port, headphone jack, or charging port. For brevity, the mobile irradiation controller110cmis sometimes simply referred to as irradiation controller110cm, where the “m” label indicates the mobile nature of this irradiation controller. The mobile phone111mitself then can be attached to the remainder of the mobile ophthalmic stimulator100m, which can be a table-top system that includes the mobile irradiation source120m, and the mobile irradiation delivery system130m, installed either in an office of an ophthalmologists, or in a user's residence, in some embodiments, the mobile phone111mcan be coupled to the rest of the ophthalmic stimulator100mby an electric connector or docking station. In other embodiments, the coupling and communication between the mobile phone111mand the rest of the ophthalmic stimulator100mcan be a wireless communication, for example through a Bluetooth, or a wi-fi system or channel.

The mobile communication platform111mcan include a memory, to store the above mentioned software implementation of the mobile irradiation controller110cm; a processor, to execute the stored software implementation of the mobile irradiation controller110cm; and a user interface, to receive input from a user in relation to an operation of the memory and the processor.

Once the mobile platform111mor mobile phone111mis coupled to the rest of the mobile ophthalmic stimulator100ma calibration process can be carried out, so that the mobile irradiation control system110macquires information about the type and characteristics of the rest of the mobile ophthalmic stimulator100m. For example, information regarding the power and type of the light beam200generated by the irradiation source120m, and information regarding the type of signaling, communication and control protocols needed for the communication between the mobile platform111mand the rest of the mobile ophthalmic stimulator100m.

The irradiation delivery system110mcan include at least one of a pattern generator, an optical beam shaper, a patterning optics, a beam profiler, and a digitally controlled irradiation optics. As in the other related embodiments, the mobile ophthalmic stimulator100mcan be configured to increase a temperature of a treatment region of the iris to a range of 45-60 degrees Celsius.

The mobile irradiation control system110mcan include a mobile imaging system114m, such as a mobile camera114m, to generate the irradiation control signal by generating, an image of the iris of the eye by the mobile imaging system114m, receiving an image-based input, and generating the irradiation control signal to control at least one of the irradiation source120mand the irradiation delivery system130mto deliver the patterned irradiation according to the received image-based input.

In a characteristic example, the mobile irradiation control system110mcart include a mobile phone111mthat can be attached to the rest of the ophthalmic stimulator100mthat is installed in a medical office as a desktop office device. As such, the irradiation source120mand the irradiation delivery system130mcan themselves be a movable, light bench-top device that is mobile, but less mobile than the fully mobile platform111m, or mobile phone111m. Accordingly, in some embodiments they can be referred to as the mobile irradiation source120m, and the mobile irradiation delivery system130m.

The mobile camera114mof the mobile phone111mcan image the iris11and pupil13of a patient who is looking into the camera114m. The mobile irradiation controller110cm, implemented on the mobile phone111m, can display the image of the pupil on the screen of the mobile phone111m, and also electronically overlay a proposed irradiation pattern210. The irradiation control application can then invite the doctor, or user, to modify the pattern within some limits of safety, as the image-based input, such as to move the inner and the outer radii Rp(inner and Rp(outer), while making sure that the pattern210remains on the iris11. Once the modification input is received, possibly together with some treatment parameters, the irradiation control application on the mobile phone111mcan send an irradiation control signal to the irradiation source120mand the irradiation delivery system130mwirelessly with a Bluetooth channel. In response, the irradiation source120mand the irradiation delivery system130mcan generate and deliver the patterned irradiation200ponto the imaged iris11.

FIG. 13Aillustrates that in some embodiments, the mobile irradiation control system110mcan include an image processor114ipm, to receive the image of the iris from the imaging system114m, and to generate the image-based input based on a processing of the image of the iris. In some designs, this image processor114ipmcan determine the inner and outer radii Rp(inner) and Rp(outer) of the ring pattern210, as well as the treatment parameters. There can be hybrid systems, where the image processor114ipmperforms the above determinations, however, a user interface118of the mobile telephone111mstill prompts a surgeon or operator to approve the displayed choices of the imager processor114ipm, as a safety measure.

In some implementations, the image processor114ipmcan generate the image-based input by correlating an alignment pattern138with the generated image of the iris, in analogy to the alignment system135inFIG. 12C. Subsequently, the mobile irradiation control system110mcan be configured to generate the irradiation control signal according to the received image-based input that includes a misalignment-warning signal, an alignment-guidance signal, or an irradiation-stop signal, if a misalignment is detected. In a characteristic case, the mobile phone111mcan alert the ophthalmologist that a misalignment was detected, possibly also generating an alignment-guidance signal, such as which way to move the eye1, or the irradiation delivery system130to realign the eye and the irradiation delivery system130.

