JP2022184907A - System and process for treatment of myopia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a system and a process for preventing or treating myopia, the system and the process applying a pulsed energy, such as a pulsed laser beam, to tissue of an eye having myopia or a risk of having myopia.

SOLUTION: The source of pulsed energy has energy parameters including wavelength or frequency, duty cycle and pulse train duration, which are selected so as to raise an eye tissue temperature up to eleven degrees Celsius to achieve therapeutic or prophylactic effect, such as stimulating heat shock protein activation in an eye tissue 38. The average temperature rise of the eye tissue over several minutes is maintained at or below a predetermined level so as not to permanently damage the eye tissue.

SELECTED DRAWING: Figure 3

COPYRIGHT: (C)2023,JPO&INPIT

Description

<Related application>
This application is a continuation-in-part of U.S. Application Serial No. 15/583,096, filed May 1, 2017, which is a continuation-in-part of U.S. Application Serial No. 15/214, filed July 20, 2016. 726, which is a continuation-in-part of U.S. Application Serial No. 14/922,885, filed October 26, 2015 (now US Pat. ) (which claims priority from U.S. Provisional Application No. 62/153,616, filed Apr. 28, 2015), which is a U.S. application filed Jan. 28, 2015. Serial No. 14/607,959 (currently US Pat. No. 9,168,174), which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013. a continuation-in-part application, which is a continuation-in-part application of U.S. Application Serial No. 13/481,124, filed May 25, 2012 (now patent number 9,381,115); This application is also a continuation-in-part of U.S. Application Serial No. 15/232,320, filed August 9, 2016, which is a continuation-in-part of U.S. Application Serial No. 15/188,608, filed June 21, 2016. which is a continuation-in-part of U.S. Application Serial No. 15/148,842, filed May 6, 2016, which was filed October 23, 2015. is a continuation-in-part of U.S. Application Serial No. 14/921,890 (now Patent No. 9,381,116), which was filed Jan. 28, 2015, U.S. Application Serial No. 14/607. , 959 (now US Pat. No. 9,168,174). This application is also a continuation-in-part of U.S. Application Serial No. 15/460,821, filed March 16, 2017, which is a continuation-in-part of U.S. Application Serial No. 15/460,821, filed July 20, 2016. 214,726, which is a continuation-in-part application, filed Oct. 26, 2015, U.S. Application Serial No. 14/922,885, now U.S. Patent No. 9,427,602 (which is , claiming the benefit of U.S. Application No. 62/153,616, filed April 28, 2015), which is the subject of U.S. Application No. 14/607, filed January 28, 2015. 959, a continuation-in-part of current U.S. Pat. This is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012, now U.S. Patent No. 9,381,115; is a continuation-in-part of U.S. Application Serial No. 15/148,842 filed on Oct. 23, 2015, which is a continuation-in-part of U.S. Patent Application Serial No. 14/921,890, filed Oct. No. 9,381,116, which is a continuation-in-part of U.S. Application Serial No. 14/607,959, filed Jan. 28, 2015, now U.S. Patent No. 9,168,174. A continuation-in-part application, which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013, which was filed May 25, 2012 U.S. Patent Application Serial No. 13/481,124, a continuation-in-part of current U.S. Patent No. 9,381,115; 075,432, which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013, which was filed May 25, 2012 No. 13/481,124 filed, which is a continuation-in-part of current US Pat. No. 9,381,115. This application is also a continuation-in-part of U.S. Application Serial No. 15/332,132, filed October 24, 2016, which is a continuation-in-part of U.S. Application Serial No. 15/232, filed August 9, 2016. , 320 and a continuation-in-part of U.S. Application Serial No. 15/148,842 filed May 6, 2016, which is a U.S. Application Serial No. A continuation-in-part application (now U.S. Patent No. 9,381,116) with Serial No. 14/921,890, which is U.S. Application Serial No. 14/607,959, filed January 28, 2015. (now U.S. Patent No. 9,168,174), which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013. , which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012 (now U.S. Patent No. 9,381,115); It is a continuation-in-part of U.S. Application Serial No. 15/188,608, filed June 21, and U.S. Application Serial No. 13/481,124, filed May 25, 2012 (now U.S. Patent No. 9,381,115); and a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013, which is filed May 25, 2012. This is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed on May 1, 2004 (now U.S. Patent No. 9,381,115). This application is also a continuation-in-part of U.S. Application Serial No. 15/291,796, filed October 12, 2016, which is a continuation-in-part of U.S. Application Serial No. 15/148, filed May 6, 2016. ,842, which is a continuation-in-part of U.S. Application Serial No. 14/921,890, filed October 23, 2015, which was filed January 28, 2015. 14/607,959 (now U.S. Pat. No. 9,168,174), which is a continuation-in-part of U.S. Application Serial No. 13/ 798,523, which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012. This application is also a continuation-in-part of U.S. Application Serial No. 15/075,432, filed March 21, 2016, which is a continuation-in-part of U.S. Application Serial No. 13/13, filed March 13, 2013. 798,523, which is a continuation of U.S. Application Serial No. 13/481,124, filed May 25, 2012. This application is also a continuation-in-part of U.S. Application Serial No. 15/232,320, filed August 9, 2016, which is a continuation-in-part of U.S. Application Serial No. 15/232,320, filed May 6, 2016. 148,842, which is a continuation-in-part of U.S. Application Serial No. 14/921,890, filed October 23, 2015 (now U.S. Patent No. 9,381,116) , which is a continuation-in-part of U.S. Application Serial No. 14/607,959, filed January 28, 2015 (now U.S. Patent No. 9,168,174), which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013, which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012 ( No. 9,381,115), which is also a continuation-in-part of U.S. Application Serial No. 15/188,608, filed June 21, 2016. , which is a continuation of U.S. Application Serial No. 13/481,124, filed May 25, 2012 (now U.S. Patent No. 9,381,115); is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed May 25, 2012, which is now U.S. Patent No. 9,124. 381,115). This application is also a continuation-in-part of U.S. Application Ser. (which claims benefit of U.S. Application No. 62/153,616, filed April 28, 2015), which was filed January 28, 2015. No. 14/607,959, a continuation-in-part of current Patent No. 9,168,174, which was filed March 13, 2013, U.S. Application Serial No. 13/798,523. which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012, current Patent No. 9,381,115. This application is also a continuation-in-part of U.S. Application Serial No. 15/188,608, filed June 21, 2016, and U.S. Application Serial No. It is a continuation application. This application is also a continuation-in-part of U.S. Application Serial No. 15/148,842, filed May 6, 2016, which is a continuation-in-part of U.S. Application Serial No. 14/14, filed October 23, 2015. 921,890, which is part of U.S. Application Serial No. 14/607,959, filed January 28, 2015 (now U.S. Patent No. 9,168,174). Continuation Application, which is a continuation-in-part of U.S. Application Serial No. 13/798,523, filed March 13, 2013, which is a U.S. This is a continuation-in-part of serial number 13/481,124; this application is also a continuation-in-part of U.S. application serial number 15/075,432 filed March 21, 2016, which is a continuation of U.S. Application Serial No. 13/798,523, filed March 13, 2012, which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012 Application. This application is also a continuation-in-part of U.S. Application Serial No. 15/075,432, filed March 21, 2016, which is a continuation-in-part of U.S. Application Serial No. 13/13, filed March 13, 2013. 798,523, which is a continuation-in-part of U.S. Application Serial No. 13/481,124, filed May 25, 2012.

The present invention relates generally to systems and processes for treating eye diseases. More specifically, the present invention provides systems and processes for preventing or treating myopia by applying pulsed energy to ocular tissues that are myopic or at risk for myopia, or to prevent permanent damage. Systems and processes that raise the temperature of ocular tissues sufficiently to provide therapeutic benefit without feeding.

Myopia is a condition known as "myopia", in which the image in front of the eye is focused in front of the retina rather than exactly on the retina. This focus of the image on the retina is also called "emmetropia." Myopic images may focus in front of the retina, causing vision impairment, for one or both of the following reasons: excessive refractive power in the front of the eye at the cornea and lens; and /or the axial length of the eye is too long, so that the retina is behind the image focus. To counteract this visual blurring, the affected person moves closer to the object to be viewed. This brings the image focus closer to the retina for sharper vision.

Myopia is prevalent in its usual medical definition, affecting as many as 50% of adults, and the incidence in school-aged children has increased by over 200% in recent generations. This rapid increase and prevalence has been attributed to improved educational opportunities through increased reading time, as well as increased use of electronic devices and media.

The typical causes of myopia appear to be genetic and environmental. Higher education and time spent working and reading at close distances are known risk factors for myopia. The stimulus for close-distance tasks that induces myopia may be a neurological and/or chemical mediator of ocular growth to increase axial length of the eye, possibly in part through accommodation of the lens. suggest that it affects Evidence for this phenomenon is that paralysis with topical atropine in children can reduce the degree and incidence of acquired myopia.

The 'emmetropic' factor, which promotes normal eye growth and formation and axial length and is reduced, blocked, or inhibited by working at close distances, leads to increased eye length and is usually the focal point of the visual image. It most likely occurs in the center of the retina, or "macula," where the eye is aligned. Innate neurological and/or diffusive chemical feedback mechanisms prevent and actively encourage autoregulation of ocular growth, or the loss of emmetropia stimuli, passively reducing axial length. The increase in height increases the myopic condition by passively allowing the eye to adapt to the myopic focus.

