Patent Description:
The methods described herein do not form part of the claimed invention. Such methods produce a treatment light for use in phototherapy treatment of an eye (e.g., the cornea and/or sclera of an eye), comprising (a) directing light from a multi-wavelength light source to a wavelength control device; (b) isolating and directing treatment light of at least one predetermined wavelength band to at least one optical treatment head ; and (c) projecting a light beam from the optical treatment head and focusing the beam to produce a light spot of predetermined size and shape on the eye (e.g., the cornea and/or sclera of the eye) at a predetermined working distance from the optical treatment head, whereby the optical treatment head is positioned at a distance from the eye sufficient to allow access to the eye (e.g., the cornea and/or sclera of the eye). The method may comprise splitting the at least one treatment light along separate first and second optical paths, and directing the separated treatment lights to a first optical treatment head and a second optical treatment head for simultaneous treatment of right and left eyes (e.g., the cornea and/or sclera of the right and left eyes). The method may further comprise adjusting a distance between the first optical treatment head and the second optical treatment head based on a distance between the right and left eyes. The method may further comprise independently adjusting the first optical treatment head and the second optical treatment head to adjust an angle at which the at least one treatment light is projected on the respective eye (e.g., the cornea and/or sclera of the eye). The method may further comprise independently adjusting the intensity of the at least one treatment light applied to the respective eye (e.g., the cornea and/or sclera of the eye). The method may further comprise blocking and unblocking the at least one treatment light beam at predetermined time intervals to provide discontinuous light projection on the cornea and/or sclera. The method may further comprise contacting the eye (e.g., the cornea and/or sclera of the eye) with a photosensitizer. The photosensitizer may be riboflavin, rose Bengal, other photosensitizers, or derivatives thereof. The method may further comprise monitoring the level of photoluminescent emissions from the eye (e.g., the cornea and/or sclera of the eye) during treatment and determining approximate photosensitizer concentration in the eye (e.g., the cornea and/or sclera of the eye) based on the level of photoluminescent emissions. The method may further comprise controlling an aperture in the optical treatment head, whereby intensity of the at least one treatment light and the size of the light spot is variable.

It should be understood that the drawings are not necessarily to scale and that the disclosed apparatus are sometimes illustrated diagrammatically and in partial views. In certain instances, details which are not necessary for an understanding of the disclosed apparatus which render other details difficult to perceive are omitted.

The present disclosure relates generally to ophthalmic treatment devices or systems for photochemical corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer, in particular for treating a cornea or sclera weakened by various medical or surgical conditions, for reducing infection, or for imparting refractive changes to the entire or selected portions of the eye (e.g., the cornea or sclera) to correct or otherwise improve vision.

Corneal and/or scleral collagen cross-linking shortens the length and increases the diameter of corneal and/or scleral collagen. In some cases, corneal and/or scleral collagen cross-linking is beneficial in corneas and/or scleras that would benefit from refractive correction to improve vision. Corneal and/or scleral tissue segments can be cross-linked selectively so as to control and customize refractive changes to meet the individual vision correction needs of the patient.

One method of cross-linking corneal and/or scleral collagen or strengthening collagen to impart refractive change and improve vision is photochemical cross-linking. The method of photochemical cross-linking uses a photosensitizer, usually riboflavin monophosphate, and UVA light to promote the cross-linking of the collagen fibrils. Photochemical cross-linking of the cornea has been demonstrated to slow, stop, or reverse the progression of compromised collagen in patients with keratoconus and ectasia.

Disclosed herein are ophthalmic treatment systems as defined in the appended claims.

As used herein, "light source array" means an ordered or disordered arrangement of a plurality of light sources. In some embodiments, the plurality of light sources are in an ordered arrangement. In some embodiments, the plurality of light sources are in a disordered arrangement.

In some embodiments of the ophthalmic treatment systems disclosed herein, the light control device includes a microprocessor-controlled mechanical light modulation device (e.g., a shutter or filter) which is placed in the path of the light beam, at the appropriate position, providing discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera). In some embodiments, the on/off times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) are dependent on the concentrations of the photosensitizer (both excited state and ground state) and/or the partial pressure of the oxygen in the eye (e.g., the cornea and/or sclera). The on/off times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) may be controlled automatically based on input by the physician at a control unit to determine overall treatment time and duration of on/off cycles. When the light is shuttered or filtered, the oxygen consumption by the riboflavin triplets stops and the eye (e.g., the cornea and/or sclera) reoxygenates from the tear film or from oxygenated ophthalmic solutions applied to the eye (e.g., the cornea and/or sclera).

In some embodiments of the ophthalmic treatment systems, the light control device includes a microprocessor-controlled optical shutter (e.g. a UVA/blue light filter) which is placed in the path of the light beam, at the appropriate position, so as to provide discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera). The filtered/unfiltered times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) may be automatically based on input by the physician at a control unit to determine overall treatment time and duration of filtered/unfiltered cycles. When the light is filtered, the oxygen consumption by the riboflavin triplets stops and the cornea and/or sclera reoxygenates from the tear film or from oxygenated ophthalmic solutions applied to the eye (e.g., the cornea and/or sclera).

In some embodiments of the ophthalmic treatment systems, the light control device includes a manual or microprocessor-controlled intensity control device (e.g. a dimming mechanism or switch) so as to provide for gradual decreases and increases in the UVA light intensity. Without wishing to be bound by any particular theory, it is contemplated that the gradual intensity adjustment mitigates one or more of startling effect, fixation loss, de-centered treatment, and Bells phenomenon. In some embodiments, the dimming mechanism is configured to provide periods of decreased UVA light, such that tissue reoxygenation occurs, and periods of increased UVA light, such that cross linking occurs. The dim/bright times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) may be automatically based on input by the physician at a control unit to determine overall treatment time and duration of dim/bright cycles. When the light is dimmed, the oxygen consumption by the riboflavin triplets stops and the eye (e.g., the cornea and/or sclera) reoxygenates from the tear film or from oxygenated ophthalmic solutions applied to the eye (e.g., the cornea and/or sclera).

In some embodiments of the ophthalmic treatment systems, the light control device includes a manual or microprocessor-controlled pattern control device, such as a light mask or a reticle, to provide patterned projection of the at least one treatment light onto the eye (e.g., the cornea and/or sclera). In some embodiments, the pattern control device is configured to simultaneously transmit part of the at least one treatment light such that cross-linking occurs, and block the rest of the at least one treatment light such that tissue reoxygenation occurs. In some embodiments, masks or reticles of different patterns may be selectively positioned in the treatment light path to the eye and may be controlled to provide for variable durations of illumination and non-illumination, resulting in varying levels and depths of corneal and/or scleral strengthening in selected areas to impart varying levels of corneal and/or scleral refractive change. In some embodiments, the pattern control device is one or more reticles having apertures that allow a variety of different light distribution patterns and sizes to be selected by the physician. The patterns and sizes allow the physician to direct light emission to pre-selected sections or portions of the eye (e.g., the cornea and/or sclera) that benefit from corneal and/or scleral strengthening, either to strengthen weakened corneal and/or scleral tissue, or to impart selective strengthening and resulting refractive changes to improve visual acuity. In some embodiments, the patterns and durations of the patterned light projection are dependent on the concentrations of the photosensitizer (both excited state and ground state) and/or the partial pressure of the oxygen in the eye (e.g., the cornea and/or sclera).

One technical feature of the present disclosure is that the discontinuous/adjustable/patterned treatment light projection allows reoxygenation during treatment. It is found that oxygen is consumed during cross-linking and needs to be replenished, such as through the anterior corneal and/or scleral surface. When excitation energy is applied to the surface of the eye (e.g., the cornea and/or sclera), the oxygen that is reentering the eye (e.g., the cornea and/or sclera) is consumed at a rate that exceeds the reoxygenation diffusion rate and the eye (e.g., the cornea and/or sclera) remains hypoxic, particularly in the posterior portions, under continuous wave conditions. It is noted that blue light excitation gives the user an option for increased reoxygenation of the posterior stroma. Blue light is less absorbed in the anterior cornea and/or sclera and accordingly the oxygen consumption rate is lowered. This allows more of the replenishment oxygen to reach the posterior stromal region.

