Patent Publication Number: US-2022211542-A1

Title: Ophthalmic treatment device, system, and method of use

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/128,303, filed on Sep. 11, 2018, which is a continuation of U.S. patent application Ser. No. 15/271,668 filed on Sep. 21, 2016, which is a continuation of U.S. patent application Ser. No. 14/206,847 filed on Mar. 12, 2014, now U.S. Pat. No 9,622,911, which claims the benefit of U.S. Provisional Patent Application No. 61/785,336 filed on Mar. 14, 2013 and is a continuation in part of U.S. patent application Ser. No. 13/034,488 filed on Feb. 24, 2011 which claims the benefit of U.S. Provisional Patent Application No. 61/388,362 filed on Sep. 30, 2010. 
    
    
     BACKGROUND 
     Corneas and scleras derive their structural strength, shape and integrity from collagen. The strength of the intertwined collagen strands is a function of covalent cross-links established between and within collagen strands and between collagen and glycoproteins in the matrix. In structurally robust corneas and scleras, an enzyme called lysyl oxidase performs the collagen cross-linking function in a process called oxidative deamination using molecular oxygen present in the tissue. The biomechanical strength of corneal and scleral collagen can be reduced by a number of conditions including iatrogenic effect from surgical intervention, prosthesis, or medications, or the cause of corneal or scleral weakness can be congenital, idiopathic or due to microbial causes or trauma. In these cases of corneal or scleral weakness, interventional strategies to strengthen the collagen or to reduce infections are often employed. 
     SUMMARY OF THE DISCLOSURE 
     Disclosed herein, in certain embodiments, are ophthalmic treatment systems, comprising (a) a light source device; (b) at least one optical treatment head operatively coupled to the light source device, comprising a light source array, and providing at least one treatment light; and (c) a light control device, which (i) provides patterned or discontinuous treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye); and/or (ii) adjusts intensity of part or all of the light source array, providing adjusted intensity treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the light control device directs the at least one treatment light. In some embodiments, the light source array device comprises a light source or a plurality of light sources. In some embodiments, the system further comprises an optical projection device configured to direct the at least one treatment light onto an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the system further comprises an optical projection device configured to direct the at least one treatment light onto a portion of an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the light control device applies the at least one treatment light to an eye (e.g., the cornea and/or sclera of an eye) in a predetermined pattern. In some embodiments, the light control device applies the at least one treatment light to an eye (e.g., the cornea and/or sclera of an eye) in a plurality of predetermined patterns. In some embodiments, the light control device independently blocks or unblocks part of the light source array and independently adjusts the intensity of part of the light source array such that the array provides a plurality of treatment lights having a plurality of intensities. In some embodiments, the light source comprises one or more laser diodes or LEDs. In some embodiments, a controller controls the light source to provide discontinuous treatment light projection onto the eye at a predetermined treatment light exposure period between 1 second and 10 minutes. In some embodiments, each treatment light exposure period of the discontinuous treatment is between around 5 seconds and 25 seconds. In some embodiments, the treatment light exposure period is around 15 seconds. In some embodiments, the treatment light is in a frequency range from 350 to 400 nm. In some embodiments, the at least one treatment light promotes collagen cross-linking. In some embodiments, the at least one treatment light promotes corneal or scleral collagen cross-linking. In some embodiments, corneal or scleral collagen cross-linking strengthens the cornea and/or sclera, or reduces or treats infections in the eye. In some embodiments, the light control device comprises a light modulating device which partially or entirely blocks or unblocks the part or all of the light source array, providing the discontinuous treatment light projection on the eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the light modulating device is a shutter or filter. In some embodiments, the light modulating device is manually operated. In some embodiments, the light modulating device is operatively connected to a controller which controls movement of the light modulating device. In some embodiments, the controller comprises a microprocessor for controlling the blocking or unblocking of the part or all of the light source array. In some embodiments, the controller comprises an input for operator selection of parameters and duration for the discontinuous light projection on the cornea and/or sclera. In some embodiments, the light control device comprises an intensity control device which adjusts intensity of part or all of the light source array, providing the adjusted intensity treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the intensity control device is manually operated. In some embodiments, the intensity control device comprises a microprocessor to adjust intensity of part or all of the light source array. In some embodiments, the intensity control device comprises an input for operator adjustment of light intensity. In some embodiments, the system further comprises a pattern control device which provides patterned treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the pattern control unit is part of a light mask. In some embodiments, the pattern control unit comprises at least one filter or shutter. In some embodiments, the pattern control unit comprises a microprocessor which controls movement of the pattern control unit. In some embodiments, the pattern control device comprises an input for operator control of the patterned treatment light projection. In some embodiments, the pattern control unit moves. In some embodiments, the pattern control unit rotates. In some embodiments, the system further comprises a control unit which adjusts movement of the pattern control device. In some embodiments, the system further comprises a sensor device. In some embodiments, the blocking and unblocking of part or all of the light source array, or the adjusting of the intensity of part or all of the light source array, is controlled or adjusted according to data collected from the sensor device. In some embodiments, the sensor device is an optical collection device. In some embodiments, the optical collection device collects photoluminescent emissions from an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the sensor device comprises a photoluminescent monitoring module which measures the intensity of photoluminescent emissions from an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the photoluminescent monitoring module comprises a first band pass filter connected to the output of the optical collection device, the first band pass filter having a center wavelength corresponding to the peak of fluorescence emission of the photosensitizer, and a first sensor which receives the output of the first band pass filter output to produce a first output signal dependent on the detected fluorescence emission from the eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the photoluminescent monitoring module further comprises a second band pass filter connected to the output of the optical collection device in parallel with the first band pass filter, the second band pass filter having a center wavelength corresponding to the peak of phosphorescence of an excited state of the photosensitizer, a second sensor which receives the output of the second band pass filter to produce a second output signal dependent on the intensity of detected phosphorescence from the eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the system further comprises a processor which receives first and second output signals and which is configured to process the first output signal and produce an output signal which varies in response to variations in a concentration of the photosensitizer in an eye. In some embodiments, the sensor device comprises an environmental monitoring module which monitors concentrations of photosensitizer, oxygen, or both in the eye. In some embodiments, the system further comprises a fixation light upon which an eye is focused, providing a static treatment area. In some embodiments, the system further comprises a periodical visual or audio cue. In some embodiments, the system further comprises an auxiliary light source configured to be turned on if the at least one treatment light is discontinued or adjusted. In some embodiments, the optical treatment head is positioned at a working distance from the eye sufficient to allow access to the eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the working distance is at least two inches. In some embodiments, the working distance is about three inches. In some embodiments, the working distance is from about three inches to about six inches. In some embodiments, the light source device comprises at least one single-wavelength light source. In some embodiments, the light source device comprises a plurality of single-wavelength light sources. In some embodiments, the at least one single-wavelength light source is an LED or a laser diode. In some embodiments, the light source device comprises a multi-wavelength light source. In some embodiments, the light source device further comprises a wavelength control device operatively coupled to the multi-wavelength light source. In some embodiments, the wavelength control device allows transmission of treatment light of at least one predetermined wavelength band and blocks transmission of light outside of the predetermined wavelength band. In some embodiments, the multi-wavelength light source comprises a short-arc lamp. In some embodiments, the short-arc lamp is a mercury lamp, a mercury halide lamp, or a xenon lamp. In some embodiments, the multi-wavelength light source further comprises a beam isolator configured to direct treatment light