Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
  • A61F9/007—Methods or devices for eye surgery
  • A61F9/008—Methods or devices for eye surgery using laser
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
  • A61F9/007—Methods or devices for eye surgery
  • A61F9/008—Methods or devices for eye surgery using laser
  • A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
  • A61F2009/00863—Retina
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
  • A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
  • A61N2005/0645—Applicators worn by the patient
  • A61N2005/0647—Applicators worn by the patient the applicator adapted to be worn on the head
  • A61N2005/0648—Applicators worn by the patient the applicator adapted to be worn on the head the light being directed to the eyes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
  • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
  • A61N2005/0662—Visible light

Definitions

• FIG. 1 a diagrammatic view of an eye, generally referred to by the reference number 1 0, is shown.
• the eye 1 0 includes a cornea 1 2 which is a transparent front part of the eye that covers the iris and pupil 1 4 which is the variable-size black circular or slit-shaped opening in the center of the iris that regulates the amount of light that enters the eye.
• the lens 16 is a transparent biconvex structure in the eye that, along with the cornea 1 2, helps to refract light to be focused on the retina 1 8.
• the retina is a thin layer of neural cells that line the back of the eyeball which captures light and transforms it into electrical signals for the brain. It has many blood vessels 20 to nourish it.
• the fovea and macular region is a portion of the eye used for color vision and fine detail vision.
• the retinal pigmented epithelium (RPE) 24 is the pigmented cell layer just outside the neurosensory retina 1 8 that nourishes the retinal visual cells. It is firmly attached to an underlying choroid 26 which is a vascular layer of the eye 10 lined between the retina 1 8 and the sclera. The choroid 26 provides oxygen and nourishment to the outer layers of the retina 1 8.
• Melanin promotes visual acuity by scattering stray light away from the rods and cones and absorbing light reflected from the back of the eye. Melanin also serves as an antioxidant to aid in the prevention of retinal diseases, such as age-related macular degeneration. [Para 6] Many of these properties result from the fact that the absorption spectrum of melanin is very broad. In this respect, it is unique among
• the broadband absorption has been attributed to chemical heterogeneity, amorphous semiconducting, and scattering.
• scattering losses only account for a few percent of the broadband attenuation.
• melanin within the eye serves many important functions. The determination of the levels or concentrations of melanin within the eye can be important to ascertain. For example, laser treatments of eye diseases are based on inducing temperature rises in the RPE, which activates the eye’s natural repair mechanisms. In the near infrared, this results from the absorption of the infrared radiation by the melanin pigment in the RPE.
• the present invention is directed to a process for safely providing retinal phototherapy by adjusting one or more treatment parameters of the retinal phototherapy if the content or concentration of melanin in the RPE of the eye exceeds a predetermined amount.
• the present invention uses a two- wavelength reflectometry process for determining the levels or concentrations of melanin in the RPE and choroid of the eye, which is relatively simple and inexpensive.
• a first light beam having a wavelength between 550 nm and 900 nm is generated.
• the first light beam may have a wavelength of between 600 nm and 850 nm.
• the first light beam is applied into the eye, such as being applied to a retinal pigment epithelium (RPE) and a choroid of the eye.
• the amount of light reflected from the eye from the first light beam is measured. This may be done by using a reflectometer to measure the amount of light reflected from the eye from the first light beam.
• a second light beam having a wavelength between 550 nm and 900 nm is generated.
• the second light beam may have a wavelength between 600 nm and 850 nm.
• the second light beam is of a different wavelength than the first light beam.
• the first and second light beams preferably differ in
• the second light beam is applied into the eye, such as to the RPE and choroid of the eye.
• the amount of light reflected from the eye from the second light beam is measured, such as using a reflectometer.
• the level of melanin within the eye is calculated using the
• the calculating step includes the step of distinguishing the amount of light reflected by the first and second light beams from the RPE and the choroid.
• One or more treatment parameters of the retinal phototherapy is adjusted if the content or concentration of melanin in the RPE of the eye exceeds a predetermined amount.
• This can comprise adjusting at least one of a retinal spot size of a treatment light beam, a pulse train duration of the treatment light beam, a duty cycle of the treatment light beam, or a power of the treatment light beam.
• a retinal spot size of the treatment light beam may be increased.
• a pulse train duration of the treatment light beam may be lowered.
• a duty cycle of the treatment light beam may be lowered.
• a power of the treatment light beam may be lowered.