For example, the triplet riboflavin molecules created during photochemical therapy either form singlet oxygen created in a Type II reaction or hydrogen peroxide by a Type I reaction. In the presence of physiological amounts of oxygen of <NUM> Hg partial pressure the Type II singlet oxygen reaction predominates. Under conditions of subnormal oxygen availability (less than <NUM> Hg of O2), the Type I hydrogen peroxide reaction predominates. It is contemplated that the stromal region is hypoxic under the current protocol of continuous <NUM> mw/ cm2 UVA and <NUM>% riboflavin cornea. The available oxygen content of the stroma is consumed almost immediately as demonstrated by the following calculation. Given the volume occupied by a <NUM>-micron thick cornea and the reported literature value of <NUM> micromolar oxygen in the stroma, the total amount of oxygen in the cornea is about <NUM> x <NUM>-<NUM> moles. The quantum yield of singlet oxygen from riboflavin irradiation is <NUM>, indicating that approximately <NUM> photons of absorbed energy consume <NUM> unit of molecular oxygen. Accordingly, only <NUM> x <NUM>-<NUM> moles of photons are required to consume all of the available stromal oxygen. Using the relationship E=hv the amount of energy to deplete all of the cornea oxygen is less than <NUM> mJ of UVA light. It is contemplated that oxygen is consumed rapidly (e.g. in seconds) after the treatment starts. Thus, the reoxygenation provided by the disclosed treatment system, such as through discontinuous/adjustable/patterned treatment light projection, allows improved cross-linking.

In some embodiments, the ophthalmic treatment systems includes a device for monitoring the concentration of the photosensitizer (e.g. riboflavin, rose Bengal, other photosensitizers, or derivatives thereof) in the eye (e.g., the cornea and/or sclera) so the physician may discontinue, adjust, or selectively apply the at least one treatment light to achieve the optimal depth of penetration while still reducing the risk of damage to the endothelial cells. In addition, the photosensitizer monitor also allows the physician to determine when sufficient riboflavin is present in the eye (e.g., the cornea and/or sclera) during light treatment. In some embodiments, an optical collection device is mounted adjacent to the optical head and is configured to collect photoluminescent emissions from the eye (e.g., the cornea and/or sclera) during treatment. The output of the optical collection device is connected to a photoluminescence monitoring unit.

Without wishing to be bound by any particular theory, it is contemplated that knowledge of the amount of photoluminescence allows the physician to adjust the treatment to reduce the potential loss of endothelial cells by excess UV radiation, which is attributable to low concentration of the riboflavin, excessive treatment light intensity, toxic peroxides or reactive oxygen species (ROS) generated under hypoxic conditions, or combinations thereof. In addition, without wishing to be bound by any particular theory, it is contemplated that excessive riboflavin in the eye (e.g., the cornea and/or sclera) not only prevents significant amounts of UV from reaching the endothelial cells in a sunscreen-like effect, but also limits the cross-linking depth to the anterior portion of the stroma. Measurement of riboflavin concentration allows the physician to monitor for excessive riboflavin during the procedure and to take appropriate steps to mitigate such conditions.

In some embodiments, the photosensitizer monitor is based upon the detection of the photoluminescence of the photosensitizer as it interacts with the excitation light. As used in the present disclosure, "photoluminescence" is defined as the combined radiation given off by the fluorescence of photosensitizer and the radiation given off as phosphorescence from the excited state of the photosensitizer (e.g. triplet state of riboflavin). The emission intensity of the photoluminescent radiation is a function of the light wavelength, the light intensity and the concentration of the riboflavin. Since the wavelength and intensity of the applied light is known, the emission intensity of photoluminescent radiation from the patient's eye (as determined by the photoluminescence monitoring unit and a suitable microprocessor receiving the output of the monitoring unit) is used to measure the riboflavin concentration. In some embodiments, the photosensitizer monitor uses colorimetry (e.g. color comparison charts) to determine the concentration of the photosensitizer.

In some embodiments, the photosensitizer concentrations measured are provided to the physician on a display unit associated with the system to allow the physician to adjust the treatment light intensity or wavelength, switch to discontinuous light projection, or take other steps in response to detected reduction or increase in concentration of riboflavin.

In some embodiments, the ophthalmic treatment system further comprises a device for monitoring molecular oxygen or oxygen partial pressure in the eye (e.g., the cornea and/or sclera). In some embodiments, the oxygen monitor is based on the triplet state riboflavin phosphorescence at <NUM> in relation to riboflavin fluorescence at <NUM>. As the ratio of triplet state of riboflavin phosphorescence of <NUM>/<NUM> fluorescence decreases, the quantum yield of the triplet state molecules decreases, thereby indicating a decrease in the partial pressure of oxygen in the eye (e.g., the cornea and/or sclera).

Without wishing to be bound by any particular theory, it is contemplated that, during the course of the irradiation, the riboflavin photo-oxidizes and degrades to a form that does not fluoresce or create triplet molecules. Under ideal conditions, the phosphorescence would degrade at the same rate. However, the presence of oxygen is required for phosphorescence of riboflavin to occur in solutions, and oxygen also quenches the phosphorescence of the riboflavin. The quenching of the phosphorescence by oxygen corresponds to the reduction in the phosphorescence signal. Since some degradation in the triplet phosphorescence signal is expected as a result of riboflavin degradation, the optimal index for monitoring the oxygen quenching of triplet riboflavin is the ratio of the phosphorescence to the fluorescence. The phosphorescence signal is compared to the fluorescence signal during calibration and expressed as a ratio (e.g. <NUM>:<NUM>). As the reaction proceeds over time, the ratio decreases as the phosphorescence signal decreases, indicating quenching of triplet riboflavin by molecular oxygen. In some embodiments, the decrease in the ratio is used as a proxy measure of the singlet oxygen production. As the ratio of the phosphorescent/fluorescent signal decreases, the efficiency of singlet oxygen production decreases, allowing the ratio to level off at some point, which signals to the operator the need to reoxygenate the eye (e.g., the cornea and/or sclera) by discontinuous/adjustable/patterned light projection.

In some embodiments, the projection optics are configured to provide a distance of the patient's eye from the optical head of approximately two inches or greater. Other working distances, such as about <NUM> (three inches) or from about <NUM> (three inches) to about <NUM> (six inches), are provided in alternative embodiments. The increased working distance between the optical head and patient's eye provides improved physician visualization and better access to the eye during treatment, for example to add more photosensitizer drops or other ophthalmic solutions, or for other treatment aids.

In some embodiments, the ophthalmic treatment system further comprises a fixation light either attached to or separated from the treatment device. During periods of continuous or discontinuous/adjustable/patterned light projection, the patient's eyes naturally deviate from the desired position. Fixing the patient's line of sight, such as on a fixation light, allows the patient's eyes to remain correctly aligned and/or focused. In some embodiments, the fixation light is independently movable in relation to the optical treatment head(s) to fix the patient's eyes at certain directions and/or angles, thereby allowing the physician to deliver light in a beam path/direction that is independent of the patient's visual axis. In some embodiments, the fixation light is positioned within the line of sight of both eyes of the patient, at a distance from each eye that is sufficient to prevent double vision of the fixation light. In some embodiments, the fixation light emits red light, or other light within the visible spectrum such as green light, which is easily viewable by a patient during treatment. In another embodiment the fixation light periodically blinks or emits an audio cue to reacquire and/or maintain the patient's attention.

The ophthalmic treatment system comprises another light source in addition to the UVA/blue treatment light which is configured to be turned on with the at least one treatment light entering a period of discontinued treatment light. In some embodiments, the auxiliary light source is configured to be turned on/off coincident with the at least one treatment light entering a period of discontinued/filtered/dimmed or entering a period of continued/unfiltered/non-dimmed treatment light. In some embodiments, the additional light emission is integral to the UVA/blue treatment light path and at least partially compensates for the changes in color and light intensity seen by patients during periods of varying UVA/blue illumination, reducing the startle effect when the UVA or the combination of UVA and blue treatment beam is turned on and off. The separate light source has a wavelength in the visible light spectrum that is not highly absorbed by riboflavin and therefore does not result in oxygen consumption from riboflavin triplet formation, yet appears to the patient to be of the same or similar color as that of excited riboflavin. In some embodiments, the auxiliary or anti-startle light source may be a green light LED. Without wishing to be bound by any particular theory, it is contemplated that the gradual intensity adjustment mitigates one or more of startling effect, fixation loss, de-centered treatment, and Bells phenomenon.

In some embodiments, the ophthalmic treatment device comprises a multi-wavelength light source. In some embodiments, the multi-wavelength light source is a full-spectrum light source that is filtered to give a narrow band of excitation energy within the UVA/blue light spectrum, and is controllable to provide output light in at least two different wavelengths. In some embodiments, the light source is a short-arc lamp such as a mercury or mercury halide lamp or a short-arc xenon lamp, which emits UVA light as well as light in other wavelengths. In some embodiments, the light source unit further comprises an optical system which isolates light to a light beam in the wavelength required for treating the patient and provides the isolated light beam to the light guide for transmission to the optical treatment head. In some embodiments, the optical system comprises a focusing device for focusing radiation from the lamp along an optical path and a beam isolating assembly in the optical path which is configured to direct light in a selected wavelength range into the first end of the light guide. In some embodiments, the beam isolating assembly comprises a reflective dichroic mirror which reflects light in the UVA/blue range of around <NUM> to <NUM> and passes other radiation emitted by the lamp, and a filter in the path of reflected light from the mirror which directs light of a predetermined wavelength or wavelength band to the wavelength control device.