of wavelength ranging from about 330 to about 380 nm to the wavelength control device. In some embodiments, the beam isolator is configured to direct both UVA and blue light to the wavelength control device. In some embodiments, beam isolator comprises a UVA and blue light reflective dichroic mirror. In some embodiments, the wavelength control device allows selective transmission of treatment light of at least two different predetermined wavelength bands. In some embodiments, the wavelength control device comprises at least first and second filters and a controller configured to alternate between the first and second filters. In some embodiments, the first filter is a UVA filter and the second filter is a blue light filter. In some embodiments, the UVA filter has about 10 nm bandwidth at 365 nm and the blue light filter has about 10 nm bandwidth at 405 nm. In some embodiments, the system further comprises a support stand, an adjustable mounting assembly on a support stand, the optical treatment head supported on the mounting assembly, wherein the mounting assembly is configured for X and Y directional adjustment of the position of the optical treatment head relative to the eye. In some embodiments, the adjustable mounting assembly comprises a goose neck mounting arm connected to the optical treatment head. In some embodiments, the mounting assembly comprises an articulated arm having a first end mounted for vertical sliding adjustment on the support stand and a second end supporting the optical treatment head. In some embodiments, the mounting assembly includes a swivel joint configured for adjustment of an angle of the light beam directed from the optical treatment head to the eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the system comprises a first and a second optical treatment head, each having a light source array. In some embodiments, the first and the second optical treatment heads each independently project treatment light onto the left eye (e.g., the cornea and/or sclera of the left eye) or the right eye (e.g., the cornea and/or sclera of the right eye). In some embodiments, the system comprises a mounting assembly having a first portion and second portion each independently associated with one of the two optical treatment heads. In some embodiments, the mounting assembly comprises an articulated arm assembly having a first portion slidably associated with the support stand, the first portion and second portions of the mounting assembly being pivotally connected to the first portion of the articulation arm assembly. In some embodiments, one of the end portions is articulated. In some embodiments, the mounting assembly further comprises first and second swivel joints between the first and second optical treatment heads, respectively. In some embodiments, the system further comprises locking devices configured for releasable locking the first optical treatment head and the second optical treatment head, at a selected X, Y and Z adjusted position relative to a respective eye of a patient. In some embodiments, the system comprises a first and a second optical treatment head each including projection optics and configured to project respective treatment light onto the right and left eyes (e.g., the cornea and/or sclera of the left and right eyes) at a predetermined working distance from the optical heads. In some embodiments, the first optical treatment head and second optical treatment head are adjustably mounted for at least x and y direction adjustment of the position of the optical treatment head relative to the respective eyes. In some embodiments, the system further comprises an intensity adjustment module configured to independently adjust intensity of part or all of the light source array projected by the first optical treatment head and second optical treatment head. In some embodiments, the system further comprises an adjustable mounting assembly configured for adjusting the separation between the first and second optical treatment heads and the distance of each optical treatment head from the respective eyes. In some embodiments, the adjustable mounting assembly includes independent swivel joints configured for adjusting an angle of each optical head relative to the respective eye. In some embodiments, the system further comprises an adjustment mechanism configured for varying distance of the optical treatment head from the eye. In some embodiments, the light source device further comprises an aesthetic light which is visible to an observer, and optionally not visible to a patient. In some embodiments, the light source device further comprises a plurality of aesthetic lights which are visible to an observer, and optionally not visible to a patient. In some embodiments, the aesthetic lights are activated when the light source device is activated and providing the at least one treatment light. 
     Described herein, in certain embodiments, are methods of producing 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). In some embodiments, the method comprises 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). In some embodiments, the method further comprises 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. In some embodiments, the method further comprises 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). In some embodiments, the method further comprises 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). In some embodiments, the method further comprises 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. In some embodiments, the method further comprises contacting the eye (e.g., the cornea and/or sclera of the eye) with a photosensitizer. In some embodiments, the photosensitizer is riboflavin, rose Bengal, other photosensitizers, or derivatives thereof. In some embodiments, the method further comprises 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) is based on the level of photoluminescent emissions. In some embodiments, the method further comprises 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. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of an embodiment of a bilateral treatment system or photochemical treatment and monitoring system; 
         FIG. 2  is a block diagram illustrating the optical source unit of  FIG. 1 ; 
         FIG. 3  is a view of an embodiment of the front control panel of the illumination source unit of  FIG. 2 ; 
         FIG. 4  is a top perspective view of the bilateral optical head of  FIG. 1 ; 
         FIG. 5  is a cross-sectional view of an embodiment of an optical treatment head; 
         FIG. 6  is a perspective view of the left hand optical treatment head and housing with sensor attached, of  FIG. 1 ; 
         FIG. 7  is a layout view of the intensity adjustment mechanism for the excitation light guides; 
         FIG. 8A  is a cross-sectional view through an eye with a normal cornea and/or sclera; 
         FIG. 8B  is a cross-sectional view through an eye affected by keratoconus offset from the central axis of the eye; 
         FIG. 9  is a side cross sectional view of the left hand optical delivery and sensor head of  FIG. 4 ; 
         FIG. 10  is a bottom view the left hand optical delivery and monitoring head of  FIG. 4 ; 
         FIG. 11  is a component layout view of one embodiment of a photo luminescent measuring module in the system of  FIGS. 1 to 10 and 15 , with the inputs from the bifurcated light guides from each optical head and the photodiodes and amplifiers for monitoring the fluorescence and phosphorescence from each eye; 
         FIG. 12  shows a top view of one embodiment of a dodging tool for use in evaluating lateral riboflavin dispersion in conjunction with fluorescent intensity monitoring; 
         FIG. 13  is a perspective view of one embodiment of a corneal and/or scleral treatment head with sensor device and manually operated mechanical light modulating device (for example, a shutter and/or filter); 
         FIG. 14  is a perspective view of one embodiment of a corneal and/or scleral treatment head with sensor device and microprocessor-controlled mechanical light modulating device (for example, a shutter and/or filter) attached; 
         FIG. 15  is a perspective view of one embodiment of a corneal and/or scleral treatment head with sensor device attached, and microprocessor-controlled dimmer switch attached to the light source and sensor device; 
         FIG. 16  is a perspective view of one embodiment of a corneal and/or scleral treatment head with sensor device and manually operated filter systems attached; 
         FIG. 17  is a perspective view of one embodiment of a corneal and/or scleral treatment head with sensor device and automatically operated filter system attached to microprocessor and sensor device; 
         FIG. 18  is a perspective view of one embodiment of a rotating radiation pattern assembly which is attached to the corneal and/or scleral treatment head casing; 
         FIG. 19  is a perspective view of one embodiment of a filter with an aperture which allows for unequal doses of UVA/blue light to be applied to various portions of the treatment area; 
         FIG. 20  illustrates one embodiment of a kit of optical masks or reticles with treatment light transmitting openings of various different patterns, shapes, and sizes; 
         FIG. 21  is a perspective view of one embodiment of an additional light source utilized to reduce the startling effect by mitigating dramatic changes in light intensity or color seen by the patient; 
         FIG. 22  is a perspective view of one embodiment of a fixation light; 
         FIG. 23  is a front perspective view of another embodiment of an ophthalmic treatment system or device for corneal and/or scleral treatment; 
         FIG. 24  is a rear perspective view of the ophthalmic treatment system of  FIG. 23 ; 
         FIG. 25  is a perspective view of the control system housing and touch screen user interface of  FIGS. 23 and 24 , with the front wall of the control system housing broken away to reveal internal parts of the system; 
         FIG. 26  is bottom plan view of one of the treatment heads of  FIGS. 23 and 24 ; 
         FIG. 27  is a view similar to  FIG. 26  with the lower wall of the treatment head housing removed to reveal the internal system components; 
         FIG. 28  is a cross-sectional view on the lines  28 - 28  of  FIG. 27 ; 
         FIG. 29  is a front plan view of the reticle wheel of  FIG. 28 ; and 
         FIG. 30  is a block diagram of the system of  FIGS. 23 to 29 . 