Retinal dysfunction and changes in retinal autoregulation in response to environmental factors have been reported in age-related macular degeneration and diabetic retinopathy, ocular nerve diseases such as chronic open-angle glaucoma, and hereditary retinopathies including retinitis pigmentosa and Stargardt disease. It is a common phenomenon and common finding in most chronic progressive retinopathies, including. In glaucoma, a setting analogous to the progression of myopia, selective complementary sparing of visual field defects suggests direct and neurological and/or chemical communication between one eye mediated by the central nervous system. , the overall visual impairment is minimized. In response to high intraocular pressure in glaucoma, the optic nerve tissue increases the odds of preserving vision in one eye, covers lost vision in the other eye, and improves vision when both eyes are used together. sacrificed in a way that maximizes overall functionality. Thus, there are distinct anatomical responses mediated by retinal signaling that alter the retina and neural structures to modulate visual stimulus quality and maximize visual function.

Childhood myopia appears to develop and progress in a similar manner and by similar mechanisms as other chronic progressive eye diseases. Abnormal stimuli (chronic near-distance work and lenticular accommodation) that cause changes in retinal function and autoregulation in response to abnormal environments are therefore abnormal, causing elongation growth to the eye, It restores sharp myopia with less accommodative power and thus progresses the myopic state.

Although typical axial or refractive myopia can be corrected with spectacles, contact lenses, or refractive surgery, myopia is also often associated with decreased visual function, including retinal detachment, choroidal neovascularization, macular atrophy, and glaucoma. Increased risk of blindness from Together, the need for refractive correction and the medical consequences of myopia constitute a significant public health problem and socioeconomic burden.

Accordingly, there continues to be a need for systems and methods that can prevent and/or treat myopic eye conditions. Such a system or method should be able to modify biological factors that may contribute to acquired myopia in order to delay or prevent acquired myopia. Such treatment systems and treatment methods should be relatively easy to implement and harmless. The present invention satisfies these needs and provides other related advantages.

The present invention belongs to the process of preventing or treating myopia. A pulsed energy source is provided having energy parameters including wavelength or frequency, duty cycle, and pulse duration. Energy parameters are selected to raise ocular tissue temperature up to 11° C. to achieve a therapeutic or prophylactic effect. The average temperature rise of the ocular tissue over several minutes is kept below a predetermined level so as not to permanently damage the ocular tissue. The eye may be determined to be myopic or at risk of becoming myopic. Pulsed energy is applied to ocular tissue that is myopic or at risk of being myopic to stimulate activation of heat shock proteins within the ocular tissue.

The pulsed energy may comprise a pulsed light beam having a wavelength between 530nm and 1300nm, more specifically between 80nm and 1000nm. This light beam may have a duty cycle of less than 10%, more preferably between 2.0% and 5%. The pulsed light beam has a power between 0.5 Watts and 74 Watts. The pulsed light beam may have a pulse train duration of between 0.1 and 0.6 seconds.

Ocular tissues to which pulsed energy is typically applied include retina and/or foveal tissue. The energy parameters of the pulsed energy source are selected such that the ocular tissue temperature rises between 6° C. and 11° C. at least during application of the pulsed energy source. However, the average temperature rise of the ocular tissue remains below about 1° C. for several minutes, such as for 6 minutes.

Pulse energy may be applied to multiple ocular tissue regions, where adjacent ocular tissue regions are separated by at least a predetermined distance to avoid thermal tissue damage. Pulsed energy may be applied to the first ocular tissue region, and after a predetermined period of time within a single treatment session, the pulsed energy is reapplied to the first ocular tissue region. Pulse energy is applied to a second ocular tissue region between intervals of application of pulsed energy to the first ocular tissue region.

Other features and advantages of the invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings, which illustrate by way of example the principles of the invention.

The accompanying drawings illustrate the invention. The description of the drawings follows.
FIG. 10 is a graph illustrating the average power of a laser source having a wavelength compared to the source radius and pulse train duration of the laser; FIG. 2 is a graph similar to FIG. 1 illustrating the average power of a higher wavelength laser source compared to the source radius and pulse train duration of the laser; 1 is a schematic diagram illustrating a system used to treat an eye in accordance with the present invention; FIG. 1 is a schematic diagram of an exemplary optical lens or mask used to generate geometric patterns in accordance with the present invention; FIG. FIG. 4 is a schematic diagram illustrating an alternative embodiment of a system used to treat ocular tissue in accordance with the present invention; FIG. 4 is a schematic diagram showing yet another alternative embodiment of a system used to treat ocular tissue in accordance with the present invention; . 1 is a front view of a camera with an iris diaphragm of the present invention; FIG. 1 is a front view of a camera with an LCD diaphragm according to the invention; FIG. 1 is a top view of an optical scanning mechanism used in accordance with the present invention; FIG. FIG. 10 is a partially exploded view of the optical scanning mechanism of FIG. 9; Its various components are shown. FIG. 4 is a schematic diagram illustrating controlled offset of exposure of an exemplary geometric pattern grid of laser spots for treating ocular tissue, in accordance with the present invention; . 1 is a schematic diagram illustrating a unit of geometric object in the form of a controllably scanned line for treating an area of ocular tissue according to the present invention; FIG. FIG. 13 is a schematic diagram similar to FIG. 12 but illustrating rotated geometric lines or bars for treating an area of the retina in accordance with the present invention; 1 is a schematic diagram illustrating application of laser light to different treatment areas and reapplication of laser light to previously treated areas for predetermined time intervals within a single treatment session, in accordance with the present invention; FIG. 1 is a schematic diagram illustrating application of laser light to different treatment areas and reapplication of laser light to previously treated areas for predetermined time intervals within a single treatment session, in accordance with the present invention; FIG. 1 is a schematic diagram illustrating application of laser light to different treatment areas and reapplication of laser light to previously treated areas for predetermined time intervals within a single treatment session, in accordance with the present invention; FIG. 1 is a schematic diagram illustrating application of laser light to different treatment areas and reapplication of laser light to previously treated areas for predetermined time intervals within a single treatment session, in accordance with the present invention; FIG. FIG. 2 is a graph showing therapeutic potency versus time in accordance with embodiments of the present invention; FIG. FIG. 2 is a graph showing therapeutic potency versus time in accordance with embodiments of the present invention; FIG. FIG. 2 is a graph showing therapeutic potency versus time in accordance with embodiments of the present invention; FIG.

As illustrated in the accompanying drawings and described more fully herein, the present invention is directed to a process for preventing or treating myopia. This involves increasing eye tissue temperature sufficiently to achieve a therapeutic or prophylactic effect while maintaining the average temperature rise of the ocular tissue below a predetermined level over time so as not to permanently damage the ocular tissue. This is accomplished by providing a pulsed energy source with an energy parameter selected to increase.

As noted above, there has been a dramatic increase in the prevalence of myopia worldwide during the last few decades. Recent studies have shown that the progression of refraction, or myopia, is influenced by environmental, behavioral and genetic factors. The inventors believe that there are modifiable biological factors behind the progression of simple acquired myopia. We show that a low-intensity, high-density subthreshold diode micropulse laser (SDM) improves eye and optic nerve physiological and psychophysical function in a myriad of chronic progressive retinal diseases and open-angle glaucoma. We proved that. The present study shows that SDM does this by normalizing retinal function and autoregulation through a mechanism we call a 'reset-to-default' effect or homeotrophy. By selectively targeting and normalizing the function of the retinal pigment epithelium (RPE), a major driver of retinal function and autoregulation, the biological function of the RPE when it becomes abnormal due to environmental or other causes. Functionality is reset to default or returned to normal functionality. By doing so, the progression of the disease is slowed, stopped, or even reversed. We have found that SDM homeotropic therapy slows the progression of myopia, particularly childhood myopia, in a manner similar to other chronic progressive retinopathies and glaucoma by restoring normal retinal physiology and autoregulation. , thinks to stop and even reverse. Clinical experience and use in other eye diseases including diabetic retinopathy, age-related macular degeneration, glaucoma, and hereditary retinopathy demonstrate that effective SDM homeotropic therapy is robust and reproducible with regularly repeated treatments. It suggests both.

The inventors have discovered that electromagnetic radiation, such as types of laser light of various wavelengths, can be applied to retinal tissue in a manner that does not destroy or damage the tissue while achieving beneficial effects on eye disease. It is believed that this may be due, at least in part, to stimulation and activation of heat shock proteins and promotion of protein repair within the tissue. Generating a thermal time course is thought to stimulate the activation or production of heat shock proteins, promoting protein repair without causing any damage.

The present inventors have found that laser light that is therapeutic but sublethal to retinal tissue cells and thus avoids photocoagulation damage in retinal tissue provides a prophylactic and protective treatment of retinal tissue in the eye. I discovered that I can generate beams. Various parameters of the light beam must be considered and selected such that the selected combination of parameters achieves a therapeutic effect without causing permanent tissue damage. These parameters include laser wavelength, laser source radius, average laser power, total pulse duration, and pulse train duty cycle. In a particularly preferred embodiment, a laser beam is used, although other pulsed energy sources, including ultrasound, ultraviolet frequencies, microwave frequencies, etc., with appropriately selected energy parameters may also be used, but eye disorders, including myopia, may also be used. and is not as convenient in treating other diseases and disorders.

The choice of these parameters can be determined by requiring the Arrhenius integral required for HSP activation to be unity or greater. The Arrhenius integral is used to analyze the effects of actions on living tissue. See, for example, The CRC Handbook of The CRC Handbook of Thermal Engineering, ed. See Frank Kreith, Springer Science and Business Media (2000). At the same time, the selected parameters must not permanently damage tissue. Therefore, the Arrhenius integral of damage can also be used, and the solved Arrhenius integral is less than or equal to one.

