Method and apparatus for treating myopia

Abstract

The invention concerns a method, apparatus and system for treating high myopia and pathological myopia, comprising introducing a photoreactive drug into the sub-Tenon space of the eye, imaging at least a portion of the eye to configure a treatment plan defining regions of the retina to irradiate with photoactivating light to convert the photoreactive drug into an active species; and irradiating the retina according to the treatment plan, for a time sufficient to achieve scleral stiffening.

Description

[0001] METHOD AND APPARATUS FOR TREATING MYOPIA

[0002] TECHNOLOGICAL FIELD

[0003] The present disclosure is in the field of ophthalmic photodynamic therapy and more specifically concerns a method, apparatus and system for preventing and treating myopia and scleral thinning, including high myopia and pathological myopia.

[0004] BACKGROUND ART

[0005] The following are references considered to be of relevance as a general background art to this disclosure:

[0006] • US 5,865,832

[0007] • US 6,099,522

[0008] • US 7,947,672

[0009] • US 9,452,172

[0010] • US 11,058,772

[0011] • US 2002 / 0133144

[0012] • US 2011 / 0288466

[0013] • US 2020 / 0129620

[0014] • WO 2005 / 120573

[0015] • EP 0584552

[0016] • Wollensak, G. and Spoerl, E., 2004. Collagen crosslinking of human and porcine sclera. Journal of Cataract & Refractive Surgery, 30(3), pp.689- 695)

[0017] BACKGROUND

[0018] Myopia, also termed nearsightedness, is a refractive defect of the eye in which collimated light produces the image focus in front of the retina when accommodation is relaxed. The global prevalence of myopia has been estimated to be 800 million to 2.3 billion. In some countries, such as China, India and Malaysia, up to 41% of the adult population is myopic to -1 diopters and about 80% to -0.5 diopters. Myopia has been related to stretching of collagenous sclera. Such globe elongation causes myopic progression in predisposed myopic children and adolescents. In addition to elongation, other pathologies may develop including staphyloma, and outpouching of the globe. The change in the size and shape of the sclera is thought to cause damage to the retina and subsequent vision degradation and loss. It usually slows down and stops during the third decade of life, when maturation of body tissues occurs with natural stiffening. This stiffening is related to glycation mediated cross linking.

[0019] At present, there is no effective treatment to stop myopic progression and reduce visual loss caused by pathologic or degenerative myopia. Surgical solutions to arrest myopic progression by applying reinforcement belts around the eye, and suturing them to the sclera, were reported. These surgical solutions were controversial and technically challenging and did not gain popularity. The critical age of intervention is during childhood or early adolescence. Thus, a simpler approach to stiffen the sclera should be applied.

[0020] Since progression of myopia is associated with elongation of the eye tissues, especially the posterior segment of the eye, and subsequent stretching of the sclera and chorioretinal tissues, stiffening of the sclera by collagen crosslinking, is expected to retard / stop the progression of the disease and related disorders such as macular stretching and atrophy or bleeding and visual loss. Wollensak and Spoerl (2004) reported the use of RF / UVA treatment to achieve such crosslinking and strengthening in human and porcine sclera in vitro. The crosslinking stiffening was demonstrated in vivo on rabbits and was shown to last several months. This treatment can be applied to arrest myopic progression.

[0021] Photodynamic therapy (PDT) is a form of phototherapy involving a photosensitizer drug and light to elicit a desired treatment. In classical PDT, photosensitizer drugs administered to a subject may preferentially accumulate in the tissues to be treated. The photosensitizer may be activated by the application of light at specific wavelengths limited to the treatment site.

[0022] Laser systems are widely used for assistance in characterization of the eye as well as therapy for treating eye conditions. While using these laser systems for treating eye conditions it is very important to work with great precaution as damage in the eye tissue due to user errors is usually not reversible. Therefore, optical treatments which involve the use of lasers must be very well planned.

[0023] US 11,058,772 and US 9,452,172 assigned to the Applicant disclose bacteriochlorophyll photosensitizers for treatment of eye diseases, e.g., keratoconus or scleral weakening associated with degenerative myopia, by PDT. US 2002 / 0133144 discloses an apparatus and method for mapping a target area of tissue for irradiation by a laser beam without irradiating tissue surrounding the target area.

[0024] US 2011 / 0288466 discloses devices and methods for activating a cross-linking agent within at least one eye component of an eye to stabilize and strengthen comeal tissue or other tissues of the eye. Cross-linking is activated within the eye component by conveying a cross-linking agent to regions of the eye component to be treated, delivering ultrasound waves to the eye component and then activating the cross-linking agent by delivering an initiating element (UV light) to at least one eye component.