In some embodiments, the light source is one single or limited wavelength light source or multiple single wavelength light source, and may be one or more light emitting diodes (LED) or laser diodes and provides isolated light beams at selected wavelengths or limited wavelength ranges.

In some embodiments, a wavelength control device selectively provides light at one or multiple wavelength bands for treatment purposes (e.g. light in a UVA band and light in a blue or blue-violet band). Two different filters may be provided which are selectively positioned in the light path, allowing selection of excitation energy in the UVA band at <NUM>, or a narrow band of blue-violet radiation at <NUM>. The option of UVA or UVA and blue radiation allows the surgeon flexibility in achieving different depths of penetration into the cornea and/or sclera for the excitation light. For example, the molar extinction coefficient of riboflavin at <NUM> is about <NUM>,<NUM> and at <NUM>, the extinction coefficient is about <NUM>. If the riboflavin in the cornea and/or sclera is <NUM> molar, the <NUM> radiation deposits about <NUM>% of its energy to the riboflavin in the first <NUM> microns of the tissue, whereas with the <NUM> radiation only about <NUM>% of the beam is absorbed in the first <NUM> microns. The blue light delivers more energy in the deeper tissue for deeper cross-linking. For patients with thin corneas and/or sclera, the UVA may be used since the energy is absorbed more quickly and less energy reaches the endothelium. For patients with thicker corneas and/or scleras, blue light may be used to penetrate deeper into the cornea and/or sclera. In a conventional procedure that uses <NUM> radiation, deepithelialization and <NUM>% riboflavin soaking, cross-linking occurs to a depth of about <NUM> microns, while damage (apoptosis) occurs deeper, at about <NUM> microns. The multi-wavelength excitation option of the disclosed system allows for deeper cross-linking (e.g. by blue light) if the surgeon determines deeper cross-linking is beneficial or necessary.

One technical feature of the present disclosure is the option to select one of multiple wavelengths of the excitation light. Without wishing to be bound by any particular theory, it is contemplated that the wavelength determines the depth of penetration of the light into the riboflavin soaked cornea and/or sclera, which in turn affects how much cross-linking is done at different depths of the corneal stroma or sclera. The molar extinction coefficient of riboflavin is <NUM>,<NUM>-<NUM>/M at <NUM> but the molar extinction coefficient of riboflavin is only <NUM>-<NUM>/M at <NUM>. Under the Beer Lambert law, for a given wavelength and excitation energy, the fluorescent intensity of the photosensitizer (e.g. riboflavin) is linearly proportional to the concentration of the fluorophore. Calculation of the light absorption by riboflavin at various depths of the cornea and/or sclera of the two wavelengths is possible using the Beer Lambert equation. In this equation A = <NUM> - log10 %T, where A is the absorbance of energy by a chemical fluorophore and T is the transmission. The Beer Lambert law states that A=Ebc where E is the molar extinction coefficient for a particular chemical and b is the path length of the measurement and c is the concentration of the chemical. For a <NUM>% solution of riboflavin at a depth of <NUM> microns the absorption value at <NUM> is calculated as A=<NUM>. The value of A for the same solution and path length for <NUM> radiation is calculated as A=<NUM>. From the formula A = <NUM> - log10 %T it is shown that <NUM>% of the incident energy of <NUM> radiation is absorbed by riboflavin in the first <NUM> microns of the cornea and/or sclera. The same calculations at <NUM> indicate only <NUM>% of the radiation is absorbed by the riboflavin in the first <NUM> microns of the stroma or sclera. If the user determines that it is desirable to cross link deeper into a cornea and/or sclera, the user has the option to select a more penetrating radiation like <NUM>. If shallow cross-linking is more desirable, the user has the option to select a less penetrating wavelength, such as <NUM>.

An additional feature of the <NUM> wavelength is the option to use less intense light to accomplish the same amount of cross-linking. The production of singlet oxygen by excited riboflavin triplet molecules is related to the number of incident photons, not the energy of the photons. Riboflavin is excited at both <NUM> and <NUM> to its higher energy states. By the formulation E=hv it is determined that a <NUM> photon is <NUM>% less energetic than a <NUM> photon, and that to have equivalent stoichiometric reactions at <NUM> and <NUM> the incident UVA light fluence is reduced to <NUM>% of the blue light fluence.

Another feature of the blue light option for excitation energy is that the lower absorption of blue light by riboflavin in the anterior cornea and/or sclera translates into less oxygen consumption in the anterior stroma or sclera, and thereby allowing better reoxygenation of the posterior stroma or sclera, as discussed in more detail below.

In some embodiments, two components in the ophthalmic treatment systems are optically coupled together through transmission of light from one to another. In some embodiments, at least some of the components in the ophthalmic treatment systems are optically coupled together through at least one UV transmissive liquid light guide to produce homogeneous light distribution. In some embodiments, the light source is coupled to the wavelength control device through the liquid light guide. In some embodiments, the wavelength control device is coupled to the optical treatment head(s) through the liquid light guide. In some embodiments, multiple liquid light guides or a bifurcated light guide are used in bilateral systems. Liquid light guides are also more efficient in transmitting light and provide cold light, avoiding the potential problem of hot spots. The flexible light guides also provide for variation in optical head spacing in a bilateral system, and allow for 3D movement of the optical head or heads if desired.

In some embodiments, other optical coupling apparatus is used for optical coupling of components in the ophthalmic treatment systems as alternative to or in combination with the liquid light guide. Those optical coupling apparatus include, but are not limited to mirrors, reflective prisms, refractive prisms, optical gratings, convex lenses, concave lenses, etc. In some embodiments, the treatment light sources are provided in one or more treatment heads and treatment light is projected directly from the light source or sources along an optical path to a treatment light output port of the treatment head.

In some embodiments, the ophthalmic treatment system is monocular, with a single optical treatment unit including the optical treatment head. In other embodiments, the ophthalmic treatment system is bilateral, with two optical treatment units adjustably mounted on a support stand for treatment of both eyes simultaneously. In some embodiments, the optical treatment head(s) is configured to focus a UVA or UVA and blue light beam(s) on a patient's eye. In other embodiments, the optical treatment head(s) incorporates additional treatment or monitoring devices. In some embodiments, the optical treatment heads are identical but are separately mounted to allow for adjusting the distance between the treatment heads. In another embodiment, more than two treatment heads are used in the ophthalmic treatment systems. In some embodiments, the optical treatment heads allow for independent angular adjustment, adjustment of the distance separating the optical treatment heads, and/or adjustment of the distance between the treatment heads and the eyes. In some embodiments, the optical treatment heads are configured to allow for angular variations as well as distance variations of the at least one treatment light. Without wishing to be bound by any particular theory, it is contemplated that the independent angle and distance adjustment allows treatment of strabismus (crossed eyes) and/or allows selective treatment (e.g. crosslinking) of specific areas of the cornea and/or sclera based on pathology of the condition to be treatment or location of the refractive correction desired.

In some embodiments, the light guide from the light source unit or the wavelength control device is bifurcated to provide two separate light guide portions which direct UVA or UVA and blue treatment light beams from the respective optical treatment heads. Treatment light is projected onto the cornea and does not require collimation.

The foregoing systems and methods allow the physician to better monitor the patient's eye during treatment. Features of the foregoing systems allow monitoring of critical variables during treatment as well as variation of the treatment criteria, for example switching between UVA and the combination of UVA and blue or blue-violet light, varying the light intensity, providing a fixation light to prevent eyes from wandering, utilizing an auxiliary light source to prevent the startling effect, varying the beam shape and size, and using a discontinuous treatment light projection to allow for tissue reoxygenation. Another technical feature of the system is that distance of the optical head from the eye is accurately controlled. The system is easy to set up and use, and allows a high degree of control and customization of treatment to a specific patient condition.

An ophthalmic treatment system is disclosed herein.

After reading this description it will become apparent to one skilled in the art how to implement the present disclosure in various alternative embodiments and alternative applications. However, although various embodiments of the present disclosure will be described herein, it is understood that these embodiments are presented by way of example only, and not limitation.

<FIG> illustrate a bilateral system for photochemical ocular treatment such as corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer. UVA/blue light is used for the excitation energy. Referring to <FIG>, an illumination source unit <NUM> contains a multi-spectral light source <NUM> that delivers a user-selected excitation wavelength to bifurcated, UV transmissive liquid light guide <NUM>. The light guide splits into separate light guide outputs <NUM> and <NUM> that are connected to illumination intensity adjustment module <NUM> mounted on a mobile pole stand comprised of pole <NUM> mounted on a base <NUM> with casters. Other support stands of different configuration may be used in place of pole <NUM> with base <NUM>. Outputs of module <NUM> are connected by light guides <NUM>, <NUM> to respective left and right optical treatment devices or units <NUM>, <NUM>. The right treatment device <NUM> is described in more detail below in connection with <FIG>. The left treatment device <NUM> is identical to the right treatment device <NUM>.