Alternatively, FDA/FCC constraints on energy deposition per gram of tissue and temperature rise as measured over minutes must be met to avoid permanent tissue damage. For example, FDA/FCC requirements for energy storage and temperature rise are commonly used, eg, for electromagnetic sources, see www. fda. gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm073817. htm#attacha, and ultrasound sources, see Anastosio and P.; La Rivero, ed. , Emerging Imaging Technologies. CRC Press (2012) can be cited.

Generally speaking, tissue temperature elevations between 6° C. and 11° C. can produce therapeutic effects, such as by activating heat shock proteins, and under certain circumstances, for extended periods of time, e.g., 6 minutes. By maintaining the average tissue temperature below a predetermined temperature, such as below 6° C. and 1° C., for several minutes, such as for several minutes, the tissue is not permanently damaged.

Sub-threshold retinal photocoagulation, often referred to as "true sub-threshold", of the present invention is defined as a retinal laser application that is invisible to biomicroscopy during the procedure. "True sub-threshold" photocoagulation as a result of the present invention includes laser therapy that is invisible and indistinguishable by FFA, FAF, or other known means such as SD-OCT. Thus, "true subthreshold" photocoagulation is defined as a laser therapy that never produces detectable retinal damage by known means of detection at any time after treatment or at any time after treatment. Thus, "below true threshold" is the absence of lesions and other tissue damage and destruction. The present invention may be more accurately referred to as photostimulation rather than photocoagulation, as it is free of typical photocoagulation damage.

Various parameters have been found to achieve effective "sub-threshold" or "low-intensity" photocoagulation. These include applying a force sufficient to produce an effective therapeutic retinal laser exposure, but not high enough to cause tissue damage or destruction. True sub-threshold laser application alone or while creating geometric objects or patterns of arbitrary size and arrangement that minimize heat build-up, such as using a low duty cycle. Applicable to maximize heat dissipation as well as ensure uniform heat distribution. The inventors have discovered a way to achieve therapeutically effective and harmless true sub-threshold retinal laser therapy. The inventors have further discovered that the placement of true sub-threshold laser applications in close proximity to the retinal surface improves and maximizes the therapeutic benefits of treatment without retinal damage.

Low duty cycle 810 nm laser beam intensities or powers between 100 and 590 Watts per square centimeter have been found to be effective as well as safe. A particularly preferred intensity or power of the laser light beam is approximately 250-350 watts per square centimeter for an 810 nm micropulse diode laser.

Power limitations in current micropulse diode lasers require fairly long exposure durations. The longer the laser exposure, the more important the heat dissipation in the center spot to the unexposed tissue in the remainder of the laser spot and to the underlying choriocapillaris. Therefore, the radiation beam of an 810 nm diode laser should have an exposure envelope duration of 500 ms or less, and preferably around 100-300 ms. Of course, if the micropulse diode laser becomes more powerful, the exposure duration will be shortened accordingly. The exposure envelope duration is the duration of time that the micropulsed laser beam is exposed to the same spot or location on the retina, whereas the actual time of tissue exposure to the laser is less than 1 millisecond in duration of the laser light pulse. , and much shorter, typically between 50 and 100 microseconds.

Invisible phototherapy or true sub-threshold photocoagulation according to the present invention can be performed with various laser light wavelengths, such as in the range of 532 nm to 1300 nm. The use of different wavelengths can affect the preferred intensity or power of the laser beam and the duration of the illumination envelope so that retinal tissue is not damaged and therapeutic effect is achieved.

Another parameter of the present invention is the duty cycle (frequency of a series of micropulses or length of thermal relaxation time between successive pulses). Micropulse laser irradiation with similar irradiance at similar MPE levels using a 10% duty cycle or greater has been found to significantly increase the risk of lethal cell damage, especially in dark fundus. However, a duty cycle of less than 10%, preferably about 5% or less demonstrates adequate heat elevation and treatment at the level of RPE cells to stimulate a biological response, but not in the dark and pigmented fundus. even below levels expected to cause lethal cytotoxicity. Furthermore, if the duty cycle is less than 5%, the duration of the exposure envelope can exceed 500 milliseconds in some cases.

A particularly preferred embodiment uses the use of a small retinal laser spot. This is due to the fact that the large spot contributes to uneven heat distribution and poor heat dissipation within the large retinal laser spot, which can cause tissue damage or even tissue destruction towards the center of the large laser spot. is. In this usage, "small" generally applies to retinal spots less than 3 mm in diameter. However, the smaller the retinal spot, the more ideal heat dissipation and uniform energy application. Therefore, at the above power intensities and exposure times, small spots, such as 25-300 micrometers in diameter, or small geometric lines or other is preferred.

Therefore, in order to produce a harmless "true sub-threshold" sub-lethal dose of micropulsed laser beam to achieve the objectives of the present invention, the following critical parameters including wavelength or frequency, duty cycle and pulse duration was found. The laser light beam should have a wavelength greater than 532 nm to avoid cytotoxic photochemical effects, such as wavelengths between 550 nm and 1300 nm, and in particularly preferred embodiments between 810 nm and 1000 nm. The duty cycle should be less than 10% and preferably between 2.5% and 5%. The pulse train duration or exposure time should be 100-600 milliseconds. The intensity or power of the laser beam should be 100-590 Watts per square centimeter at the retina, or approximately 1 Watt per laser spot at each treatment spot on the retina. This is sufficient power to produce a retinal laser irradiation of 18-55 times the maximum permissible exposure (MPE) and a retinal irradiance of 100-590 W/cm ² . Preferably, a small spot size is used to minimize heat build-up and ensure uniform heat distribution within a given laser spot to maximize heat dissipation.

Using the aforementioned parameters, retinal photostimulation of all areas of the RPE exposed to laser radiation, a harmless but therapeutically effective "below true threshold" or Invisible phototherapy treatment can be achieved. The present invention has been found to provide the advantages of conventional photocoagulation and phototherapy while avoiding the drawbacks and complications of conventional phototherapy. According to the present invention, a physician can apply laser light to treat the entire retina, including sensitive areas such as the macula and fovea, without loss of vision or other damage. This is not possible with conventional phototherapy as it can cause eye damage and blindness.

The conventional wisdom is that tissue damage and lesions must be created in order to be therapeutically effective. However, the inventors have discovered that this is simply not the case. In the absence of laser-induced retinal damage, there is no loss of functional retinal tissue and no inflammatory response to treatment. Adverse treatment effects are therefore completely eliminated and a functional retina is preserved rather than sacrificed. This may produce superior visual acuity results compared to conventional photocoagulation therapy.

The present invention spares the retinal neurosensory epithelium and is selectively absorbed by the RPE. Current theories about the pathogenesis of retinal vascular disease specifically implicates cytokines, potent additional cellular vasoactive factors produced by the RPE, as key mediators of retinal vascular disease. The present invention selectively targets and avoids lethal accumulation within the RPE. Thus, with the present invention, the ability of the treated RPE to participate in therapeutic response is preserved and enhanced rather than eliminated as a result of their destruction of the RPE in conventional photocoagulation therapy.

The clinical effects of cytokines follow a "U-shaped curve", where small physiological changes in cytokine production, indicated by the left side of the curve, are followed by high-dose (pharmacologic) treatments (shown by the right side of the curve). It is noted that they may have comparable clinical efficacy. Using sublethal laser exposure according to the present invention works on the left side of the curve, where the treatment response can approximate an "on/off" phenomenon rather than a dose response. This may explain the observed clinical efficacy of the present invention at the low reported irradiances. This is also consistent with clinical experience and in vitro studies of laser-tissue interactions, where increased irradiance simply increases the risk of thermal retinal damage without improving therapeutic efficacy. can increase.

Another mechanism by which SDM may act is believed to be the activating action of heat shock proteins (HSPs). Despite an almost endless variety of possible cellular abnormalities, all cell types share a common and highly conserved repair mechanism: heat shock proteins (HSPs). HSPs are induced instantly, within seconds to minutes, by almost any type of cellular stress or injury. In the absence of lethal cell damage, HSPs are extremely effective in repairing and restoring living cells to a more normal functional state. HSPs are temporary, generally peaking in hours and lasting for days, but their effects can be long lasting. HSPs reduce inflammation, a common factor in many retinal disorders, including diabetic retinopathy (DR) and AMD.

Laser therapy induces HSP activation and, in the case of retinal treatment, therefore alters and normalizes retinal cytokine expression. The more sudden and severe the non-lethal cellular stress (such as laser irradiation), the more rapid and robust HSP production. Thus, a burst of repeated bursts at a very abrupt rate of change (~7°C rise in each 100 μs micropulse, or 70,000°C/sec) produced by each SDM exposure. Cold heat spikes have been shown to stimulate HSP production, particularly compared to non-lethal exposure to subthreshold treatment with continuous wave lasers, which can only duplicate low mean tissue temperature rises. Especially effective.

Laser wavelengths below 532 nm produce increasingly cytotoxic photochemical effects. At 532 nm-1300 nm and especially 880 nm-1000 nm, SDM produces radiant heat rather than photochemical cellular stress. Therefore, SDM can affect tissue, including the RPE, without damaging the tissue. Consistent with HSP activation, SDM produced rapid and significant improvements in retinal electrophysiology, visual acuity, and contrast visual acuity, in addition to rapid clinical effects such as improved macular sensitivity as measured by microperimetry. , also provide long-term effects such as reduction of DME and regression of retinal neovascularization.