     
    
    
     It should be understood that the drawings are not necessarily to scale and that the disclosed embodiments are sometimes illustrated diagrammatically and in partial views. In certain instances, details which are not necessary for an understanding of the disclosed apparatus or method which render other details difficult to perceive are omitted. It should be understood, of course, that this disclosure is not limited to the particular embodiments illustrated herein. 
     DETAILED DESCRIPTIONS 
     The present disclosure relates generally to ophthalmic device, system, and method for treating a cornea or sclera of an eye, 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, in certain embodiments, are ophthalmic treatment systems, comprising a light source device or light source array and a light control device, which blocks or unblocks the part or all of the light source array for predetermined intervals, and which may be configured to provide patterned or discontinuous treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye); or which may adjust intensity of part or all of the light source array, providing adjusted intensity treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye). In some embodiments, the light source may comprise a plurality of light sources. 
     As used herein, “light source array” means an ordered or disordered arrangement of at least one light source. In some embodiments, the light source array comprises one light source. In some embodiments, the light source array comprises 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. 
     Discontinuous/Adjustable/Patterned Light Projection 
     In some embodiments of the ophthalmic treatment systems disclosed herein, the light control device includes a manual or 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) is 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). In some embodiments, the on/off times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is controlled manually. In another embodiment, the on/off times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is controlled automatically based on input by the physician at a control unit to determine overall treatment time and duration of on/off cycles. In another embodiment, the on/off times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is microprocessor-controlled on the basis of the ratio of riboflavin phosphorescence at 605 nm in relation to riboflavin fluorescence at 525 nm detected from a measurement/sensor device in each treatment head. As the ratio of triplet state riboflavin phosphorescence of 605 nm/525 nm fluorescence drops, the microprocessor controls on/off times in accordance with the riboflavin concentration and/or oxygen partial pressure. 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 another embodiment, the discontinuous/adjustable/patterned light projection device is provided separately for use in other commercially available UVA/blue light emitting devices. 
     In some embodiments of the ophthalmic treatment systems, the light control device includes a manual or 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). In some embodiments, the filtered/unfiltered times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is 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). In some embodiments, the filtered/unfiltered times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is controlled manually. In another embodiment, the filtered/unfiltered times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is automatically based on input by the physician at a control unit to determine overall treatment time and duration of filtered/unfiltered cycles. In another embodiment, the filtered/unfiltered times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) are microprocessor-controlled on the basis of the ratio of riboflavin phosphorescence at 605 nm in relation to riboflavin fluorescence at 525 nm detected from a measurement/sensor device in each treatment head. As the ratio of triplet state riboflavin phosphorescence of 605 nm/525 nm fluorescence drops, the microprocessor controls filtered/unfiltered times in accordance with the riboflavin concentration and/or oxygen partial pressure. 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. In some embodiments, the dim/bright times for the adjustable projection of treatment light on the eye (e.g., the cornea and/or sclera) is 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). In some embodiments, the dim/bright times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is controlled manually. In another embodiment, the dim/bright times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) is automatically based on input by the physician at a control unit to determine overall treatment time and duration of dim/bright cycles. In another embodiment, the dim/bright times for the discontinuous projection of treatment light on the eye (e.g., the cornea and/or sclera) are microprocessor-controlled on the basis of the ratio of riboflavin phosphorescence at 605 nm in relation to riboflavin fluorescence at 525 nm detected from a measurement/sensor device in each treatment head. As the ratio of triplet state riboflavin phosphorescence of 605 nm/525 nm fluorescence drops, the microprocessor controls dim/bright times in accordance with the riboflavin concentration and/or oxygen partial pressure. When the light is 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 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 20 mm Hg partial pressure the Type II singlet oxygen reaction predominates. Under conditions of subnormal oxygen availability (less than 5 mm 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 3.0 mw/ cm2 UVA and 0.1% 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 500-micron thick cornea and the reported literature value of 35 micromolar oxygen in the stroma, the total amount of oxygen in the cornea is about 1.4×10-9 moles. The quantum yield of singlet oxygen from riboflavin irradiation is 0.52, indicating that approximately 2 photons of absorbed energy consume 1 unit of molecular oxygen. Accordingly, only 2.8×10-9 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 1 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. 
     Photosensitizer/Oxygen Monitor 
     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&#39;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 systems 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 605 nm in relation to riboflavin fluorescence at 525 nm. As the ratio of triplet state of riboflavin phosphorescence of 605 nm/525 nm 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. 30:100). 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. 
     Projection Distance 
     In some embodiments, the projection optics are configured to provide a distance of the patient&#39;s eye from the optical head of approximately two inches or greater. Other working distances, such as about three inches or from about three inches to about six inches, are provided in alternative embodiments. The increased working distance between the optical head and patient&#39;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. 
     Fixation Light 
     In some embodiments, the ophthalmic treatment systems 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&#39;s eyes naturally deviate from the desired position. Fixing the patient&#39;s line of sight, such as on a fixation light, allows the patient&#39;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&#39;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&#39;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&#39;s attention. 
     Auxiliary Light Source 
     In some embodiments, the ophthalmic treatment systems comprises another light source in addition to the UVA/blue treatment light which is 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 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 blue treatment bean is turned on and off. In some embodiments, 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. 
     Light Source 
     In some embodiments, the 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 340 nm to 470 nm 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. 
     Wavelength Control Device 
     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/or light in a blue or blue-violet band). In some embodiments, two different filters are provided which are selectively positioned in the light path, allowing selection of excitation energy in the UVA band at 365 nm, or a narrow band of blue-violet radiation at 405 nm. The option of UVA or 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 365 nm is about 10,000 and at 405 nm, the extinction coefficient is about 8000. If the riboflavin in the cornea and/or sclera is 0.003 molar, the 365 nm radiation deposits about 75% of its energy to the riboflavin in the first 200 microns of the tissue, whereas with the 405 radiation only about 68% of the beam is absorbed in the first 200 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 is used in some embodiments since the energy is absorbed more quickly and less energy reaches the endothelium. For patients with thicker corneas and/or scleras, blue light is used in some embodiments to penetrate deeper into the cornea and/or sclera. In a conventional procedure that uses 365 nm radiation, deepithelialization and 0.1% riboflavin soaking, cross-linking occurs to a depth of about 200 microns, while damage (apoptosis) occurs deeper, at about 300 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. This technical feature is heretofore unknown as currently marketed systems use monochromatic LEDs and do not allow for selectable excitation wavelengths. 