The pole allows attachment and vertical positioning of an adjustable mounting mechanism including articulating arm <NUM> on which the treatment devices <NUM>, <NUM> are mounted, and provides mounting points for illumination intensity adjustment module <NUM> and an optical monitoring module <NUM>. Modules <NUM>, <NUM> and <NUM> may be combined in a single unit. The illumination source unit <NUM> is shown as separate from the mobile stand but may be affixed to the stand. The end of articulating arm <NUM> connects to rotating arm <NUM> which further connects to rotating arm <NUM>. The distal end of rotating arm <NUM> carries the two optical treatment devices or units <NUM>, <NUM> encased in housing units <NUM>, <NUM> on adjustable arms 29A, 29B. Each housing unit includes an externally mounted sensor <NUM>, <NUM>. Each housing unit holds in place an optical treatment device <NUM>, <NUM>. Each optical treatment device includes an optical treatment head <NUM> which directs light onto the patient's eye, in addition to other components described in more detail below in connection with <FIG>. Light guides <NUM>, <NUM>, <NUM>, <NUM> and <NUM> which conduct the excitation energy to each optical treatment head may be liquid light guides, because the water-based liquid in the light guide absorbs infrared radiation from the lamp source that could adversely affect tissues. Liquid light guides generally have greater transmission efficiency for UV and visible light than fiber bundles while providing greater flexibility to allow for adjustment of the position of each treatment unit. An additional benefit of using liquid light guides is that they are effective in homogenizing light beams collected from non-homogeneous light sources or reflectors. The light sources and other system components may be mounted in the respective treatment heads.

<FIG> illustrates the layout of the illumination source assembly with an ellipsoidal reflector short-arc lamp <NUM> as the light source, as in the system described above. This lamp may be a <NUM> watt short-arc mercury or mercury halide lamp. This lamp may be a <NUM> watt short-arc xenon lamp that is characterized by a lower UVA output and a greater continuum of high intensity blue wavelength light. Microprocessor <NUM> controls the opening and closing of light modulating device (for example, a shutter and/or filter) <NUM> that either blocks or allows passage of radiation emitted from the lamp. Light modulating device (for example, a shutter and/or filter) <NUM> is a mirrored aluminum material to reflect radiation away from the optical path. The reflective quality of the material prevents a heat buildup on the shutter and potential transfer of heat to the connecting solenoid assembly. The light modulating device (for example, a shutter and/or filter) <NUM> is affixed to a rotary solenoid <NUM> to affect the opening and closing operation. Rotary solenoids are high reliability components with normal lifetimes exceeding <NUM> million cycles. When light modulating device (for example, a shutter and/or filter) <NUM> is opened, the light from the lamp reflector is collected by collimating lens <NUM> and directed to dichroic <NUM> degree turning mirror <NUM> that reflects UVA and blue light in a wavelength range of around <NUM> to <NUM>, while passing infrared radiation. The reflected light from the mirror is collected by focusing lens <NUM> and directed through one of the filters on filter assembly <NUM> into the input of bifurcated light guide <NUM>. Filter assembly <NUM> is on a slide mechanism connected to an actuating switch on the front panel. Two narrowband band pass filters 16A, 16B are mounted on the optics filter assembly <NUM> and an actuating switch position determines which band pass filter is placed in front of the light guide. Filter 16A may be a UVA filter that has a <NUM> bandwidth (FWHM) at <NUM> and filter 16B may have a <NUM> bandwidth (FWHM) at <NUM>. Such filters are commercially available from various optical suppliers.

Various adjustable features of the system described below involve manual input by an operator at the various units in order to vary operating conditions, such as intensity adjustment via module <NUM>, selection between the UVA and blue light filters 16A and 16B, and positioning of the optical treatment heads. These features may be adjusted by an operator by input at remote input device or keyboard, and the controller in this alternative has control outputs to the selectable filter assembly 16A, 16B, and intensity adjustment module <NUM>. An automatic emergency shut off feature may be provided.

<FIG> illustrates a control panel <NUM> provided on the front of illumination source unit <NUM> including user input devices and display unit <NUM>. The controller may be a standalone desktop or laptop computer, or a personal digital assistant or the like, with a standard display unit and a keyboard input device for user input control selections for the various selectable control parameters of the system, which is transmitted by wired or wireless communication signals to control various system components. Panel <NUM> has a manual wavelength selection control switch <NUM> to allow an operator to switch between UVA and blue light, and a manual light modulating device (for example, a shutter and/or filter) control switch <NUM> to switch between continuous and discontinuous illumination. Soft key inputs <NUM> below display <NUM> on the panel are used by an operator to control the light modulating device (for example, a shutter and/or filter) cycle. The soft keys are switches that change function as the display changes.

Referring to <FIG> and <FIG>, the mobile pole stand with the mounted articulating arm and height adjustment wheel, provides for easy positioning of the optical treatment heads over the patient's eyes.

<FIG> is an enlarged top plan view of the articulated arm assembly and treatment devices <NUM>, <NUM> of <FIG>. The height adjustment wheel <NUM> shown in <FIG> provides for vertical adjustment of the arm. Lateral adjustment of the optical heads to accommodate different interpupillary distance is provided by the pivot arms 29A, and 29B on the distal end of the articulating arm, as illustrated in <FIG>. When knob <NUM> is loosened, both arms 29A and 29B are free to pivot around the center of arm <NUM> and knobs <NUM>, <NUM> are loosened to telescope arms 29A, 29B to adjust the interpupillary distance and to align each optical head with the respective eyes of a patient. When optical heads on arm 29A, 29B are positioned over the eyes of the patient, knobs <NUM> - <NUM> are tightened to fix the position. Heads <NUM> and <NUM> are still movable at this point and a combined movement of the heads allows for XY axis adjustment of the optical heads over the patient's eyes for bilateral operation. Knobs <NUM> and <NUM> are tightened to secure the position of the optical heads over the patient's eyes. The manual positioning knobs may be eliminated and another system may be provided for vertical and horizontal positioning of the treatment heads.

The manual positioning knobs may be eliminated and a remotely controlled drive system may be provided for vertical, horizontal, and angular positioning of the treatment heads. X, Y and Z direction positioning are then controlled remotely by the operator via a computer input device, touch screen or the like, or are carried out automatically on entry of patient eye parameters by the physician, for example as described below in connection with the system of <FIG>.

In the ophthalmic treatment system of <FIG>, the at least one treatment light beam of each optical head may be directed concentric to the optical axis passing through the center of the cornea to the center of the lens. It is desirable in some circumstances to position the light beam on an optical axis different than the corneal-lens optical axis. For example, if the apical distortion from keratoconus is in the inferior portion of the cornea, it may be desirable to place the optical axis of the illumination beam concentric with the central axis of the apical distortion to maximize the radiation concentrically around the apical distortion. <FIG> illustrate one example of the apical distortion of keratoconus compared to a normal cornea. <FIG> illustrates an eye <NUM> with a normal cornea <NUM>, with the dotted line <NUM> representing the optical axis passing through the center of the cornea. <FIG> illustrates eye <NUM> with keratoconus causing an off-axis conical distortion and resultant thinning of the cornea at <NUM>. This requires an XYZ positioning flexibility for the optical head, and this may be achieved by the mechanical arrangement shown in <FIG> as described above.

The output light intensity adjustment for each eye in the system of <FIG> is accomplished using the intensity adjustment module <NUM> illustrated in layout view in <FIG>. Mechanical brackets are affixed to the output light guides and these brackets are connected to commercial screw-driven linear slides <NUM> and <NUM>. The bifurcated input light guide ends <NUM> and <NUM> are fixed at the bottom of the module. Turning the externally accessible knobs on slides <NUM> and <NUM> clockwise advances the delivery light guides <NUM> and <NUM> toward the input light guides and increases the intensity of the output. Likewise, turning the knobs in a counterclockwise direction reduces the intensity. The output is measured by using an external hand held radiometer under the output optics. Appropriate radiometers for UVA or blue light are commercially available from a variety of sources. Adjustment of the output of each optical head within <NUM> mw/cm<NUM> may be obtained. Adjustable neutral density filters may be placed between the input and output light guides but these filters are often subject to long term UVA deterioration. <FIG> illustrates the maximum intensity adjustment for excitation light guide <NUM> and the minimum intensity adjustment for excitation light guide <NUM>.