In the retina, the clinical utility of SDM is therefore mediated by sublethal photothermal RPE HSP activation. In dysfunctional RPE cells, HSP stimulation with SDM results in normalization of cytokine expression and improves retinal structure and function. The therapeutic effect of this 'low-intensity' laser/tissue interaction is then amplified by 'high-density' laser application to recruit all the dysfunctional RPE to the targeted area, thereby increasing the therapeutic effect. maximize. These principles define the treatment strategies for SDM described herein. The ability of SDM to produce therapeutic effects similar to both drugs and photocoagulation is such that laser-induced retinal damage (for effects other than ablation) is unnecessary and non-therapeutic; It has been shown to be harmful due to loss of retinal function and triggering inflammation.

Since normally functioning cells do not require repair, HSP stimulation in normal cells tends to have no significant clinical effect. The "patho-selectivity" of near-infrared laser effects, such as SDM, on a variety of cell types, affecting diseased cells but not normal cells, has been demonstrated in clinical practice of SDM. consistent with observations. This ability is key to the suitability of SDM for early and prophylactic treatment of eyes with chronic progressive disease and eyes with minimal retinal abnormalities and minimal dysfunction. Finally, SDM was reported to have a clinically broad therapeutic window, unique among retinal laser modalities, consistent with the American National Standards Institute's "maximum permissible exposure" prediction. Although SDM can cause direct photothermal effects such as entropic protein unfolding and disaggregation, it has been optimized for clinically safe and effective stimulation of HSP-mediated retinal repair. It looks like there is

SDM does not produce laser-induced retinopathy (photocoagulation), has no known adverse treatment effects, and is associated with many retinopathies (diabetic macular edema (DME), proliferative diabetic retinopathy ( PDR), macular edema due to branch retinal vein occlusion (BRVO), central serous chorioretinopathy (CSR), reversal of drug resistance, and dry age-related macular degeneration, Stargardt disease, cone dystrophy, and retinal pigment It has been reported to be an effective treatment for prophylactic therapy of progressive degenerative retinopathies such as degeneration). The safety of SDM is such that it can be used transfoveally in eyes with 20/20 vision to reduce the risk of vision loss due to DME involving the early fovea. is.

As noted above, while SDM stimulation of HSPs is non-specific with respect to disease processes, the outcome of HSP-mediated repair is due to its own properties specific to dysfunctional states. HSPs tend to fix whatever is wrong. Thus, the observed effects of SDM on retinal conditions vary as widely as BRVO, DME, PDR, CSR, age-related and genetic retinopathies, and drug-resistant NAMD. Conceptually, this capability can be viewed as a kind of "Reset to Default" mode of SDM operation. For a wide range of disorders where cellular function is critical, the SDM triggers a "reset" (to "factory default settings") through HSP-mediated cellular repair. normalize cell function by subtracting

The inventors have discovered that SDM treatment of patients suffering from age-related macular degeneration (AMD) can slow progression and even stop progression of AMD. Most of the patients found significant improvement in dynamic functional logMAR mesopic visual acuity and mesopic contrastive acuity after SDM treatment. SDM is believed to act by targeting, preserving, and "normalizing" (approaching normality) the function of the retinal pigment epithelium (RPE).

SDM has also been shown to halt or reverse the development of the disease state of diabetic retinopathy without treatment-related damage or side effects despite persistence of systemic diabetes. On this basis, SDM has been shown to induce a return to normal cellular function and cytokine expression in diabetic RPE cells (pressing the 'reset' button on electronic devices to restore factory settings). similar to). Based on the above information and studies, SDM treatment may directly affect cytokine expression through heat shock protein (HSP) activation in targeted tissues.

As shown above, subthreshold diode micropulse laser (SDM) photostimulation was effective in stimulating direct repair of slightly misfolded proteins in ocular tissues. In addition to HSP activation, this can also occur in other ways. Because the spike in temperature caused by the micropulse in the form of a heat time course allows the diffusion of water inside the protein, which prevents the protein from reverting to its native state of peptide-peptide hydrogen bonds. This is because it enables cutting. Diffusion of water into the protein increases the number of inhibitory hydrogen bonds approximately 1000-fold. Therefore, it is believed that this process can be advantageously applied to other diseases as well.

As explained above, the energy source applied to the target tissue has energy and operating parameters that must be determined and selected to achieve a therapeutic effect while not permanently damaging the tissue. As an example, using a light beam energy source such as a laser light beam, the laser wavelength, duty cycle, and total pulse train duration parameters must be taken into account. Other parameters that can be considered include the radius of the laser source as well as the average laser power. Adjusting or selecting one of these parameters may have an effect on at least one other parameter.

1 and 2 illustrate graphs showing average power in Watts comparing laser source radius (between 0.1 cm and 0.4 cm) and pulse train duration (0.1 to 0.6 seconds). is doing. FIG. 1 shows a wavelength of 880 nm and FIG. 2 has a wavelength of 1000 nm. It can be seen from these figures that the required power decreases monotonically as the laser source radius decreases, the total train duration increases, and the wavelength decreases. A preferred parameter for the radius of the laser source is between 1 mm and 4 mm. For a wavelength of 880 nm, the power minimum is 0.55 Watts, the laser source radius is 1 mm, and the total pulse train duration is 600 ms. With a laser source radius of 4 mm and a total pulse train duration of 100 ms, the maximum power for a wavelength of 880 nm is 52.6 Watts. However, if we choose a laser with a wavelength of 1000 nm, the minimum power value is 0.77 Watts, the radius of the laser source is 1 mm, the total pulse train duration is 600 ms, and the With a radius of 4 mm and a total pulse duration of 100 ms, the maximum power value is 73.6 Watts. The corresponding peak power during each pulse is obtained from the average power by dividing by the duty cycle.

The volume of the tissue portion heated is determined by the wavelength, the absorption length in the relevant tissue, and the beam width. The total pulse duration and average laser power determine the total energy delivered to warm the tissue, and the duty cycle of the pulse train gives the associated spike or peak, power related to the average laser power. Preferably, the pulsed energy source energy parameters are selected such that approximately 20-40 Joules of energy are absorbed into each cubic centimeter of target tissue.

To maintain the average temperature of the target tissue in a low temperature range, such as less than 6° C. or less than 1° C., for an extended period of time, such as minutes, while producing the therapeutic effects of the present invention, maximum It has been found that the target tissue can be heated to about 11°C at . The selection of duty cycle and total pulse train duration provides a time interval during which heat can dissipate. A duty cycle of less than 10%, preferably between 2.5% and 5% has been found to be effective, along with a total pulse duration of 100 ms to 600 ms.

It has been found that an average temperature rise of the desired target area, increasing from at least 6° C. to a maximum of 11° C., and preferably approximately 10° C., during the total irradiation period results in HSP activation. Control of target tissue temperature is determined by choosing source and target parameters whereby the integral Arrhenius for HSP activation is greater than 1, while ensuring conservative FDA/FCC requirements to avoid damage or the damage Arrhenius integral is less than one.

To meet conservative FDA/FCC constraints that avoid permanent tissue damage, the average temperature rise of the target tissue over a period of 6 minutes is no more than 1°C for light beams and other sources of electromagnetic radiation. A typical decay time required for the temperature in the heated target region to decrease by thermal diffusion from a temperature rise of approximately 10° C. to 1° C., a wavelength of 880 nm, and a source diameter of 1 millimeter. , the temperature decay time is 16 seconds. The temperature decay time is 107 seconds when the source diameter is 4 mm. For a wavelength of 1000 nm, the temperature decay time is 18 seconds when the source diameter is 4 mm and the temperature decay time is 136 seconds when the source diameter is 1 mm. This is well within the time of the average temperature rise being maintained over several minutes, such as 6 minutes or less. Although the temperature of the target tissue is raised very quickly, such as C, such as a fraction of a second, to approximately 10° C., during application of the energy source to the tissue, a relatively low duty cycle may Providing relatively long periods between pulses of applied energy, relatively short pulse train durations provide sufficient temperature within relatively short periods of time, including minutes, such as six minutes or less, without permanent tissue damage. ensure the diffusion and decay of

As far as therapeutic HSP activation and protein repair promotion are concerned, the pulse train mode of energy delivery has distinct advantages over single pulse or stepwise modes of energy delivery. There are two considerations about this advantage: First, a significant advantage for HSP activation and protein repair in the SDM energy delivery mode results from the generation of spike temperatures of approximately 10°C. This large temperature increase has a large impact on the Arrhenius integral, which quantitatively describes the number of HSPs that are activated, and the rate of water diffusion into proteins, which promotes protein repair. This is because temperature enters an exponential function which has a large amplifying effect. Secondly, it is important that the temperature rise does not remain at a high value (above 10°C) for a long time, because this means that over a period of minutes the average temperature rise is 1°C (6°C for ultrasound). ) to violate FDA and FCC requirements.

The SDM mode of energy delivery uniquely meets both of these previous considerations through judicious selection of power, pulse time, pulse interval, and volume of the target area to be treated. The temperature is rapidly increased by approximately 10°C so that the long-term average temperature rise does not exceed the long-term FDA/FCC limits of 6°C for ultrasonic frequencies and 1°C or less for electromagnetic radiation energy sources. The volume of the treatment area enters because it must decay from its high value in °C.

Referring now to Figure 3, a schematic diagram illustrates a system for implementing the process of the present invention. The system, generally referred to by reference numeral (30), includes a laser console (32), such as, for example, an 810 nm near-infrared micropulse diode laser in the preferred embodiment. The laser produces a beam of laser light that is passed through an optical element, such as an optical lens or mask, or optionally multiple optical lenses and/or masks (34). Laser projector optics (34) provide a coaxial wide field of view non-contact digital optical viewing system/camera (36) for projecting the formed light beam onto the patient's eye (38). pass through It is understood that the box labeled (36) can represent both the laser beam projector and the viewing system/camera, which in practice can include two different components. A coaxial, wide-field, non-contact digital optical viewing system/camera (36) provides the necessary computerization to operate the laser (32), optics (34), and/or projection/viewing components (36). provide feedback to a display monitor (40) which may also include hardware, data inputs and controls, etc.