     One technical feature of the present disclosure heretofore unknown 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 10,066 cm-1 /M at 365 nm but the molar extinction coefficient of riboflavin is only 7884 cm-1 /M at 405 nm. 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=2−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 0.1% solution of riboflavin at a depth of 500 microns the absorption value at 365 nm is calculated as A=1.10. The value of A for the same solution and path length for 405 nm radiation is calculated as A=0.86. From the formula A=2−log10% T it is shown that 64% of the incident energy of 365 nm radiation is absorbed by riboflavin in the first 200 microns of the cornea and/or sclera. The same calculations at 405 nm indicate only 55% of the radiation is absorbed by the riboflavin in the first 200 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 405 nm. If shallow cross-linking is more desirable, the user has the option to select a less penetrating wavelength, such as 365 nm. 
     An additional feature of the 405 nm 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 365 nm and 405 nm to its higher energy states. By the formulation E=hv it is determined that a 405 nm photon is 10% less energetic than a 365 nm photon, and that to have equivalent stoichiometric reactions at 405 nm and 365 nm the incident UVA light fluence is reduced to 90% of the blue light fluence. 
     Another additional 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. 
     Optical Coupling 
     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. 
     Bilateral Treatment 
     In some embodiments, the ophthalmic treatment systems is monocular, with a single optical treatment unit including the optical treatment head. In other embodiments, the ophthalmic treatment systems 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 blue light beam on a patient&#39;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 lights. 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 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&#39;s eye during treatment. Some embodiments allow monitoring of critical variables during treatment as well as variation of the treatment criteria, for example switching between UVA and blue or blue-violet light, varying the light intensity, providing a fixation light to prevent eyes from wandering, utilizing an additional light source to prevent the startling effect, varying the beam shape and size, and using a discontinuous/adjustable 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. 
     Non-Limiting Examples 
     Certain embodiments as disclosed herein provide for an ophthalmic treatment system and method. 
     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. 
       FIGS. 1 to 12  illustrate one embodiment of a bilateral system for photochemical ocular treatment such as corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer. In this embodiment, UVA/blue light is used for the excitation energy. Referring to  FIGS. 1 and 2 , an illumination source unit  10  contains a multi-spectral light source  11  that delivers a user-selected excitation wavelength to bifurcated, UV transmissive liquid light guide  18 . The light guide splits into separate light guide outputs  21  and  22  that are connected to illumination intensity adjustment module  30  mounted on a mobile pole stand comprised of pole  25  mounted on a base  23  with casters. Other support stands of different configuration are used in place of pole  25  with base  23  in alternative embodiments. Outputs of module  30  are connected by light guides  50 ,  51  to respective left and right optical treatment devices or units  150 ,  151 . The right treatment device  151  is described in more detail below in connection with  FIGS. 9 and 10 . The left treatment device  150  is identical to the right treatment device  151 . 
     The pole allows attachment and vertical positioning of an adjustable mounting mechanism including articulating arm  24  on which the treatment devices  150 ,  151  are mounted, and provides mounting points for illumination intensity adjustment module  30  and an optical monitoring module  40 . Modules  10 ,  30  and  40  are combined in a single unit in other embodiments. The illumination source unit  10  is shown as separate from the mobile stand but is affixed to the stand in another embodiment. The end of articulating arm  24  connects to rotating arm  27  which further connects to rotating arm  28 . The distal end of rotating arm  28  carries the two optical treatment devices or units  150 ,  151  encased in housing units  260 ,  261  on adjustable arms  29 A,  29 B. Each housing unit includes an externally mounted sensor  158 ,  159 . Each housing unit holds in place an optical treatment device  150 ,  151 . Each optical treatment device includes an optical treatment head  81  which directs light onto the patient&#39;s eye, in addition to other components described in more detail below in connection with  FIGS. 9 and 10 . In some embodiments, light guides  18 ,  21 ,  22 ,  50  and  51  which conduct the excitation energy to each optical treatment head are 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. In alternative embodiments, the light sources and other system components may be mounted in the respective treatment heads. 
       FIG. 2  illustrates the layout of the illumination source assembly with an ellipsoidal reflector short-arc lamp  11  as the light source, as in the first embodiment. In some embodiments this lamp is a 100 watt short-arc mercury or mercury halide lamp. In a different embodiment, this lamp is a  100  watt short-arc xenon lamp that is characterized by a lower UVA output and a greater continuum of high intensity blue wavelength light. Microprocessor  17  controls the opening and closing of light modulating device (for example, a shutter and/or filter)  12  that either blocks or allows passage of radiation emitted from the lamp. Light modulating device (for example, a shutter and/or filter)  12  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)  12  is affixed to a rotary solenoid  160  to affect the opening and closing operation. Rotary solenoids are high reliability components with normal lifetimes exceeding 1 million cycles. When light modulating device (for example, a shutter and/or filter)  12  is opened, the light from the lamp reflector is collected by collimating lens  13  and directed to dichroic 45 degree turning mirror  14  that reflects UVA and blue light in a wavelength range of around 340 nm to 470 nm, while passing infrared radiation. The reflected light from the mirror is collected by focusing lens  15  and directed through one of the filters on filter assembly  16  into the input of bifurcated light guide  18 . Filter assembly  16  is on a slide mechanism connected to an actuating switch on the front panel. Two narrowband band pass filters  16 A,  16 B are mounted on the optics filter assembly  16  and an actuating switch position determines which band pass filter is placed in front of the light guide. In some embodiments, filter  16 A is a UVA filter that has a 10 nm bandwidth (FWHM) at 365 nm and filter  16 B has a 10 nm bandwidth (FWHM) at 405 nm. 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  30 , selection between the UVA and blue light filters  16 A and  16 B, and positioning of the optical treatment heads. In an alternative embodiment, these features are 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  16 A,  16 B, and intensity adjustment module  30 . An automatic emergency shut off feature is provided in some embodiments. 
       FIG. 3  illustrates one embodiment of a control panel  110  provided on the front of illumination source unit  10  including user input devices and display unit  123 . In other embodiments, the controller is 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  110  has a manual wavelength selection control switch  20  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  19  to switch between continuous and discontinuous illumination. Soft key inputs  121  below display  123  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  FIGS. 1 and 4 , 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&#39;s eyes. 
       FIG. 4  is an enlarged top plan view of the articulated arm assembly and treatment devices  150 ,  151  of  FIG. 1 . The height adjustment wheel  26  shown in  FIG. 1  provides for vertical adjustment of the arm. Lateral adjustment of the optical heads to accommodate different interpupillary distance is provided by the pivot arms  29 A, and  29 B on the distal end of the articulating arm, as illustrated in  FIG. 4 . When knob  405  is loosened, both arms  29 A and  29 B are free to pivot around the center of arm  28  and knobs  406 ,  407  are loosened to telescope arms  29 A,  29 B to adjust the interpupillary distance and to align each optical head with the respective eyes of a patient. When optical heads on arm  29 A,  29 B are positioned over the eyes of the patient, knobs  405 - 407  are tightened to fix the position. Heads  260  and  261  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&#39;s eyes for bilateral operation. Knobs  408  and  409  are tightened to secure the position of the optical heads over the patient&#39;s eyes. In alternative embodiments, the manual positioning knobs are eliminated and another system is provided for vertical and horizontal positioning of the treatment heads. 