In the illustrated system, a manually operable switch <NUM> allows a user to convert from bilateral to monocular operation. Switch <NUM> is connected to light modulating device (for example, a shutter and/or filter) <NUM>. In the position of light modulating device (for example, a shutter and/or filter) <NUM> as shown in <FIG> the light entering from light guide <NUM> is blocked from entering the delivery light guide <NUM> and the instrument is set for monocular operation. When the switch is rotated from this position, the light modulating device (for example, a shutter and/or filter) rotates out of the light path and closes a microswitch. Light now travels to both output heads and the closed microswitch completes a circuit to light an LED on top of the module alerting the user that the instrument is in bilateral mode. The manual switch may be replaced by a remote control device such as a computer module with a user control input or touch screen for switching between bilateral or monocular operation. The same control input may be used to enter commands to vary other adjustable features of the system, such as the excitation energy frequency, intensity, continuous or discontinuous illumination, treatment period, treatment head height, separation, and angle, and the like.

One of the optical treatment devices <NUM> is illustrated in more detail in <FIG>, <FIG>. As illustrated, each optical treatment device comprises optical treatment head <NUM> vertically mounted on support <NUM> at the end of the respective arm 29A or 29B, and optical collection device <NUM> also mounted on support <NUM> adjacent the optical treatment head <NUM>, as illustrated in <FIG>. Treatment head <NUM> incorporates an optical mask or reticle holder <NUM> in which a selected reticle or mask <NUM> may be positioned for controlling shape and/or size of the output treatment beam projected from treatment head <NUM> via projection optic or lens <NUM> located at the output port of the treatment head. Aiming or positioning apparatus <NUM>, <NUM> mounted in each optical treatment unit <NUM> and <NUM> assists an operator in positioning the projection optic or lens <NUM> at a desired working distance from the cornea. In <FIG>, <FIG>, the aiming devices <NUM>, <NUM> are laser diodes. The distance of optic <NUM> from the cornea is determined to be equal to the desired working distance when the two aiming beams from laser diodes <NUM> and <NUM> coincide with each other as a single spot on the patient's eye. If the aiming beams do not cross at the eye, the height adjustment knob <NUM> on the articulating arm can move the optical heads up or down until the beams coincide at the correct position. This provides a more accurate method for positioning the optical heads at a predetermined distance relative to the patient's eyes.

Filters <NUM> or <NUM> may be selectively positioned in the path of the aiming beams emitted from aiming devices <NUM>, <NUM> via mechanical slide <NUM> (see <FIG>). This may provide a secondary use to the aiming beams for providing red light phototherapy to ameliorate oxidative damage to the cells. The aiming devices <NUM>, <NUM> may be red or green light laser diodes with no filters in the output path.

The ophthalmic treatment system also may include monitoring system <NUM> for the photoluminescence emitted from the riboflavin interaction with UVA/blue light, using optical collection device <NUM> as illustrated in <FIG>. This photoluminescence consists of fluorescence from the riboflavin photonic emission from the S1 to S0 state and phosphorescence emitted from the triplet riboflavin state. These photoluminescent emissions allow measuring of riboflavin concentration in the eye (e.g., the cornea or sclera), a relative measure of the depth of penetration of the riboflavin into the stroma, a relative measure of the lateral homogeneity of the riboflavin and a relative measure of the oxygen utilization and triplet state formation. The reaction of riboflavin and UVA/blue radiation involves two electronically excited states of riboflavin. When ground state S0 (unexcited riboflavin) absorbs UVA/blue light it transitions into an excited state called the S1 state. From the excited S1 state, the molecule loses its energy by two mechanisms. The first mechanism is the relaxation back to the ground state by emitting a photon of light in a process called fluorescence. The peak fluorescence of riboflavin is about <NUM>. The average quantum yield for riboflavin in aqueous solutions is about <NUM>, meaning that the ratio of photons emitted/photons absorbed is about <NUM>. The second mechanism for relaxation from the S1 state is called the formation of triplet riboflavin and this is accomplished by a mechanism called intersystem crossing. The triplet state of riboflavin imparts energy to molecular oxygen and creates singlet oxygen for cross-linking. From this triplet state the riboflavin molecule can react and give up the excess energy to oxygen or water, or it can phosphoresce to the ground state. The phosphorescence of triplet riboflavin occurs at around <NUM>. Since phosphorescence is a direct measure of the active species that creates singlet oxygen, optical collection device <NUM> and optical monitoring device <NUM> of <FIG> are configured to monitor both the fluorescent and phosphorescent signals.

Optical collection device <NUM> of <FIG> comprises light collection lens <NUM> and bifurcated light guide <NUM> which receives the light collected by lens <NUM>. This bifurcated light guide has one single end that splits into two output ends 70A, 70B. The lens <NUM> is directed to the center of the eye (e.g., the cornea or sclera) treatment zone and receives the photoluminescent emissions from the eye (e.g., the cornea and/or sclera) and focuses these emissions to the proximal or receiving end <NUM> of the single-ended portion <NUM> of the bifurcated light guide. The light guide may provide <NUM>% of the proximal input light into each of the two distal light guide portions 70A, 70B. The distal portions of the light guides are routed to the optical monitoring module <NUM> shown in layout view on <FIG>. The optical heads or ends <NUM> on each of the light guides <NUM>, <NUM> of the treatment devices <NUM> and <NUM> receive the photoluminescent emissions from the irradiated corneas and/or scleras of the patient's left and right eyes, and the emission light is transmitted by light guides <NUM> and <NUM>, respectively, into left eye guide portions 71A, 71B and right eye guide portions 70A, 70B. The photoluminescent emission from each eye includes both fluorescence and phosphorescence due to different types of riboflavin interactions, as discussed in detail below. The emission light is directed onto filters <NUM> and <NUM> for separating fluorescence emission from phosphorescence emissions for each eye, as illustrated in <FIG>. Filter <NUM> is a narrowband band pass filter with a center wavelength of <NUM>-<NUM> to capture the peak of the fluorescence emission from the riboflavin. Filter <NUM> is a narrowband band pass filter centered at <NUM>-<NUM> to capture the peak of the phosphorescence of the triplet riboflavin. By splitting the emissions collected from each eye being treated, both the phosphorescence and fluorescence for each eye may be monitored. The filtered emission light from each light guide is directed onto a respective sensor <NUM>, which comprises a PIN silicon photodiode <NUM> that incorporates an integral preamplifier or thermoelectric cooling, and the output voltage of the photodiode is transmitted to high impedance amplifier <NUM> for conversion of the photonic energy into voltage. Alternatively, items <NUM> and <NUM> are purchased as an integral unit from commercial sources such as Thorlabs and are capable of detection of signals as small as a few femtowatts (<NUM>-<NUM> watts).

<FIG> illustrates a hand held dodging fixture or tool <NUM> that may be used to provide a relative measure of the lateral dispersion of riboflavin in the eye. Tool <NUM> has a handle <NUM> with a plastic holder <NUM> at one end which holds a UV transparent/visible blocking glass with a <NUM> hole drilled at its center. Commercial glasses such as Schott UG <NUM> and Schott BG <NUM>, respectively, are suitable for use with UVA and blue treatment light, respectively. The only emitted light to reach the collection device <NUM> is via the hole in the center of glass <NUM>. The dodging fixture may be held over the central cornea and the resultant fluorescence reading from the optical monitoring module <NUM> then reflects emissions from only a limited area of the cornea. The fixture can be moved over different areas of the cornea to obtain readings relative to the central area and other areas. This tool can therefore provide a relative quantitative measure of lateral dispersion of riboflavin in the eye. If readings show that more riboflavin than the peripheral areas, the physician may choose to wait for a longer period for the riboflavin to disperse, or may take other action to promote dispersion, e.g. placing a warm cloth over the closed eye for a few minutes.

The phosphorescence of the riboflavin triplet state may be used to monitor the efficiency of the reaction particularly with relation to singlet oxygen formation. Each eye is monitored for both fluorescence and phosphorescence using optical collection devices <NUM> and photoluminescence monitoring unit <NUM>, as described above. The light modulating device (for example, a shutter and/or filter) <NUM>, <NUM> in <FIG> provides discontinuous light projection and the operation of the light modulating device (for example, a shutter and/or filter) cycle may be directed by the operator by the soft key inputs on the control panel shown in <FIG>.

<FIG> illustrates a perspective view of the right hand optical collection device <NUM> in housing <NUM> with optical collection node <NUM> encased by head unit <NUM>. Housing unit <NUM> is attached to casing unit <NUM> which envelopes the right hand optical treatment device shown in <FIG>, <FIG>. Mounting unit <NUM> is attached to the treatment end of casing unit <NUM>. Mounting unit <NUM> is fitted in each corner with holes <NUM> - <NUM> such that another plate is affixed to the unit with a screw and nut, or like method.