[0025] US 2020 / 0129620 is directed to compositions based on certain heptamethine dyes useful for generating singlet oxygen using near-infrared irradiation. Methods using these compositions are for treating myopia and other ocular conditions. In some cases, the mechanical strength of the sclera may be improved.

[0026] GENERAL DESCRIPTION

[0027] The present disclosure provides a method, an apparatus, and a system for treating myopia and preventing scleral thinning by generating a treatment plan based on images of the eye.

[0028] According to one aspect, the present disclosure provides a method for treating high myopia and pathological myopia in a subject’s eye, comprising: introducing a photoreactive drug into the subject’s sub-Tenon’s space of the eye, the photoreactive drug being convertible by photoactivating light into an active species capable of causing scleral stiffening; imaging at least a portion of the eye to configure a treatment plan, the treatment plan defining regions of the retina to irradiate with the photoactivating light; and irradiating a photoactivating light on said regions of the retina for a time sufficient to achieve scleral stiffening.

[0029] According to an embodiment, the irradiating comprises feeding the treatment plan into a beam shaping unit and passing the photoactivating light through said unit to output a beam directed and shaped to irradiate said region. The irradiating may also comprise tracking eye movement and altering direction or shape of the beam to continuously irradiate said region even upon eye movement. In an embodiment, at least one of: a portion of the retina, the choroid or the sclera is imaged. According to an embodiment, the photoactivating light is emitted at a visible or near infrared (NIR) wavelength. The photoactivating light is emitted at a wavelength in the range of 750-756 nm . The photoactivating light is provided on the surface of the retina at ImW / cm2- lOOOmW / cm2. The photoreactive drug is Palladium 3 '-oxo- 15- methoxycarbonylmethyl-rhodobacteriochlorin-131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof.

[0030] The imaging is performed by at least one of: an ocular fundus camera, optical coherence tomography (OCT), optical coherence elastography (OCE), ultrasound, Scheimpflug imaging, or non-linear optical imaging. The imaging provides a scleral thickness or scleral stiffness map. The beam shaping unit comprises at least one of: a digital micromirror device, a liquid crystal panel, a liquid crystal on silicon panel (LCOS panel), or a high-speed laser scanner.

[0031] According to an embodiment, the treatment plan further comprises a specified irradiation dose over a given irradiation period.

[0032] The step of introducing the photoreactive drug occurs up to about 15 minutes before the step of irradiating the photoactivating light. In another embodiment, the step of introducing the photoreactive drug occurs between about 15 minutes and about 4 hours before the step of irradiating the photoactivating light. In a further embodiment, the step of introducing the photoreactive drug occurs more than about 4 hours before the step of irradiating the photoactivating light.

[0033] According to a further aspect, the present subject matter provides an apparatus for treating high myopia and pathological myopia in subject’s eye, comprising: a light source configured for emitting a photoactivating light that causes a photoreactive drug to convert into an active species that can induce scleral stiffening; an imaging unit for imaging at least a portion of the eye’s retina and permitting a user to configure a treatment plan that comprises a region of the retina to be irradiated by the photoactivating light; and a beam shaping unit for shaping a light beam emitted by the light source such that the light irradiated on said region irradiates only said region.

[0034] In an embodiment, the light source is configured to emit light at a visible or near infrared (NIR) wavelength. The light source is configured to emit light at a wavelength in the range of 750-756 nm. The apparatus is configured to provide intensities of 1- 1000mW / cm2 on the surface of the retina. The photoreactive drug is palladium 3 '-oxo- 15-methoxycarbonylmethyl-rhodobacteriochlorin-131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof.

[0035] In an embodiment, the retina is imaged by at least one of: an ocular fundus camera, optical coherence tomography (OCT), optical coherence elastography (OCE), ultrasound, Scheimpflug imaging, or non-linear optical imaging. The beam shaping unit comprises at least one of: a digital micromirror device, a liquid crystal panel, a liquid crystal on silicon panel (LCOS panel), or a high-speed laser scanner. The apparatus further comprises a controller configured to retrieve the treatment plan from the imaging unit; and control the beam shaping unit.

[0036] The imaging unit provides a scleral thickness or scleral stiffness map. The treatment plan further comprises a specified irradiation dose over a given irradiation period. The apparatus also comprises an eye-tracking system for tracking eye movement and altering direction or shape of the beam to continuously irradiate said region even upon eye movement.

[0037] The apparatus may be used in photodynamic therapy (PDT).