     In alternative embodiments, the manual positioning knobs are eliminated and a remotely controlled drive system is 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 embodiment of  FIGS. 23 to 29 . 
     In the ophthalmic treatment system of  FIGS. 1 to 11 , the at least one treatment light beam of each optical head is directed concentric to the optical axis passing through the center of the cornea to the center of the lens in some embodiments. 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 is desirable to place the optical axis of the illumination beam concentric with the central axis of the apical distortion in some embodiments to maximize the radiation concentrically around the apical distortion.  FIGS. 8A and 8B  illustrate one example of the apical distortion of keratoconus compared to a normal cornea.  FIG. 8A  illustrates an eye  500  with a normal cornea  502 , with the dotted line  504  representing the optical axis passing through the center of the cornea.  FIG. 8B  illustrates eye  500  with keratoconus causing an off-axis conical distortion and resultant thinning of the cornea at  506 . This requires an XYZ positioning flexibility for the optical head, and this is achieved in one embodiment by the mechanical arrangement shown in  FIG. 4  as described above. 
     The output light intensity adjustment for each eye in the system of  FIGS. 1 to 17  is accomplished using the intensity adjustment module  30  illustrated in layout view in  FIG. 7 . Mechanical brackets are affixed to the output light guides and these brackets are connected to commercial screw-driven linear slides  31  and  32 . The bifurcated input light guide ends  21  and  22  are fixed at the bottom of the module. Turning the externally accessible knobs on slides  31  and  32  clockwise advances the delivery light guides  50  and  51  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 0.01 mw/cm2 is obtained in this embodiment. In another embodiment, adjustable neutral density filters are placed between the input and output light guides but these filters are often subject to long term UVA deterioration. 
       FIG. 7  illustrates the maximum intensity adjustment for excitation light guide  51  and the minimum intensity adjustment for excitation light guide  50 . 
     In the illustrated embodiment, a manually operable switch  55  allows a user to convert from bilateral to monocular operation. Switch  55  is connected to light modulating device (for example, a shutter and/or filter)  56 . In the position of light modulating device (for example, a shutter and/or filter)  56  as shown in  FIG. 7  the light entering from light guide  21  is blocked from entering the delivery light guide  51  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. In alternative embodiments, the manual switch is 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 is used in some embodiments 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  151  is illustrated in more detail in  FIGS. 5, 9 and 10 . As illustrated, each optical treatment device comprises optical treatment head  155  vertically mounted on support  154  at the end of the respective arm  29 A or  29 B, and optical collection device  158  also mounted on support  154  adjacent the optical treatment head  155 , as illustrated in  FIG. 9 . Treatment head  155  incorporates an optical mask or reticle holder  80  in which a selected reticle or mask  90  may be positioned for controlling shape and/or size of the output treatment beam projected from treatment head  155  via projection optic or lens  81  located at the output port of the treatment head. Aiming or positioning apparatus  65 ,  66  mounted in each optical treatment unit  150  and  151  assists an operator in positioning the projection optic or lens  81  at a desired working distance from the cornea. In the embodiment of  FIGS. 5, 9 and 10 , the aiming devices  65 ,  66  are laser diodes. The distance of optic  81  from the cornea is determined to be equal to the desired working distance when the two aiming beams from laser diodes  65  and  66  coincide with each other as a single spot on the patient&#39;s eye. If the aiming beams do not cross at the eye, the height adjustment knob  26  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&#39;s eyes. 
     In one embodiment, filters  85  or  86  may be selectively positioned in the path of the aiming beams emitted from aiming devices  65 ,  66  via mechanical slide  84  (see  FIG. 10 ). This may provide a secondary use to the aiming beams for providing red light phototherapy to ameliorate oxidative damage to the cells. In another embodiment, the aiming devices  65 ,  66  may be red or green light laser diodes with no filters in the output path. 
     In some embodiments, the ophthalmic treatment system also includes monitoring system  40  for the photoluminescence emitted from the riboflavin interaction with UVA/blue light, using optical collection device  158  as illustrated in  FIG. 9 . 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 525 nm. The average quantum yield for riboflavin in aqueous solutions is about 0.3, meaning that the ratio of photons emitted/photons absorbed is about 0.3. The second mechanism for relaxation from the Si 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 605 nm. Since phosphorescence is a direct measure of the active species that creates singlet oxygen, optical collection device  158  and optical monitoring device  40  of  FIG. 11  are configured to monitor both the fluorescent and phosphorescent signals. 
     Optical collection device  158  of  FIG. 9  comprises light collection lens  83  and bifurcated light guide  70  which receives the light collected by lens  83 . This bifurcated light guide has one single end that splits into two output ends  70 A,  70 B. The lens  83  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  185  of the single-ended portion  70  of the bifurcated light guide. The light guide in some embodiments provides 50% of the proximal input light into each of the two distal light guide portions  70 A,  70 B. The distal portions of the light guides are routed to the optical monitoring module  40  shown in layout view on  FIG. 11 . The optical heads or ends  185  on each of the light guides  70 ,  71  of the treatment devices  150  and  151  receive the photoluminescent emissions from the irradiated corneas and/or scleras of the patient&#39;s left and right eyes, and the emission light is transmitted by light guides  71  and  70 , respectively, into left eye guide portions  71 A,  71 B and right eye guide portions  70 A,  70 B. 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  42  and  43  for separating fluorescence emission from phosphorescence emissions for each eye, as illustrated in  FIG. 11 . Filter  42  is a narrowband band pass filter with a center wavelength of 525 nm-535 nm to capture the peak of the fluorescence emission from the riboflavin. Filter  43  is a narrowband band pass filter centered at 600 nm-605 nm 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 are monitored in some embodiments. The filtered emission light from each light guide is directed onto a respective sensor  41 , which comprises a PIN silicon photodiode  41  that incorporates an integral preamplifier or thermoelectric cooling, and the output voltage of the photodiode is transmitted to high impedance amplifier  45  for conversion of the photonic energy into voltage. Alternatively, items  41  and  45  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 (10 −15  watts). 
       FIG. 12  illustrates one embodiment of a hand held dodging fixture or tool  250  that may be used to provide a relative measure of the lateral dispersion of riboflavin in the eye. Tool  250  has a handle  202  with a plastic holder  201  at one end which holds a UV transparent/visible blocking glass with a 3 mm hole drilled at its center. Commercial glasses such as Schott UG 11 and Schott BG 4, respectively, are suitable for use with UVA and blue treatment light, respectively. The only emitted light to reach the collection device  158  is via the hole in the center of glass  200 . The dodging fixture may be held over the central cornea and the resultant fluorescence reading from the optical monitoring module  40  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. 
     In some embodiments, the phosphorescence of the riboflavin triplet state is 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  158  and photoluminescence monitoring unit  40 , as described above. The light modulating device (for example, a shutter and/or filter)  305 ,  315  in  FIGS. 13 and 14  provides discontinuous light projection and the operation of the light modulating device (for example, a shutter and/or filter) cycle in one embodiment is directed by the operator by the soft key inputs on the control panel shown in  FIG. 3 . 
       FIG. 6  illustrates a perspective view of the right hand optical collection device  158  in housing  264  with optical collection node  83  encased by head unit  280 . Housing unit  264  is attached to casing unit  260  which envelopes the right hand optical treatment device shown in  FIGS. 5, 9 , and  10 . Mounting unit  262  is attached to the treatment end of casing unit  260 . Mounting unit  262  is fitted in each corner with holes  271 - 274  such that another plate is affixed to the unit with a screw and nut, or like method. 