• the one or more treatment parameters are adjusted when the content of melanin in the RPE of the eye is determined to be at least four times greater than a normal content of melanin in the RPE. For example, if the content of the melanin in the RPE is determined to be four to eight times a normal melanin content of the RPE, for pulse train durations of the pulsed light beam retina therapy ranging from 0.2 to 0.5 seconds, one or more treatment parameters are adjusted. For example, the one or more treatment parameters are adjusted when the content of the melanin in the RPE is determined to be greater than 8xl 0 10 crrr 3 .
• the one or more treatment parameters of the retina therapy system may be automatically adjusted when the content of the melanin in the RPE of the eye exceeds the predetermined amount. A notification may be given that one or more retinal treatment parameters have been adjusted.
• FIGURE 1 is a diagrammatic view of an eye
• FIGURE 2 is a diagrammatic view of a system used in accordance with the present invention for determining concentrations of melanin within portions of an eye;
• FIGURE B is a graph illustrating wavelength dependence of the absorption of primary ocular pigments
• FIGURE 4 is a graph illustrating absorbance of eumelanin as a function of wavelength
• FIGURE 5 is a graph depicting two-way transmission through RPE melanin at ordinary concentrations
• FIGURE 6 is a graph illustrating variation of the RPE melanin transmission at different wavelengths
• FIGURE 7 is a graph illustrating angular distribution of an intensity function that is proportional to the differential cross-section for scattering from a prolate spheroid and spheres;
• FIGURE 8 is a graph depicting a comparison of RPE melanin absorption coefficient, melanin scattering coefficient, and structural matrix scattering coefficient;
• FIGURE 9 is a graph depicting a comparison of choroid melanin absorption coefficient, choroid melanin scattering coefficient, and choroid structural matrix scattering coefficient;
• FIGURE 1 0 is a graph depicting the reflectivity of choroid as a function of wavelength at a normal choroid melanosome density
• FIGURE 1 1 is a graph depicting the reflectivity of RPE as a function of wavelength at normal RPE and choroid melanosome densities;
• FIGURE 1 2 is a graph depicting a transmission factor of anterior retina versus wavelength
• FIGURE 1 3 is a graph depicting percentage changes in total reflectivity as a function of wavelength as RPE and choroid melanosome densities vary from the normal;
• FIGURE 1 4 is a contour plot at a first wavelength of percentage change in the total reflectivity in accordance with two-wavelength
• FIGURE 1 5 is a contour plot at a second wavelength of the percentage change in the total reflectivity in accordance with two-wavelength reflectometry, in accordance with the present invention
• FIGURE 1 6 is a graph showing the damage ratio of abnormal RPE melanin content to normal RPE melanin content at which damage can occur compared to a pulse train duration of pulsed light phototherapy;
• FIGURE 1 7 is a graph similar to FIG. 1 6, illustrating the damage ratio in a range of 200 milliseconds to 500 milliseconds of light phototherapy pulse train duration.
• the present invention is directed to a process for safely providing retinal phototherapy by determining concentrations of melanin within an eye, and particularly within the retinal pigment epithelium (RPE) and choroid of the eye. Determining the concentrations or levels of melanin within the RPE and choroid of the eye can be important in determining the health of the eye. For example, melanin functions as an antioxidant to aid in the prevention of retinal diseases, such as age-related macular degeneration. Determining the concentrations of melanin within the RPE or choroid of the eye can also be important in determining treatment of eye diseases.
• RPE retinal pigment epithelium
• an individual has abnormally elevated concentrations or levels of melanin within the RPE this can cause unanticipated elevated heating, and thus tissue destruction, when treating the eye, and particularly the retina, with light sources, such as infrared or near infrared laser light beams, such as those used in retinal phototherapy, such as photocoagulation or photostimulation.
• light sources such as infrared or near infrared laser light beams, such as those used in retinal phototherapy, such as photocoagulation or photostimulation.
• the invention takes into account the light absorbed and scattered by both the RPE and choroid layers in order to get an accurate picture of the amount of melanin in the RPE.
• the invention utilizes two wavelengths within a predetermined range of wavelengths in which melanin both absorbs and reflects these wavelengths.
• the wavelengths are distinct from one another, preferably towards the lower end and the upper end of the predetermined wavelength range, and the present invention measures the amount or degree of reflections and then determines the levels or concentrations of melanin within the RPE and choroid by taking into account both the absorption and the scattering or reflections of the two wavelengths.