As discussed above, current treatments require the application of multiple individual laser beam spots that are applied singly to the target tissue to be treated. The number can be in the hundreds or thousands for the desired treatment area. This is very time consuming and laborious.

Referring now to Figure 4, in one embodiment, a laser light beam (42) is passed through a collimator lens (44) and then through a mask (46). In a particularly preferred embodiment, mask (46) comprises a diffraction grating. The mask/grating (46) provides a geometric object, or more typically a geometric pattern of multiple simultaneously generated laser spots, or other geometric object. This is represented by a plurality of laser light beams labeled (48). Alternatively, multiple laser spots can be generated by multiple fiber optic wires. Both methods of generating laser spots allow simultaneous generation of a large number of laser spots over a very large treatment field, such as consisting of the entire retina. In fact, a large number of laser spots, perhaps in the hundreds, thousands or more, can cover the entire fundus and retina, including the macula and fovea, retinal vessels and optic nerve. The intent of the process in the present invention is to ensure complete and total coverage and treatment by generously applying the laser to the retina to improve vision.

Using optical features with feature sizes comparable to the wavelength of the laser utilized permits simultaneous application of a large number of laser spots for very large target areas, for example using diffraction gratings. It is possible to exploit quantum mechanical effects. All the individual spots produced by such a grating are optically shaped like the incident beam with minimal power variation for each spot. As a result, multiple laser spots with sufficient irradiance provide simultaneous harmless yet effective therapeutic application over a large target area. The present invention also contemplates the use of geometric objects and patterns provided by other diffractive optical elements.

Laser light passing through the mask (46) is diffracted, resulting in a periodic pattern spaced from the mask (46), indicated by the laser beam labeled (48) in FIG. A single laser beam (42) was then shaped into a plurality of hundreds or even thousands of individual laser beams (48) to create the desired pattern of spots or other geometric objects. These laser beams (48) may be passed through additional lenses and collimators (50), (52), etc. to transmit the laser beams and form the desired pattern on the patient's retina. Such additional lenses and collimators (50), (52), etc. can further transform and redirect the laser beam (48) as desired.

Arbitrary patterns can be constructed by controlling the shape, spacing and pattern of the optical mask (46). Patterns and exposure spots can be arbitrarily created and changed as desired according to application requirements by professionals in the field of optical engineering. Photolithographic techniques, particularly those developed in the field of semiconductor manufacturing, can be used to create patterns of simultaneous geometric spots or other objects.

Although hundreds or thousands of simultaneous laser spots can be generated, created, and shaped into patterns that are applied to eye tissue, due to the requirement not to overheat the eye tissue, and particularly the lens of the eye, the present invention There is a limit to the number of treatment spots or beams that can be used simultaneously according to . Each individual laser beam or spot requires a minimum average power over the effective column duration. At the same time, however, eye tissue cannot exceed a certain temperature rise without being damaged. For example, there is a 4° C. constraint on the temperature rise of the eye lens that sets an upper limit on the average power that can be sent through the lens without overheating and damaging it. For example, using an 810 nm wavelength laser, the number of simultaneous spots generated and used is 0.04 (4%) duty cycle and 0.3 seconds (300 ms) total train Duration can be as little as 1 to approximately 100 when used for pan-retinal coverage. As the wavelength increases, the water absorption increases, resulting in heating over a long path through the vitreous humor in front of the retina. For shorter wavelengths, eg 577 nm, the absorption coefficient in the melanin of the RPE can be higher and therefore the laser power can be lower. For example, at 577 nm, the power can be lowered by a factor of 4 for the present invention to be effective. Therefore, when using 577 nm wavelength laser light, there can be as little as a single laser spot or up to approximately 400 laser spots and still the eye is not harmed or damaged.

The present invention can use a large number of simultaneously generated therapeutic beams or spots, such as dozens or hundreds, and the parameters and methodology of the present invention are therapeutically effective, non-destructive, and non-permanent. Generating a targeted damaging treatment allows a laser light spot to be applied to any part of the retina, including the fovea, while the prior art does not remove damage from exposure to conventional laser beam methods. , resulting in visual loss and other complications, the inability to use a large number of simultaneous laser spots to avoid accidental exposure of sensitive areas of the retina such as the fovea, and frequently limited to only one treatment laser beam.

FIG. 5 diagrammatically illustrates a system that couples multiple light sources to the pattern-generating optical subassembly described above. Specifically, this system (30') is similar to the system (30) described in Figure 3 above. The main difference between the alternative system (30') and the previously described system (30) is the inclusion of multiple laser consoles (32), the outputs of which are each fed to a fiber coupler (54). The fiber coupler produces a single output that is passed to laser projector optics 34 as described in previous systems. Coupling of multiple laser consoles 32 into a single optical fiber is accomplished using fiber couplers 54 as is known in the art. Other known mechanisms for combining multiple light sources are also available and may be used to replace the fiber couplers described herein.

In this system (30'), the multiple light sources (32) follow paths similar to those described in the previous system (30): collimated, diffracted, re-collimated, and steered. Oriented to the retina using a mechanism. In this alternative system (30'), the diffractive element must function differently than previously described, depending on the wavelength of the light passing through, which results in a slightly different pattern. change. The change is linear with the wavelength of the light source being diffracted. Generally, the difference in diffraction angles is small enough that different overlapping patterns can be directed along the same optical path through the steering mechanism 36 towards the retina 38 for treatment. Small differences in diffraction angles affect how the steering pattern achieves retinal coverage.

Since the resulting pattern changes slightly for each wavelength, the successive offsetting to achieve full coverage is different for each wavelength. Continuous offset can be achieved in two modes. In the first mode, all wavelengths of light are applied simultaneously without identical coverage. An offset steering pattern is used to achieve full coverage for one of the multiple wavelengths. Thus, light of the selected wavelength achieves complete coverage of the retina, whereas application of other wavelengths achieves either incomplete or overlapping coverage of the retina. The second mode applies each light source of varying or different wavelengths sequentially with appropriate steering patterns to achieve complete coverage of the retina for that particular wavelength. This mode precludes the possibility of simultaneous treatment using multiple wavelengths, but makes it possible to achieve identical coverage for each wavelength by optical means. This avoids incomplete coverage and overlapping coverage for any of the optical wavelengths.

These modes can also be combined and matched. For example, two wavelengths may be applied simultaneously, one wavelength to achieve complete coverage and another wavelength to achieve incomplete or overlapping coverage, followed by a third wavelength in succession. may be applied to achieve complete coverage.

Figure 6 diagrammatically illustrates yet another alternative embodiment of the system (30'') of the present invention. This system (30'') is configured substantially similarly to the system (30) depicted in FIG. The main difference is the inclusion of subassembly channels that produce multiple patterns tuned to the specific wavelengths of the light source. A plurality of laser consoles (32) are arranged in parallel, each one leading directly to its own laser projector optics (34). The laser projector optics of each channel (58a), (58b), (58c) include a collimator (44), a mask or grating (48), and a recollimator, as described above in connection with FIG. The entire set of optical elements, including (recollimators) (50), (52), are tuned to the specific wavelengths produced by the corresponding laser consoles (32). The output from each set of optical elements (34) is then directed to a beam splitter (56) for combination with other wavelengths. It is known to those skilled in the art that beamsplitters used in reverse can be used to combine multiple light beams into a single output.

The combined channel output from the final beamsplitter (56c) is then directed through the camera (36) applying a steering mechanism to allow full coverage of the retina (38).

In this system (30''), the optical elements for each channel are adjusted to produce a precise specified pattern for the wavelength of that channel. Consequently, when the channels are all combined and properly aligned, a single steering pattern can be used to achieve complete coverage of the retina for all wavelengths.

The system (30'') includes as many channels (58a), (58b), (58c), etc. and beam splitters (56a), (56b), (56c), etc. as there are wavelengths of light being used for treatment. can be used.

Implementations of the system (30'') may exploit different symmetries to reduce the number of alignment constraints. For example, the proposed grid pattern is periodic in two dimensions and manipulated in two dimensions to achieve complete coverage. As a result, if the pattern for each channel is identical to the specified pattern, the actual pattern for each channel need not be aligned to the same steering pattern to achieve full coverage for all wavelengths. do not have. Each channel only needs to be optically aligned to achieve efficient combining.

In system (30''), each channel begins with a light source (32), which may be from an optical fiber, such as in other embodiments of the pattern generating subassembly. This light source (32) is directed to a light assembly (34) for collimation, diffraction, recollimation and to a beam splitter that combines the channels with the main output.

The field of photobiology has revealed that different biological effects can be achieved by exposing target tissue to lasers of different wavelengths. The same can also be achieved by sequentially applying multiple lasers of different or the same wavelength in sequence with variable periods of separation and/or different irradiation energies. The present invention contemplates the use of multiple lasers, light or emission wavelengths (or modes) applied simultaneously or in sequence to maximize or customize the desired treatment effect. This method also minimizes potential adverse effects. The optical techniques and systems illustrated and described above provide simultaneous or sequential application of multiple wavelengths.