[0038] According to a further aspect, the present subject matter relates to a system for treating high myopia and pathological myopia in subject’s eye, comprising: the apparatus as disclosed hereinabove; a source of photoreactive drug, and an applicator configured for applying the drug into an eye’s sub-Tenon’s space.

[0039] BRIEF DESCRIPTION OF THE DRAWINGS

[0040] To better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of a non-limiting example only, with reference to the accompanying drawings, in which:

[0041] Figure 1 is a schematic illustration of PDT treatment of the sclera according to the prior art.

[0042] Figures 2A and 2B are block diagrams illustrating an apparatus for treating myopia according to embodiment of the present subject matter.

[0043] Figure 3 is a schematic illustration of an apparatus for treating myopia according to embodiment of the present subject matter.

[0044] Figures 4 A and 4B are exemplary illustrations of a retina including exclusion areas according to embodiment of the present subject matter.

[0045] Figure 5 issan exemplary method using the apparatus of Figure 2 according to embodiment of the present subject matter.

[0046] Figure 6 is a schematic chart illustrating a method for treating myopia in a subject’s eye according to embodiment of the present subject matter.

[0047] DETAILED DESCRIPTION OF EMBODIMENTS

[0048] Prior to setting forth the present subject matter in detail, it may be helpful to provide definitions of certain terms to be used herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this subject matter pertains.

[0049] The term “PDT” as used herein is meant to denote all these types of photodynamic therapy.

[0050] The terms “PDT drug”, “PDT-effective drug”, “photosensitizer drug”, “photoreactive drug ” or the like, are meant to denote one or a combination of agents that are administered to the subject and that can be activated by light to cause them to generate a chemically reactive species, typically, but not exclusively, a reactive oxygen species. Alternatively, light may be absorbed by the PDT drug thereby generating thermal energy.

[0051] The terms “PDT-effective light”, “photosensitizing-effective light”, "photoactivating light” or the like, are meant to denote light that has the effect of activating the PDT-effective drug.

[0052] The term "myopia" as used herein, which may also be referred to as nearsightedness, refers to the ability to clearly see objects up close but not those at a distance. As used herein, the term “myopia” refers to all forms and degrees of myopia. In specific embodiments, myopia is pathological and refers to eyeball elongation and is associated with thinning of the scleral tissue. High myopia may be defined as greater than 5 diopters. Pathological myopia and myopic macular degeneration may refer to consequent stretching of the posterior eye wall causes various specific complications including cataract, chorioretinal atrophy, and macular hole with or without retinal detachment, myopic foveoschisis, or optic nerve head changes. (Ikuno, Y,, 2017. Overview of the complications of high myopia. Retina, 37(12), pp.2347-2351 .)

[0053] The term "sclera" as used herein refers to the outer fibrous coat of the eye, which covers the entire eye except a portion which is covered by the cornea.

[0054] The term “about” denotes a quantity which may deviate (namely being higher or lower) by up to 10%, 15%, 20%, 25% or even 30%, from the stated quantity. For example, about 10 should be understood to be in the range of 9-11, 8.5-11.5, 8-12, 7.5- 12.5, or even 7-13. Even where values are given without the “about” qualification, these should be construed to mean to be about the indicated value, namely the value with a possible deviation as noted in this paragraph.

[0055] The terms used herein are for the purpose of description and should not be viewed as limiting. The use of "including," "comprising," "having," "containing," "involving," and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof, as well as additional items. The terms "optional" or "optionally" mean that the described component may or may not be present, or that the described step in a process may or may not occur, and that the description includes instances where the component is present or the step does occur, and instances where the component is not present, or the step does not occur.

[0056] The term "a" or "an" as used herein includes the singular and the plural, unless specifically stated otherwise. Therefore, the terms "a," "an" or "at least one" can be used interchangeably in this application.

[0057] In some embodiments of the method, the photoreactive drug is a bacteriochlorophyll derivative having a major light absorption at about 750-756 nm, e.g., about 753 nm, and capable of generating oxygen radicals upon illumination and / or has the ability to convert the absorbed light into heat. The photoreactive drug may be Palladium 31-oxo- 15-methoxycarbonylmethyl-rhodobacteriochlorin- 131-(2-sulfoethyl) amide (Padeliporfm; WST11), or a pharmaceutically acceptable salt thereof.

[0058] In some embodiments, the method makes use of the system provided in this disclosure.