• Laser console 102 generates a first light beam having a wavelength within a predetermined range.
• the range may be between 550 nm and 900 nm, typically between 600 nm and 850 nm.
• Wavelengths below the predetermined wavelength range begin to absorb and scatter light from other pigments, and wavelengths above the predetermined range of wavelengths of the present invention are increasingly absorbed by water.
• the predetermined wavelength range of the present invention is ideal for measuring the melanin levels of the RPE and choroid.
• the generated light beam is then passed through optics 106, which may be used to focus the light beam, filter the light beam, generate a plurality of light beams from the generated first light beam, or the like.
• optics 106 which may be used to focus the light beam, filter the light beam, generate a plurality of light beams from the generated first light beam, or the like.
• the light beam is then passed through projector 1 08, which may be a retina camera or the like, for projection into the eye 10, and more particularly so as to apply the first light beam to the RPE 24 and choroid 26 of the eye 1 0. Reflections from the RPE and choroid are detected by detector 1 1 0.
• the detector 1 1 0 in a particularly preferred embodiment is a reflectometer although other detector devices could be utilized such as those using interferometry such as an Optical Coherent Tomography (OCT) device.
• OCT Optical Coherent Tomography
• a second light beam is generated, such as by laser console 1 04.
• the second light beam has a wavelength between 550 nm and 900 nm, preferably 600 nm-850 nm, that is a different wavelength than the first light beam.
• the first and second light beams preferably differ in wavelength by at least 25 nm, and more preferably are near opposite ends or ranges of the wavelength range so that they can be more easily distinguished from each other when the light reflected by each is detected.
• the second light beam may pass through optics 106, as described above, and then through projector 1 08 into the eye 10, and particularly the RPE and choroid 24 and 26 of the eye 1 0.
• the light scattered and reflected by the second light beam is detected and measured by detector 1 10. It will be understood that the first and second light beams generated by consoles 1 02 and 104 can be applied to the eye 1 0 sequentially or simultaneously.
• the amount of light reflected from the RPE and the choroid by the first and second light beams is measured, and then a concentration of melanin within the RPE and choroid of the eye is determined using the measured amount of light reflected from the RPE and the choroid from the first and second light beams.
• the invention distinguishes the amount of light reflected by the first and second light beams from the RPE and the choroid and the measurements of the amount of light reflected from the first and second light beams may be applied to calculations and/or graphs or tables to determine the levels or concentrations of melanin within the choroid and more particularly the RPE.
• the determined level or concentration of melanin within the RPE can then be compared to anticipated or average levels of melanin within the RPE to determine if the melanin levels within the RPE of that eye are elevated or outside of the anticipated range.
• the melanin in the eye is primarily eumelanin, and its monomer has the chemical formula C1 8H1 0N2O4, and a molecular weight of 31 8.283, with a density of 1 .7 g/cc and an index of refraction of 1 .772.
• melanin is contained in protein-coded organelles, called
• melanosomes Inside the melanosomes, the melanin monomers, which have dimensions of less than ten Angstroms, combine to form aggregates.
• the aggregates have dimensions of several tens of Angstroms, and are made up of stacked sheets of covalently-bonded monomer, with the sheets having separations of 3.4 Angstroms. The sheets are held together by weaker pi-pi bonding forces.
• melanosomes in the RPE are different from those in the choroid.
• the melanosomes are located mainly in the apical region of the RPE cells and are elongated in shape, with the long dimension aligned with the apices in order to make close contact with the rods and cones.
• Typical widths of all foreign RPE melanosome are 250-500 nm, and typical lengths are 640-800 nm. These give 6.5x1 0 14 cubic centimeters for a typical melanosome volume.
• the melanin is rather densely packed in the RPE melanosomes, the melanin density in a monomer being 1 .7 g/cc.
• the melanosomes do not need to be elongated and are believed to be globular in shape.
• the density of melanin in the choroid is less than that in the RPE, with ranges of B.61 -8.05 mmol/L for RPE melanin, and 0.07-9.1 5 mmol/L for choroidal melanin.
• the choroid depth is 200 microns compared to 6-1 0 microns for the REP, there is much more melanin in the choroid than in the RPE.
• the number density of melanin is 3.38x10 18 crrr 3 with a mass density of 1 .8x10 3 g/cc, and since the melanin is all contained within melanosomes, the corresponding number density of melanosomes in the RPE is 1 0x10 10 crrr 3 .