The invention described herein is generally safe for pan-retinal and/or trans-foveal procedures. However, the user, the surgeon, should be prepared to limit treatment to specific areas of the retina where disease markers are located, or to prevent treatment in specific areas with darker pigmentation, such as from scar tissue. (preparing) is possible. In this case, the camera (36) may be equipped with an iris diaphragm (72) configured to selectively widen or narrow an aperture through which light is directed into the patient's eye (38). ). Figure 7 illustrates an aperture (74) on a camera (36) equipped with such an iris diaphragm (72). Alternatively, the iris diaphragm (72) may be replaced or supplemented by a liquid crystal display (LCD) (76). The LCD 76 acts as a dynamic diaphragm by allowing each pixel in the display to transmit or block light passing through. Such an LCD (76) is depicted in FIG.

Preferably, any one of the systems (30), (30'), (30'') of the present invention includes a display on user interface having a live image of the retina as viewed through the camera (36). . A user interface may include an overlay of this live image of the retina to select areas where treatment light is confined or restricted or excluded by iris diaphragm 72 and/or LCD 76 . A user may draw an outline on a live image, such as on a touch screen, and then select either inside or outside that outline to have limited or excluded coverage.

As an example, if a user were to identify scar tissue on the retina to be excluded from treatment, the user would draw an outline around the scar tissue and then mark within that outline for exclusion from laser therapy. . The control system and user interface will then send appropriate control signals to the LCD 76 to block the projected treatment light through the pixels over the selected scar tissue. The LCD 76 provides an additional effect that is useful for area attenuation of the projected pattern. This feature may be used to limit the peak power output of specific spots within the pattern. Limiting the peak power of a particular spot in the pattern with the highest power output can be used to make the treatment power more uniform across the retina.

Alternatively, the surgeon may use the fundus monitor to delineate the area of the retina to be treated or avoided, and the designated area is then marked on the obstructing LCD (76). Treated or avoided by software directing the treatment beam to treat or avoid the area without the need or use of a diaphragm.

Typically, the system of the present invention incorporates a guidance system to ensure complete and holistic retinal treatment with retinal photostimulation. This guidance system is to be distinguished from conventional retinal laser guidance devices that are used to both direct treatment to specific retinal locations; To supervise at a distance, the treatment method of the present invention can treat the fovea, the entire retina, the fovea, including the fovea optic nerve, etc., which are damaged by conventional laser therapy, in a harmless manner. Furthermore, protection from accidental vision loss due to accidental patient movement is not an issue. Instead, patient motion will primarily affect the guidance in tracking the application of laser light to ensure adequate coverage. Fixation/tracking/registration systems, consisting of visual targets, tracking mechanisms, and linked system operations, are common in many ophthalmic diagnostic systems and can be incorporated into the present invention.

In a particularly preferred embodiment, the geometric pattern of simultaneous laser spots are successively offset to achieve confluent and complete treatment of the retinal surface. Segments of the retina may be treated according to the present invention, but more ideally the entire retina is treated within one treatment session. This is done saving time by applying multiple spots to the entire fundus at once. This pattern of simultaneous spots is scanned, shifted, and reoriented as an entire array in succession to cover the entire retina in a single treatment session.

This can be done in a controlled manner using the optical scanning mechanism (60). Figures 9 and 10 illustrate an optical scanning mechanism (60) that may be used in the form of MEMS mirrors, which comprises a base (62) with electronically actuated controls (64) and (66). The controller acts to tilt and pan the mirror (68) when electricity is applied and removed therefrom. By applying electricity to the controllers (64) and (66), the mirror (68) is moved so that the simultaneous pattern of laser spots, or other geometric objects reflected thereon, is changed accordingly. are moved onto the patient's retina. This can be done, for example, using an electronic software program that adjusts the light scanning mechanism (60) until complete coverage of the retina, or at least the portion of the retina desired to be treated, is exposed to phototherapy. It can be done in an automated way. The optical scanning mechanism may also be a small beam diameter scanning galvanometer mirror system, or similar system such as that distributed by Thorlabs. Such systems can scan the laser with the desired offset pattern.

Since the parameters of the present invention determine that the applied radiant energy or laser light is not destructive or damaging, the geometric pattern of the laser spot can be, for example, nondestructive or permanent to tissue. Can be duplicated without damage. However, in a particularly preferred embodiment, as illustrated in FIG. 11, the pattern of spots creates spaces between immediately preceding exposures to allow heat dissipation and prevent possible thermal damage or tissue destruction. are offset with each exposure. Thus, as illustrated in FIG. 11, the pattern illustrated for typical purposes as a grid of 16 spots is offset with each exposure such that the laser spots occupy a different space than the previous exposure. . It is understood that the graphical use of filled dots in addition to round or empty dots is for graphical purposes only to illustrate prior and subsequent exposure of a pattern of spots onto an area in accordance with the present invention. be. Laser spot spacing prevents overheating and damage to tissue. It is understood that this is done until the entire retina (the preferred methodology) has received phototherapy or the desired effect has been achieved. This can be done, for example, by a scanning mechanism, such as by applying an electrostatic torque to a micromachined mirror, as illustrated in FIGS. 9 and 10. FIG. By combining small retinal laser spots separated by exposure-free areas, prevention of heat accumulation, and the use of grids with a large number of spots per surface, large retinal laser spots with short exposure durations can be produced much more rapidly than current techniques possible. It is possible to treat the target area atraumatically and invisibly.

By rapidly and continuously repeating the reorientation or offset across a simultaneously applied grid array of spots or geometric objects, complete coverage of a target such as the human retina is rapidly achieved without thermal tissue damage. can be This offset can be algorithmically determined to ensure the fastest treatment time and the least risk of thermal tissue damage, depending on the laser parameters and desired application. The following were modeled using the Fraunhoffer Approximation. A mask with a 9×9 square grid was used, with an aperture radius of 9 μm, an aperture spacing of 600 μm, a wavelength laser of 890 nm, a mask-lens separation of 75 mm, and a doublet of 2.5 mm×2.5 mm. With the following mask sizes, the following parameters yield a grid with 19 spots per side separated by 133 μm with a spot size radius of 6 μm. Desired area side length 'A', output pattern spots per side of square 'n', separation between spots 'R', spot radius 'r', and desired square side length 'A' for treating the area. Considering , the number of exposures "m" needed to treat (concentrated coverage with small spot applications) can be given by the following formula:

With the setup described above, the number of manipulations m required to treat the different field areas of exposure can be calculated. For example, a 3 mm by 3 mm area useful for treatment requires 98 offset operations, requiring a treatment time of approximately 30 seconds. Another example would be a 3 cm×3 cm area representing the entire surface of the human retina. For such a large treatment area, a much larger secondary mask size of 25 mm×25 mm was used, resulting in a treatment grid of 190 spots per side separated by 133 μm with a spot size radius of 6 μm. obtain. Since the secondary mask size was increased by the same factor as the desired treatment area, the number of offset operations of approximately 98, and therefore the treatment time of approximately 30 seconds, remains constant. These treatment times represent at least a 10- to 30-fold reduction in treatment time compared to current methods of sequential individual laser spot application. A 3 mm field allows treatment of the entire human macula in a single exposure, which is useful, for example, in treating common blindness diseases such as diabetic macular edema and age-related macular degeneration. Running through 98 consecutive offsets ensures full macular coverage.

Of course, the number and size of retinal spots generated in a simultaneous pattern array may be easily and highly varied, thereby increasing the number of successive offset operations required to complete the procedure. , can be readily adjusted according to the therapeutic requirements of a given application.

In addition, quantum mechanical behavior can be observed that allows arbitrary distribution of laser input energy due to small apertures utilized in diffraction gratings or masks. This allows the generation of arbitrary geometric shapes or patterns, such as multiple spots in a grid pattern, lines, or other desired pattern. Other methods of generating geometric shapes or patterns, such as using multiple fiber optic fibers or microlenses, may also be used in the present invention. Time savings from the use of simultaneous projection of geometries or patterns allows treatment of novel sizes, such as 1.2 cm^2 areas, to achieve treatment of the entire retina in a single clinical setting or treatment session. Allows irradiation fields.

12 and 13, instead of geometric patterns of small laser spots, the present invention contemplates the use of other geometric objects or patterns. For example, a single line of laser light (70) can be produced, either continuous or formed by a series of closely spaced spots. An offset optical scanning mechanism can be used to sequentially scan a line over an area, illustrated by the downward pointing arrows in FIG. Referring now to Figure 13, the same geometric object of line (70) can be rotated to create a circular field of view for phototherapy, as illustrated by the arrows. However, a potential drawback of this approach is that the central area may be exposed repeatedly and reach unacceptable temperatures. However, this may be overcome by increasing the time between exposures or by creating gaps in the lines so that the central area is not exposed.

Power limitations in current micropulse diode lasers require fairly long exposure durations. The longer the exposure, the more important the heat dissipation at the center spot to unexposed tissue in the remainder of the laser spot and to the underlying choriocapillaris plate, such as in the retina. Therefore, the micropulsed laser light beam of an 810 nm diode laser should require an exposure envelope duration of 500 milliseconds or less, and preferably approximately 300 milliseconds. Of course, if the micropulse diode laser becomes more powerful, the exposure duration should be shortened accordingly.

Apart from power limitation, another parameter of the invention is the duty cycle, ie the frequency of the train of micropulses, or the length of thermal relaxation time between consecutive pulses. The use of adjusted duty cycles of 10% or greater to deliver micropulsed lasers at similar irradiances at similar MPE levels could significantly increase the risk of lethal cell damage, especially in denser fundus. Do you get it. However, duty cycles of less than 10%, and preferably around 5% or less, demonstrate sufficient heat elevation and treatment at the level of MPE cells to stimulate a biological response, but dark staining. It remains below levels predicted to cause lethal cell damage even in the treated fundus. However, the lower duty cycle increases the exposure envelope duration, which in some instances can exceed 500 milliseconds.