The ability of the mobile platform111mto communicate can play a very useful role in some implementations. In these designs, the mobile irradiation control system110mcan include an on-board communication application, to receive the image of the iris from the imaging system114m, to communicate the received image to a central station410having an image processor, and to receive the image-based input from image processor of the central station410.

FIGS. 13B-Cillustrate advanced embodiments, where not the mobile phone111mis attached to the rest of the ophthalmic stimulator100m, but the rest of the ophthalmic stimulator100m, is attached to the mobile phone111m, to create a fully mobile ophthalmic stimulator100m.

FIG. 13Billustrates a design of the mobile ophthalmic stimulator100m, wherein the irradiation source120mand the irradiation delivery system130mare part of a small, compact irradiation device120m/130m; and the mobile irradiation control system110mis coupled to the irradiation device120m/130mto send the irradiation control signal by at least one of an electronic coupling, an electric coupling, a wireless coupling, and an optical coupling.

In the shown example, the irradiation source120mand the irradiation delivery system130mare configured to be electrically coupled to, and mechanically attached to the mobile irradiation control system110m. For example, the irradiation device120m/130mcan be plugged into one of the ports of the mobile phone111m, such as into the USB port, or into the headphone jack, or the power charging port. In another example, the irradiation device120m/130mcan be attached to the mobile phone111mby a clip, mini-pliers, or pincer.

FIG. 13Cillustrates an example, in which the irradiation source120mis a light source of the mobile irradiation control system110m; and the irradiation delivery system130mis mechanically attached to the mobile irradiation control system110m, to receive a light, generated by the irradiation source120m. In a characteristic example, the flashlight of the mobile phone111mitself can be used as the irradiation source120m. The flashlight of the mobile phone111m, of course, needs to be calibrated to gain control over the power irradiated by its irradiation200, and possibly filtered or dampened. Nevertheless, using the imaging capabilities of the mobile phones111mand their flashlight can make the mobile ophthalmic stimulator100mmuch cheaper and compact, and therefore suitable for being carried by a patient as a personal accessory. This aspect can be very useful if irradiation treatments are utilized that cause a temporary constriction of the pupil that lasts less than a day, and thus a once-a-day application in the morning does not secure the pupil constriction for the entire day. Such treatments may need to be refreshed as the day goes on. A portable, personalized, mobile phone-based ophthalmic stimulator100mcan be the answer for the need for refreshing treatments during the day.

Obviously, safety is a high priority consideration for the mobile embodiments of the stimulator100mthat are not operated by trained ophthalmologists. Moreover, achieving and preserving alignment for the duration of the treatment also becomes an elevated challenge for mobile stimulator100m. Mobile stimulators100mcan address these concerns by practicing the method, or process540, illustrated inFIG. 16D. It is recalled here, that in step543, if the imaging system114, the alignment system116c, or the eye tracker116dsense a misalignment, then they can induce the generation of a feedback-based irradiation control signal that makes the irradiation source120mstop the irradiation200. Implementing this imaging-triggered “safety stop” process makes mobile stimulators100msafe, and minimizes undesirable retinal exposure.

Moreover, if the eye gets realigned, for example, because the user moves either the hand-held mobile phone111m, or moves her/his gaze, then the imaging system114, or its equivalents, can sense the realignment in step545, and the irradiation controller110mcan cause the restart the irradiation. These stop543restart545steps can be performed repeatedly, as, for example, the handheld mobile phone111mis moving in the patient's hand.

An interrupted, or multiply interrupted irradiation treatment may take longer to achieve the temperature rise required for the desired pupil constriction, and to administer the treatment for the time necessary for efficacy. Therefore, mobile stimulators100mcan include at least one of a thermal camera, an infrared camera and a thermal sensor116b, to track an amount of time a treatment region of the iris had a temperature in a predetermined range. In an example, the irradiation controller110may add up the multiply interrupted time-segments, when the treatment region of the iris was at the prescribed temperature, and ensure that the treatment region has been held at the prescribed temperature range for the time interval necessary to achieve the targeted pupil constriction. For example, the IR sensor116bcan track that the treated ring210rof the iris11remains at 55 Celsius for a prescribed time, such as for 20 seconds, or for 40 seconds, in order to achieve a pupil constriction that will last all day.

In some embodiments, the safety stop543restart.545steps can be also performed under the control of the central station410. In such embodiments, it can be the image processor of the central station410that senses the misalignment of the patterned irradiation relative to the iris or the pupil, as well as that senses the realignment prompting the generation of the restart command.

Finally, the central station410can perform monitoring functions over a series of treatments performed by the mobile ophthalmic stimulator100m. In some embodiments, the mobile stimulator100mcan be configured to take and send the image of the iris to the central station410for monitoring, to receive a monitoring-based control signal from the central station, and to generate the irradiation control signal in accordance with the received monitoring-based control signal. For example, the images, sent by the stimulator100m, can be analyzed by the central station410. This analysis can recognize that the treatment is inducing an undesirable effect in the retina over the term of several treatments. In such case, the central station may send out a monitoring-based control signal to the mobile stimulator100mto either prevent the user from administering further treatments, or to change a treatment parameter, such as to reduce a power or intensity of the patterned irradiation200p. Such central station-related systems are described next.