[0059] Figure 1 shows a schematic PDT treatment scheme as is known in the prior art for reinforcing the sclera. A photosensitizing agent (also referred to as photoreactive drug) is injected into the back of the eye where the drug diffuses into the tissue and then a non- hazardous photosensitizing light source, configured to emit light at a visible (350-750nm) or near infrared (NIR) wavelength (750-1400nm), illuminates the front of the eye. The light penetrates through biological tissue, allowing for delivery of light through the front of the eye to the sclera where the photosensitizing agent is activated.

[0060] In an embodiment, the PDT treatment may alter the sclera by for example, increasing its tensile and / or compression strength, increasing its flexibility, increasing its extensibility, or increasing the toughness of its tissue. The treatment may also result in strengthening the sclera, stabilizing the sclera shape, changing the shape of the sclera, or a combination thereof.

[0061] The photosensitizing agents may be administered directly to the tissue of the patient. The agent may be administered, for example either topically or by ocular inj ection or intravenous injection. In an embodiment, the photosensitizing agent is administered to the sclera, for example, into the sub-Tenon’s space of the eye. Alternatively, the agent may be applied to the suprachoroidal space.

[0062] The time between delivery of the photosensitizing agent and the irradiation may vary and is dependent on several different factors. This may include but is not limited to the concentration of the photosensitizing agent, the diffusion rate of the photosensitizing agent into the target area or specific characteristics of the patient. For example, the photosensitizing agent may be administered to the patient, after waiting an amount of time to ensure that it has reached a particular location and / or sufficient concentration, the irradiation may then be applied to the target area. It is possible to monitor the photosensitizing agent as it passes through the eye and the irradiation may occur once the required depth is reached. The photoreactive drug may be administered to the subject for a period before or concurrently with the initiation of light irradiation. In an embodiment, the introduction of the photoreactive drug occurs up to about 15 minutes before light irradiation is initiated. In some embodiments, the photoreactive drug is administered between about 5 to about 15 minutes, typically about 10 minutes, before light irradiation is initiated. In another embodiment, the photosensitizer drug is introduced more than about 15 minutes and less than about 4 hours before light irradiation is initiated. In a further embodiment, the photoreactive drug is administered more than 4 hours before light irradiation is initiated.

[0063] The eye is irradiated with a light at a visible, or near infrared (NIR) wavelength for enough time and under specific conditions such that the target treatment of the sclera is obtained.

[0064] As shown with regards to the prior art Figure 1, the photosensitizing agent (photoreactive drug) may be applied by a curved plastic or metal glide 12. The guide may be inserted through a conjunctival opening at the limbus. After the photoreactive drug is administered to the desired region at the desired concentration, the sclera may be illuminated by applying near infrared light directly onto the area to be treated. Figures 2A and 2B are block diagrams illustrating an apparatus 1 for treating myopia according to embodiment of the present subject matter.

[0065] According to an embodiment, apparatus 1 for treating myopia is configured to treat myopia in a subject’s eye. The apparatus 1 comprises a light source 10, and imaging unit 20 and a beam shaping unit 30.

[0066] According to the embodiment of Figure 2B, imaging unit 20 is collinear with light source 10.

[0067] Light source 10 is configured for emitting a photoactivating light that causes a photoreactive drug to convert into an active species or heat that can induce scleral stiffening. In an embodiment, the light source is configured to emit light in the visible or NIR wavelength to allow transmission of the light through the ocular tissues to the retina. In a specific example, the light source is configured to emit light at a wavelength in the range of 750-756 nm. In some embodiments, the light source may be a laser emitting light with an intensity of ImW / cm2- lOOOmW / cm2on the retina.

[0068] In some embodiments, the photoreactive drug is a bacteriochlorophyll derivative having a major light absorption at about 750-756 nm, and capable of generating oxygen radicals upon illumination and / or heating the tissues to be treated.

[0069] In an embodiment, the photoreactive drug is a bacteriochlorophyll derivative. The bacteriochlorophyll derivatives used in the invention can be prepared by the methods described in US 7,947,672 or in WO 2005 / 120573. For the preparation of compounds wherein R8 is the residue of an amino acid, peptide or protein, the methods described in EP 0584552 may be applied. For the preparation of negatively charged bacteriochlorin derivatives wherein R8 is a residue of amino acid, the method disclosed in EP 0584552 may be combined with the method described in Scheme 1 of US 7,947,672. In a specific embodiment, the photoreactive drug is Palladium 3 oxo- l5-mcthoxycarbonylmcthyl- rhodobacteriochlorin-131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof (padeliporfm, WST-11). Palladium S '-oxo- I S-mcthoxycarbonylmcthyl- rhodobacteriochlorin-131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof is specifically disclosed in US 11,058,772 as having a particular efficacy in PDT of scleral weakening.