Each micropulse lasts only milliseconds and is typically 50-100 microseconds in duration. Therefore, for exposure envelope durations of 300-500 ms, and at duty cycles of less than 5%, a significant amount of time is wasted between micropulses to allow for thermal relaxation times between successive pulses. be. Typically, a thermal relaxation time delay of 1-3 milliseconds and preferably approximately 2 milliseconds is required between successive pulses. For adequate treatment, the retinal cells are typically exposed or hit with laser light for 50-200, and preferably 75-150 times at each location. Total according to the embodiments described above to treat a given area, or more specifically, a location on the retina that has been exposed to the laser spot, with a relaxation or interval time of 1-3 milliseconds. The time is on average between 200 ms and 500 ms. A thermal relaxation time is required in order not to overheat the cells within the location or spot and to prevent the cells from being damaged or destroyed. A time of 200-500 milliseconds does not appear to be long, but given the small size of the laser spot and the need to treat a relatively large area of the retina, treatment of the entire macula or the entire retina is particularly recommended. From the point of view of the patient undergoing

Accordingly, the present invention provides for applying laser light to a second treatment area of the retina and/or fovea that is spaced apart from the first treatment area, i.e. an additional area. Intervals between laser light applications (typically between 1-3 milliseconds) are utilized. The laser beam is returned to the first, or previous, treatment position within a predetermined time interval to allow sufficient thermal relaxation between successive pulses to achieve the desired therapeutic benefits of the present invention. Time is provided, and yet the cells at those locations or regions are sufficiently treated by adequately raising the temperature of those cells over time by repeatedly applying laser light to the location.

It is important to return to the previously treated position within 1-3 milliseconds, and preferably within approximately 2 milliseconds, so that the area cools sufficiently during that time, and within the required time window. It is also possible to treat For example, one cannot wait a second or two because the treatment will not be effective, or perhaps not effective at all, and then return to the previously treated area that has not yet received the necessary and sufficient treatment. However, during that time interval, typically approximately 2 milliseconds, at least one other region, and typically a plurality of regions, has a laser light pulse of typically 50-100 microseconds duration. As such, it can be treated by the application of laser light. The number of additional regions that can be treated is limited only by the duration of the micropulses and the ability to controllably move the laser light beam from one region to another. Currently, approximately four additional regions, well spaced apart from each other, can be treated during the thermal relaxation interval beginning with the first treatment region. Thus, multiple regions can be treated, at least partially, during an exposure envelope of 200-500 milliseconds relative to the first region. Thus, instead of only 100 simultaneous light spots being applied to the treatment area in a single time interval, approximately 500 light spots can be applied at different treatment areas during that time interval. This would apply, for example, to a laser light beam with a wavelength of 810 nm. For shorter wavelengths, such as 570 nm, even multiple individual locations can be exposed to the laser beam to create light spots. Thus, instead of up to approximately 400 spots simultaneously, approximately 2,000 spots can be covered during the micropulse treatment interval for a given area or location.

As mentioned above, typically each position is 50-200 and more typically 75-50 over the exposure envelope duration (typically 200-500 milliseconds) to achieve the desired treatment. It has 150 light applications. According to one embodiment of the invention, laser light will be reapplied to previously treated regions in sequence during the relaxation time interval for each region or location. This is repeated until a predetermined number of applications of laser light for each area to be treated is achieved.

This is illustrated graphically in FIGS. 14A-14D. FIG. 14A exemplifies the first region where the laser light is applied as the first application with a solid line circle. The laser beam is directed to the second, as illustrated in FIG. 14B, until the position in the first exposure area needs to be re-treated by letting the laser light again be applied within the thermal relaxation time interval. is offset or microshifted to the exposure area of 1, followed by a third exposure area and a fourth exposure area. Locations within the first exposure area are then reapplied with laser light, as illustrated in FIG. 14C. Shaded lines are entered until the desired number of exposures or hits or applications of light, illustrated schematically by the darkened circles of exposed areas 1 in FIG. 14D, are achieved to therapeutically treat those areas. A secondary or subsequent exposure occurs in each exposed area, as illustrated in FIG. 14D by the dots or circles. Once the first or previous exposure areas have been treated, the system can add additional exposure areas and the process is repeated until the entire area of the retina to be treated has been sufficiently treated. Solid circles, dashed circles, partially shaded circles, and so on, because exposure to laser light in accordance with the present invention is in fact invisible and undetectable to the human eye as well as known detection equipment and techniques. , and the use of fully shaded circles is for illustrative purposes only.

Adjacent exposed areas must be separated by at least a predetermined minimum distance to avoid thermal tissue damage. Such distance is at least 0.5 diameters, and more preferably 1-2 diameters away from the most recently treated location or area. Such spacing is related to the actual treated position in the previous exposure field.
It is contemplated by the present invention that a relatively large area may actually include multiple exposure areas that are offset in a different manner than illustrated in Figures 14A-D. For example, the exposed areas may include the thin lines illustrated in Figures 12 and 13, which are exposed repeatedly in sequence until all the required areas have been sufficiently exposed and treated. In accordance with the present invention, the area can include a limited area of the retina, a full macular or panmacular treatment area, or an area of the entire retina including the fovea. However, with the methodology of the present invention, the time required to treat the retina to be treated or that area of the entire retina is such that a single treatment session would take much less time for the healthcare provider. , and so that the long duration does not have to be uncomfortable for the patient, such as by a factor of 4 or 5.

In accordance with this embodiment of the invention, in which one or more treatment beams are applied to the retina once and the treatment beams are moved to a series of new positions, repeatedly returning the beams to the same position or area to re-treat requires a total exposure. It has been found that less power is required compared to methodologies that maintain the laser beam in the same position or area for the envelope duration. With reference to FIGS. 15-17, there is a linear relationship between required pulse length and power, but a logarithmic relationship between heat generated.

With reference to FIG. 15, a graph is provided in which the X-axis represents logarithm (Log) of average power in Watts and the Y-axis represents treatment time in seconds. The lower curve is for panmacular treatment and the upper curve is for panretinal treatment. This is for a laser light beam with a micropulse time of 50 microseconds, a time of 2 milliseconds between pulses, and a train-on-spot duration of 300 milliseconds. The area of each retinal spot is 100 microns and the laser power for these 100 micron retinal spots is 0.74 watts. The panmacular area is 0.55 cm ² , requiring a total of 7,000 panmacular spots, and the panretinal area requires 42,000 laser spots for complete coverage.3. 30 ^cm2 . Each RPE spot requires a minimum energy, namely 38.85 Joules for panmacular and 233.1 Joules for panretinal, to fully activate its reset mechanism according to the present invention. As expected, the shorter the treatment time, the higher the average power required. However, there is an upper limit to the average power that can be tolerated, which limits the extent to which treatment times can be shortened.

As mentioned above, not only are there power limitations on available and used laser light, but there are also limitations on the amount of power that can be applied to the eye without damaging eye tissue. For example, the temperature rise in the lens of the eye is limited to, say, 4° C. so as not to overheat and damage the lens, such as causing cataracts. Therefore, an average power of 7.52 Watts can raise the lens temperature to approximately 4°C. This limitation of power increases the minimum treatment time.

However, referring to FIG. 16, the total power per pulse required is in the case of a microshift, which repeatedly and continuously moves the laser spot back to the previous treated position. less so that the total energy transmitted and the total average power during the treatment time are the same. Figures 16 and 17 show how the total power depends on treatment time. This is shown in FIG. 16 for pan-macular treatment and in FIG. 17 for pan-retinal treatment. The upper solid line or curve represents a microshift-free embodiment that exploits the thermal relaxation time interval, such as described and illustrated in FIG. 11, while the lower dashed line, such as described in FIG. and exemplified represent the situation for such microshifts. Figures 16 and 17 show that for a given treatment time, the peak total power is less with microshift than without microshift. This means that less power is required for a given treatment time using the microshift embodiment of the present invention. Alternatively, acceptable peak power can be used to advantage, reducing overall treatment time.

Thus, according to FIGS. 15-17, a logarithmic power of 1.0 (10 Watts) requires a total of 20 seconds of treatment using the microshift embodiments of the present invention as described herein. need time. Without the microshift it takes more than 2 minutes, instead leaving the micropulsed light beam in the same location or area for the entire treatment envelope duration. There is a minimum treatment time according to wattage. However, this treatment time with microshift is much shorter than without microshift. Because much less laser power is required for microshifts, power can be increased in some cases to reduce treatment time for a given desired retinal treatment area. The product of treatment time and average power is fixed for a given treatment area to achieve therapeutic treatment according to the present invention. This can be done, for example, by applying more therapeutic laser light beams or spots simultaneously with reduced power. Of course, since the parameters of the laser light are chosen to be therapeutically effective, yet not destructive or permanently damaging to the cells, no guiding or tracking beams are required and the present invention According to the invention, the treatment beam alone can treat all areas of the retina, including the fovea. Indeed, in particularly preferred embodiments, the entire retina, including the fovea, is treated according to the present invention, which is simply not possible using conventional techniques.