FIG. 14illustrates a networked system400of ophthalmic stimulators for temporarily constricting eye-pupils. The networked system400, or mobile network400, can include a set of mobile ophthalmic stimulators100m-1,100m-2,100m-N, collectively referred to as mobile ophthalmic stimulators100m-i, each mobile ophthalmic stimulator100m-iincluding a mobile irradiation control system110m-i, to generate an irradiation control signal; an irradiation source120m-i, coupled to the irradiation control system110m-i, to generate an irradiation; and an irradiation delivery system130m-i, coupled to the mobile irradiation control system110m-i, to receive the irradiation from the irradiation source120m-i, and to deliver a patterned irradiation200pto an iris of the eye; wherein the mobile irradiation control system110m-icontrols at least one of the irradiation source120m-iand the irradiation delivery system130m-iwith the irradiation control signal so that the patterned irradiation200pcauses a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil.

The networked system400further includes a central station410, including a central image processor, wherein the mobile irradiation control systems111m-iof the mobile ophthalmic stimulators100m-iand the central station410are configured to communicate through a communication network. In this section, the term mobile ophthalmic stimulator100m-iencompasses all embodiments described in relation toFIGS. 13A-C.

In embodiments of the networked system400, each mobile irradiation control system110m-ican include a mobile communication platform111m-i, including at least one of a mobile telephone, a mobile communication device, and a mobile tablet; and a mobile irradiation controller110cm-i, implemented on the mobile communication platform110m-i, to generate the irradiation control signal. In embodiments, the mobile communication platforms111m-ican include a memory, to store a software implementation of the mobile irradiation controller110cm-i; a processor, to execute the stored software implementation of the mobile irradiation controller110cm-i; and a user interface, to receive input from a user in relation to an operation of the memory and the processor. In embodiments, the mobile ophthalmic stimulators can be configured to increase a temperature of a treatment region of the iris to a range of 45-60 degrees Celsius.

Each mobile irradiation control system110m-ican include an imaging system114m-i, to generate the irradiation control signal by generating an image of the iris of the eye by the imaging system114m-i, receiving an image-based input, and generating the irradiation control signal to control at least one of the irradiation120m-isource and the irradiation delivery system130m-ito deliver the patterned irradiation200paccording to the received image-based input.

In some characteristic embodiments, the mobile irradiation control systems11m-ican include an image processor114ipm-i, to receive the image of the iris from the imaging system, and to generate the image-based input based on a processing of the image of the iris. InFIG. 14, the image processors114ipm-iare not shown for scarcity of space. Embodiments of the image processors114ipm-ihave been shown and described earlier, such as inFIG. 6A. As described earlier, the on-board image processors114ipm-i, can generate an image-based input for the irradiation control systems110m-i, which then can control the rest of the mobile ophthalmic stimulators100m-iaccordingly. In such embodiments, the communications of the mobile ophthalmic stimulators100m-iwith the central station410can be a recording of the results of the image processing, and the record of the treatments performed by the mobile ophthalmic stimulators100m-i.

In other embodiments, each ophthalmic stimulator100m-ican be configured to send the image of the iris to the central station410; and the central station410can be configured to analyze the received image by a central image processor410ip, and to respond to the sending mobile ophthalmic stimulator100m-iwith the image-based input based on the analysis. This communication and analysis can be real-time, actionable. In other cases, it can be a post-treatment, recording the actions type communication.

In real-time embodiments, each ophthalmic stimulator100m-ican be configured to generate and to send the image of the iris to the central station410before the irradiation delivery system delivers130m-ithe patterned irradiation to the iris; and the central station410can be configured to respond to the sending ophthalmic stimulator100m-iwith the image-based input that indicates whether the central station410authorizes the irradiation delivery system130-iof the ophthalmic stimulator100m-ito deliver the patterned irradiation to the iris.

Clearly, such preauthorization-based networked systems400have safety benefits, as when the patient intends to use the mobile ophthalmic stimulator100m-i, the stimulator100m-ifirst needs to send an image of the iris to be treated to the central station410. This gives a chance for the central image processor410ipto analyze the image of the iris, and if it finds anything that raises a medical concern, such as a shape change, or an unexpected discoloration, the central station410can communicate a “Treatment not authorized” imaging-based input to the mobile stimulator100m-i, which then prevents the mobile stimulator100m-ifrom irradiating the iris when medical concerns have been raised by the image analysis.