• the density of melanin is 0.49x1 0 3 g/cc, corresponding to a melanosome number density of 5.4x10 9 crrr 3 .
• the linear spacing between the melanosomes is 5.7x10 4 cm, or 5.7 microns.
• FIG. B the absorption of blood, melanin, macular pigments, the lens, water, long wavelength sensitive visual pigments (LWS) and medium wavelength sensitive visual pigments (MWS) primarily within the visible range of wavelengths is illustrated.
• the blood layer is taken to be 23 microns thick with an oxygenation of 95%.
• the melanin density is 1 .32 at 500 nm
• the macular density is 0.54 at 460 nm.
• the lens density is 0.54 at 420 nm and the water density is 0.025 at 740 nm.
• the visual pigment densities are both 0.57 at their peaks.
• melanin dominates the absorption of laser light in the wavelength range generally between 550 nm and 900 nm, and more particularly between 600 nm and 850 nm as shown in FIG. 3.
• the absorption coefficient of melanin decreases considerably as the wavelength increases.
• the RPE melanin absorption is much larger than it is at the 850 nm upper end of a particularly preferred range of wavelengths.
• FIGURE 4 is a graph illustrating the absorbance of eumelanin as a function of wavelength, particularly between 250 nm and 700 nm.
• Eumelanin is the dominant component of the melanin in the eye.
• the present invention assumes exponential dependence of exp[-0.062X(nm), which is reflected in FIG. 4. If this result is combined with the prior finding of an optical density of 0.22 at 500 nm, this gives for the two-way transmission through the RPE of:
• the absorption coefficient of RPE melanin becomes sufficiently large that less of the reflected signal from the choroid can pass through to the detector.
• the reflected signal from the choroid at 600 nm is diminished considerably on passing through the RPE, while at 800 nm is not diminished nearly as much.
• the optical density of 500 nm is 0.22 for a normal RPE concentration.
• the thickness of the choroid is 200 microns.
• the optical density of the RPE melanin is 0.22 at 500 nm
• the choroid melanin has an optical density at 500 nm of 2.00.
• most of the radiation is absorbed. This means that the reflection from the sclera does not contribute appreciably to the reflection signal.
• a globular choroid melanosome has a comparable volume to an RPE melanosome, so as to have a radius of 2.5x10 5 cm, i.e. 250 nm.
• the cross-section for the scattering may be given by the Rayleigh expression:
• n med index of refraction of the medium in which the sphere is
• the solid line curve labeled“2” is for a sphere of the same volume as a prolate spheroid.
• the figure shows the resemblance of the scattering behavior to that described by Mie scattering from spheres.
• the semi major axis of the prolate spheroid is denoted by “a” and corresponds to one-half of the 720 nm (640-800 nm) dimension of the RPE melanosome.
• the semi minor axis of the prolate spheroid is denoted by “b”, and corresponds to one-half of the B00 nm (250-400 nm) dimension of the RPE melanosome.
• the wave number defined in equation [Be] is“k”.
• the radiation is assumed to be incident on the prolate spheroid along its major axis.
• the differential cross section for scattering is proportional to the intensity function of the ordinate in the figure. Accordingly, measurement of the areas under the dashed curve and under the solid curve of the sphere of equal volume (labeled“2”) in the figure reveals that the cross section for forward scattering (0 to 90 degrees) in the prolate spheroid is 1 .45 times that for forward scattering from a sphere of equal volume. Also, the cross section for backwards scattering (90-1 80 degrees) in the prolate spheroid is 0.6 that for backwards scattering from a sphere of equal volume.
• a choroidal melanosome is 1 .65 times more effective than an RPE melanosome in scattering radiation in the backwards direction.
• the ratio of the backwards scattering cross section to the total scattering cross section is 0.01 8, i.e. only 1 .8% of the scattered radiation is in the backwards direction. This is consistent with our earlier observation that most of the radiation is scattered in a small cone about the forward direction (eq. [4]).
• • l(-) is the intensity of the reflected radiation as it travels backwards through the RPE to the front of the RPE.
• N is the number density of the melanin aggregates that absorb and scatter the radiation
• a a denotes the cross section of a melanin aggregate for absorption
• Mbac k scat is the coefficient for backscattering for the structural matrix
• Equations [1 6] and [1 7] can be further simplified by ignoring the term + Na s l(-) in eq. [1 6], the rationale for this being that the reflected signal l(-) is much smaller than the input signal l(+). Then, on requiring that:
• RCH is the reflection coefficient at the interface between the ROE and choroid.