[0070] Imaging unit 20 is for imaging at least a portion of the eye. The imaging unit may image at least a portion of the retina or other ocular tissue such as, for example, the choroid or the sclera. Imaging unit 20 may further be used for permitting a user to configure a treatment plan that comprises a region of the retina to be irradiated by the photoactivating light. The imaging of the retina, for example, may provide a flat map or a 3D image of the inner surface of the eye. The eye may be imaged by any known ocular imaging method and device such as for example an ocular fundus camera, optical coherence tomography (OCT), optical coherence elastography (OCE), ultrasound, Scheimpflug imaging, or non-linear optical imaging or a combination of these types of imaging. The imaging unit 20 may be adapted to receive an image of an area of the retina. An image provided by the imaging unit 20 may include imaging data, such as imaging data indicating tissue structures along a depth of the eye. The imaging unit may be used to image a portion of a retina for which imaging data is desired. By performing imaging of the eye, the overall shape of the eye and the relative location of different parts of the eye may be determined. Further, the imaging may provide an indication as to the thickness or stiffness of the sclera. Specifically, the imaging may determine the scleral thickness or stiffness at different points around the eye, thereby providing a scleral thickness or stiffness map. The produced image can be used to provide a treatment plan by allowing the user to determine which areas of the eye need to be treated by PDT and which are to be excluded by the irradiation. The exclusion area may be, for example, areas which are sensitive to NIR light, or areas of the eye which do not require treatment. For example, excluded areas may include the optic nerve, macula, or fovea. An example of an exclusion area is shown in Figures 4A and 4B. Figure 4A is an illustration of a retina. Figure 4B is an illustration of a retina which includes exclusion areas 51. In the example of Figure 4B, exclusion areas 51 include the fovea and the optic nerve.

[0071] Beam shaping unit 30 is for shaping a light beam emitted by the light source such that the light irradiates only the region of the retina which requires treatment. The light emitted from the light source 10 may be shaped for example, by a combination of lenses and mirrors, thereby generating a treatment beam. In an embodiment, beam shaping unit 30 may be at least one of a digital micromirror device, a liquid crystal panel, a liquid crystal on silicon panel (LCDS panel). Shaping the light beam emitted from light source 10 allows the user to control the precise location to which the light is provided. For example, the light may be directed such that only the section of the sclera which has undergone thinning is illuminated. As the photoreactive drug only reacts in the presence of the photoactivating light, it may be desired that although the drug may be present in areas which do not require treatment, only the areas which require treatment (i.e. strengthening of the sclera) receive the photoactivating light. Further, as certain areas of the eye such as the fovea may be sensitive to light, the beam shaping allows for these areas to be avoided.

[0072] The apparatus 1 may further comprise a controller 40 which is configured to retrieve the treatment plan from the imaging unit and to control the beam shaping unit.

[0073] Controller 40 may include a processor 41 and a memory device 42 which is in communication with processor 41. The memory device 42 may include inter alia a treatment plan module 43. The treatment plan module 43 may provide instructions for operating aspects of apparatus 1, such as for example, the light source 10, the imaging unit 20 or the beam shaping unit 30.

[0074] It will be appreciated that the modules, processes, systems, and sections described above can be implemented in hardware, hardware programmed by software, software instruction stored on a non-transitory computer readable medium or a combination of the above. The method for treating myopia may be implemented, for example, by using a processor configured to execute a sequence of programmed instructions stored on a non- transitory computer readable medium. The processor can include, but is not limited to, a personal computer or workstation or other such computing system that includes a processor, microprocessor, microcontroller device, or is comprised of control logic including integrated circuits such as, for example, an Application Specific Integrated Circuit (ASIC). The instructions can be compiled from source code instructions provided in accordance with a programming language such as Java, C++, C#.net or the like. The instructions can also comprise code and data objects provided in accordance with, for example, the Visual Basic™ language, or another structured or object-oriented programming language. The sequence of programmed instructions and data associated therewith can be stored in a non-transitory computer- readable medium such as a computer memory or storage device which can be any suitable memory apparatus, such as, but not limited to read-only memory (ROM), programmable read-only memory (PROM), electrically erasable programmable read-only memory (EEPROM), randomaccess memory (RAM), flash memory, disk drive, etc.

[0075] Furthermore, each of the individual components of the apparatus of the present subject matter can be implemented as a single processor or as a distributed processor. Further, it should be appreciated that the steps discussed herein can be performed on a single or distributed processor (single and / or multi -core). Further, the distribution may be implemented across multiple computers or systems or can be co-located in a single processor or system.