       FIGS. 1 and 13-18 , illustrate several embodiments of a bilateral system for discontinuous/adjustable/patterned photochemical ocular treatment such as corneal and/or scleral collagen cross-linking using riboflavin as a photosensitizer. In those embodiments, UVA/blue light is used for the excitation energy. Referring to  FIGS. 1 and 2 , an illumination source unit  10  contains a multi-spectral light source  11  that delivers a user-selected excitation wavelength to bifurcated, UV transmissive liquid light guide  18 . The light guide splits into separate light guide outputs  21  and  22  that are connected to illumination intensity adjustment module  30  mounted on a mobile pole stand comprised of pole  25  mounted on a base  23  with casters. Other support stands of different configuration are used in place of pole  25  with base  23  in alternative embodiments. Outputs of module  30  are connected by light guides  50 ,  51  to respective left and right optical treatment devices or units  150 ,  151 . As described in detail above, the ophthalmic treatment system also includes monitoring system  40  for the photoluminescence emitted from the riboflavin interaction with UVA/blue light, using optical collection device  158  as illustrated in  FIG. 9 , and shown encased in housing unit  264  in  FIG. 6 . The left treatment device  260  is described in more detail below in connection with  FIGS. 13 to 18 . The right treatment device  261  is identical to the left treatment device  260 . 
       FIG. 13  illustrates a manually operated mechanical light modulating device (for example, a shutter and/or filter) housed in mounting unit  300  which is affixed to treatment mounting unit  262  at points  271 - 274 , with a screw and nut, or like method, through points  301 - 304 . When lever  306  is moved to the down position, mechanical light modulating device (for example, a shutter and/or filter)  305  will open, allowing UVA/blue light from treatment head  81  to pass unobstructed onto the treatment area. Mechanical light modulating device (for example, a shutter and/or filter)  305  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  264  mounted to treatment head casing  260 , and connected to monitoring system  40 ,  FIG. 1 . Light collection guide  71  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  264 . The mechanical light modulating device (for example, a shutter and/or filter) remains open for a period of photochemical crosslinking lasting 15 seconds to 10 minutes. Lever  306  is then moved to the up position, closing mechanical light modulating device (for example, a shutter and/or filter)  305 . When mechanical light modulating device (for example, a shutter and/or filter)  305  is closed, no UVA/blue light from optical treatment head  81  will reach the treatment area. The mechanical light modulating device (for example, a shutter and/or filter) remains closed for a period of 15 seconds to 10 minutes in some embodiments 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. 14  illustrates an automatic mechanical light modulating device (for example, a shutter and/or filter) housed in mounting unit  310  which is affixed to treatment mounting unit  262  at points  271 - 274 , with a screw and nut, or like method, through points  311 - 314  ( 313  and  314  not shown). Automatic control unit  316  is affixed to mounting unit  310 , and connected by cable  317  to UVA light source housing and control unit  10 ,  FIGS. 1, 2 . When treatment begins, mechanical light modulating device (for example, a shutter and/or filter)  315  is opened by control unit  316 , allowing UVA light from treatment head  81  to pass unobstructed onto the treatment area. The mechanical light modulating device (for example, a shutter and/or filter)  315  remains open for a treatment session of 15 seconds to 10 minutes, off-set by periods of discontinuous illumination lasting 15 seconds to 10 minutes. When mechanical light modulating device (for example, a shutter and/or filter)  315  is closed, no UVA/blue light from optical treatment head  81  reaches the treatment area. Duration of discontinuous illumination, and number of treatment cycles is set on display control unit  110 ,  FIG. 3 . In one embodiment, UVA or blue light may be provided in a fractionation cycle of 15 seconds ON/15 seconds OFF, and in this case the shutter is opened and closed automatically. 
     In another embodiment, automatic control unit  316  affixed to mounting unit  310  is connected by cable  317  to optical collection monitoring system  40 ,  FIG. 1, 11 . When treatment begins, mechanical light modulating device (for example, a shutter and/or filter)  315  is opened by control unit  316 , allowing UVA light from treatment head  81  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  40  (not shown), determines singlet oxygen levels are sufficiently depleted. Light modulating device (for example, a shutter and/or filter)  315  is then automatically closed, allowing no UVA/blue light from optical treatment head  81  to reach the treatment area. Light modulating device (for example, a shutter and/or filter)  315  remains closed for a period of time lasting 15 seconds to 10 minutes. This process is repeated until treatment is complete. 
       FIG. 15  illustrates a manually or automatically controlled dimmer unit  320  mounted on a mobile pole stand comprised of pole  25  mounted on a base  23  with casters. Other support stands of different configuration are used in place of pole  25  with base  23  in alternative embodiments. During treatment, dials  321 - 324  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 0% to 100% intensity will mitigate the startling effect. The UVA/blue light remains at 100% 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  264  mounted to treatment head casing  260 , and connected to monitoring system  40 . The UVA/blue light remains at 100% intensity for a period of time lasting 15 seconds to 10 minutes. Knobs  321324  are then engaged to gradually decrease the intensity of the UVA/blue light from 100% to at or near 0%, in order to mitigate the startling effect. At or near 0% intensity, little or no UVA/blue light from optical treatment heads reaches the treatment areas. The intensity remains at or near 0% for a period of 15 seconds to 10 minutes to allow for tissue reoxygenation. The process of increasing and decreasing the intensity continues as many times as the physician deems necessary. 
     In another embodiment, intensity is increased and decreased automatically by a microprocessor-controlled dimmer switch housed in dimmer unit  320  (not shown). The microprocessor controlled dimmer switch is connected by cable  325  to UVA light source housing and control unit  10 ,  FIGS. 1,2 . When treatment begins, light intensity is gradually increased to 100% allowing UVA light from treatment head  81  to pass un-dimmed onto the treatment area. The light remains un-dimmed for a treatment session lasting 15 seconds to 10 minutes, off-set by period of discontinuous illumination wherein the light is slowly reduced in intensity from 100% to at or near 0%. Light intensity remains at or near 0% for 15 seconds to 10 minutes. When light intensity is at or near 0%, 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  110 ,  FIG. 3 . 
     In another embodiment, during treatment, intensity is increased and decreased automatically by a microprocessor-controlled dimmer switch housed in dimmer unit  320  (not shown). The microprocessor-controlled dimmer switch is connected by cable  325  to optical collection and monitoring system  40 . When treatment begins, UVA/blue light automatically increases intensity from at or near 0% to 100%. The light intensity remains at 100% until a microprocessor housed in optical monitoring system  40  (not shown), determines singlet oxygen levels are sufficiently depleted. Dimmer unit  320  then automatically reduces UVA/blue light intensity from 100% to at or near 0%, allowing no UVA/blue light from optical treatment heads to reach the treatment area. Light intensity remains at or near 0% for a period of time lasting 15 seconds to 10 minutes. This process is repeated until treatment is complete. 