• RTOT 1 - (1 - RRPE )exp[-2 m back scatRET d RET] [21 ]
• dc H denotes the thickness of the choroid (200 microns)
• d RET is the thickness of the anterior retina(200 microns)
• a typical width for an RPE melanosome has been found to be approximately BOO nm, whereas the typical length is 720 nm.
• the melanosomes do not need to be elongated and are primarily globular in shape. The differences in the shapes lead to the differences in the cross- sections as noted above.
• the melanin sheets stack to form the aggregates in a melanosome, and thus the RPE melanosomes are represented as lossy dielectric prolate spheroids.
• the globular melanosomes of the choroid are represented by lossy spherical dielectrics.
• CT S RPE 0.03x1 0 -14 Xnm 2 cm 2 [24]
• NRPE 2x1 0 10 cm- 3 for a normal patient [27a]
• FIGURES 8-1 5 are graphs providing the implications of equations [1 9]-[21 ], and particularly equation [21 ] for the overall reflectivity of the anterior retina, RPE and choroid. They display variations in the parameters with wavelengths, RPE and choroid melanosome number densities.
• FIG. 8 a comparison of RPE melanin absorption coefficient (top curve), RPE melanin scattering coefficient (middle curve) and RPE structural matrix scattering coefficient (bottom curve) is shown.
• the logs (to the base 1 0) of the coefficients are shown, with the coefficients expressed in cm 1 .
• the logarithms are plotted versus wavelengths and nanometers between 600 nm and 800 nm.
• a normal RPE melanosome concentration of 2xl 0 10 crrr 3 has been assumed.
• FIG. 8 shows that in the RPE at normal melanosome densities, the absorption coefficient is largest followed by the scattering coefficient due to the melanin and the scattering coefficient of the structural matrix.
• melanosomes is the largest, followed by the scattering coefficient from the structural matrix, with a much smaller scattering coefficient from the
• the difference between the melanosome absorption coefficient and the matrix scattering coefficient is small at 800 nm. If the choroid melanosome density decreases, the matrix scattering coefficient can become larger than the melanosome absorption coefficient. This is especially true at wavelengths near 800 nm.
• FIGURE 1 0 is a graph illustrating reflectivity RQ H of choroid (top curve) as a function of wavelength (in nm), at a normal choroid melanosome density (5.4x10 9 crrr 3 ). Two other curves are also shown, one for each of the components of eq. [20] comprising the expression for RQH.
• the middle curve is the fractional term containing the choroid scattering coefficients in the numerator and the sum the of the scattering and absorption coefficients in the denominator.
• the bottom curve is the exponential term with its factor.
• FIG. 1 0 shows that the reflectivity increases as the wavelength increases. This results from the increase in the (backwards) scattering coefficient with wavelength in the Mie regime of scattering. By far the dominant contribution to the
• reflectivity of the choroid at normal choroid melanosome densities is the fraction containing the ratios of the scattering and absorption coefficients.
• FIGURE 1 1 is a graph depicting reflectivity RRPE of RPE (top curve) as a function of wavelength (in nm), at normal RPE and choroid melanosome densities (2x1 0 10 cm- 3 and 5.4x1 0 9 cm- 3 , respectively). Two other curves are also shown, one for each of the components of eq. [1 9] comprising the expression for RRPE.
• the middle curve is the fractional term containing the RPE scattering coefficients in the numerator and the sum the of the scattering and absorption coefficients in the denominator.
• the bottom curve is the
• FIG. 1 1 shows that the reflectivity increases as the wavelength increases, just as with the reflectivity from the choroid. Again, this results from the increase in the (backwards) scattering coefficient with wavelength in the Mie regime of scattering.
• the dominant contribution to the reflectivity of the RPE at normal RPE and choroid melanosome densities is the fraction containing the ratios of the RPE scattering and absorption coefficients.
• the exponential term is much smaller, due to the large RPE absorption coefficient due to the melanosomes.
• FIGURE 1 2 illustrates that equation [21 ] shows how the total reflectivity RTOT is derived from the reflectivity of the RPE RRPE, contains an exponential attenuation factor that contains the extinction coefficient due to scattering in the anterior retina.