<FIG> and <FIG>, illustrate bilateral systems for discontinuous/adjustable/patterned photochemical ocular treatment such as corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer. In those systems, UVA/blue light is used for the excitation energy. Referring to <FIG>, an illumination source unit <NUM> contains a multi-spectral light source <NUM> that delivers a user-selected excitation wavelength to bifurcated, UV transmissive liquid light guide <NUM>. The light guide splits into separate light guide outputs <NUM> and <NUM> that are connected to illumination intensity adjustment module <NUM> mounted on a mobile pole stand comprised of pole <NUM> mounted on a base <NUM> with casters. Other support stands of different configuration may be used in place of pole <NUM> with base <NUM>. Outputs of module <NUM> are connected by light guides <NUM>, <NUM> to respective left and right optical treatment devices or units <NUM>, <NUM>. As described in detail above, the ophthalmic treatment system also includes monitoring system <NUM> for the photoluminescence emitted from the riboflavin interaction with UVA/blue light, using optical collection device <NUM> as illustrated in <FIG>, and shown encased in housing unit <NUM> in <FIG>. The left treatment device <NUM> is described in more detail below in connection with <FIG>. The right treatment device <NUM> is identical to the left treatment device <NUM>.

<FIG> illustrates a manually operated mechanical light modulating device (for example, a shutter and/or filter) housed in mounting unit <NUM> which is affixed to treatment mounting unit <NUM> at points <NUM> - <NUM>, with a screw and nut, or like method, through points <NUM> - <NUM>. When lever <NUM> is moved to the down position, mechanical light modulating device (for example, a shutter and/or filter) <NUM> will open, allowing UVA/blue light from treatment head <NUM> to pass unobstructed onto the treatment area. Mechanical light modulating device (for example, a shutter and/or filter) <NUM> remains open until the treating physician deems it necessary to provide a period of discontinued light projection. The determination is assisted by data from optical collection device <NUM> mounted to treatment head casing <NUM>, and connected to monitoring system <NUM>, <FIG>. Light collection guide <NUM> is not shown in this view for purposes of clarity but the receptacle for this light guide connects to the rear end of optical collection device <NUM>. The mechanical light modulating device (for example, a shutter and/or filter) remains open for a period of photochemical crosslinking as described herein. Lever <NUM> is then moved to the up position, closing mechanical light modulating device (for example, a shutter and/or filter) <NUM>. When mechanical light modulating device (for example, a shutter and/or filter) <NUM> is closed, no UVA/blue light from optical treatment head <NUM> will reach the treatment area. The mechanical light modulating device (for example, a shutter and/or filter) remains closed for a period as described herein to allow for tissue reoxygenation. The process of opening and closing mechanical light modulating device (for example, a shutter and/or filter) continues as many times as the physician deems necessary.

<FIG> illustrates an automatic mechanical light modulating device (for example, a shutter and/or filter) housed in mounting unit <NUM> which is affixed to treatment mounting unit <NUM> at points <NUM> - <NUM>, with a screw and nut, or like method, through points <NUM> - <NUM> (<NUM> and <NUM> not shown). Automatic control unit <NUM> is affixed to mounting unit <NUM>, and connected by cable <NUM> to UVA light source housing and control unit <NUM>, <FIG>. When treatment begins, mechanical light modulating device (for example, a shutter and/or filter) <NUM> is opened by control unit <NUM>, allowing UVA light from treatment head <NUM> to pass unobstructed onto the treatment area. The mechanical light modulating device (for example, a shutter and/or filter) <NUM> remains open for a treatment session as described herein, off-set by periods of discontinuous illumination as described herein. When mechanical light modulating device (for example, a shutter and/or filter) <NUM> is closed, no UVA/blue light from optical treatment head <NUM> reaches the treatment area. Duration of discontinuous illumination, and number of treatment cycles is set on display control unit <NUM>, <FIG>. UVA or blue light may be provided in a fractionation cycle of <NUM> seconds ON/<NUM> seconds OFF, and in this case the shutter is opened and closed automatically.

Automatic control unit <NUM> affixed to mounting unit <NUM> may be connected by cable <NUM> to optical collection monitoring system <NUM>, <FIG>, <FIG>. When treatment begins, mechanical light modulating device (for example, a shutter and/or filter) <NUM> is opened by control unit <NUM>, allowing UVA light from treatment head <NUM> to pass unobstructed onto the treatment area. The mechanical light modulating device (for example, a shutter and/or filter) remains open until a microprocessor housed in monitoring system <NUM> (not shown), determines singlet oxygen levels are sufficiently depleted. Light modulating device (for example, a shutter and/or filter) <NUM> is then automatically closed, allowing no UVA/blue light from optical treatment head <NUM> to reach the treatment area. This process is repeated until treatment is complete.

<FIG> illustrates a manually or automatically controlled dimmer unit <NUM> mounted on a mobile pole stand comprised of pole <NUM> mounted on a base <NUM> with casters. Other support stands of different configuration may be used in place of pole <NUM> with base <NUM>. During treatment, dials <NUM> - <NUM> are turned manually to increase or decrease the intensity of the UVA/blue light administered to the treatment areas. When treatment begins, gradually increasing from <NUM>% to <NUM>% intensity will mitigate the startling effect. The UVA/blue light remains at <NUM>% intensity until the administering physician deems it necessary to provide a period of discontinued UVA/blue light projection. This determination is assisted by data from optical collection device <NUM> mounted to treatment head casing <NUM>, and connected to monitoring system <NUM>. Knobs <NUM> - <NUM> are then engaged to gradually decrease the intensity of the UVA/blue light from <NUM>% to at or near <NUM>%, in order to mitigate the startling effect. At or near <NUM>% intensity, little or no UVA/blue light from optical treatment heads reaches the treatment areas. The process of increasing and decreasing the intensity continues as many times as the physician deems necessary.

Intensity may be increased and decreased automatically by a microprocessor-controlled dimmer switch housed in dimmer unit <NUM> (not shown). The microprocessor controlled dimmer switch is connected by cable <NUM> to UVA light source housing and control unit <NUM>, <FIG>. When treatment begins, light intensity is gradually increased to <NUM>% allowing UVA light from treatment head <NUM> to pass un-dimmed onto the treatment area. When light intensity is at or near <NUM>%, no or little UVA/blue light from optical treatment head reaches the treatment area. Duration of discontinuous illumination, and number of treatment cycles are set on display control unit <NUM>, <FIG>.

During treatment, intensity is increased and decreased automatically by a microprocessor-controlled dimmer switch housed in dimmer unit <NUM> (not shown). The microprocessor-controlled dimmer switch is connected by cable <NUM> to optical collection and monitoring system <NUM>. When treatment begins, UVA/blue light automatically increases intensity from at or near <NUM>% to <NUM>%. The light intensity remains at <NUM>% until a microprocessor housed in optical monitoring system <NUM> (not shown), determines singlet oxygen levels are sufficiently depleted. Dimmer unit <NUM> then automatically reduces UVA/blue light intensity from <NUM>% to at or near <NUM>%, allowing no UVA/blue light from optical treatment heads to reach the treatment area. This process is repeated until treatment is complete.

<FIG> illustrates a manually operated UVA/blue light filter housed in mounting unit <NUM> which is affixed to treatment mounting unit <NUM> at points <NUM> - <NUM>, with a screw and nut, or like method through points <NUM> - <NUM>. UVA filters <NUM> are held in place by housing units <NUM> which is slid into mounting unit <NUM> such that UVA filters <NUM> are directly in the path of the UVA/blue light emitted by treatment head <NUM>. When slides <NUM> are removed from mounting unit <NUM>, this allows UVA/blue light from treatment head <NUM> to pass unobstructed onto the treatment area. The slides remain free of the mounting unit until the treating physician deems it necessary to provide a period of discontinued light projection. This determination is assisted by data from optical collection device <NUM> which is mounted to treatment head casing <NUM>, and connected to monitoring system <NUM>, <FIG>. Light collection guide <NUM> is not shown in this view for purposes of clarity but the receptacle for this light guide connects to the rear end of optical collection device <NUM>. Slides <NUM> are then inserted into mounting unit <NUM>. When slides <NUM> are inserted into mounting unit <NUM>, no UVA/blue light from optical treatment head reaches the treatment area. The process of inserting and removing the slides continues as many times as the physician deems necessary.