[0076] Embodiments of the apparatus and method, can be implemented on a general- purpose computer, a special-purpose computer, a programmed microprocessor or microcontroller and peripheral integrated circuit element, an ASIC or other integrated circuit, a digital signal processor, a hardwired electronic or logic circuit such as a discrete element circuit, a programmed logic circuit such as a programmable logic device (PLD), programmable logic array (PLA), field-programmable gate array (FPGA), programmable array logic (PAL) device, etc. In general, any process capable of implementing the functions or steps described herein can be used to implement the embodiments described herein.

[0077] Treatment plan module 43 may include a program or group of programs containing instructions configured to utilize received data, such as in one or more algorithms, to determine a result or output, i.e. a treatment plan. The treatment plan module 43 may include instructions for controlling aspects of a treatment plan, such as treatment area and providing specified irradiation dose over a given irradiation period. The treatment plan module 34 may further include instructions, such as one or more algorithms, for determining and controlling light parameters. Control of the emitted light parameters may be based on information inputted by a user and / or data received into the system, such as by one or more sensors. Input data may be for example, the imaging data received from imaging unit 20.

[0078] In some instances, the treatment plan module 43 may provide instructions to obtain one or more images of the retina for treatment, identify one or more areas of the eye which has undergone scleral thinning or weaking, generate a treatment plan, irradiate the photoactivating light to the one or more regions of the retina and irradiate the light for a time sufficient to achieve scleral stiffening. The treatment plan module 43 may also include instructions for controlling one or more components of apparatus 1 and / or additional devices attached to apparatus 1. In some embodiments, treatment plan module 43 may provide instructions for controlling aspects of light source 10, imaging unit 20, beam shaping unit 30 and display device 50.

[0079] Processor 41 may be configured to execute instructions and manipulate data to operate apparatus 1. Although Figures 2A and 2B illustrate a single processor 41 , multiple processors may be used according to needs and design of the apparatus. In some embodiments, processor 41 may include one or more microprocessors. Processor 41 may be configured for receiving and / or transmitting data from the various components of the apparatus. Processor 41 may also be configured to process the data.

[0080] Display device 50 may be used to display information to a user. The display 50 may be a monitor for displaying information. In an embodiment, display device 50 may operate both as a display and an input device. For example, display 50 may be a touch screen display which a touch by a user with the display produces an input to the apparatus 1.

[0081] Figure 3 is an example of a more detailed schematic of the apparatus of the present subject matter. Imaging unit 20 may comprise multiple components, which when combined provide an image of the retina. A user may use surgical microscope 71 to get a clear picture of the retina. Fundus camera 72 may be used to obtain an image of the eye. It may be understood that fundus camera 72 may be substituted by another imaging unit described hereinabove. Beam splitter 73 may be used to direct the transmitted image of the retina to microscope 71 and a portion of the reflected image to camera 72. The transmitted image is seen by the user using microscope 71 and is redirected by beam splitter toward camera 72. A fixation point, for fixing the eye of the patient to be treated, may be presented in a location. User interface 74 may be used by the user to manually input data into the apparatus. Display 50 may be used to view images provided by imaging unit 20. Display 50 may be used for example to display a scleral thickness map, scleral stiffness map, or an image of the retina.

[0082] As described in detail hereinabove, controller 40 is interconnected with light source 10, imaging unit 20, beam shaping unit 30, and individual components of each unit. This allows for the configuration of a treatment plant and implementation thereof for the treatment of myopia.

[0083] Light source 10 is configured for emitting a photoactivating light which is directed to beam shaping unit 30. Light entering beam shaping unit 30 is first directed through a fiber collimating lens 76. The light then passes through prism 77. Prism 77 may be comprised of two complementary prisms. Two or more prisms may be used to compensate for aberrations in the beam and allow for reflection of the light beam to a digital micromirror device 75 from which the beam is reflected and passes through prism 77. The final shape of the beam is configured as the light passes through DMD lens 78 and image size adjustment assembly (e.g. a telocentric zoom lens) 79. In an embodiment, light combiner 80 is used to combine the optical path of the treatment beam of photoactivating light and the light from the imaging unit. In another embodiment, an additional light combiner 83 is used to combine the optical path of the imaging units with an illumination source 70 to image the eye. An additional lens 81 may be used with or without a contact lens 82 to complete the image of the treatment beam on the retina. The shaped beam irradiates the region of the retina of eye 15 which was defined by the treatment plan. It may be understood that Figure 3 is exemplary and imaging unit 40 may comprise all or some of the components listed hereinabove. It is also understood that a visible wavelength aiming beam that can be seen with the surgical microscope 71 may be emitted by the light source 10 and be collinear with treatment beam. The aiming beam allows for alignment of the treatment beam before treatment beam illumination.