• FIG. 1 2 illustrates the transmission factor of the anterior retina as given by the exponential factor of equation [21 ] versus the wavelength in nanometers. The transmission of the reflected radiation through the anterior retina is quite good, varying from 93+% at 600 nm to 88+% at 800 nm.
• the RPE melanin concentration varies with lateral position in the eye. It peaks at the center of the macula and then decreases on either side over a range of approximately 5° to a relatively constant value for about 10° on either side, before rising again towards the equator at -20° and + 1 5°. To get consistent results, it is best to operate the detector 1 1 0, preferably a reflectometer in accordance with the present invention, in the regions where the concentration is relatively constant, or in other words on the order of approximately 10° away from the center of the macula.
• FIGS. 5-1 2 show the behavior at normal RPE and normal choroid melanosome densities (2xl 0 10 crrr 3 and
• the present invention is particularly interested in how the total reflectivity R TOT changes as the RPE melanosomes densities change. This is illustrated and described in connection with FIGS. 1 3-1 5.
• FIGURE 1 3 illustrates the percentage changes in the total reflectivity R TOT as a function of wavelength in nanometers, as RPE and choroid
• FIG. 1 3 shows that comparable percentage changes occur in R TOT from comparable changes in RPE melanosome densities and in choroid melanosome densities, but that the changes from RPE densities have a different wavelength dependence from changes in choroid densities. Accordingly, measurements of the percentage changes in the total reflectivity at two different wavelengths can uniquely determine what the changes in RPE and choroid melanosome densities are.
• FIG. 1 4 shows the plot at 600 nm
• FIG. 1 5 shows the plot at 800 nm. It is apparent that the
• percentage change contours at 600 nm have a different shape than the contours at 800 nm.
• a given percentage change at 600 nm and another given percentage change at 800 nm then provide two different contours, and the intersection of these two contours provides uniquely the abnormal melanosome densities for both the RPE and the choroid.
• One way to solve the expressions for the unique RPE and choroid melanosome densities that give the measured reflectivities at the two wavelengths may be simply to store in computer memory a look-up table of the reflectivity contours at two different
• FIGS. 1 4 and 1 5 show percentage change contours for abnormalities rather than absolute value contours of the reflectivity.
• Table 1 shows the peak laser power that will maintain the Arrhenius integral for HSP activation at a conservative value of unity when the RPE melanin content takes on different values. Peak power for different values of spot radius, train duration, duty cycle and abnormal RPE melanin ratio content is shown. The table assumes a treatment pulsed wavelength at 81 0 nm.
• Psdm depends on the laser’s retinal spot radius (R), the duration of the laser
• FIGURES 1 6 and 1 7 are graphs that show the ratio rda mage of abnormal RPE melanin content to normal RPE melanin content at which damage can occur. These graphs are based on rough approximate expressions for the Arrhenius integrals for HSP activation and for damage that give surprisingly close matches to the exact expressions. Both graphs plot the ratio r damage vs the pulse train duration t F .
• the graph of FIG. 1 6 covers the range of t F from 0.01 sec to 1 sec.
• the graph of FIG. 1 7 covers a more realistic clinical range of t F from 0.2 to 0.5 sec.
• the critical ratio rda mage of abnormal RPE melanin content to normal RPE melanin content at which damage can occur varies from 4 to about 8 for pulse train durations ranging from 0.2 sec to 0.5 sec.
• one or more treatment parameters are adjusted when the content of melanin in the RPE is determined to be at least four times greater than a normal content of melanin in the RPE.
• the one or more treatment parameters are adjusted when the content of melanin in the RPE is determined to be greater than 8x1 0 10 crrr 3 .
• the retinal spot radius R can be increased from its normal value Rnormai to lie in the range
• a single laser phototherapy parameter may be adjusted, it will be understood that more than one of these parameters can also be adjusted simultaneously.
• the laser spot radius can be increased in diameter and the power lessened, but not lessened to the extent it would otherwise require if only the power were lessened.
• all of the parameters can be adjusted slightly, such as slightly increasing the retinal spot size for the treatment light beam, lowering the pulse train duration of the treatment light beam, lowering the duty cycle of the treatment light beam, and lowering the power of the treatment light beam such that unity in the Arrhenius integral is achieved in order to avoid damage to the retina and eye of the patient having an abnormally large concentration or amount of melanin in his or her RPE.

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• 2019
  • 2019-04-29 WO PCT/US2019/029636 patent/WO2020112163A1/en not_active Ceased
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