<FIG> illustrates an automatically operated UVA/blue light filter housed in mounting unit <NUM> which is affixed to treatment mounting unit <NUM> at points <NUM> - <NUM>, with a screw and nut, or like method, through points <NUM> - <NUM>. Automatic control unit <NUM> is affixed to mounting unit <NUM>, and connected by cable <NUM> to optical collection monitoring system <NUM>, <FIG>, <FIG>, <FIG>. UVA/blue light filters 345A are housed in retractable units 345B controlled by unit <NUM>. When treatment begins, slides 345B are retracted, allowing UVA/blue light from treatment head <NUM> to pass unobstructed onto the treatment area. Filters 345B remain retracted until a microprocessor housed in monitoring system <NUM> (not shown), determines singlet oxygen levels are sufficiently depleted. Automatic control unit <NUM> then slides filters 345B into the path of light emitted from treatment head <NUM>. When UVA/blue light filters are in the path of the UVA/blue light emitted from treatment head <NUM>, no UVA/blue light reaches the treatment area. This process is repeated until treatment is complete.

An automatically operated UVA/blue light filter unit housed in mounting unit <NUM> may be affixed to treatment mounting unit <NUM>. Automatic control unit <NUM> is affixed to mounting unit <NUM>, and connected by cable <NUM> to UVA light source housing and control unit <NUM>, <FIG>. When treatment begins, slides 345B are retracted, by control unit <NUM> allowing UVA light from treatment head <NUM> to pass unobstructed onto the treatment area. When UVA/blue light filters 345A are obstructing the path of light emanating from treatment head <NUM>, no UVA/blue light reaches the treatment area. Duration of discontinuous light projection, and number of treatment cycles is set on display control unit <NUM>, <FIG>.

<FIG> illustrates a rotating UVA/blue light filter assembly, <NUM>. Filter discs 355A, 355B, 355C, or 355D allow for variable treatment areas. Filter disc 355A has a UVA transparent spot <NUM> offset from the center of the disc, filter disc 355B has a UVA transparent region <NUM> of around <NUM> degrees of the circular disc area with the rest of the disc being solid or black, filter disc 355C has a UVA transparent region <NUM> of about <NUM> degrees with the rest of the disc being solid, and filter disc 355D has a transparent region of <NUM> degrees with the rest of the disc being solid. Filter discs with other arrangements of UVA transparent and solid areas may be provided. Filter discs are housed in rotating disc assembly <NUM>, held in place by pin <NUM>, and rotated by gear assembly <NUM>. Light filter assembly <NUM> is affixed to treatment mounting unit <NUM> at points <NUM> - <NUM> (not shown), with screw and nut, or like method, through points <NUM> - <NUM>. Automatic control unit <NUM> is affixed to filter assembly <NUM>, and connected by cable <NUM> to UVA light source housing unit <NUM>, <FIG> (not shown). Before treatment begins, a treatment disc 355A, 355B, 355C, or 355D is inserted into housing unit <NUM>. When treatment begins, disc is rotated in a circular motion. Selected disc allows UVA/blue light to pass through the transparent portion, and no UVA/blue light to pass through the solid portion. The period of time for disc to make one full rotation is a treatment cycle. Duration of treatment cycles is set on display control unit <NUM>, <FIG>. In the case of disc 355A, an annular treatment area is provided by one full rotation of the disc.

<FIG> illustrates a perspective view of a UVA/blue light treatment head and casing with holder <NUM> for changeable irradiation pattern reticle or mask <NUM> with handle <NUM> for positioning purposes. <FIG> illustrates some examples of additional reticles or masks <NUM>, <NUM>, <NUM> and <NUM> to <NUM> which have apertures or windows of UVA and/or blue light transparent material providing a variety of different light distribution patterns and sizes desired by the physician, allowing more light to reach selected parts of the treatment area. For example, reticle <NUM> has an oval aperture, reticle <NUM> has a slit shaped aperture, reticle <NUM> has a square shaped aperture, reticle <NUM> has an annular ring shaped aperture, reticle <NUM> has two apertures of different shapes, reticle <NUM> has a pseudo tilde or "squiggly line" aperture, and reticle <NUM> has a crescent shaped aperture. The squiggly line aperture of reticle <NUM> may be thicker or wider in one segment, as illustrated, or may be of the same proportions throughout. As illustrated in reticle or mask <NUM>, two or more apertures of the same or different shapes may be provided where different areas of the eye are to be treated simultaneously. Additional masks with apertures or patterns of apertures of different shapes and sizes may also be provided in a patterned mask kit, to provide expanded custom treatment options.

Although the mask <NUM> is positioned in holder <NUM> by hand in the treatment head of <FIG>, the treatment head may have an automatic control unit affixed to housing <NUM>, and connected by cable to a controller or microprocessor. The reticles or masks of different aperture sizes and shapes are housed in retractable units controlled by the automatic control unit. When treatment begins, the operator selects a pattern at an input device (for example as described below in connection with the system of <FIG>) and the automatic control unit slides the selected reticle or mask into the path of light emitted from treatment head <NUM>. This may be used in conjunction with a shutter for discontinuous treatment as described above.

<FIG> illustrates a perspective view of a UVA/blue light treatment head and casing <NUM> with a secondary non-treatment light source or anti-startle light source <NUM>. The secondary light source is powered on in such a way as to mitigate dramatic changes in light seen by the patient as the UVA/blue light is filtered, blocked, or dimmed. The secondary light source is of a wavelength and intensity fitting to reduce the startling effect a patient experiences as a result of dramatic changes in light intensity or color. The light source <NUM> may be a green LED light. The secondary light source may be affixed to the treatment head casing in such a way that it is visible by the patient during periods of discontinuous illumination.

<FIG> illustrates a fixation light <NUM> in housing <NUM> attached to a supporting arm or gooseneck <NUM> which can be manually adjusted so that the fixation light is positioned over the patient's eyes <NUM> at a distance of <NUM> to <NUM> (<NUM> to <NUM> inches) or greater, and serve as a focus point in order to maintain a stable treatment area. Fixation light may be controlled by a controller or microprocessor via cables extending through arm <NUM> to the light. The fixation light is a red light or any other light in the visible spectrum. The fixation light also may perform a periodic blink or auditory cue to remind the patient to focus their attention on the fixation point. Each treatment head may have its own separate fixation light.

<FIG> illustrate an ophthalmic treatment device or system <NUM> according in which various control parameters are controlled remotely by the operator or physician via a computer input device, touch screen or the like, or are carried out automatically on entry of patient eye parameters by the physician. Treatment device <NUM> includes a control unit <NUM> mounted on a support stand having a wheeled base <NUM> and a telescoping pole <NUM> extending upwardly from the base and adjustable via rotatable telescoping pole lock <NUM> at a desired height. The control unit <NUM> comprises an enlarged housing <NUM> at the top of pole <NUM> and a touch screen user interface unit <NUM> mounted on top of housing <NUM>. Treatment heads <NUM> are supported on respective flexible cable arms or goosenecks <NUM> extending from housing <NUM> and components within heads <NUM> are linked to control unit <NUM> via a wireless connection or wired connection through arms or goosenecks <NUM>, as described in more detail below in connection with <FIG>. Fixation light <NUM> of <FIG> is also supported on stand <NUM> via gooseneck <NUM> extending from cable junction <NUM> and adjustable cable arm <NUM> extending from junction <NUM> to control unit <NUM>.

As best illustrated in <FIG>, each treatment head <NUM> may comprise a generally elongate outer housing <NUM> secured to gooseneck <NUM> at one end and having a lower, generally flat wall <NUM> in which a large UVA/blue light output port <NUM> is located, along with two adjustment or positioning light output ports 424A and 424B for adjustment or positioning light, and a photoluminescence monitor input port <NUM> (see <FIG>). As illustrated in <FIG> and <FIG>, one side of the housing contains the optical system or light path from UVA and/or blue light emitter or LED <NUM> to the UVA/blue light output port <NUM>. The other side of the housing contains printed circuit boards <NUM> and <NUM> carrying red and green light adjustment LEDs directed to respective red and green light positioning output ports 424A and 424B, respectively, along with associated control circuitry. A third printed circuit board (PCB) <NUM> carries a photoluminescence sensor or monitor <NUM> (<FIG>) which receives input from input port <NUM>. The output from photoluminescence monitor <NUM> is communicated via leads in arm <NUM> to the controller or microprocessor <NUM> in the control housing <NUM> at the upper end of stand <NUM>.

As illustrated in <FIG> and <FIG>, the UVA or UVA/blue light source <NUM> has an output directed through light homogenizer or light guide <NUM> along a light path through lens <NUM> to <NUM> degree mirror <NUM>, which directs the light downward through output port <NUM> of <FIG>. A mask or reticle wheel <NUM> is rotationally mounted on shaft <NUM> in the light path. As illustrated in <FIG>, reticle wheel <NUM> has a series of openings of different diameter around its periphery. Part of the periphery of wheel <NUM> extends out through a slot <NUM> in housing to allow the wheel to be turned manually in order to align a selected opening with the UVA or UVA blue light path. The openings in the pupil or reticle wheel allow adjustment of the beam spot size in the range from around <NUM> to <NUM>. A drive motor, stepper, or external gear wheel (as in <FIG>) may be provided for moving wheel <NUM> according to a user input at user interface <NUM>, which may be a touch screen as illustrated in <FIG> or a keypad. Additionally, a plurality of reticle wheels with openings of different sizes and shapes, such as the shapes shown in <FIG> and other alternative shapes, may be provided for selective placement in the light path in place of wheel <NUM>. The reticle wheel may be replaced manually or automatically under the control of microprocessor <NUM>, for example as described above in connection with <FIG>. Thus, beam size and shape may be modified in order to produce a selected size and pattern of the treatment light projection onto an eye.