Unique features of the present invention allow for a simplified user experience while allowing a single set of optimized laser parameters that are less affected by midoptic opacification, retinal condensation, or fundus pigmentation. Interfaces are allowed. Although the motion controls are presented and can function in many different ways, the system allows a very simplified user interface with only two control functions available. That is, the first control function is the "activate" button, and pressing this button once during "standby" activates and initiates the treatment. Pressing this button during treatment prematurely interrupts treatment and returns to "standby" mode. Machine activation may be identified and indicated by an LED or the like adjacent to or within the button. A second control function may be a "field size" knob. A single depression of this button could program the unit to provide, for example, a 3 mm focus or "macular" field spot. A second depression of this knob allowed the unit to be programmed to yield a 6 mm or "posterior pole" spot. A third depression of this knob allowed the unit to be programmed to provide a "panretinal" or approximately 160°-220° panoramic retinal spot or coverage area. Manual rotation of this knob could result in different spot fields. Within each field, the density and intensity of treatment are identical. Field size variations are provided by optical or mechanical masking or apertures such as the described iris diaphragm or LCD aperture.

The fixed software allowed monitoring of the displayed image of the fundus. Prior to beginning the fundus landmark procedure, the optic nerve, or any part or feature of the patient's eye (assuming euphoria), etc., can be marked on the display screen by the operator. Treatment is initiated and the software takes an image of the fundus or other image-registered to any part of the patient's eye (assuming euphoria) to ensure adequate fixation. ) are monitored. A fixation break automatically precludes treatment. Displacement of fixation can be detected optically or by interception of a low-energy infrared beam projected parallel to and at the outer edge of the treatment beam by the edge of the pupil. As soon as fixation is established, treatment automatically resumes towards completion. At the end of the procedure, determined by the completion of convergent delivery of the desired laser energy to the target, the unit automatically ends exposure and defaults to "on" or "standby" mode. Due to the unique properties of this procedure, disruption of fixation only prolongs the treatment session without causing harm or risk of patient injury.

The laser can be projected onto the fundus through a wide-field, non-contact lens. Customized orientation of specific targets or regions of the fundus other than the laser field of view or the central region can be achieved by operator joystick or eccentric patient gaze. The laser delivery optics can be coaxially coupled to a wide field of view, non-contact digital fundus viewing system. The generated fundus image can be displayed on a video monitor visible to the laser operator. Maintaining a clear and focused image of the fundus can be facilitated by a joystick on the camera assembly that is manually oriented by the operator. Alternatively, adding a target registration and tracking system to the camera software results in a fully automated treatment system.

A fixation image may be displayed coaxially to the patient to facilitate eye alignment. This image may be altered in shape and size, color, intensity, blink rate, oscillation rate, or other factors during the procedure to avoid photoreceptor exhaustion, patient fatigue, and promote good fixation. The normal or continuous variation of is altered.

Additionally, results or images from other retinal diagnostic methods, such as OCT, retinal angiography, or autofluorography, may be used to guide, assist, or otherwise facilitate treatment of the patient's fundus. May be displayed alongside or overlaid with the display image. This juxtaposition or overlay of images can facilitate the identification of disease, damage or scar tissue on the retina.

The inventors have discovered that treatment according to the invention of patients suffering from age-related macular degeneration (AMD) can slow or even stop the progression of AMD. Further evidence of this restorative treatment effect is the inventor's finding that treatment can uniquely reduce the risk of vision loss in AMD due to choroidal neovascularization by 80%. Most of the patients had significantly improved dynamic functional logMAR visual acuity and contrast visual acuity after treatment with the present invention, and some had better visual acuity. It is thought to act by targeting, protecting, and "normalizing" (bringing closer to normal) the retinal pigment epithelium (RPE) in its function.

Treatment according to the present invention has been shown to be able to halt or reverse the development of the disease state of diabetic retinopathy, despite the persistence of systemic diabetes, without treatment-related damage or side effects. A study published by the inventors showed that restorative effects of treatment can uniquely reduce the risk of developing diabetic retinopathy by 85%. On this basis, the present invention suggests that, analogous to pressing the "reset" button on an electronic device to restore factory settings, more normal cellular function and cytokines in diabetes-affected RPE cells may be achieved. It is hypothesized that it may act by inducing a return to expression.

Based on the above information and studies, SDM treatment may directly affect cytokine expression and heat shock protein (HSP) activation in target tissues, particularly in the retinal pigment epithelium (RPE) layer. Panretinal and panmacular SD are noted by the inventors to slow the progression of many retinal diseases, including severe nonproliferative and proliferative diabetic retinopathy, AMD, DME, etc. It's here. The known therapeutic treatment benefits of individuals with these retinal diseases, coupled with the lack of known adverse treatment effects, include early and preventive treatment, open-ended treatment, as appropriate. Liberal application and retreatment can be considered. The theory of reset also suggests that the present invention may be applied to various types of RPE-mediated retinal disorders. Indeed, the inventors recently found that panmacular treatment has been shown to improve retinal function and health in dry age-related macular degeneration, retinitis pigmentosa, cone-rod retinal degeneration, and Stargardt's disease. It has been shown to be able to significantly improve retinal sensitivity and dynamic logMAR and contrast acuity, something no other treatment has been able to do before.

Retinal imaging and visual acuity testing now guide the management of chronic progressive retinal disease. Structural damage to tissues and/or organs and loss of vision are late symptoms of the disease, so treatment prescribed at this time must be intensive, often lengthy, expensive and It frequently fails to improve vision and rarely restores normal vision. The present invention has been shown to be an effective treatment for many retinopathies without adverse treatment effects, and by virtue of its safety and efficacy, it may also prevent the development or symptoms of retinopathy prophylactically or such. It can be used to treat the eye to stop or delay retinal disease as a prophylactic treatment. Treatments that improve retinal function, and therefore health, should also reduce disease morbidity, progression, maladjustment and visual loss of the disease. By initiating treatment early, before pathological structural changes, and maintaining treatment benefit with periodic functionally-directed retreatment, structural degeneration and vision loss, if not prevented, may be avoided. can be delayed. Even modest initial reductions in the rate of disease progression can lead to significant long-term reductions in vision loss and complications. By mitigating the consequences of primary deficits, the disease course can be muted, progression slowed, and complications and vision loss reduced. This is reflected in our study, which found that treatment reduced the risk of progression and vision loss in diabetic retinopathy by 85% and AMD by 80%.

The application of SDM has been used successfully in homeotrophy or "reset to default" by normalizing RPE function, retinal function and autoregulation, and RPE biofunction. , normal retinal physiology and autoregulation to slow, halt or even reverse the progression of myopia, particularly myopia in children, in the same way it does other chronic progressive retinopathies is believed to be recoverable.

A laser light beam is generated that is sub-lethal and produces true sub-threshold photocoagulation and retinal tissue, at least a portion of which is so as to provide prophylactic and protective treatment of the retinal tissue of the eye. Then, the exposed retinal or foveal tissue is exposed to the generated laser light beam without damaging the tissue. The treated retina can include fovea, fovea, retinal pigment epithelium (RPE), choroid, choroidal neovascular membrane, subretinal fluid, macula, macular edema, parafovea, and/or perifovea. The laser light beam may expose only a portion of the retina, or substantially the entire retina and fovea, or other eye tissue. This procedure is applied to ocular tissues such as retina and/or foveal tissue in eyes that are myopia or at risk of myopia.

Although most treatment effects appear to be long-lasting, if not permanent, clinical observations suggest that they may appear to wane from time to time. Therefore, the retina is periodically re-treated. This may occur according to a set schedule or when it is determined that the patient's retina is to be re-treated, such as by periodically monitoring the patient's visual and/or retinal function or symptoms.

Although several embodiments have been described in detail for purposes of illustration, various changes may be made without departing from the spirit and scope of the invention. Accordingly, the invention is not to be restricted except as by the appended claims.

Claims (10)

1. A system for applying a light beam to an eye having myopia or at risk of myopia, comprising:
A laser console for generating pulsed energy consisting of a light beam having energy parameters including a wavelength of 530 nm to 1300 nm, a duty cycle of less than 10%, and a pulse train duration of 0.1 seconds to 0.6 seconds, wherein the pulse energy is applied to ocular tissue. The pulse raises the eye tissue temperature up to 11° C. when applied to the eye tissue while maintaining the average temperature rise of the eye tissue for several minutes below a predetermined level so as not to permanently damage the eye tissue. a laser console that produces energy;
a projector that projects the pulse energy into an eyeball that has myopia or is determined to have myopia risk;
A system characterized by comprising: 2. The system of claim 1, wherein the pulsed energy raises the temperature of the ocular tissue by 6[deg.]C to 11[deg.]C during at least application of the pulsed energy source, causing activation of heat shock proteins in the ocular tissue. 3. The system of any one of claims 1-2, wherein the average temperature rise of the ocular tissue is maintained at approximately 1[deg.]C or less for several minutes. 4. The system of claim 3, wherein the average temperature rise of the ocular tissue is maintained at 1[deg.]C or less for 6 minutes. 5. The system of any one of claims 1-4, wherein the projector projects the pulse energy onto a plurality of ocular tissue regions separated by at least a predetermined distance to avoid thermal tissue damage. A scanning mechanism, wherein the scanning mechanism applies the pulsed energy to the first ocular tissue region, and after a predetermined period of time within a single treatment session, the pulsed energy source reapplies to the first ocular tissue region. and wherein the pulsed energy source is applied to a second ocular tissue area during intervals between application of pulsed energy to the first ocular tissue area. . 7. The system of any one of claims 1-6, wherein the pulsed light beam has a wavelength between 880 nm and 1000 nm and a duty cycle between 2.5% and 5%. 8. The system of any one of claims 1-7, wherein the pulsed light beam has a power between 0.5 and 74 Watts. 9. A system as claimed in any preceding claim, comprising an optical system consisting of an optical lens positioned between the laser console and the projector. 10. The system of Claim 9, wherein the optical system includes a mask that shapes the light beam into a plurality of spaced apart light beams that are simultaneously projected onto the ocular tissue.

Images