       FIG. 16  illustrates a manually operated UVA/blue light filter housed in mounting unit  330  which is affixed to treatment mounting unit  262  at points  271 - 274 , with a screw and nut, or like method through points  331 - 334 . UVA filters  336  are held in place by housing units  335  which is slid into mounting unit  330  such that UVA filters  336  are directly in the path of the UVA/blue light emitted by treatment head  81 . When slides  335  are removed from mounting unit  330 , this allows UVA/blue light from treatment head  81  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  264  which is mounted to treatment head casing  260 , and connected to monitoring system  40 ,  FIG. 1 . Light collection guide  71  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  264 . Slides  335  remain clear of mounting unit  330  for a period of time lasting 15 seconds to 10 minutes. Slides 335 are then inserted into mounting unit  330 . When slides  335  are inserted into mounting unit  330 , no UVA/blue light from optical treatment head reaches the treatment area. The slides remain in the mounting unit for a period of 15 seconds to 10 minutes to allow for tissue reoxygenation. The process of inserting and removing the slides continues as many times as the physician deems necessary. 
       FIG. 17  illustrates an automatically operated UVA/blue light filter housed in mounting unit  340  which is affixed to treatment mounting unit  262  at points  271 - 274 , with a screw and nut, or like method, through points  341 - 344 . Automatic control unit  346  is affixed to mounting unit  340 , and connected by cable  347  to optical collection monitoring system  40 ,  FIG. 1, 11, 15 . UVA/blue light filters  345 A are housed in retractable units  345 B controlled by unit  346 . When treatment begins, slides  345 B are retracted, allowing UVA/blue light from treatment head  81  to pass unobstructed onto the treatment area. Filters  345 B remain retracted until a microprocessor housed in monitoring system  40  (not shown), determines singlet oxygen levels are sufficiently depleted. Automatic control unit  346  then slides filters  345 B into the path of light emitted from treatment head  81 . When UVA/blue light filters are in the path of the UVA/blue light emitted from treatment head  81 , no UVA/blue light reaches the treatment area. Filters  345 B remain in the path of the light emitted from treatment head  81  for a period of 15 seconds to 10 minutes. This process is repeated until treatment is complete. 
     In another embodiment, an automatically operated UVA/blue light filter unit housed in mounting unit  340  is affixed to treatment mounting unit  262 . Automatic control unit  346  is affixed to mounting unit  340 , and connected by cable  347  to UVA light source housing and control unit  10 ,  FIGS. 1,2 . When treatment begins, slides  345 B are retracted, by control unit  346  allowing UVA light from treatment head  81  to pass unobstructed onto the treatment area. The slides remain retracted for a treatment period of 15 seconds to 10 minutes, off-set by periods of discontinuous illumination where the slides are engaged, lasting 15 seconds to 10 minutes. When UVA/blue light filters  345 A are obstructing the path of light emanating from treatment head  81 , no UVA/blue light reaches the treatment area. Duration of discontinuous light projection, and number of treatment cycles is set on display control unit  110 ,  FIG. 3   
       FIG. 18  illustrates a rotating UVA/blue light filter assembly,  350 . Filter discs  355 A,  355 B,  355 C, or  355 D allow for variable treatment areas. Filter disc  355 A has a UVA transparent spot  170  offset from the center of the disc, filter disc  355 B has a UVA transparent region  171  of around 90 degrees of the circular disc area with the rest of the disc being solid or black, filter disc  355 C has a UVA transparent region  172  of about 30 degrees with the rest of the disc being solid, and filter disc  355 D has a transparent region of 180 degrees with the rest of the disc being solid. Filter discs with other arrangements of UVA transparent and solid areas may be provided in other embodiments. Filter discs are housed in rotating disc assembly  359 , held in place by pin  361 , and rotated by gear assembly  358 . Light filter assembly  350  is affixed to treatment mounting unit  262  at points  271 - 274  (not shown), with screw and nut, or like method, through points  351 - 354 . Automatic control unit  356  is affixed to filter assembly  350 , and connected by cable  357  to UVA light source housing unit  10 ,  FIGS. 1, 2  (not shown). Before treatment begins, a treatment disc  355 A,  355 B,  355 C, or  355 D is inserted into housing unit  359 . 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  110 ,  FIG. 3 . In the case of disc  355 A, an annular treatment area is provided by one full rotation of the disc. 
       FIG. 19  illustrates a perspective view of a UVA/blue light treatment head and casing with holder  196  for changeable irradiation pattern reticle or mask  190  with handle  195  for positioning purposes.  FIG. 20  illustrates some examples of additional reticles or masks  186 ,  188 ,  189  and  191  to  194  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  191  has an oval aperture, reticle  192  has a slit shaped aperture, reticle  193  has a square shaped aperture, reticle  194  has an annular ring shaped aperture, reticle  186  has two apertures of different shapes, reticle  188  has a pseudo tilde or “squiggly line” aperture, and reticle  189  has a crescent shaped aperture. The squiggly line aperture of reticle  188  may be thicker or wider in one segment, as illustrated, or may be of the same proportions throughout. As illustrated in reticle or mask  186 , 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  190  is positioned in holder  196  by hand in the embodiment of  FIG. 19 , alternative embodiments may have an automatic control unit affixed to housing  260 , 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 embodiment of  FIGS. 23 to 28 ) and the automatic control unit slides the selected reticle or mask into the path of light emitted from treatment head  81 . This may be used in conjunction with a shutter for discontinuous treatment as described above. 
       FIG. 21  illustrates a perspective view of a UVA/blue light treatment head and casing  260  with a secondary non-treatment light source or anti-startle light source  196 . In some embodiments, 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. In one embodiment, light source  196  is 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. 22  illustrates one embodiment of a fixation light  197  in housing  198  attached to a supporting arm or gooseneck  200  which can be manually adjusted so that the fixation light is positioned over the patient&#39;s eyes  199  at a distance of 10 to 24 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  200  to the light. The fixation light is a red light or any other light in the visible spectrum. The fixation light also performs a periodic blink or auditory cue to remind the patient to focus their attention on the fixation point in some embodiments. In another embodiment, each treatment head has its own separate fixation light. 
       FIGS. 23 to 30  illustrate an ophthalmic treatment device or system  400  according to another embodiment 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  400  includes a control unit  401  mounted on a support stand having a wheeled base  410  and a telescoping pole  402  extending upwardly from the base and adjustable via rotatable telescoping pole lock  403  at a desired height. The control unit  401  comprises an enlarged housing  404  at the top of pole  402  and a touch screen user interface unit  405  mounted on top of housing  404 . Treatment heads  406  are supported on respective flexible cable arms or goosenecks  412  extending from housing  404  and components within heads  406  are linked to control unit  401  via a wireless connection or wired connection through arms or goosenecks  412 , as described in more detail below in connection with  FIGS. 27 to 30 . Fixation light  198  of  FIG. 22  is also supported on stand  402  via gooseneck  200  extending from cable junction  403  and adjustable cable arm  414  extending from junction  403  to control unit  401 . 