Although the treatment LED or light source in the illustrated system is a single LED, an array of multiple light sources or LEDs, e.g. two or more LEDs, may be provided as the UVA or UVA/blue light source. As illustrated in <FIG>, an anti-startle light source <NUM> is positioned in the housing directly above UVA LED <NUM>, and light output from source <NUM> is directed via light guide or beam homogenizer <NUM> and lens <NUM> in a path parallel to the treatment light beam up to <NUM> degree mirror <NUM>, which directs the anti-startle light beam downwards through output port <NUM>. The anti-startle light source may be a green light LED or a visible light of other colors.

Microprocessor <NUM> may be programmed to turn the UVA or UVA/blue light source or LED on and off at predetermined intervals, to provide discontinuous UVA treatment light. The green anti startle LED <NUM> is turned on when the UVA treatment light is off, for the reasons stated above in connection with the treatment head of <FIG>. The ON and OFF periods for discontinuous UVA treatment may be <NUM> sec. ON, <NUM> sec. OFF, and the total treatment time may be of the order of <NUM> to <NUM> minutes, with an intensity or irradiance of <NUM>-<NUM> mW/cm<NUM>. The irradiance or intensity may be gradually increased at the start of each ON period, and gradually dimmed at the end of each ON period down to. <NUM> mW/cm<NUM>, and is not completely turned off before it is replaced by the green anti-startle light. Using this system, a UVA light of wavelength from <NUM> to <NUM> or UVA/blue light of wavelength of from <NUM> - <NUM> for deeper cross-linking is used to deliver an irradiance of from <NUM> to <NUM> mW/cm<NUM>, in discontinuous cycles as described herein, and through a selected reticle or pupil wheel with apertures that provide a specific light distribution pattern to cross-link selected areas of the cornea and/or sclera. However, all of these parameters (frequency and length of treatment light exposure periods, irradiance, total treatment time, beam size, beam shape) may be varied based on the particular treatment requirements, and some or all of the treatment parameters may also be varied automatically based on feedback to the microprocessor <NUM> from the photoluminescence monitoring device <NUM>.

X, Y and Z positioning of the treatment heads may be carried out manually by the operator or physician using the flexible goosenecks, with the assistance of the red and green positioning LEDs 424A and 424B for locating each head at the desired height above the eye and with the treatment beam aligned with the desired position on the eye. By providing two angled alignment beams of different colors, it is easier for the operator to determine when the treatment head is at the desired working distance from the eye with the UVA/blue light output port aligned with the desired treatment area, when the red and green aiming beams coincide with each other as a single yellow spot on the eye. A robotic positioning system controlled by the microprocessor may be used to position the treatment heads.

The UVA light source was a NCSU033B UV LED manufactured by Nichia Corporation of Tokushima, Japan, but other UVA LEDs with similar properties may be used. The green anti-startle LED, red and green positioning LEDs, and red fixation LED are selected to have flux densities well below the maximum safe or allowable flux onto the pupil of an eye. The green and red LEDs were parts LT T673 N1S <NUM><NUM> Z (green LED) and LR T67F-U1AA-<NUM>-<NUM> manufactured by Osram GmbH of Munich, Germany, but other red and green LEDs with similar properties may be used.

<FIG> is a block diagram of the control system for the treatment device of <FIG>. As illustrated, microprocessor <NUM> controls the on/off treatment cycle or discontinuous irradiation <NUM> of the UVA or UVA/Blue light source or light source array <NUM>, and also controls turning on and off of the green anti-startle LED <NUM> so that it is ON when the UVA light is OFF. It should be understood that the UVA treatment LED is not necessarily turned off completely during the treatment OFF periods, but may be turned down to a minimal irradiance or intensity during these periods. The system also includes an irradiance or dimmer control <NUM> which controls irradiance level based on input from controller <NUM> in response to programmed instructions or input from the operator. UVA/blue output sensor or monitor <NUM> detects irradiance level and provides a feedback input to controller <NUM>. The UV or UVA beam size and shape is controlled by selected reticles in pupil wheel or reticle holder <NUM> located between the UVA LED and the output port <NUM> as described above in connection with <FIG>, and selection of the appropriate size and shape opening for alignment with the LED output may be performed manually by the operator at the start of each treatment, or automatically via an input from microprocessor or controller <NUM>.

The red and green positioning LEDs 424A and 424B are also controlled by microprocessor <NUM> and may be switched on by user input on the touch display screen, for example, when positioning the treatment heads. Once positioning is completed, the positioning LEDs are turned off. Output from the photoluminescence monitor <NUM> is also provided to microprocessor <NUM> and may be displayed on the display screen or touch screen <NUM> for use in determining various treatment parameters including amount of riboflavin solution to be added, variation of ON/Off treatment cycles, and the like. Fixation light or LED <NUM> is switched on at all times during treatment so that the patient can focus their eyes on the light and maintain a static or substantially static.

The systems described above allow for bilateral or monocular photochemical cross-linking of corneal and/or scleral collagen employing selectable UVA/blue light as the excitation source and riboflavin as the photosensitizer. The system may have an illumination source with multi-spectral capability, light guides for delivery of light to bilateral optical heads for projection onto the corneal and/or scleral surface of both eyes simultaneously, and in this system the light source is an Hg or Xe short arc lamp. The light source is connected to the treatment head or heads via liquid light guides, which produces improved homogeneity in the light beam. The system may have treatment heads each incorporating one or more treatment light sources and optics for directing a treatment beam from the light source out of an outlet port which may be positioned to direct the treatment beam onto a patient's eye. In this system, the light sources may be single wavelength or limited wavelength light sources such as LEDs or laser diodes.

The image projection optics are designed to produce a relatively large working distance between the treatment head and the eye. This provides better visualization for the surgeon as well as better access for discontinuous or diffusion augmentation technique, described in detail above. Provision may be made for an adjustable working distance.

A highly oxygenated topical solution may be placed on the cornea and/or sclera for stromal reoxygenation during cross-linking treatment, such as a solution containing iodide ion or a lipid or oil-based fluid that is pre-oxygenated at a high oxygen partial pressure. A hydrogen peroxide reducing agent or solution may be applied to the eye which converts hydrogen peroxide produced in the stroma during irradiation of the eye into oxygen and water. Suitable reducing agents for application to the eye for this purpose are topical solutions containing iodide ion or the enzyme catalase. These agents may be added to any standard riboflavin solution or as a separate solution applied to the cornea and/or sclera during photochemical treatment.

The disclosed treatment system may be used to treat conditions including iatrogenic effect or the prevention of iatrogenic effect, from surgical intervention such as cataract surgery or corneal grafting, refractive intervention such as Laser-Assisted in Situ Keratomileusis (LASIK) or photorefractive keratectomy (PRK), radial keratotomy (RK), or prosthesis, corneal inlays or onlays, or medications, or the cause of corneal or scleral weakness can be congenital, idiopathic or due to microbial causes or trauma.

The disclosed treatment system may be used to treat keratoconus, ectasia, Terrien's marginal degeneration, pellucid marginal degeneration, and corneal melting or ulcer, or normal or weakened corneas that require from <NUM> to <NUM> diopters or more of refractive correction for the treatment of myopia, hyperopia, astigmatism or other refractive errors of the eye, or corneal inflammatory disorders such as infectious keratitis and/or corneal ulcers.

Claim 1:
An ophthalmic treatment system (<NUM>, <NUM>) for photochemical corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer, comprising:
a light source device (<NUM>) comprising a light source array (<NUM>);
at least one optical treatment head (<NUM>) operatively coupled to the light source device (<NUM>), and configured to provide at least one treatment light comprising UVA light or a combination of UVA and blue light;
a light control device (<NUM>) comprising a controller (<NUM>) that controls the light source to provide discontinuous treatment light projection onto an eye at a predetermined treatment light exposure period between around <NUM> seconds and <NUM> seconds; and
an auxiliary light source (<NUM>) characterised in that the auxiliary light source (<NUM>) is configured to be turned on with the at least one treatment light entering a period of discontinued treatment light, wherein the auxiliary light source (<NUM>) has a wavelength in the visible light spectrum that is not highly absorbed by riboflavin.