[0084] The present subject matter also provides a method for treating myopia and preventing scleral thinning in a subject’s eye. The method comprises, in the stated or any suitable order, the following: (i) introducing a photoreactive drug into the subject’s subTenon’s space of the eye, the drug being convertible into an active species by a photoactivating light in which the drug is active to cause scleral stiffening; (ii) imaging the eye’s retina to configure a treatment plan, the treatment plan defining regions of the retina to irradiate with the photoactivating light; and (iii) irradiating a photoactivating light on said regions of the retina for a time sufficient to achieve scleral stiffening.

[0085] In some embodiments of the method, the irradiating comprises feeding the treatment plan into a beam shaping unit and passing the photoactivating light through the beam shaping unit to output a beam directed and shaped so as to irradiate the region of the retina which was identified as requiring treatment.

[0086] In some embodiments of the method, the irradiating comprises tracking the eye movement and altering the direction or shape of the beam so as to continuously irradiate said region even upon eye movement. Tracking can be achieved by adjusting the beam shaping element to move the desired beam shape with the motion of the eye.

[0087] Tracking the movement of the eye can be used to track minor eye movements. By tracking the movement of the eye, treatment can continue uninterrupted until the entire irradiation treatment has been completed. In an embodiment, processor 41 may be programmed to track movement of the treatment target area in real time, and at the same time continuously send the current position of the target to memory 42. Any of various suitable automatic tracking techniques can be employed, including techniques similar to those described in US 5,865,832 and US 6,099,522.

[0088] An automatic shut off module may also be incorporated into the apparatus in which the apparatus is automatically turned off when the threshold of a pre -determined amount of eye movement is exceeded.

[0089] Figure 5 illustrates the relation between the treatment plan 100 to other components of the apparatus. Treatment plan 100 forms the focus of an exemplary method of treating myopia using apparatus 1. In certain embodiments, an eye-tracking system is configured to track eye movement, for use by the treatment plan 100. The eyetracking system 110 can calculate a three-dimensional image of the patient's eye via user input as well as data obtained from imaging unit 20 and can include real-time tracking of movement of the subject’s eye. The eye-tracking system may obtain data for determining and updating PDT planning. For example, the eye-tracking system 110 may create an image of the posterior region of the patient's eye using the data it obtains to update the treatment plan during treatment.

[0090] The treatment planning system 100 may utilize, or be coupled to, imaging unit 20. In some embodiments, imaging unit 20 is integrated into real-time feedback systems with the light source 10 beam shaping unit 30 such that instant updates of eye position can take place.

[0091] As depicted in Figure 5, imaging unit data 120 and user inputs 170 such as anatomic structure and radiation parameters may be inputted into the treatment planning system 100. Other inputs include information from an eye-tracking system 110. The output from the treatment planning system 100 consists of commands sent to the light source 10 and beam shaping unit 30 to characterize the size, shape and power of the light source move.

[0092] Figure 6 demonstrates an exemplary treatment method using apparatus 1 for treating myopia in a subject’s eye. Imaging unit 20 and a physical exam 210 are used to create a map of the eye 220. In some embodiments, a scleral thickness map is generated by imaging unit 20. Information from 210 is used to configure a treatment plan which identifies the region to be treated, the light power and dosage as well as the region to be avoided. These variables can be determined by treatment software as well as user input. The patient is then positioned, such that the eye to be treated and the emitted light are aligned 230. The treatment of irradiating a photoactivating light on the regions of the retina is applied 240. Treatment 240 is applied treated for a time sufficient to achieve scleral stiffening.

[0093] While the present subject matter has been shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that many alternatives, modifications and variations may be made thereto without departing from the spirit and scope thereof. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the claims.

[0094] All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference.

Claims

CLAIMS:

1. A method for treating high myopia and pathological myopia in a subject’s eye, comprising: introducing a photoreactive drug into the subject’s sub-Tenon’s space of the eye, the photoreactive drug being convertible by photoactivating light into an active species capable of causing scleral stiffening; imaging at least a portion of the eye to configure a treatment plan, the treatment plan defining regions of the retina to irradiate with the photoactivating light; and irradiating a photoactivating light on said regions of the retina for a time sufficient to achieve scleral stiffening.