In a related embodiment of the networked system400, each ophthalmic stimulator100m-ican be configured to generate, and to send, the image of the iris to the central station410before the irradiation delivery system130m-idelivers the patterned irradiation200pto the iris; and the central station410can be configured to respond to the sending mobile ophthalmic stimulator100m-iwith the image-based input that indicates irradiation parameters to be used by the irradiation delivery system130m-iof the mobile ophthalmic stimulator100m-iwhen delivering the patterned irradiation to the iris.

The safety aspects of this embodiment are quite similar to the previous one. One of the differences is that the imaging-based input from the central station is not a binary “authorized-not authorized” input, but a quantitative input, nuanced input. In a characteristic example, the central image processor410ipcan notice a small discoloration of the iris in the image, sent in by the mobile stimulator100m-i. However, the discoloration may be small enough so that a hard-stop “Treatment not authorized” input may be excessive. In such cases, the central image processor410ipcan respond instead by a message of “Reduce power of irradiation in next treatment” input. In some embodiments, the central image processor410ipcan even schedule a follow-up imaging, to check how the iris reacted to the reduced power irradiation: was the reduction sufficient to eliminate the discoloration, or further analysis is needed.

In some embodiments, the central imaging processor410ipof the central station410can be configured to perform a medical analysis of the image of the iris, and to respond to the sending ophthalmic stimulator100m-iwith the image-based input that indicates if a negative medical condition was found by the analysis. The medical analysis can take place in a number of ways. The central station410can engage in an automated medical analysis, where for example past images of the iris, recalled from a memory, are compared to the present image. Or, the image of the iris can be compared to a database, compiled from tracking a large number of irises. Some embodiments can use artificial intelligence systems to recognize, and to evaluate the negative medical condition, such as an inflammation of the iris. Or, the image processor can flag the image, and request an opinion or analysis by a human specialist.

The negative medical condition can also be a wide range of conditions, including a change of color of the iris, a change of an optical characteristic, and a change of shape of the iris.

In some advanced embodiments, the mobile ophthalmic stimulators100m-ican be configured to test the iris11and to send a test result to the central station410; and the central station410can be configured to perform a medical analysis of the test result, and to respond to the sending mobile ophthalmic stimulators100m-iwith the image-based input that indicates if a negative medical condition was found by the analysis. The mentioned test of the iris can include irradiating the iris with a test irradiation, and measuring a constriction of the pupil in response to the test irradiation. The performing a medical analysis can include recalling a previous test result, as mentioned. Finally, the detection of a negative medical condition can include comparing the test result with the previous test result, and finding the test result less acceptable than the previous test result. In other embodiments, the comparison can be made not with past measurements or tests on the same iris, but to a database of a large number of irises. This database can be organized into groups according to many shared traits, so that patients with comparable medical situations and characteristics are compared by the database.

As mentioned in relation to the mobile stimulators100mofFIGS. 13A-Cearlier, in another class of embodiments, the mobile ophthalmic stimulators100m-ican be configured to send alignment data to the central station410regarding an alignment of the patterned irradiation200pwith at least one of the iris and the pupil; and the central station410can be configured to evaluate the alignment data; and to send a control signal to stop the patterned irradiation200pwhen the patterned irradiation200pis evaluated to be misaligned with at least one of the iris and the pupil. In some embodiments, the alignment data can be generated by the imaging system114m. In others, by various embodiments of the alignment system135, possibly using the patient interface137and the alignment pattern138. In imaging-based embodiments, the control signal can be analogous to the image-based input, described earlier.

Generally speaking, in some embodiments of the networked system400the mobile irradiation control systems110m-iof the mobile ophthalmic stimulators100m-iand the central station410can be configured to communicate regarding safety monitoring of the irradiations and treatments by an interface, or dedicated block or code413. This is a generic concept that encompasses communication regarding all major safety monitoring channels, including expected and unexpected medical outcomes, treatment parameters, proper alignment, and test results, from the viewpoint of safety. As described, the safety monitoring can result prompting a dedicated block, processor, or code416to signal or order preventive shutdowns of the mobile stimulators.

Analogous communications can be performed by a treatment outcome monitoring block, dedicated processor, or code412. Communications about treatment outcomes can then be used by a block, dedicated processor, or piece of code415, to develop and assemble a statistics of the treatment outcomes with the purpose of improving the understanding and the operations of the networked system400for the benefit of the patients. This communication channel can, of course, also be useful for pushing out new versions of treatment software from the central station410to the individual mobile stimulators100m-i.

These communications may not be real time, or actionable in some embodiments, for example, the mobile irradiation control systems110m-iof the mobile ophthalmic stimulators100m-iand the central station410can be configured to communicate treatment outcomes after an irradiation has been performed. In other embodiments, they can be configured to communicate regarding patient data, which then can be stored in a dedicated processor and memory411.