     As best illustrated in  FIGS. 26 to 28 , in one embodiment each treatment head  406  comprises a generally elongate outer housing  411  secured to gooseneck  412  at one end and having a lower, generally flat wall  413  in which a large UVA/blue light output port  426  is located, along with two adjustment or positioning light output ports  424 A and  424 B for adjustment or positioning light, and a photoluminescence monitor input port  425  (see  FIG. 26 ). As illustrated in  FIGS. 27 and 28 , one side of the housing contains the optical system or light path from UVA and/or blue light emitter or LED  428  to the UVA/blue light output port  426 . The other side of the housing contains printed circuit boards  434  and  435  carrying red and green light adjustment LEDs directed to respective red and green light positioning output ports  424 A and  424 B, respectively, along with associated control circuitry. A third printed circuit board (PCB)  436  carries a photoluminescence sensor or monitor  436  ( FIG. 30 ) which receives input from input port  425 . The output from photoluminescence monitor  436  is communicated via leads in arm  412  to the controller or microprocessor  418  in the control housing  404  at the upper end of stand  400 . 
     As illustrated in  FIGS. 27 and 28 , the UVA or UVA/blue light source  428  has an output directed through light homogenizer or light guide  429  along a light path through lens  438  to  90  degree mirror  440 , which directs the light downward through output port  426  of  FIG. 26 . A mask or reticle wheel  432  is rotationally mounted on shaft  433  in the light path. As illustrated in  FIG. 29 , reticle wheel  432  has a series of openings of different diameter around its periphery. Part of the periphery of wheel  432  extends out through a slot  431  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. In one embodiment, the openings in the pupil or reticle wheel allow adjustment of the beam spot size in the range from around 9 to 12 mm. In an alternative embodiment, a drive motor, stepper, or external gear wheel (as in  FIG. 18 ) may be provided for moving wheel  432  according to a user input at user interface  416 , which may be a touch screen as illustrated in  FIG. 25  or a keypad. Additionally, a plurality of reticle wheels with openings of different sizes and shapes, such as the shapes shown in  FIG. 20  and other alternative shapes, may be provided for selective placement in the light path in place of wheel  432 . The reticle wheel may be replaced manually or automatically under the control of microprocessor  418 , for example as described above in connection with  FIGS. 17 and 18 . 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 this embodiment is a single LED, an array of multiple light sources or LEDs, e.g. two or more LEDs, may be provided as the UVA, blue or UVA/blue light source in alternative embodiments. As illustrated in  FIG. 28 , an anti-startle light source  450  is positioned in the housing directly above UVA LED  428 , and light output from source  450  is directed via light guide or beam homogenizer  451  and lens  439  in a path parallel to the treatment light beam up to 90 degree mirror  441 , which directs the anti-startle light beam downwards through output port  426 . In one embodiment, the anti-startle light source is a green light LED but it may be a visible light of other colors in alternative embodiments. 
     In one embodiment, microprocessor  418  is 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  450  is turned on when the UVA treatment light is off, for the reasons stated above in connection with the embodiment of  FIG. 21 . In one embodiment, the ON and OFF periods for discontinuous UVA treatment may be 15 sec. ON, 15 sec. OFF, and the total treatment time may be of the order of 20 to 30 minutes, with an intensity or irradiance of 3-4 mW/cm 2 . In one embodiment, the irradiance or intensity is gradually increased at the start of each ON period, and gradually dimmed at the end of each ON period down to 0.1 or 0.2 mW/cm 2 , 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 350 to 400 nm or UVA/blue light of wavelength of from  365 - 420  nm for deeper cross-linking is used to deliver an irradiance of from 3 to 30 mW/cm2, in discontinuous cycles variable from 1 second to 1 minute or more, 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  418  from the photoluminescense monitoring device  436 . 
     In this embodiment, 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  424 A and  424 B 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. In other embodiments, a robotic positioning system controlled by the microprocessor may be used to position the treatment heads. 
     In one embodiment, 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 in other embodiments. 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 in one embodiment were parts LT T673 N1S1 25 Z (green LED) and LR T67F-U1AA-1-1 manufactured by Osram GmbH of Munich, Germany, but other red and green LEDs with similar properties may be used in other embodiments. 
       FIG. 30  is a block diagram of the control system for the treatment device of  FIGS. 23 to 30 . As illustrated, microprocessor  445  controls the on/off treatment cycle or discontinuous irradiation  445  of the UVA or UVA/Blue light source or light source array  428 , and also controls turning on and off of the green anti-startle LED  450  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  446  which controls irradiance level based on input from controller  418  in response to programmed instructions or input from the operator. UVA/blue output sensor or monitor  430  detects irradiance level and provides a feedback input to controller  418 . The UV or UVA beam size and shape is controlled by selected reticles in pupil wheel or reticle holder  432  located between the UVA LED and the output port  426  as described above in connection with  FIGS. 28 and 29 , 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  418 . 
     The red and green positioning LEDs  424 A and  424 B are also controlled by microprocessor  418  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  436  is also provided to microprocessor  418  and may be displayed on the display screen or touch screen  416  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  199  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 and methods 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. One embodiment of the system has 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. In another embodiment, the system has 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&#39;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, which is at least 50% greater than the working distance in prior art corneal treatment systems. This provides better visualization for the surgeon as well as better access for discontinuous or diffusion augmentation technique, described in detail above. In some embodiments, provision is made for an adjustable working distance. 
     In some or all of the foregoing embodiments, a highly oxygenated topical solution is 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. In another alternative, a hydrogen peroxide reducing agent or solution is 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 are added to any standard riboflavin solution or as a separate solution applied to the cornea and/or sclera during photochemical treatment in some embodiments. In some or all of the foregoing embodiments, the iodide is kept in ionized (I − ) form. 
     In some embodiments, the disclosed treatment system treats 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. 
     In some embodiments, the disclosed treatment system treats keratoconus, ectasia, Terrien&#39;s marginal degeneration, pellucid marginal degeneration, and corneal melting or ulcer, or normal or weakened corneas that require from 0.25 to 4.0 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. 
     A non-limiting example for using the ophthalmic treatment systems to treat a patient with keratoconus is provided as follows. After topical local anesthesia of the eye, a proprietary sponge (e.g. the sponge disclosed in U.S. patent appplication No. 14/275, 192 filed on May 12, 2014, the contents of which are incorporated herein by reference) is used to gently wipe the surface of the eye to remove tears, mucous, lipids, and other macromolecules, and to mildly disrupt but not remove the epithelium. A surgical sponge is then placed over a selected portion or the entire surface of the cornea and/or sclera, onto which a 0.1% or greater riboflavin solution is applied every 30-60 seconds for 5-30 minutes. During this time, periodic assessments using slit-lamp microscopy are used to assess the concentration and homogeneity of stromal saturation. Thereafter, a custom mask is applied to the surface of the cornea and/or sclera, thereby allowing for UVA or UVA and blue light irradiation of selected areas of the cornea and/or sclera. A UVA or UVA/blue light of wavelength of from 365-420 nm for deeper cross-linking is used to deliver an irradiance of from 3 to 30 mW/cm2, in discontinuous cycles variable from 1 second to 1 minute or more, and through a reticule with an apertures that provides a specific light distribution pattern to cross-link selected areas of the cornea and/or sclera. 
     While only certain embodiments have been set forth, alternative embodiments and various modifications will be apparent from the above descriptions to those skilled in the art. These and other alternatives are considered equivalents and within the spirit and scope of this disclosure. The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles described herein can be applied to other embodiments without departing from the spirit or scope of the invention. Thus, it is to be understood that the description and drawings presented herein represent a presently preferred embodiment of the invention and are therefore representative of the subject matter which is broadly contemplated by the present invention. It is further understood that the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and that the scope of the present invention is accordingly limited by nothing other than the appended claims.