2. The method of claim 1, wherein said irradiating comprises: feeding the treatment plan into a beam shaping unit and passing the photoactivating light through said unit to output a beam directed and shaped to irradiate said region.

3. The method of claim 1 or 2, wherein said irradiating comprises: tracking eye movement and altering direction or shape of the beam to continuously irradiate said region even upon eye movement.

4. The method of any one of claims 1-3, wherein at least one of: a portion of the retina, the choroid or the sclera is imaged.

5. The method of any one of claims 1-4, wherein the photoactivating light is emitted at a visible or near infrared (NIR) wavelength.

6. The method of claim 5, wherein the photoactivating light is emitted at a wavelength in the range of 750-756 nm.

7. The method of any one of claims 1-6, wherein the photoreactive drug is Palladium 31-oxo-15-methoxycarbonylmethyl-rhodobacteriochlorin-131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof.

8. The method of any one of claims 1-7, wherein said imaging is performed by at least one of: an ocular fundus camera, optical coherence tomography (OCT), optical coherence elastography (OCE), ultrasound, Scheimpflug imaging, or non-linear optical imaging.

9. The method of any one of claims 1-8, wherein the imaging provides a scleral thickness or scleral stiffness map.

10. The method of any one of claims 2-9, wherein the beam shaping unit comprises at least one of: a digital micromirror device, a liquid crystal panel, a liquid crystal on silicon panel (LCOS panel), or a high-speed laser scanner.

11. The method of any one of claims 1-10, wherein the treatment plan further comprises a specified irradiation dose over a given irradiation period.

12. The method of any one of claims 1-11, wherein the photoactivating light is provided on the surface of the retina at ImW / cm2- 1000mW / cm2.

13. The method of any one of claims 1-12, wherein the step of introducing the photoreactive drug occurs up to about 15 minutes before the step of irradiating the photoactivating light.

14. The method of any one of claims 1-12, wherein the step of introducing the photoreactive drug occurs between about 15 minutes and about 4 hours before the step of irradiating the photoactivating light.

15. The method of any one of claims 1-12, wherein the step of introducing the photoreactive drug occurs more than about 4 hours before the step of irradiating the photoactivating light.

16. An apparatus for treating high myopia and pathological myopia in subject’s eye, comprising: a light source configured for emitting a photoactivating light that causes a photoreactive drug to convert into an active species that can induce scleral stiffening; an imaging unit for imaging at least a portion of the eye’s retina and permitting a user to configure a treatment plan that comprises a region of the retina to be irradiated by the photoactivating light; and a beam shaping unit for shaping a light beam emitted by the light source such that the light irradiated on said region irradiates only said region.

17. The apparatus of claim 16, wherein the light source is configured to emit light at a visible or near infrared (NIR) wavelength.

18. The apparatus, of any one of claims 16 or 17, wherein the light source is configured to emit light at a wavelength in the range of 750-756 nm.

19. The apparatus of claim 18, configured to provide intensities of l-1000mW / cm2 on the surface of the retina.

20. The apparatus of any one of claims 16-19, wherein the photoreactive drug is palladium 31-oxo- 15-methoxycarbonylmethyl-rhodobacteriochlorin- 131-(2-sulfoethyl) amide, or a pharmaceutically acceptable salt thereof.

21. The apparatus of any one of claims 16-20, wherein the retina is imaged by at least one of: an ocular fundus camera, optical coherence tomography (OCT), optical coherence elastography (OCE), ultrasound, Scheimpflug imaging, or non-linear optical imaging.

22. The apparatus of any one of claims 16-21, wherein the beam shaping unit comprises at least one of: a digital micromirror device, a liquid crystal panel, a liquid crystal on silicon panel (LCOS panel), or a high-speed laser scanner.

23. The apparatus of any one of claims 16-22, further comprising a controller configured to retrieve the treatment plan from the imaging unit; and control the beam shaping unit.

24. The apparatus of any one of claims 16-23, wherein the imaging unit provides a scleral thickness or scleral stiffness map.

25. The apparatus of any one of claims 16-24, wherein the treatment plan further comprises a specified irradiation dose over a given irradiation period.

26. The apparatus of any one of claims 16-24, further comprising an eye-tracking system for tracking eye movement and altering direction or shape of the beam to continuously irradiate said region even upon eye movement.

27. The apparatus of any one of claims 16-26 for use in photodynamic therapy (PDT).

28. A system for treating high myopia and pathological myopia in a subject’s eye, comprising: the apparatus of any one of claims 16-27, a source of photoreactive drug, and an applicator configured for applying the drug into an eye’s sub-Tenon’s space.

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